Clonidine tablets

What is this medicine?

CLONIDINE (KLOE ni deen) is used to treat high blood pressure.

This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

COMMON BRAND NAME(S): Catapres

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:

• kidney disease
• an unusual or allergic reaction to clonidine, other medicines, foods, dyes, or preservatives
• pregnant or trying to get pregnant
• breast-feeding

How should I use this medicine?

Take this medicine by mouth with a glass of water. Follow the directions on the prescription label. Take your doses at regular intervals. Do not take your medicine more often than directed. Do not suddenly stop taking this medicine. You must gradually reduce the dose or you may get a dangerous increase in blood pressure. Ask your doctor or health care professional for advice.

Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.

NOTE: This medicine is only for you. Do not share this medicine with others.

What if I miss a dose?

If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.

What may interact with this medicine?

Do not take this medicine with any of the following medications:

• MAOIs like Carbex, Eldepryl, Marplan, Nardil, and Parnate

This medicine may also interact with the following medications:

• barbiturate medicines for inducing sleep or treating seizures like phenobarbital
• certain medicines for blood pressure, heart disease, irregular heart beat
• certain medicines for depression, anxiety, or psychotic disturbances
• prescription pain medicines

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What should I watch for while using this medicine?

Visit your doctor or health care professional for regular checks on your progress. Check your heart rate and blood pressure regularly while you are taking this medicine. Ask your doctor or health care professional what your heart rate should be and when you should contact him or her.

You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how this medicine affects you. To avoid dizzy or fainting spells, do not stand or sit up quickly, especially if you are an older person. Alcohol can make you more drowsy and dizzy. Avoid alcoholic drinks.

Your mouth may get dry. Chewing sugarless gum or sucking hard candy, and drinking plenty of water will help.

Do not treat yourself for coughs, colds, or pain while you are taking this medicine without asking your doctor or health care professional for advice. Some ingredients may increase your blood pressure.

If you are going to have surgery tell your doctor or health care professional that you are taking this medicine.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:

• allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
• anxiety, nervousness
• chest pain
• depression
• fast, irregular heartbeat
• swelling of feet or legs
• unusually weak or tired

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):

• change in sex drive or performance
• constipation
• headache

This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

Keep out of the reach of children.

Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F). Protect from light. Keep container tightly closed. Throw away any unused medicine after the expiration date.

NOTE: This sheet is a summary. It may not cover all possible information. If you have questions about this medicine, talk to your doctor, pharmacist, or health care provider.

Clonidine 25mcg Tablets BP – Summary of Product Characteristics (SmPC)

This information is intended for use by health professionals

Clonidine 25 microgram Tablets BP

Each tablet contains clonidine, as 25 micrograms of clonidine hydrochloride.For the full list of excipients, see section 6.1

Tablet A white biconvex uncoated tablet.

a) The prophylactic management of migraine or recurrent vascular headacheb) The management of vasomotor conditions commonly associated with the menopause and characterised by flushing.

Posology

Adults:

Initially 2 tablets twice daily. If after two weeks there has been no remission, increase to 3 tablets twice daily.The duration of treatment depends upon the severity of the condition. If symptoms continue to occur the patient should be informed that it may take 2 – 4 weeks until clonidine is fully effective.

Older poeple:

No specific information on the use of this product in the older people is available. Clinical trials have included patients over 65 years and no adverse reactions specific to this age group have been reported.

Paediatric population:

There is insufficient evidence for the application of clonidine in children and adolescents younger than 18 years. Therefore the use of clonidine is not recommended in paediatric subjects under 18 years.

Patients with renal impairment:

Clonidine should be used with caution in patients with renal insufficiency. Careful monitoring of blood pressure is required.

Method of administration

For oral administration.

Clonidine should not be used in patients with severe bradyarrhythmia resulting from either sick-sinus syndrome or AV block of 2nd or 3rd degree, or in patients with known hypersensitivity to the active substance or to any of the excipients listed in section 6.1.In case of rare hereditary conditions that may be incompatible with an excipient of the product (please refer to section 4.4. Special warnings and precautions for use) the use of this product is contraindicated.

Clonidine should be used with caution in patients with cerebrovascular disease, coronary insufficiency, heart failure, occlusive peripheral vascular disorders such as Raynaud’s disease, polyneuropathy, constipation or those with a history of depression.At doses higher than those recommended above, clonidine is an effective antihypertensive agent. Caution should therefore be observed where antihypertensive agents are being used, as potentiation of the hypotensive effect may occur. Provided the recommended Clonidine dosage regimen is followed, no difficulty with hypotension should arise during the routine management of patients with either migraine or menopausal flushing.Depending on the dose given, Clonidine can cause bradycardia. In patients with pre-existing cardiac conduction abnormalities, arrhythmias have been observed after high doses of Clonidine.Patients with renal failure require extreme care (see section 4.2).Patients should be instructed not to discontinue therapy without consulting their physician. Following sudden discontinuation of Clonidine after prolonged treatment with high doses, agitation, restlessness, palpitations, rapid rise in blood pressure, nervousness, tremor, headache or nausea have been reported. When discontinuing therapy with Clonidine, the physician should reduce the dose gradually over 2-4 days.Patients who wear contact lenses should be warned that treatment with clonidine may cause decreased lacrimation. The use and the safety of clonidine in children and adolescents under 18 years have insufficient evidence in randomized controlled trials and therefore can not be recommended for use in this population. Serious adverse events, including sudden death, have been reported in concomitant use with methylphenidate. The safety of using methylphenidate in combination with clonidine has not been systematically evaluated. This medicine contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

This medicine contains less than 1 mmol sodium (23 mg) per tablet , that is to say essentially ‘sodium-free’.

Concurrent administration of antihypertensive agents, vasodilators or diuretics may lead to an increased hypotensive effect.Substances with alpha₂-receptor blocking properties, such as mirtazapine, may abolish the alpha₂– receptor mediated effects of clonidine in a dose-dependent manner.Concomitant use of beta-blockers and/or cardiac glycosides can cause bradycardia or dysrhythmia (AV-block) in isolated cases.It cannot be ruled out that concomitant administration of a beta-receptor blocker will cause or potentiate peripheral vascular disorders. If during combined treatment with a beta-blocker there is need to interrupt or discontinue antihypertensive therapy, the beta-blocker must always be discontinued slowly first (reducing the dose gradually to avoid sympathetic hyperactivity) and then the clonidine, which should also be reduced gradually over several days if previously given in high doses.Orthostatic hypotension may be provoked or aggravated by concomitant administration of tricyclic antidepressants or neuroleptics with alpha-receptor blocking properties.As the effects of clonidine can be antagonised by tricyclic anti-depressants, it may be necessary to adjust the dosage of clonidine, if these agents are administered concurrently. Although there is no experience from clinical trials, the effect of tranquillisers, hypnotics or alcohol could theoretically be potentiated by Clonidine.

Pregnancy

There are limited amount of data from the use of clonidine in pregnant women. As with all medicines, clonidine should not be used in pregnancy, especially the first trimester, unless the expected benefit is thought to outweigh any possible risk to the foetus. In animal studies involving doses higher than the equivalent maximum therapeutic dose in man, effects on foetal development were only seen in one species. Foetal malformations did not occur.Careful monitoring of mother and child is recommended.Clonidine passes the placental barrier and may lower the heart rate of the foetus. Postpartum a transient rise in blood pressure in the newborn cannot be excluded.There is no adequate experience regarding the long term effects of prenatal exposure.

Breast-feeding

Clonidine is excreted in human milk. However, there is insufficient information on the effect on newborns. The use of clonidine is therefore not recommended during breast feeding.

Fertility

No clinical studies on the effect on human fertility have been conducted with clonidine. Non-clinical studies with clonidine indicate no direct or indirect harmful effects with respect to the fertility index.

No studies on the effects on the ability to drive and use machines have been performed. However, patients should be advised that they may experience undesirable effects such as dizziness, sedation and accommodation disorder during treatment with clonidine. If patients experience the above mentioned side effects they should avoid potentially hazardous tasks such as driving or operating machinery.

Most adverse effects are mild and tend to diminish with continued therapy. Adverse events have been ranked under headings of frequency using the following convention:

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme (www.mhra.gov.uk/yellowcard).

Symptoms:

Manifestations of intoxication are due to a generalised sympathetic depression and include pupillary constriction, somnolence including coma, hypotension, orthostatic hypotension, bradycardia, hypothermia, respiratory depression including apnoea, occasionally vomiting, very occasionally hypertension and dryness of the mouth.

Treatment:

There is no specific antidote for clonidine overdose. Administration of activated charcoal should be performed where appropriate. Supportive care may include atropine sulfate for symptomatic bradycardia, and intravenous fluids and/or inotropic sympathomimetic agents for hypotension. Severe persistent hypertension may require correction with alpha-adrenoceptor blocking drugs. Naloxone may be a useful adjunct for the management of clonidine-induced respiratory depression.

ATC Code: N02C X02

Clonidine is an antihypertensive agent which acts centrally by stimulating alpha₂-adrenergic receptors and producing a reduction in sympathetic tone, resulting in a fall in diastolic and systolic blood pressure and a reduction in heart rate. Treatment with clonidine diminishes the responsiveness of peripheral vessels to constrictor and dilator stimuli, thereby preventing the vascular changes associated with migraine. The same direct action on peripheral vessels moderates the vascular changes associated with menopausal flushing.

Paediatric population

The efficacy of clonidine in the treatment of hypertension has been investigated in five clinical studies in paediatric patients. The efficacy data confirms the properties of clonidine in reduction of systolic and diastolic blood pressure. However, due to limited data and methodological insufficiencies, no definitive conclusion can be drawn on the use of clonidine for hypertensive children. The efficacy of clonidine has also been investigated in a few clinical studies with paediatric patients with ADHD, Tourette syndrome and stuttering. The efficacy of clonidine in these conditions has not been demonstrated.There were also two small paediatric studies in migraine, neither of which demonstrated efficacy.In the paediatric studies the most frequent adverse events were drowsiness, dry mouth, headache, dizziness and insomnia. These adverse events might have serious impact on daily functioning in paediatric patients.Overall, the safety and efficacy of clonidine in children and adolescents have not been established (see section 4.2).

Absorption and distribution

The pharmacokinetics of clonidine is dose-proportional in the range of 75-300 micrograms; over this range, dose linearity has not been fully demonstrated. Clonidine, the active ingredient of Clonidine Tablets, is highly absorbed and undergoes a minor first pass effect. Peak plasma concentrations are reached within 1-3 h after oral administration. The plasma protein binding is 30-40 %. Clonidine is rapidly and extensively distributed into tissues and crosses the blood-brain barrier, as well as the placental barrier. Clonidine is excreted in human milk. However, there is insufficient information on the effect on newborns.

Biotransformation and elimination

The terminal elimination half-life of clonidine has been found to range from 5 to 25.5 hours. It can be prolonged in patients with severely impaired renal function up to 41 hours.About 70 % of the dose administered is excreted with the urine mainly in form of the unchanged parent drug (40-60 % of the dose). The main metabolite p-hydroxy-clonidine is pharmacologically inactive. Approximately 20% of the total amount is excreted with the faeces. There is no definitive data about food or race effects on the pharmacokinetics of clonidine.The antihypertensive effect is reached at plasma concentrations between about 0.2 and 2.0 ng/ml in patients with normal renal function. The hypotensive effect is attenuated or decreases with plasma concentrations above 2.0 ng/ml.

There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

Microcrystalline Cellulose Maize Starch Lactose Pregelatinised Maize Starch Sodium starch glycollate Magnesium stearate Talc

Do not store above 30°C.

White opaque PVC/PVDC/Aluminium foil blister strips containing 28 tablets per strip. Four strips are packed in an outer carton. Pack size: 112.

Sandoz Limited

Park View, Riverside Way

Watchmoor Park

Camberley, Surrey

GU15 3YL

United Kingdom

Date of first authorisation: 25th September 2002Date of latest renewal: 12 January 2009

Catapres, Catapres-TTS (clonidine) dosing, indications, interactions, adverse effects, and more

Clonidine – an overview | ScienceDirect Topics

4.1.1 Clonidine

Clonidine immediate release (IR) is an alpha 2(α₂)-agonist approved only for hypertension in adults. The Food and Drugs Administration (FDA) of the USA approved the use of once-daily clonidine extended release (ER) tablets as adjunctive therapy to stimulants for the treatment of ADHD in children and adolescents aged 6–17 years.

The tablet form of clonidine has a duration of action of 3–5 h, with a half-life of 12–16 h (Palumbo et al., 2008). Clonidine is often prescribed and dosed after dinner or at bedtime for its sedating effects. Clonidine primarily activates presynaptic autoreceptors in the locus coeruleus and reduces norepinephrine release and turnover. Previous studies have suggested that clonidine may be useful as a potential treatment for youths with ADHD, targeting not only ADHD symptoms but also tics, insomnia, and explosive behaviors (Connor, Fletcher, & Swanson, 2009).

Although clonidine has been used for nearly three decades in the treatment of TS, there are relatively few controlled studies evaluating its effects on ADHD symptoms (Robertson, 2000). Singer et al. (1995) performed a double-blind, placebo-controlled trial on 34 children (7–13 years) with TS and ADHD of normal intellect. Each subject received in a randomly assigned fashion, 1-week medication cycles with either clonidine 0.05 mg four times daily, desipramine 25 mg four times daily, or placebo. The use of clonidine did not significantly reduce outcome measures for ADHD, including parent and teacher Child Behavior Checklists (CBCL), continuous performance tests, and executive functioning tests, with the exception of the “nervous/overactive” subscale of the CBCL. Improvement with desipramine was always superior to that rated with clonidine. Specific side effects of treatment were not reported.

Gaffney et al. (2002) conducted an 8-week double-blind randomized trial on 21 subjects aged 7–17 years comparing clonidine, titrated to a maximum dose of 0.005 mg/kg per day or 0.35 mg/day over 3–4 weeks, to risperidone, titrated to a maximum tolerable dose of 0.06 mg/kg per day over 3–4 weeks. Their results suggested that both risperidone and clonidine demonstrate significant benefits in the treatment of ADHD symptoms. Overall, the response rates for ADHD symptoms were 29% versus 50% for the risperidone and clonidine groups, respectively. The standardized score changes (mean change from baseline) were 0.80 for risperidone and 1.06 for clonidine. These results indicate a relatively more robust response with clonidine compared to risperidone. The most common adverse events with clonidine were sedation, dizziness, stiffness, and dry mouth.

Hedderick, Morris, and Singer (2009) compared levetiracetam and clonidine in a randomized double-blind 6-week flexible dose crossover study on 10 TS patients (age 8–27). Initial medication doses were clonidine 0.05 mg twice daily, and the dose was increased weekly by 0.05–0.1 mg with a maximum dose of 0.4 mg per day. The mean total tic score improved slightly, but significantly more from baseline with clonidine compared with levetiracetam. No significant change occurred in any secondary behavioral outcome measures for either group. The most commonly reported side effect with clonidine was sedation (n = 5) and irritability for levetiracetam (n = 4).

A single-blind, placebo-controlled trial (Leckman et al., 1985) demonstrated a significant improvement in behavioral problems, as well as motor and phonic tics, in 6 out of 13 patients treated with clonidine for 60 weeks. A subsequent randomized controlled study on 47 TS patients (aged 7–48 years) treated for 12 weeks demonstrated that clonidine was more effective than placebo on parent-rated measures of impulsivity and hyperactivity and on clinician-rated measures of tics (Leckman et al., 1991). On the other hand, Goetz et al. (1987), in their double-blind study on 30 children and adults with TS, concluded that the use of clonidine does not significantly reduce impulsivity, hyperactivity, and tics, without any dose dependency of effects.

The Tourette’s Syndrome Study Group (2002) conducted the largest double-blind trial on orally administered clonidine and MPH which randomized 136 children with ADHD + TS to a flexible dose of MPH (mean dose 25.7 mg per day), clonidine (mean dose 0.25 mg per day), a combination of clonidine and MPH (mean doses 0.28 and 26.1 mg per day, respectively), or placebo for 16 weeks each. Clonidine alone and clonidine plus MPH significantly improved hyperactivity/impulsive symptoms of ADHD observed on ADHD Conners abbreviated symptoms questionnaire for teachers (ASQ). Yale Global Tic Severity Scale (YGTSS) scores showed a statistically significant improvement with clonidine alone and clonidine plus MPH treatment. The proportion of subjects reporting a worsening of tics was not higher in the pharmacologically treated groups compared to the placebo group.

Clonidine adhesive patches were tested in two double-blind, placebo-controlled Chinese studies (Du et al., 2008; Zhong, Zhou, & Hu, 2007), in which the dosage of clonidine was adjusted to body weight (1, 1.5, or 2 mg per week). Clonidine was found to be significantly more effective than placebo. The therapeutic response was evidenced by the Clinical Global Impression (CGI) scale and by improvement of YGTSS scores, but specific measures of behavior or ADHD symptoms were not reported.

Clonidine in the Management of Blood Pressure During Rhytidectomy | Aesthetic Surgery Journal

Abstract

Blood pressure control is an important part of any surgical procedure and is especially important during rhytidectomy to reduce the risk of bleeding, improve visualization, and reduce the risk of postoperative fluid accumulations. For patients given general anesthetic, blood pressure control is regulated by intravenous fluids, inhalational gas concentrations, and pharmacologic manipulation. For those given local anesthetic with intravenous sedation, blood pressure manipulation can be difficult. Clonidine (Catapres®, Boehringer Ingelheim) has been shown to effectively reduce blood pressure in individuals with hypertension, as well as those with normal blood pressure. We compared both intraoperative and postoperative blood pressure, pulse, and drug use, as well as complications in 100 patients treated with preoperative oral clonidine (0.1 mg) and in 100 patients who did not receive Clonidine. The group that received clonidine had reduced systolic, diastolic, and mean blood pressure, and pulse rate (114/64, 80, 79 vs 129/74, 92, 86, p < 0.001). Blood pressure measured 12 hours after surgery remained lower in the Clonidine group (119/67 vs 126/72, p < 0.001). There was no difference in intraoperative diazepam (Valium®) or midazolem (Versed®) requirements. Intraoperative fentanyl requirements were lower in the non-Catapres®-treated group. Postoperative narcotic requirements were reduced in the clonidine-treated group. The patients treated with clonidine had a lower rate of hematoma and postoperative antihypertensive drug requirement than the untreated group. We propose that clonidine is a safe and effective drug to use in the perioperative period in patients undergoing rhytidectomy to regulate blood pressure.

Clonidine has been used as an effective antihypertensive since 1966. Its significant side effects of sedation and dry mouth limit its clinical use,^1–6 although these can be a useful aid in the perioperative period. Little has been mentioned of cloni-dine’s use for perioperative blood pressure reduction, although its use as an analgesic when given via the epidural or spinal route has been widely reported in the anesthesia literature.^7,8

Clonidine is an alpha-adrenergic agonist. It acts on the central postsynaptic alpha,-adrenergic receptors and as a partial agonist of presynaptic alpha₂-adrenergic receptors. Efferent sympathetic neuronal vasoconstrictor tone to the heart, kidneys, and peripheral vasculature is diminished, although vagal tone to the cardiovascular system is enhanced. This results in a reduction in the total peripheral resistance, renal vascular resistance, heart rate, and arterial blood pressure. The central action also results in sedation, anxiolysis, drying of secretions (especially salivary), as well as analgesia and potentiation of narcotics.^{1–3,6,9–11}

Clonidine is well absorbed, with an oral bioavailability of 75% to 95%. Clinical effects are noticeable by 90 minutes, with a peak effect at 2 to 3 hours. It has been previously demonstrated that effects are still present 8 hours after administration; half-life is approximately 12 hours.^1–3,6,12 The drug is excreted by the renal system.^1–3,6,12 Baker et al.¹³ mention the use of clonidine before surgery in their patients undergoing rhytidectomy, but scientific literature on the use and effectiveness of clonidine is lacking.

Material and Methods

A retrospective chart analysis was performed on 100 sequential patients undergoing rhytidectomy who received clonidine between August 1995 and April 1997. A comparison group of 100 sequential patients undergoing rhytidectomy who did not receive clonidine was gathered from surgery performed between January 1994 and July 1995. The surgeon (S.J.P.) and surgical technique were the same for both groups. All surgery was performed in a private surgical center where patients were kept overnight. Only those patients who received local anesthetic with intravenous sedation were included in the study group. Blood pressure was monitored by automatic cuff, and readings were taken every 15 minutes (Spacelabs Inc., Redmond, WA). A hard copy printout was placed in the chart at the completion of surgery, which was used to tabulate blood pressure and pulse data. Postoperative blood pressure readings were written in the nursing notes and data gathered for analysis beginning 12 hours after Catapres® dosing or 12 hours after surgery was started in the control group. Intraoperative benzodiazepine and narcotic drug requirements were tabulated, as were postoperative narcotic requirements. Charts were analyzed for complications that included postoperative antihypertensive use, hematoma requiring surgical removal, hematoma requiring aspiration, and seroma. Numerical data were analyzed, and means and standard deviations were computed. Data were further evaluated to compare groups consisting of only patients without a history of hypertension or groups with a history of hypertension.

Statistics

Two-tailed Student’s t test was used to compare patient weight, operative time, drainage, drug requirements, systolic, diastolic, and mean blood pressures, and pulse. A chi-squared test was performed to analyze postoperative complication rates.

Results

Data were unavailable for two patients who received clonidine and for one patient who did not receive the drug. These data were deleted from the study.

Of the 99 patients in the noncionidine group, seven had a previous history of hypertension and were being treated. Of the 98 patients in the clonidine group, four were being treated for hypertension.

Both groups were of similar age, weight, sex, and surgical time (which included adjunctive procedures). Postoperative drainage was also similar in both groups. Intraoperative drug requirements were similar, although the clonidine group required more fentanyl (510 mg vs 465 mg; p > 0.05). Postoperative meperidine (Demerol®) requirement in the clonidine group was considerably less than in the nontreated group (92 mg vs 136 mg; p < 0.001). Acetaminophen with codeine phosphate (Tylenol® with codeine, no. 3) requirements were similar in both groups. Intraoperative blood pressure and mean blood pressure were reduced in the patients treated with clonidine (114/64, 80 vs 129/74, 92; p < 0.001). The reduced blood pressure was maintained in the postoperative period (119/67 vs 126/72; p < 0.001). Intraoperative pulse was reduced (79 vs 86; p < 0.001), although this effect was not noticed in the postoperative period (73 vs 76; p> 0.15) (Table 1).

Table 1.

All patients treated with and without clonidine

Table 1.

All patients treated with and without clonidine

The data from the patients with normal blood pressure were analyzed and the same comparisons made (Table 2). A reduction in blood pressure, mean blood pressure, and pulse was noted during the operative period (113/64, 80, 80 vs 128/74, 91, 85; p < 0.001). A reduction in blood pressure was also seen after surgery (119/66 vs 126/72; p < 0.001). The reduction in mean blood pressure and pulse was not significant (84 and 73 vs 87 and 75; p > 0.1).

Table 2.

Patients with normal blood pressure treated with and without clonidine

Table 2.

Patients with normal blood pressure treated with and without clonidine

When only the patients with hypertension were compared, there was a reduction in intraoperative blood pressure, mean, and pulse that was significant (114/65, 80, 70 vs 139/76, 96, 87; p < 0.05). A significant reduction in postoperative blood pressure, mean, and pulse was not observed (119/76, 90, 72 vs 127/72, 90, 80; p > 0.2) (Table 3).

Table 3.

Patients with hypertension treated with and without clonidine

Table 3.

Patients with hypertension treated with and without clonidine

Postoperative complications are summarized in Table 4. There was a significant reduction in the use of antihyper-tensive medication in the postoperative period, as well as a reduction in the number of hematomas (4, 0 vs 12, 4; p < 0.05). There was no difference in the rate of seromas or in the aspiration of fluid collections (0 and 3 vs 1 and 6;p<0.5).

Table 4.

Postoperative complications in all patients (n = 197) treated with and without clonidine

Table 4.

Postoperative complications in all patients (n = 197) treated with and without clonidine

Discussion

A statistically suggested reduction in blood pressure was seen in the patients treated with clonidine. Table 1 illustrates that there was a reduction in systolic pressure of 15 mm Hg (12%), diastolic pressure of 10 mm Hg (14%), mean blood pressure of 12 mm Hg (13%), and pulse of 7 beats/min (8%). These results are similar to those observed by previous researchers.^3,5,11 This reduction in pressure extends into the postoperative period as well, with a reduction of 7 mm Hg (6%) in systolic pressure, 5 mm Hg (7%) in diastolic pressure, 3 mm Hg (4%) in the mean blood pressure, and 3 beats/min (4%) in the pulse. These results were seen during the 12- to 24-hour post-operative period. Previous studies have demonstrated an effect from the administration of clonidine for 8 to 12 hours, but none have looked beyond this time frame.^1–4,6

The duration of the surgery was the same in both groups. Many of these patients underwent other procedures at the time of their rhytidectomies. Clonidine may have a beneficial effect during these other procedures as well, although this was not investigated. Although there was no reported difference in the postoperative drainage, this could be an erroneous assumption. Several patients in the clonidine group had endoscopie brow lifts, and these were also drained (this drainage was included in the data). Similarly, there were patients in the non-Catapres®-treated group who had coronal or anterior brow lifts performed; this did not affect the results.

Clonidine has been shown to potentiate narcotics and benzodiazepines; it also has intrinsic sedating and analgesic effects.^3,6,10 In our practice, midazolem (Versed®) has been used consistently only for the past 18 months, and thus an accurate comparison of its use in these two groups is difficult. Also, in the non-Catapres®-treated group, diphenhydramine (Benadryl®) was used during surgery to increase sedation and as an analgesic. There was an increased use of fentanyl in the clonidine group; this might be explained by the use of Benadryl® in the comparison group. After surgery no other analgesics were given, other than those in the data. There was a significant reduction in the amount of Demerol® required in the clonidine group. The amount of oral analgesic, Tylenol® with codeine, no. 3, was similar. This might be explained by the fact that oral analgesics were given in the late postoperative period, and the analgesic effect of clonidine may have worn off.

Most patients given clonidine have decreased salivary flow and complain of dry mouth, depending on the dose administered.^1–4,9–11 This was not investigated in the study. Although these are unpleasant side effects in ambulatory patients being treated for hypertension, they are desirable results during surgery in patients who are sedated and may have impaired airway protection from oral secretions.

When the data from all patients with a preoperative history of hypertension were omitted and the same comparisons made, similar results were found. This is not unexpected because of the large number of patients in the study (« = 197) and the low number of patients with hypertension (n = 11 [6%]).

The data from the patients with a history of hypertension were compared. Differences were less often statistically significant, which might be attributed to the small number of subjects studied. There was significantly greater drainage noted in the patients who received clonidine, but this might be explained by the fact that three of five patients in the clonidine-treated group had an endoscopie brow lift and increased drainage (this drainage was also included in the total drainage figure). In the group that did not receive clonidine, two of seven patients had an open brow lift and no drain was used in the brow. No patients in this group underwent endoscopie brow lifts. Intraoperative drug requirement was similar in both groups, although postoperative Demerol® requirement was less in the clonidine-treated group. This result was not significant, which is likely a result of the small sample size. A significant result was again observed in the intraoperative blood pressure and pulse. A reduction was seen in the postoperative blood pressure and pulse, although it was not significant.

Before a new treatment is instituted, one must be sure that it reduces the incidence of complications and does not contribute to side effects. No patients in this study had a reduction in blood pressure that resulted in symptomatic complaints such as dizziness, light-headedness, fainting, bradycardia, or arrhythmias. There was a significant reduction in the rate of hematomas and the use of antihypertensive medications in the postoperative period. No difference was observed in the incidence of seromas or fluid collections that required aspiration in the immediate postoperative period. It is important to note that the number of complications was low in both groups, and the small sample size could lead to an observed or unobserved difference.

Although our results indicate a reduction in blood pressure with the use of clonidine, it was observed that in some subjects who received the drug, little or no effect was seen. This might be explained by patients receiving too small a dose of clonidine or being less sensitive to the drug.⁶ Studies have shown that good results are observed when larger doses of clonidine, such as 0.15 or 0.2 mg, are given; however, when patients were given 0.3 mg doses, a significant number of patients experienced light-headedness or felt faint.^11,14 Symptomatic hypotension responds to intravenous fluid administration and to pres-sor agents such as noradrenaline and phenylephrine. In fact, pressor responses may be potentiated with the use of phenylephrine in patients who have received clonidine.¹⁴ Bradycardia responds to the administration of atropine. Tolazoline may be an effective antidote to clonidine, although we do not have any experience with this drug.¹² Clonidine does not affect blood sugar and can be safely used in diabetic patients, although its dose must be decreased in those patients with kidney damage.^1,3

Summary

Clonidine can safely reduce blood pressure in the perioperative period. Its use might improve visualization during the procedure because of the decrease in blood in the surgical field and result in fewer hematomas and more uniform blood pressure readings throughout the perioperative period. Its additional beneficial effects include sedation, anxiolysis, drying of secretions, and potentiation of analgesia. Ongoing investigation to determine the most appropriate dose of clonidine required by other patient populations—normotensive, hypertensive, and male—is being performed to define further its role in patients undergoing rhytidectomy.

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© 1998 American Society for Aesthetic Plastic Surgery

Treatment Choices for Severe Hypertension

Primary Care Update
Brief summaries for Clinical Practice

Here, we will review the contemporary armamentarium for severe hypertension. The pros and cons of the drugs used to manage hypertensive crises will be highlighted.

In our article, “Extremely Elevated Blood Pressures: An Update on Hypertensive Urgencies and Emergencies,” we defined a terminology for severe hypertension (eg, hypertensive urgency and emergency). We also offered treatment suggestions and outlined an appropriate workup for secondary causes of resistant hypertension in the ambulatory setting.

CLONIDINE
Mechanism of action. Oral clonidine stimulates central alpha-2 adrenergic receptors in the brain stem, which reduces sympathetic outflow. A rapid and immediate antihypertensive effect is obtained in 30 to 60 minutes with a peak effect in 2 to 4 hours. The duration of action for clonidine, however, is variable and lasts between 6 and 24 hours. This variability makes it difficult to titrate doses.¹

Cautions. The use of clonidine in hypertensive urgencies is limited by its adverse-effect profile as well as its variable duration. While the hypotensive risk is small, the incidence of sedation can be significant.² Clonidine should not be used in patients with heart failure or heart block or in those with hypertensive encephalopathy (sedation and confusion from the drug may complicate management).

Clonidine does have an important continuing role in the treatment of hypertensive urgencies consequent to clonidine withdrawal.

NIFEDIPINE
Mechanism of action. Nifedipine is a dihydropyridine calcium-channel blocker; this potent oral or sublingual agent has been used in hypertensive crises. Although it is not absorbed well from the buccal mucosa, the drug is rapidly absorbed in the GI tract and causes direct arteriolar vasodilation.³

Immediate-release formulations of nifedipine produce a rapid and significant reduction in blood pressure, usually within 5 to 20 minutes. Peak effects occur at 30 to 60 minutes, and the duration of action can last as long as 6 hours.⁴

Cautions. Nifedipine produces an unpredictable decline in blood pressure that can cause cerebral, renal, and cardiac ischemic events. These events have been associated with fatal outcomes. As a result, immediate-release nifedipine should be avoided for blood pressure control in acute episodes of severe hypertension.⁵

SODIUM NITROPRUSSIDE
Mechanism of action. Sodium nitroprusside acts as a nitric oxide donor, causing vascular smooth muscle relaxation in both the venous and arterial vessels.

Cautions. Nitroprusside administration has been associated with decreased flow to areas of coronary ischemia; this is known as “the coronary steal effect.”⁶ In addition, nitroprusside may preferentially cause a decrease in systemic vascular resistance, generating an increase in blood flow to the systemic vasculature, which may result in decreased cerebral blood flow and increased intracranial pressure.⁷

Nitroprusside has been used to treat hypertensive emergencies for decades. Nitroprusside is as effective as fenoldopam in lowering blood pressure in hypertensive emergencies, but it is not as effective in improving renal function.⁸

As a result of its organ-specific detrimental pharmacological profile, nitroprusside should not be used in patients with CNS-associated end organ damage. Nitroprusside should also be avoided in the early treatment of hypertension (within 9 hours) in patients with an acute myocardial
infarction (MI).⁹ Because cyanide is released during its metabolism, nitroprusside should be avoided in patients with liver and kidney dys-function. Cyanide toxicity can result in cardiac arrest, coma, and encephalopathy. Lactic acidosis may be an early indication of toxicity.¹⁰

Although nitroprusside may not be the best choice to treat severe hypertension because of safety concerns, it may be used effectively in patients with hypertensive emergencies. It is recommended that the smallest dose and shortest duration be used.

NITROGLYCERIN
Mechanism of action. Nitroglycerin is also a nitric oxide donor, resulting in smooth muscle vasodilation. This drug primarily acts on the veins but also affects arteries at high doses.¹¹ Unlike nitroprusside, nitroglycerin can increase coronary blood flow to the coronary vessels.

Nitroglycerin may be considered for blood pressure control during an acute MI, heart failure, and hypertensive emergency with acute pulmonary edema.  

Cautions. Nitroglycerin should be avoided in patients with volume depletion because hypotension may result.Intravenous nitroglycerin may also be associated with increased intracranial pressure. Thus, it should be avoided in patients with CNS end organ damage.¹²

FENOLDOPAM
Mechanism of action. Fenoldo–pam, a peripheral dopamine type-1 receptor agonist, causes vasodilation of coronary, renal, mesenteric, and peripheral arteries.¹³ Through this mechanism of action, fenoldopam decreases blood pressure in a dose-related manner with a concomitant reflex tachycardia. Dopamine type-1 receptors are also located on renal tubular cells.

Fenoldapam causes vasodilation of the renal artery and afferent and efferent arterioles.¹⁴ An increase in renal blood flow and glomerular filtration rate can be seen with fenoldopam use.

Studies that compared fenoldopam with nitroprusside in the treatment of hypertensive emergencies showed no difference in time to goal blood pressure or mean arterial pressure.¹⁵ Although fenoldopam was not superior to nitroprusside in lowering blood pressure, its use was associated with greater improvement in urine output, sodium excretion, and creatinine clearance. Studies also support the use of fenoldopam in cardiac surgery patients with perioperative hypertension. The results demonstrated improved outcomes over both nifedipine and nitroprusside in the setting of coronary artery bypass graft surgery.¹⁶

With such a favorable renal profile, fenoldopam is a preferred treatment option in patients with
hypertensive emergency and renal dysfunction.

Cautions. Although fenoldopam’s pharmacological profile can be ideal for certain settings, it should probably be avoided in patients with CNS end organ damage or glaucoma. Dose-dependent increases in intraocular pressure have been observed in patients.¹⁷ Effects on intracranial pressure (ICP) are unknown. When dosing fenoldopam in elderly patients, it is best to start at a low dose and increase gradually.

HYDRALAZINE
Mechanism of action. Hydralazine is a direct arterial vasodilator that is associated with a reduction in afterload. This parenteral agent has been a mainstay in the treatment of eclampsia or preeclampsia most likely because it can improve uterine blood flow.

Hydralazine can be given intramuscularly or intravenously via injection or infusion. Given intravenously, the onset of action usually occurs in 5 to 15 minutes. Although the half-life of the drug is short, its pharmacological effect on blood pressure can last up to 12 hours or even longer.¹⁸

Cautions. As a result of this effect on blood pressure and the drug’s unpredictable hypotensive effect, it may be difficult to effectively titrate hydralazine. The adverse effects include reflex tachycardia, palpitations, headache, nausea, vomiting, flushing, and fluid retention. The reflex tachycardia and palpitations seen with this agent contraindicate its use in coronary artery disease and aortic dissection and may require the addition of a beta-blocker. In addition, the drug may raise ICP in patients with a preexisting
increase in ICP.¹⁹

Because of an unpredictable and prolonged response, hydralazine is not recommended for general treatment of hypertensive crises. Although it has long been the drug of choice for the treatment of preeclampsia and eclampsia, a meta-analysis has shown an increased risk of maternal hypotension, resulting in an excess of cesarean sections, placental abruptions, and low Apgar scores.²⁰ As a result, it has been suggested that hydralazine no longer be recommended as the first-line agent in pregnancy.

NICARDIPINE
Mechanism of action. Nicardipine is a non-dihydropyridine calcium-channel blocker that can be used for both hypertensive urgencies and emergencies. Intravenous and oral dosage forms are available. It is able to cross the blood-brain barrier and cause vasodilatation of cerebrovascular smooth muscle.²¹ 

Nicardipine is generally considered the drug of choice for hypertension in the setting of stroke. It is also used in perioperative hypertension, preeclampsia, eclampsia, hypertensive encephalopathy, and postoperative hypertension. Oral nicardipine can be used to treat hypertensive urgencies.

When compared with sodium nitroprusside, nicardipine was shown to be as effective, but without the risk of thiocyanate toxicity.²² Target blood pressure was also achieved faster with less variability in blood pressure than with sodium nitroprusside.

CLEVIDIPINE
Mechanism of action. Clevidipine is a short-acting calcium-channel blocker used for hypertensive emergencies. It decreases 

arterial blood pressure through a reduction in systemic vascular resistance. Clevidipine is not dependent on renal or hepatic metabolism
or clearance. Clevidipine has been studied in multiple settings for blood pressure reduction.²³ It has been used successfully to treat severe hypertension and perioperative, preoperative, and postoperative hypertension.²⁴

Cautions. Clevidipine should not be used in persons with aortic stenosis because it can decrease oxygen delivery to the myocardium. It can also cause heart failure as a result of its negative inotropic effects.

Clevidipine is contraindicated in patients with egg, egg product, soybean, and soybean product allergy; as well as persons with defective lipid metabolism.

LABETALOL
Mechanism of action. Labetalol is an alpha-1 and nonselective 

beta-adrenergic receptor antagonist used in the treatment of hypertensive urgencies and emergencies. Beta-blockade is more prevalent than alpha-blockade in a 3-10:1 ratio.²⁵ Labetalol lowers blood pressure by reducing systemic vascular resistance without decreasing total peripheral blood flow. It has very
little effect on cerebral, renal, or coronary vasculature.²⁶

Labetalol has been used to treat hypertension in ischemic and hemorrhagic stroke, hypertensive encephalopathy, aortic dissection, acute MI, catecholamine excess, postoperative hypertension, and preeclampsia and eclampsia.²⁷ Labetolol does not appear to induce fetal distress in the treatment of eclampsia.²⁸

ESMOLOL
Mechanism of action. Esmolol is a beta-1 selective adrenergic receptor antagonist with negative inotropic and chronotropic effects that is used to treat hypertensive emergencies. Administration should be accompanied by invasive blood pressure monitoring.

Esmolol has been used in the treatment of hypertension after
MI as well as perioperative and postoperative hypertension, during repair of coarctation, and in acute aortic dissection (given with sodium nitroprusside).^29-31 Esmolol is the beta-antagonist of choice in aortic dissection.³²

Cautions. Esmolol can exacerbate heart failure.

PHENTOLAMINE
Mechanism of action. Phentolamine, a competitive peripheral alpha-1 and alpha-2 receptor antagonist, has been used to treat hypertension associated with catecholamine excess. It is most commonly used in the alpha-blockade phase of pheochromocytoma treatment and is the drug of choice for adrenergic crises only.³³ It has been used to treat hypertension related to cocaine toxicity, amphetamine overdose, clonidine withdrawal, and monoamine oxidase inhibitor interactions with food and other drugs.¹⁰

Cautions. In patients with coronary artery disease, phentolamine use has induced angina and MIs.

ENALAPRILAT
Mechanism of action. Enalaprilat is an angiotensin-converting enzyme (ACE) inhibitor with effects identical to those of captopril. The drug is administered intravenously at an initial dosage of 1.25 mg over 5 minutes every 4 to 6 hours. This initial dosage may be titrated in 1.25-mg increments at 12 to 24 hour intervals to a maximum of 5 mg every 6 hours. The onset of action varies from 10 to 60 minutes with a duration of action from 2 to 6 hours or more. Because enalaprilat does not impair cerebral blood flow, it may be indicated for patients with severe hypertension and heart failure or high levels of angiotensin II, as well as patients at risk for cerebral hypotension.³⁴

Cautions. Enalaprilat can lead to rapid untoward decreases in blood pressure in patients who are hypovolemic and in those with bilateral renal artery stenosis. Note that these agents are contraindicated in pregnancy, bilateral renal artery
stenosis, and acute MI. Because of the delayed peak, long duration of action, and varied response, enalaprilat is not ideal for the rapid titration of blood pressure needed in the emergency setting. ACE inhibitors should also be used cautiously in hyperkalemic patients.■

The Clinical Utility of Clonidine

US Pharm. 2006;5:HS-2-HS-16.

Clonidine was originally
developed in 1962 for use as a nasal decongestant.¹ However, rapid
recognition of its ability to reduce blood pressure led to the FDA approval of
this agent for the treatment of hypertension in 1974.² During the
1970s, clonidine gained popularity as treatment for hypertension since it was
not linked with the postural and exercise-induced hypotension common in other
antihypertensive regimens. However, unwanted side effects of drowsiness, dry
mouth, and sympathetic overactivity upon abrupt discontinuation led to a
decline in its use. In 1996, a transdermal formulation renewed interest in the
drug, as reported side effects were less pronounced than with oral treatment.

Today, with the development
and marketing of newer products, the use of clonidine in the treatment of
hypertension is limited; however this agent’s ability to modify both central
and peripheral adrenergic transmission is proving to be of increasing interest
to health care practitioners. Clonidine’s unique mechanism of action has
prompted many to investigate its therapeutic potential in several different
disease states.

DOSAGE FORMS

Clonidine is available as an oral
tablet form, a transdermal therapeutic system (Catapres-TTS), and as an
injection for epidural use (Duraclon) (Table 1). The oral and topical
formulations are FDA approved only for the treatment of hypertension, while
the injectable form is FDA approved only for  intractable cancer pain, in
combination with opioids.^3-6

ADVERSE EFFECTS

Most of the
common adverse effects with oral clonidine are mild and tend to diminish with
continued treatment or with a reduction in dosage. The most frequent adverse
effects seen with oral and transdermal clonidine therapy are dry mouth and
drowsiness; however, dizziness, sedation, constipation, and headache are also
common reactions noted. Systemic effects with transdermal clonidine appear to
be less severe and may occur with less frequency than with oral therapy. Some
localized skin reactions have been reported with the transdermal system, with
the most common dermatologic reactions being localized pruritus and erythema.^3-7

The injectable form of
clonidine has an adverse effect profile similar to both the oral and
transdermal forms. The most commonly reported adverse event during clinical
trials was a major decrease in blood pressure, particularly during the first
few days of therapy. Other common side effects include postural hypotension,
dry mouth, somnolence, dizziness, and confusion. Accidental dislodging of the
catheter can result in rebound hypertension secondary to abrupt withdrawal.^3-7

DRUG INTERACTIONS

Clonidine is not
without its share of drug interactions (see Table 2). Of particular note is
the additive effect that is exhibited when combined with central nervous
system depressants and anesthetic agents. Tricyclic antidepressants have been
found to block the hypotensive effect of clonidine, whereas diuretics and
other hypertension agents may enhance the hypotensive effect. Furthermore,
clinicians should be aware that beta-adrenergic antagonists might exacerbate
hypotension upon withdrawal of clonidine.^3-7

THERAPEUTIC USES

The clinical
utility of clonidine has been reported in many clinical trials and case
reports (table 3). A representative study or report highlights each
therapeutic use (Table 4). Notably, there may be more citations published for
a given therapeutic use than referenced in this article. The only FDA-approved
indication for clonidine is for the treatment of hypertension, and when given
epidurally, for cancer pain relief; all other uses described are off-label.

Cardiovascular/Circulatory

Hypertension:^4,6
The recommended regimen is 100 to 200 mcg/day in two divided doses, with a
maximum of 2,400 mcg/day. Dosage for the transdermal therapeutic system is 100
mcg per 24 hours every week, with a maximum of 600 mcg per 24 hours every
week. Doses up to 5,000 mcg/day have been attempted with unwanted side effects
and no additional efficacy.

Hypertensive Emergency:
Karachalios⁷ studied 38 severely hypertensive patients (systolic
175 to 210 mmHg, diastolic 105 to 130 mmHg). After observing patients at rest
for one to two hours, an oral loading dose of clonidine 200 mcg was given,
followed by 100 mcg/hour, to a maximum total dose of 800 mcg. Thirty-five
patients responded well with a decreased mean blood pressure in six hours of
145 ± 20 mmHg systolic and 98 ± 15 mmHg diastolic. Side effects were minimal.

Atrial Fibrillation:
In 1992, Roth et al.⁸ determined that low-dose clonidine was
effective in slowing ventricular rate in patients with rapid atrial
fibrillation. In 2001, Simpson et al.⁹ used clonidine to treat
atrial fibrillation in 40 patients with new-onset, stable, rapid atrial
fibrillation. Thus, clonidine controls ventricular rate with an efficacy
comparable to that of digoxin and verapamil.

Congestive Heart
Failure (CHF): Manmontri
and MacLeod¹⁰ studied clonidine in CHF treatment. Clonidine 200 to
400 mcg/day orally significantly reduced heart rate and increased left
ventricular ejection fraction, as well as improved New York Heart Association
functional status. However, defects in the design require more study before
clonidine can be recommended. Azevedo et al.¹¹ studied the effect
of intravenous (IV) clonidine on cardiac sympathetic activity and left
ventricular function in CHF patients. Nine patients received a 50- or 100-mcg
bolus of IV clonidine. The authors concluded that use of clonidine in CHF
warrants further exploration.


Orthostatic
Hypotension (OH):
Stumpf and Mitrzyk¹² conducted a clinical review of treatment
options for OH. Oral clonidine was titrated in patients with refractory OH.
Patients given doses of 400 and 800 mcg showed improvement in standing time
and blood pressure. Dry mouth and sedation were reported as the major side
effects; however, these disappeared with long-term use.

Portal Pressure:
Lin et al.¹³ studied the effect of combining propranolol with
clonidine in patients with posthepatitic cirrhosis. Twenty patients received
an IV injection of 0.1 mg/kg propranolol, followed 30 minutes later by 150 mcg
of clonidine. Researchers concluded that the reduction in mean arterial
pressure might limit the clinical utility of this combination in patients with
already low arterial pressure.

Analgesia

Allodynia:
Allodynia is a condition of sympathetically maintained pain, with ongoing pain
and hyperalgesia.¹⁴ Davis et al. examined the use of topical
clonidine patches to treat the hyperalgesia. Clonidine 200 and 300 mcg patches
were applied to affected areas; each patch was left in place for two to 10
days. Topical clonidine significantly reduced hyperalgesia.¹⁴ Olson
et al.¹⁵ reported on a patient with an electrical injury who was
treated with topical clonidine. Eisenach et al.¹⁶ studied the use
of intrathecal and IV clonidine to treat hyperalgesia from intradermal
capsaicin injection in volunteers. Volunteers were randomized into four
treatment groups: IV 50-mcg or 150-mcg injections and intrathecal 50-mcg or
150-mcg injections. Both doses of IV injections and the lower dose intrathecal
administration did not produce any relief, whereas the 150-mcg intrathecal
dose lessened pain within 45 minutes, with effects lasting at least four
hours.

Intraoperative and
Postoperative: De
Kock et al.¹⁷ compared epidural clonidine to sufentanil in the
perioperative period. Patients received epidural clonidine or sufentanil for
12 hours. Clonidine improved intraoperative hemodynamic stability and provided
the same amount of postoperative analgesia as did sufentanil. Yet, clonidine
had a longer-lasting residual analgesic effect, thus decreasing postoperative
analgesic demands.

Pediatric Caudal
Anesthesia (ages 1 to 7 years):
Jamali et al.¹⁸ studied pediatric patients ages 1 to 7 years who
received 1 mcg/kg of clonidine, 1/200,000 of epinephrine, or control in
addition to 1 mL/kg of 0.25% bupivacaine. The duration of postoperative
analgesia was significantly increased in the clonidine group, compared to
bupivacaine alone or bupivacaine with epinephrine. Fewer clonidine patients
required postoperative analgesia.

Intractable Cancer
Pain: Eisenach et
al.¹⁹ conducted a double-blind study in patients unresponsive to
morphine who received 30 mcg/hour of epidural clonidine or placebo for 14
days. Pain was assessed using visual analog score and daily epidural morphine
use. Patients with neuropathic pain gained the best relief from clonidine,
with an overall success rate over placebo.

Cluster Headache
Prophylaxis: Leone
et al.²⁰ studied transdermal clonidine in doses of 200 to 300
mcg/day. Five of 15 patients reported improvement during days 7 to 12 of
therapy. That the improvement was a result of reaching the final phase of the
cluster periods could not be ruled out. More studies are needed to clarify the
efficacy of transdermal clonidine to treat cluster headaches.

Chronic Headaches: Dalessio²¹
began therapy with transdermal clonidine 100 mcg/day for women under 130 lb
and 200 mcg/day for women more than 130 lb and for all men. After 18 weeks,
patients were switched to oral clonidine 100 to 200 mcg/day; dosage was
tapered off over three to five days. This protocol was successful in nine of
12 patients with chronic headaches.

Migraine Headaches: A
review by Wood²² suggests oral clonidine 50 mcg twice daily,
titrated to 75 mcg twice daily, was effective, with mild side effects.

Labor Analgesia: Gautier
et al.²³ randomized patients requiring labor analgesia to various
intrathecal solutions for analgesia, consisting of clonidine and sufentanil.
Clonidine injection 30 mcg combined with intrathecal sufentanil significantly
increased the duration of analgesia during the first stage of labor without
adverse maternal or fetal effects.

Postoperative Pain in
Children: Mikawa et
al.²⁴ examined clonidine in children undergoing minor surgery.
Ninety children ages 5 to 12 years received placebo or clonidine (2 or 4
mcg/kg) 105 minutes before anesthesia induction. Clonidine 4 mcg/kg provided
more postoperative analgesia than did the other treatment groups.

Reflex Sympathetic
Dystrophy: Rauck et
al.²⁵ randomized 26 patients with chronic pain to 300 or 700 mcg of
epidural clonidine or placebo. Responders then received a continuous epidural
infusion of 10 to 50 mcg/hour of clonidine. Clonidine was shown to provide
pain relief.


Spinal
Cord Injury Pain: Siddall
et al.²⁶ reported on a patient who had received multiple agents to
treat spinal cord injury pain for one year. Intrathecal clonidine 17 mcg/day
combined with morphine 10 mg/day produced a 50% reduction in previous pain
levels.

Neurology

Akathisia: Blaisdell²⁷
referenced a study with six patients who showed major improvement, four of
whom obtained complete remission. Adler et al.²⁸ titrated
oral clonidine to a maximum of 150 to 400 mcg/day and observed significantly
reduced akathisia and anxiety at the maximum dose. Sedation was a problematic
side effect.

Peripheral Neuropathy:
Tan and Croese²⁹ reported cases where excellent pain relief of
disabling leg pain was obtained using oral clonidine 75 to 100 mcg/day.
Schwartz and Rosenfeld³⁰ reported a case in which oral clonidine 75
mcg twice daily was used with rapid and complete relief of painful muscle
cramps and pruritus. Kingery³¹ reported that transdermal clonidine
at doses of 300 mcg daily had little effect on pain, yet a subset of patients
did have analgesia. Oral clonidine at doses of 200 mcg/day provided pain
relief.

Neuropathic Orofacial
Pain: Epstein et al.³²
examined 17 patients who applied clonidine in a cream (200 mcg/g) four times
daily to the site of pain. Improvement was noticed in patients diagnosed with
both neuropathic pain (50% of patients) and neuralgia (67% of patients).

Diabetic Gastroparesis:
Rosa-e-Silva et al.³³ evaluated the effects of clonidine in
patients with longstanding diabetes and evidence of autonomic neuropathy.
Treatment with oral clonidine was given in doses ranging from 200 to 600
mcg/day. Results showed that gastric emptying half-time and symptoms decreased
in all patients.

Essential Tremor:
Koller et al.³⁴ evaluated clonidine in 10 patients randomized to
receive either placebo or incremental doses of clonidine until a dose of 600
mcg was reached or unwanted side effects occurred. Neither placebo nor
clonidine significantly reduced hand tremor.

Memory Enhancement in
Korsakoff’s Psychosis: McEntee
and Mair³⁵ studied patients with chronic memory disorder to assess
if clonidine, d-amphetamine, or methysergide would improve memory. Clonidine
was linked with major memory improvement.

Postepidural Shivering:
Yang et al.³⁶
studied 40 patients who were randomly assigned to receive either normal saline
or clonidine 150 mcg diluted in 10 mL of normal saline 20 minutes before
epidural administration. Other studies suggest that shivering occurs in 30% to
64% of people receiving epidural lidocaine. This study showed that the
incidence of shivering in the clonidine group was 5%, and clonidine was
effective in preventing shivering associated with epidural anesthesia.

Postanesthesia
Shivering: Generali
and Cada³⁷ conducted a literature review of 295 patients who
received a single clonidine dose of 3 mcg/kg at various times throughout the
surgical procedure. Single-dose clonidine 3 mcg/kg was as effective as
meperidine and superior to placebo in the prevention of postanesthetic
shivering.

Restless Legs Syndrome:
Zoe et al.³⁸ reported a case that was resistant to traditional
therapy. The patient was then treated with clonidine 100 mcg at bedtime,
titrated to 900 mcg/day. After 15 months of successful treatment, the dosage
was reduced to 450 mcg/day due to the reported side effect of dry mouth.

Hypertonicity:
Donovan et al.³⁹ studied the use of clonidine in 55 patients with
spasticity after sustaining a spinal cord injury. Over half (56%) of patients
treated with oral clonidine 100 to 400 mcg daily showed some relief.

Tetanus-Induced
Autonomic Dysfunction: Sutton
et al.⁴⁰ reported the case of a man sustaining a compound fracture
in which tetanus had set in. After inadequate response to magnesium sulfate,
clonidine 300 mcg every eight hours was added to control sympathetic
overactivity. Clonidine dramatically improved cardiovascular instability and
allowed reduction of muscle relaxants and sedation.

Hyperkinetic Movement
Disorders: Two
reviews^41,42 suggest that oral clonidine, titrated to a range of
100 to 800 mcg/day, may relieve symptoms in children. Phonic tics were more
responsive to clonidine. Main adverse effects included sedation, dry mouth,
and potential rebound hypertension upon withdrawal.

Tourette’s Syndrome:
Leckman et al.⁴³
randomized 47 patients to receive clonidine 4 to 5 mcg/kg to a maximum of 250
mcg/day or placebo. Clonidine reduced symptoms of impulsivity, hyperactivity,
and tics associated with Tourette’s syndrome.

Psychology

Substance
Withdrawal: Robinson
et al.⁴⁴ examined the effectiveness of clonidine in the treatment
of alcohol withdrawal. The study was double-blind, and patients were
randomized to receive either clonidine or chlormethiazole. Clonidine was found
less effective and had greater serious adverse effects than chlormethiazole.
Keshavan et al.⁴⁵ used oral clonidine 600 mcg/day to treat a
patient undergoing benzodiazepine withdrawal. After previous failure of a
medically supervised taper of lorazepam, the addition of clonidine allowed
lorazepam to be tapered over two weeks without any withdrawal symptoms. McGee
and Murray⁴⁶ reviewed four cases in which clonidine had been used
to treat nicotine withdrawal. Doses of 100 to 300 mcg/day were useful adjuncts
to a cessation program. Clonidine helped relieve patients’ anxiety related
symptoms. Cheskin et al.⁴⁷ compared clonidine to buprenorphine for
the treatment of acute opioid detoxification. Patients were randomly assigned
to receive either buprenorphine or clonidine. Buprenorphine provided greater
relief of withdrawal symptoms and had fewer side effects than clonidine. Sovner⁴⁸
reported two cases of patients who were experiencing thioridazine
withdrawal–induced behavior. They were given oral clonidine 300 mcg twice
daily or transdermal clonidine 300 mcg/day. Clonidine enabled a successful
withdrawal from thioridazine, and successful tapering of clonidine dosage was
later achieved.

Acute Anorexia Nervosa:
Casper et al.⁴⁹ studied four treatment-resistant patients in a
placebo-controlled crossover trial. Clonidine was initiated at 150 mcg/day  and
was gradually increased to a maximum of 500 to 700 mcg/day. Clonidine was not
superior to placebo for promoting weight gain, nor did clonidine intensify the
urge to eat before and after meals.

Attention-Deficit/Hyperactivity
Disorder (ADHD) and Conduct Disorder:
Schvehla et al.⁵⁰ conducted a retrospective study of 18
prepubescent boys who received clonidine after failed trials of conventional
psychostimulants. Each child received oral clonidine 50 mcg/day, titrating
upward until clinical improvement or a maximum dose of 400 mcg was reached.
The average clonidine dose used was 8 mcg/kg. Eleven of the 18 children
exhibited marked clinical improvement. Sedation was the primary side effect,
lasting two to three days in 40% of patients following dosage increase.

Behavioral Symptoms of
HIV-1 Encephalopathy:
Ceseña et al.⁵¹ reported the case of a four-year-old boy
with AIDS who exhibited hyperactivity and impulsive behavior. The patient was
given oral clonidine 25 mcg/day, which was slowly increased to 25 mcg three
times daily. Improvement was seen in hyperactivity, impulsivity, and sleeping
patterns, and aggressive behavior decreased.

Bipolar Disorder:
Janicak et al.⁵² studied clonidine in the acute mania phase of
bipolar disorder. Twenty-one patients received placebo or clonidine for two
weeks. The average maximum daily dose of clonidine was 470 mcg. Clonidine was
no more effective than placebo, and side effects contributed to a
significantly higher dropout rate. Kontaxakis et al.⁵³ reported a
case in which oral clonidine was used in the treatment of refractory mixed
bipolar disorder. Oral clonidine 125 mcg twice daily was added to the
patient’s regimen. Within two days, the patient had rapid improvement in
psychopathology, followed by a decline in effect. The dose was eventually
titrated slowly to 600 mcg/day with no significant side effects noted.
Bakchine et al.⁵⁴ reported a case of a woman with focal brain
damage in a manic-like state who was given alternating trials of clonidine 300
mcg twice daily, placebo tablets, carbamazepine, and then
levodopa-benserazide. Clonidine produced a marked decrease in manic symptoms
and improved cognitive functions.

Narcolepsy:
Salín-Pascual et al.⁵⁵ studied the effects of clonidine on two
patients given 150 mcg/m² in the morning. One week later, they were
given placebo, followed by clonidine on two consecutive nights. Following the
blind trial, patients were then given oral clonidine 225 mcg at bedtime, and
recordings were taken at predefined intervals. A rapid improvement was seen in
both patients receiving clonidine. Sleep attacks, daytime sleepiness, and
cataplexy disappeared.

Panic Disorder: Puzantian
and Hart⁵⁶ cited four studies demonstrating that oral clonidine in
doses of 100 mcg twice daily to 2 mg/day should be considered as a last-line
anxiolytic agent. However, no clinical indicators of success were identified.

Posttraumatic Stress
Disorder: Kinzie
and Leung⁵⁷ examined patients who received 50 mg of imipramine at
night, which was increased to 150 mg over three weeks. If there was no
response after three weeks, clonidine 100 mcg twice daily was added. Results
showed that combined with imipramine 150 mg/day, all patients receiving
clonidine symptomatically improved.

Schizophrenia:
Freedman et al.⁵⁸ compared clonidine to a neuroleptic and placebo
in eight patients with schizophrenia. Oral clonidine was dosed initially at
100 mcg twice daily and increased to 900 mcg/day. Results suggested that
clonidine and neuroleptics may be equally efficacious as antipsychotics in
treating schizophrenia. Clonidine reduced symptoms of psychosis resulting from
withdrawal of drugs that have produced tardive dyskinesia.

Sleep Disorders: Horacek⁵⁹
used clonidine extemporaneously compounded extended-release capsules for sleep
disorders. The combination of immediate-release oral clonidine one hour before
bedtime with extended-release clonidine several hours before bedtime helped
prevent sleep disorders. The immediate-release capsule aids in onset of sleep,
while the extended release prevents rebound hyperarousal during the night. The
extended-release capsules were compounded to release clonidine over an
eight-hour period. Rubinstein et al.⁶⁰ reported the case of a child
with ADHD who had chronic sleep problems due to the use of dextroamphetamine.
Oral clonidine 50 mcg was started 45 minutes prior to sleep. Clonidine had an
almost immediate impact in the child’s sleep pattern, which greatly improved
over a two-month period.

Social Phobia: Goldstein⁶¹
reported the case of a patient with increased discomfort and anxiety in social
situations. After several trials with other agents, clonidine 100 mcg twice
daily was started. After one week, the patient had a remarkable decrease in
frequency and intensity of panic attacks. After four months, the patient had
only infrequent attacks. No side effects were reported.

Gastrointestinal

Carcinoid-Associated
Diarrhea: Schwörer
et al.⁶² reported a case in which a man with carcinoid syndrome
treated with octreotide and interferon developed diarrhea (six to eight watery
stools a day). The patient was treated with oral clonidine 75 mcg three times
a day and 150 mcg at bedtime. This reduced stool frequency to two to three
stools per day, with no defecation at night. Mild sedation and dry mouth were
noted.

High Intestinal Output
Associated with Small Bowel Transplant: Rovera
et al.⁶³ conducted a study of 13 patients who underwent small bowel
transplant to assess the efficacy of clonidine in reducing intestinal output.
Oral clonidine was initiated at doses of 25 mcg twice daily in children and 50
mcg twice daily in adults. Loperamide, tincture of opium, paregoric, diphen­
oxylate/atropine, and somatostatin were used alone or in combination for
control of output. Results showed that intestinal output was unchanged in
children; however, adult output decreased by a mean of 700 mL.

Ulcerative Colitis and
Proctitis: Melander
et al.⁶⁴ reported seven cases in which oral clonidine was used to
treat ulcerative colitis or proctitis. At doses of 150 to 450 mcg daily, some
patients temporarily experienced diminished and more solid stools. Adverse
effects of fatigue and nausea seemed to outweigh the possible benefits of
clonidine.

Anesthesia/Sedation/Surgery

Antiemetic
in Children: Mikawa
et al.⁶⁵ conducted a trial to determine if preoperatively
administered oral clonidine reduced the incidence of vomiting in children
following strabismus surgery. One hundred forty children (ages 3 to 12 years)
were randomized to placebo, diazepam 0.4 mcg/kg, clonidine 2 mcg/kg, or
clonidine 4 mcg/kg in 2 mL/kg of apple juice. Agents were administered 100
minutes prior to induction of anesthesia. The incidence and frequency of
vomiting was found to be lower in the clonidine 4 mcg/kg group.

Maintenance of Stable
Hemodynamics: Costello
and Cormack⁶⁶ compared clonidine to temazepam in controlling
hemodynamics during pin head-holder application during a craniotomy. Fifty
patients took oral clonidine 3 mcg/kg or oral temazepam 10 to 20 mg given 90
minutes before induction of anesthesia. Clonidine was effective in reducing
mean arterial blood pressure increases that result from pin head-holder
application.

Laryngoscopy:
Laurito et al.⁶⁷ studied the effects of oral clonidine
premedication on sedation, and hemodynamic responses during preoperative
period, laryngoscopy, and postanesthesia recovery. Patients took clonidine 100
mcg, clonidine 200 mcg, triazolam 0.25 mg, or placebo. Oral clonidine 200 mcg
given 90 minutes prior to anesthetic induction effectively sedated and blunted
the hemodynamic response, but anxiolytic effects were not seen.

Liver Transplantation: De
Kock et al.⁶⁸ examined the effectiveness of clonidine on fluid
requirements and hemodynamic stability during liver transplantation surgery.
Twenty patients were randomized to receive either slow IV bolus of clonidine 4
mcg/kg during anesthesia induction or control. IV clonidine significantly
reduced the need for IV fluids and blood products and did not compromise
circulatory stability.

Intraoperative
Propofol Requirements:
Guglielminotti et al.⁶⁹ studied 28 patients randomized in this
double-blind study to receive hydroxyzine 1 mg/kg or clonidine 5 mcg/kg two
hours before induction of anesthesia. Clonidine significantly reduced
intraoperative propofol requirements, compared to hydroxyzine, without adverse
effects on recovery or hemodynamic stability.

Pharmacy Cost in
Preoperative Administration:
Vallès et al.⁷⁰ examined 80 patients randomly assigned to
receive 300 mcg of oral, intramuscular, or epidural clonidine or placebo at a
set time prior to surgery. Results indicated that in all groups premedicated
with clonidine, independent of route of administration, the expense of
isoflurane during anesthesia of about two hours’ duration was significantly
reduced. Notably, the cost of epidural clonidine offset the savings in
isoflurane.

Rhinoplasty: Britto
et al.⁷¹ studied clonidine in 20 patients  randomized to
receive temazepam 10 mg or temazepam 10 mg plus clonidine 3 mcg/kg 45 minutes
prior to induction of anesthesia. Clonidine with temazepam 10 mg was superior
to temazepam alone in decreasing mean arterial blood pressure, attenuating
response to intubation, and providing a better blood-free surgical field.

Sedation in Intensive
Care: Böhrer et al.⁷²
reported on a patient who underwent distal esophagectomy and proximal
gastrectomy who was not achieving adequate sedation through the combination of
midazolam and fentanyl infusions. Clonidine 0.014 mcg/kg/min continuous
infusion was then added with excellent analgesia and sedation control.
Clonidine abrupt withdrawal led to circulatory problems requiring a 12-day
weaning period.

Endocrinology

Hyperthyroidism:
Herman et al.⁷³
studied the effect of clonidine on inhibiting biological effects of
catecholamines released during hyperthyroidism. Patients with hyperthyroidism
received either nadolol 40 mg twice daily for one week or clonidine 150 mcg
twice daily for one week. Clonidine had similar clinical effects to nadolol.

Treatment of Growth
Delay: Moreno
Esteban et al.⁷⁴ studied clonidine in 112 prepubescent children.
Oral clonidine 75 mcg/m² was given daily for at least one year.
Clonidine may increase growth velocity in at least 65% of prepubescent
patients with constitutional growth delay.

Miscellaneous

Miscellaneous
uses have also been documented, including prevention of cyclosporine-induced
nephrotoxicity, excessive sweating, hot flashes, trichorrhexis nodosa, and as
a diagnostic tool for pheochromocytoma.^18,75-83

CONCLUSION

The clinical
utility of clonidine has been demonstrated through many varied applications.
This article compiles case reports and studies to clarify dosage and outcomes
associated with each therapeutic use. The available literature on clonidine
and its clinical utility was reviewed. However, there may be more reports for
a given therapeutic use than cited in this article; original references should
be checked for more information before the drug is used for the listed disease
states. Many of these studies involved the use of oral clonidine, which
resulted in an undesirable outcome or a discontinuation of treatment due to
unwanted side effects. Sedation and dry mouth are more pronounced with oral
therapy and when doses are initiated at 200 mcg/day or greater. Initiating
therapy with doses of 100 mcg each night can minimize these adverse effects.
Due to the small number of patients in these studies, the findings cannot be
extrapolated to the general population. These factors should be considered
before applying these data to clinical practice. Although clonidine may have
limited use in the initial treatment of hypertension, this article evidences
its clinical utility in various disease states.

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Memorial Sloan Kettering Cancer Center

This document, provided by Lexicomp ^® , contains all the information you need to know about the drug, including the indications, route of administration, side effects and when you should contact your healthcare provider.

Trade names: USA

Catapres [DSC]; Catapres-TTS-1; Catapres-TTS-2; Catapres-TTS-3; Duraclon; Kapvay

Trade names: Canada

APO-CloNIDine; DOM-CloNIDine; MINT-CloNIDine; TEVA-CloNIDine

Warning

Epidural:

• This drug is not intended to relieve pain before, during, or after surgery.In most cases, this drug is not used during or after labor. Low blood pressure and bradycardia associated with this drug can cause complications in these people. Consult your doctor.

What is this drug used for?

• Used to treat high blood pressure.
• Used to treat attention deficit hyperactivity disorder.
• Used to relieve pain during spinal infusion.
• This medicinal product may also be used for other indications. Consult your doctor.

What should I tell my doctor BEFORE taking this drug?

All forms of issue:

• If you are allergic to this drug, any of its ingredients, other drugs, foods or substances. Tell your doctor about your allergy and how it manifested itself.
• If you are taking another drug that contains the same drug.
• If you are taking any of these medicines: digoxin, diltiazem, verapamil, or a beta blocker such as metoprolol or propranolol.

Epidural:

• If you have bleeding.
• If you have an infection at the injection site.
• If you are taking anticoagulants (to thin the blood).

This list of drugs and diseases that may be adversely associated with this drug is not exhaustive.

Tell your doctor and pharmacist about all medicines you take (both prescription and over-the-counter, natural products and vitamins) and your health problems. You need to make sure that this drug is safe for your medical condition and in combination with other drugs you are already taking. Do not start or stop taking any drug or change the dosage without your doctor’s approval.

What do I need to know or do while taking this drug?

All forms of issue:

• Tell all healthcare providers that you are taking this drug. These are doctors, nurses, pharmacists and dentists.
• Avoid driving or other activities that require increased attention until you see how this drug affects you.
• To reduce the risk of dizziness or loss of consciousness, get up slowly from a lying or sitting position.Use caution when climbing and descending stairs.
• Measure blood pressure and heart rate as directed by your doctor.
• If you are taking this drug and have high blood pressure, talk to your doctor before taking any over-the-counter drugs that can raise blood pressure. These drugs include medicines for coughs and colds, diet pills, stimulants, nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen, and some naturally occurring drugs.
• Caution should be exercised in hot weather and during vigorous activity. Drink plenty of fluids to prevent dehydration.
• If you are 65 years of age or older, use this drug with caution. You may have more side effects.
• This drug may affect fertility. Fertility disorders can lead to infertility in both men and women. If you are planning to become pregnant or conceive a child, talk with your doctor before taking this drug.
• Tell your doctor if you are pregnant, planning to become pregnant, or breastfeeding. The benefits and risks for you and your child will need to be discussed.

Extended release tablets:

• Avoid alcohol, marijuana, or other forms of cannabis, or prescription or over-the-counter drugs that can slow you down.

All other dosage forms:

• Consult your doctor before using alcohol, marijuana or other forms of cannabis, or prescription and over-the-counter drugs that may slow you down.

All oral preparations:

• Talk to your doctor about what to do if you vomit after taking a dose of this drug.

Skin patch:

• The patch may contain conductive metal. Remove the patch before the MRI scan.
• If you have to undergo certain procedures to normalize your heart rate (defibrillation or cardioversion), tell your doctor.Make sure your doctor knows you are taking this drug.

What side effects should I report to my doctor immediately?

WARNING. In rare cases, some people with this drug can have serious and sometimes deadly side effects. Call your healthcare professional or get medical attention right away if you have any of the following signs or symptoms, which may be associated with serious side effects:

All forms of issue:

• Signs of an allergic reaction such as rash, hives, itching, reddened and swollen skin with blistering or scaling, possibly associated with fever, wheezing or wheezing, tightness in the chest or throat, difficulty breathing, swallowing or speaking, unusual hoarseness, swelling in the mouth, face, lips, tongue, or throat.
• Severe dizziness or fainting.
• Rapid, slow heartbeat, or irregular heartbeat.
• Change in contact lens tolerance.

Skin patch:

• Redness.
• Burn.
• Skin discoloration.

Epidural:

• Difficulty breathing or shallow breathing.
• Confusion of consciousness.

What are some other side effects of this drug?

Any medicine can have side effects.However, many people have little or no side effects. Call your doctor or get medical help if these or any other side effects bother you or do not go away:

All forms of issue:

• Dry mouth.
• Constipation.
• Feeling dizzy, sleepy, tired, or weak.
• Headache.
• Nausea.

Extended release tablets:

• Sleep disorders.
• Nightmares.
• Lack of hunger.
• Pain in the intestines.
• Feeling irritable.

Skin patch:

• Skin irritation.

Epidural:

• Excessive sweating.
• Vomiting.
• Ringing in the ears.

This list of potential side effects is not exhaustive. If you have any questions about side effects, please contact your doctor.Talk to your doctor about side effects.

You can report side effects to the National Health Office.

You can report side effects to the FDA at 1-800-332-1088. You can also report side effects at https://www.fda.gov/medwatch.

What is the best way to take this drug?

Use this drug as directed by your healthcare practitioner. Read all the information provided to you.Follow all instructions strictly.

All oral preparations:

• Take this medication with or without food.
• Take this drug at about the same time of the day.
• Continue taking this drug as directed by your doctor or other healthcare professional, even if you feel well.
• Do not stop taking this drug abruptly without talking to your doctor.This can increase the risk of side effects. If necessary, this drug should be stopped gradually as directed by your doctor.

Extended release tablets:

• Swallow whole. Do not chew, break, or crush.
• If you have difficulty swallowing, consult your doctor.

Skin patch:

• Continue using this drug as directed by your doctor or other healthcare professional, even if you feel well.
• First remove the previously attached patch.
• Wash hands before and after use.
• Apply the patch to clean, dry, healthy chest or shoulder skin. Change the overlay location for each new patch.
• Apply the patch to the hairless area.
• Do not apply to irritated or damaged skin. Do not apply to areas of skin folds or skin that will be chafed by tight-fitting clothing.
• This preparation comes with a retainer to hold the patch as it looses contact with the skin.The patch retainer does not contain any medicinal substances. Do not use the retainer without a patch. If the contact between the patch and skin looses, attach the retainer over the patch as instructed.
• After removing the patch, fold it in half, joining the adhesive sides together. Throw away used patches where they will be out of the reach of children and pets.
• Do not stop taking this drug abruptly without talking to your doctor.This can increase the risk of side effects. If necessary, this drug should be stopped gradually as directed by your doctor.

Epidural:

• For insertion into the spine.

What should I do if a dose of a drug is missed?

Extended release tablets:

• Skip the forgotten dose and return to your normal schedule.
• Do not take 2 doses at the same time or an additional dose.

All other oral preparations:

• Take the missed dose as soon as you can.
• If it is time for your next dose, do not take the missed dose and then return to your normal dose schedule.
• Do not take 2 doses at the same time or an additional dose.

Skin patch:

• Apply the missed patch as soon as you can, after removing the old one.
• If it is time to change the dressing, put on a new one.
• Begin a new patch placement schedule after reapplying the patch.
• Do not use 2 doses at the same time or an additional dose.

Epidural:

• Call your doctor for further instructions.

How do I store and / or discard this drug?

All oral medicinal products and skin patch:

• Store at room temperature in a dry place.Do not store in the bathroom.

All oral preparations:

• The lid must be tightly closed.

Epidural:

• If you need to store this drug at home, ask your doctor, nurse, or pharmacist for information about how it is stored.

All forms of issue:

• Store all medicines in a safe place. Keep all medicines out of the reach of children and pets.
• Dispose of unused or expired drugs. Do not empty into toilet or drain unless directed to do so. If you have any questions about the disposal of your medicinal products, consult your pharmacist. Your area may have drug recycling programs.

General information on medicinal products

• If your health does not improve or even worsens, see your doctor.
• You should not give your medicine to anyone and take other people’s medicines.
• Some medicines may have different patient information sheets. If you have questions about this drug, talk with your doctor, nurse, pharmacist, or other healthcare professional.
• Some medicines may have different patient information sheets. Check with your pharmacist. If you have questions about this drug, talk with your doctor, nurse, pharmacist, or other healthcare professional.
• If you think an overdose has occurred, call a Poison Control Center immediately or seek medical attention. Be prepared to tell or show which drug you took, how much and when it happened.

Use of information by consumer and limitation of liability

This information should not be used to make decisions about taking this or any other drug. Only the attending physician has the necessary knowledge and experience to make decisions about which drugs are appropriate for a particular patient.This information does not guarantee that the drug is safe, effective, or approved for the treatment of any disease or specific patient. Here are only brief general information about this drug. It does NOT contain all available information on the possible use of the drug with instructions for use, warnings, precautions, information about interactions, side effects and risks that may be associated with this drug. This information should not be construed as a guide to treatment and does not replace the information provided to you by your healthcare professional.For complete information on the possible risks and benefits of taking this drug, consult your doctor. Use of this information is governed by the Lexicomp End User License Agreement available at https://www.wolterskluwer.com/en/solutions/lexicomp/about/eula.

Copyright

© UpToDate, Inc. and its affiliates and / or licensors, 2021. All rights reserved.

90,000 Clinical study of high blood pressure: methyldopa vs.clonidine, clonidine patch – Clinical Trials Registry

Study Objective:

The aim of an open-label, randomized clinical trial is to compare the patch to clonidine. (Catapres-TTS®) and methyldopa (Aldomet®) orally over a 4-week period during compliance in pregnant women between 14 and 28 weeks of gestation. In addition, this study will assess blood pressure (BP) control, patient tolerance and development side effects of each medication.Patients will be randomized to receive methyldopa in turn. (standard of care) or clonidine patch.

Hypothesis:

Clonidine is an effective antihypertensive agent with a mechanism of action similar to methyldopa. Transdermal clonidine may provide a better match profile, adequate blood pressure. control and therefore can be used as an alternative to methyldopa for the treatment of CHTN in pregnancy.

The primary outcome of the study is patient compliance.diary, timeliness of appointment and pill / patch count at each visit. compliance will be calculated over a 4-week training period by adding matching points for each visit as indicated on the data sheet.

Secondary results:

1. change in mean arterial blood pressure at 1, 2, 3, 4 weeks compared with the initial level of blood pressure at the initial stage. visit (it will be used in patients who have recently started taking medications, or in patients with uncontrolled blood pressure at baseline).

2. Side effects of each drug reported by patients.

Background and significance

Chronic hypertension (CGN) occurs in 1-5% of pregnancies and is defined as BP 140/90 or higher before the 20th week of pregnancy or after 12 weeks after delivery. with an increased risk of preeclampsia, premature birth, intrauterine growth restriction, intrauterine fetal death, placental abruption and caesarean section. defined as BP & lt; 150/100 mm Hg. Art.and severe hypertension such as BP & gt; 160/110 mm Hg. Art. Direct correlation of adverse perinatal outcomes with the duration and severity of PTS in Pregnancy. Treatment of lungs with CHTN during pregnancy does not improve perinatal outcomes, and therefore antihypertensive therapy is intended only for the treatment of moderate to severe hypertension.

Methyldopa is used as first line therapy for CHTN during pregnancy. an alpha-adrenergic agonist, which reduces peripheral sympathetic outflow and thus leads to a decrease in peripheral resistance and blood pressure, does not affect uteroplacental blood flow and fetal hemodynamics.Methyldopa is a weak antihypertensive agent and often the need to increase the dose, frequency and / or add another drug to optimize blood pressure control with increasing gestational age. Side effects of methyldopa include sedation, orthostatic hypotension, edema, weight gain, bradycardia and dry mouth, rarely exacerbation. angina pectoris, congestive heart failure, pancreatitis, colitis, hyperprolactinemia, bone marrow depression, hemolytic anemia, false positive antinuclear antibodies and rheumatoid factor can be seen.

The use of different classes of antihypertensive drugs during pregnancy is limited due to: potential teratogenic effects. Angiotensin-converting enzyme inhibitors are contraindicated during pregnancy. The use of beta-blockers and diuretics is controversial and limited data on calcium channel blockers in pregnancy.

Clonidine is an effective antihypertensive agent and is available for oral, parenteral and transdermal dosage forms.Although oral and parenteral forms are commonly used for short-term use in hypertension, there are no data on its use in pregnancy. acts by stimulating α2-adrenergic receptors in the central nervous system (CNS), which suppress the outflow of the peripheral sympathetic nervous system and thus lower blood pressure. not associated with teratogenic effects in the fetus. rabbits at doses up to 3 times the maximum recommended daily dose of clonidine for humans (MRDHD) hydrochloride showed no signs of teratogenic or embryotoxic effects.Studied the pharmacokinetics of clonidine during pregnancy. Clonidine crosses the placenta and the fetal concentration is 0.89 of the maternal level. There are no side effects in newborns. Clonidine is reported to be metabolized in the liver and excreted unchanged in the urine.

The therapeutic levels of orally administered drugs are influenced by the transit time through the small intestine and the presence of food and fluids in the gastrointestinal tract. Transdermal drug administration permits first pass metabolism through the liver, requires lower doses to achieve a therapeutic effect, and promotes patient compliance.In addition, the drug is absorbed through the skin at a constant rate, eliminating the peaks and troughs associated with oral administration, which may lead to more sustained blood pressure control with transdermal clonidine. It can be useful during pregnancy as the transit time through the gastrointestinal tract is significantly increased due to the effects of progesterone and nausea, vomiting in the first trimester can limit oral medications. In addition, an improvement in patient compliance would be expected by eliminating repeated dosing, such as the four times daily schedule of methyldopa.

Transdermal Clonidine (Catapres-TTS®) is a clonidine hydrochloride formulation that can be released and absorbed transdermally over a 7 day period. The side effect profile is similar to that of methyldopa, including fatigue, lethargy, drowsiness, constipation, and dry mouth. Orthostatic hypotension occurs in 3% of patients with oral administration and has not been exposed. A transdermal form has been reported. Skin reactions including redness, itching, and darkening. skin can occur with clonidine patches.Rarely, angioedema, atrioventricular block, chest pain, congestive heart failure, hepatitis, thrombocytopenia, or urinary retention may occur.

A study of hypertension in non-pregnant women in the United Kingdom found that only 40% of patients who were prescribed a new antihypertensive drug agreed after six months. There is no evidence of adherence to antihypertensive drugs during pregnancy. although our anecdotal evidence suggests improved drug adherence during pregnancy compared to nonpregnant conditions.

Our study will determine the differences in adherence between the two antihypertensive drugs. and will provide additional comparisons of patient tolerance and adequacy of blood pressure control. This may be of particular importance for pregnant women who cannot tolerate oral feed, for example, patients with hyperemesis during pregnancy or in the immediate postoperative period. provide information on an alternative blood pressure control option not described in the obstetric literature.

1.National High Blood Pressure Education Program Working Group. High blood pressure report. Pressure during pregnancy. Am J Obstet Gynecol 1990; 163: 1691-1712.

2.National High Blood Pressure Education Program Working Group Report. Pressure during pregnancy. Am J Obstet Gynecol 2000; 183: S1-S22.

3. Chronic Hypertension in Pregnant Women, ACOG Practice Bulletin No. 29. American College of Obstetricians and Gynecologists, Obstet Gynecol 2001; 98: 177-185.

4.Montan S., Anandakumar S., Arulkumaran S., Ingemarsson I., Ratnam S.S. Effects of methyldopa on uteroplacental and fetal hemodynamics in pregnancy-induced hypertension. Am J Obstet Gynekol 1993; 168: 152-6.

5. Horrath JS, Phippard A, Korda A, Hendersen-Sart DJ, Child A, Tiller DJ. Clonidine Hydrochloride is a safe and effective antihypertensive drug for pregnancy. Obstet Gynecol 1985; 66: 634-8.

6. Turnbull AS, Ahmad S. Catapress in the treatment of hypertension in pregnancy, A Preliminary study: hypertension, Royal College of Surgeons Symposium, London 1970: 237-45

7.Hartikainen-Sorri AL, Heikkinen JE, Koivisto M. Pharmacokinetics of clonidine during pregnancy and lactation, Obstet Gynecol 1987; 69: 598-600.

8.Ala-Kokko T.I., Pienimaki P., Lampela E., Hollmen A.I., Pelkonen O., Vakhakangas K. Clonidine and dexmedetrmidine in isolated perfused human placenta. Anesthesiol Scand 1997; 41 (2): 313-19.

9. Jones JK, Gorkin L, Liane JF, Staffa JA, Fletcher AP Discontinuation and change Treatment after initiation of new courses of antihypertensive drugs: a collaborative study in the Kingdom’s population.BMJ 1995; 311: 293-5,

Reserpine for lowering blood pressure

Reserpine is an extract from the roots of the naturally occurring plant Rauwolfia serpentina . It has been used in the past as a first-line drug to lower blood pressure. However, today reserpine is a second-line drug and is used less frequently. The purpose of this review is to evaluate the efficacy of reserpine as a first-line drug in lowering blood pressure in primary hypertension. Method – search and summarize the best available evidence from randomized controlled trials.We judged the quality of the included studies to be acceptable, with acceptable randomization and blinding, and overall methods, as shown in the Risk of Bias (Bias) Chart. We judged studies to be weak if they did not provide a detailed description of the methods and results, which indicated the potential for unreliability of the report. It was the result of selective reporting or other factors interfering with objectivity, such as the lack of concealment of the identification of participants in the study group.To ensure that we only include good quality studies. They were recognized as such only when there was a clear indication that neither the participants, the clinicians, nor the evaluators knew which medication the participant was taking. All efforts were made to conceal the distribution order and to implement a blind method of scientific inquiry.

From this systematic meta-analysis, it was concluded that reserpine is effective in lowering systolic blood pressure as a first-line drug.Effectiveness is mild to moderate. Due to the fact that four studies did not cover a wide range of doses, there is no data to draw a conclusion about dose dependence. There is also insufficient information to assess the adverse effects of reserpine treatment. This update did not reveal new research; Thus, the conclusions of this review remain unchanged and represent the most up-to-date evidence up to October 2016.

Treatment and emergency care for high blood pressure.- Health – Articles Directory

City Clinical Hospital No. 31 – Arterial hypertension

Olga Beklemishcheva: Today we are talking about the treatment of hypertension. Rather, we continue the conversation – not so long ago we already started our topic, but due to the large number of calls we did not manage to open it properly. And arterial hypertension is an extremely common disease that, unfortunately, leads to disability and, even, sadly, to death if it is not treated or treated incorrectly.So, arterial hypertension – how to deal with it. Today in our studio Viktor Solomonovich Segelman , doctor of the highest category, head of the second therapeutic department of the 31st city clinical hospital in Moscow. Our permanent American medical expert Professor Daniil Borisovich Golubev will also take part in our conversation. So we begin.

Viktor Solomonovich, who is at risk of hypertension? Are there people who never get sick with it?

Segelman: There is such an expression: not everyone who wants to become a cirrhotic becomes one.This means that if a person even drinks a lot of alcohol, he does not necessarily become a cirrhotic. The same goes for hypertension. Many different factors converge here. First of all, heredity, profession, lifestyle, diet. The ability to rest is very important – not formally rest, spend some time outside of work, outside the office, but psychologically rest, relax. Therefore, not all people are threatened by arterial hypertension. There are so-called risk factors.

Olga Beklemishcheva: And what are they?

Segelman: There are many risk factors, this is a hereditary predisposition, hereditary burden of arterial hypertension, other diseases of the cardiovascular system, these are metabolic disorders, primarily diabetes mellitus, this is smoking, these are dietary habits, this is obesity.Well, and once again we are talking about the patient’s personality traits – this is the inability to relax, this is when on vacation all the time they think about work, about problems that cannot be resolved, in any case …

Olga Beklemishcheva: Some workaholism.

Segelman: Workaholism.

Olga Beklemishcheva: And now I want to ask our American interlocutor, Professor Golubev, about what role American medicine attaches to nutrition in the genesis of arterial hypertension?

Daniil Golubev: We can say – the presenter, in any case – one of the main ones.In all educational and instructional materials, the leading causal factors of hypertension (this term is equivalent to the concept of “essential hypertension”, or “hypertension” in Russian terminology) are listed in this order: smoking, overweight, alcoholism, diabetes, and in fifth place – stress. Such ideas have developed historically, but they are fully consistent with modern concepts and modern realities, when the terms “obesity epidemic”, “diabetes epidemic” (in particular, childhood) have become firmly established in the medical lexicon, and both of these forms of pathology almost inevitably entail hypertension.Hence, attempts to optimize the nutrition and physical activity of Americans of all ages, races and social groups are understandable in order to prevent obesity and diabetes, and, accordingly, the incidence of hypertension.

Olga Beklemishcheva: And how successful are these attempts?

Daniil Golubev: I would say: almost nothing. The average weight of Americans of all ages is not only not decreasing, but even increasing. The number of diabetics is not decreasing in any way – again in all age groups.Serious success in America has been achieved only in the fight against smoking, especially in comparison with European countries and Russia. Naturally, this affected the number of all types of pathologies one way or another induced by smoking. But as for hypertension itself, despite all the successes in the fight against smoking and all the advances in drug therapy, the number of Americans with hypertension is still very large. If medical encyclopedias and reference books 10 years ago indicated that 10% of the entire adult population of the United States owned it, then in 2003-2004 this figure at least doubled.I believe that the increased role of stress as one of the factors in the onset of hypertension plays an important role in this. This is evidenced by modern realities filled with wars, threats and acts of terrorism and horrific natural disasters, including the danger of an avian flu pandemic. All this affects the neuropsychological status of the population and allows, unfortunately, to remember that essential hypertension can also be the result of cortico-visceral pathology.

Olga Beklemishcheva: What attitudes of modern American medicine in relation to the treatment of hypertension are the most essential?

Daniil Golubev: In the United States, essential hypertension is diagnosed with a persistent increase in blood pressure above 140 by 90 millimeters of mercury. In the treatment of hypertension in America in recent years, the practice of rigidly bringing the blood pressure level of patients of all age groups of adults, including those over 65, to a normal level, that is, up to 120-125 / 80 mm Hg, has been established.But a few decades ago, for the elderly, a blood pressure of 140 and even 150 to 90 was considered quite acceptable.

To actively reduce blood pressure indicators to a specified level, American doctors widely use a whole range of antihypertensive drugs with different mechanisms of action, and the treatment of uncomplicated hypertension is regarded as successful only if, through individual selection of antihypertensive drugs and optimization of lifestyle (nutrition, physical activity , giving up bad habits) manages to keep blood pressure indicators within the specified limits.At the same time, the main obstacle in the way of treatment and the main reason for the most severe complications of hypertension is the “indiscipline” of patients who do not monitor their blood pressure levels, do not follow the prescribed antihypertensive drug regimen prescribed by doctors and do not lead a healthy lifestyle. In general, hypertension in America cannot be classified as a controlled disease. It is very relevant and deserves the most serious attention from both doctors and patients.

Olga Beklemishcheva: Doctors began to talk about the benefits of a healthy lifestyle with Hippocrates, nevertheless, people still do not really listen.But there comes a time when even the most careless person realizes that his health needs help. What are the early signs of hypertension?

Segelman: Unfortunately, there are practically none. One of the insidiousness of arterial hypertension, hypertension, first of all, is the formal mildness of its course. The first symptoms of arterial hypertension, in fact, are already an advanced stage of the disease. These are headaches, these are some sensations in the region of the heart, this is dizziness.If anything, the brain and heart are the two main target organs. Their defeat is, as a rule, the first symptoms. If a person has high physical activity, then it may decrease: he gets up faster, shortness of breath decreases faster. But once again it must be said that, unfortunately, hypertension, arterial hypertension, like many other serious diseases, do not make themselves felt for a long time, at least with some specific symptoms.

Olga Beklemishcheva: These are clinical symptoms.Maybe at the laboratory level something can be figured out in advance?

Segelman: There is little to be learned at the laboratory level; blood pressure must be measured. Blood pressure should be measured at any doctor’s visit, at every occasion. If a person has conjunctivitis, if a person has a nail pain, any contact with a healthcare professional should be accompanied by a blood pressure measurement. This is especially true for people with risk factors – smokers, obese, diabetics, people leading a very active life associated with stress, well, and people who have cardiovascular diseases in their family, whose parents are sick or died from heart attacks, strokes.

Olga Beklemishcheva: But there is such a thing as “white coat hypertension”, when a person just looks like a doctor rises in blood pressure? Maybe you need to make some kind of amendment when you measure the pressure in the clinic?

Segelman: Of course, an amendment needs to be made. But why does this man have pressure on his white coat? After all, his sugar does not decrease, dizziness does not develop, which is not associated with blood pressure, his blood pressure rises.

Olga Beklemishcheva: This means that this is his bottleneck.

Segelman: So this is his bottleneck. As the old doctors said, the place of least resistance. This means that we can, if we do not take into account the white coat syndrome, somewhat overestimate the level of his blood pressure. But that this patient has this weak point, it is probably so.

Olga Beklemishcheva: And you should know that. Viktor Solomonovich, well, the person somehow found out that his blood pressure is increasing.How can you draw the line – this is a normal increase in pressure caused by some kind of stress, overexertion, but this is already a disease?

Segelman: In recent years, a more rigid concept of arterial hypertension has emerged. If earlier we introduced some age norms, we said that, for example, after 60 years, the pressure of 140-150 is more or less possible, yes, a person of age, he has blood vessels, now we have a common opinion, that as soon as the pressure rises above normal, if during the day it is more than 135 and 85, and at night more than 120 and 70 millimeters of mercury, then this is arterial hypertension, this is hypertension or syndromic arterial hypertension, regardless of the patient’s age.Another question is that if a patient suffers from some other diseases, then we can set ourselves a slightly higher target level of lowering blood pressure, arterial hypertension. But this is a topic for another conversation.

Olga Beklemishcheva: And you said “night pressure”, “day pressure”, which of them is more important?

Segelman: A person, while he is alive, his pressure constantly rises, falls. When we say that normal blood pressure, roughly speaking, is 120 and 70, this does not mean that at any moment of human life a healthy person has 120 and 70.During physical, emotional stress, in some other periods of a person’s life, pressure can increase significantly. And therefore, if after a marathon run, if an ordinary person climbs several floors, he will have 140-150 and 80, or after a tough conversation with the boss he will have the same pressure, this does not mean that the person is hypertensive. It simply means that all systems are working adequately for him. Another question is that it should be normalized within 10-20, maximum 30 minutes.Therefore, during the day, blood pressure can be above 120 and 70 under certain conditions. Night pressure should always be normal. Therefore, there are rules for measuring blood pressure in order to say that a person has high blood pressure. A person should sit for 20-30 minutes in calm conditions, he should not smoke half an hour before that, he should not drink coffee, he should get used to the office, the measurement should be, if this is the first time, several times on both hands, and only then we can talk about an increase in blood pressure.

Olga Beklemishcheva: Why can there be different pressure on different hands?

Segelman: It happens – it is determined often, but it happens not so often. As a rule, when you measure the pressure on the other hand, whatever it is – left or right, then it will be lower. The patient gets used to it, and this white coat syndrome, which they talked about, it seems to subside …

Olga Beklemishcheva: Is being leveled.

Segelman: Is leveled.There is simply an innate ratio of the size of the arteries, the characteristics of the blood supply to the hands. You need to focus on the pressure that is greater, and then measure the pressure on the arm on which the pressure is determined at a higher level.

Olga Beklemishcheva: And now the person is really convinced that his blood pressure rises not in some critical situations, but in an asymptomatic way. Are there any analyzes that need to be done that would make it possible to isolate that it is arterial hypertension, and not some other types of pathology, which are also accompanied by an increase in pressure? What is the need to differentiate arterial hypertension?

Segelman: The syndrome of arterial hypertension is the same in both hypertension and arterial hypertension, which occurs within the framework of some other pathology – renal, endocrine, vascular.With each, unfortunately, not a year, but a decade, there are more and more diseases, from which we single out the symptoms of arterial hypertension. For example, if earlier we talked about vasorenal hypertension, only isolated it associated with damage to the vessels of the kidneys, now they are already quite actively talking about cerebro-ischemic arterial hypertension, about arterial hypertension associated with narrowing of the cerebral vessels, that the brain gives a signal to increase the pressure, to provide yourself with blood. The cardioischemic form of arterial hypertension is at the stage of isolation.A certain cycle is carried out, a certain list of various studies aimed at isolating arterial hypertension of a renal, vascular, endocrine nature, but, in general, this is the doctor’s task.

Olga Beklemishcheva: I observed at your appointment how you listened attentively to the pulse – not only the heart, but also in the carotid arteries, in the abdominal arteries. Does this help determine the type of hypertension?

Segelman: An experienced doctor has a lot to say in the blood pressure measurement phase.When you measure blood pressure, then these Korotkov tones, these are the sounds of blood that break through the cuff, they can be quiet, at the same level, they can be powerful. Thus, we can already roughly say at once: this arterial hypertension is mainly associated with spasm of peripheral vessels, or with a large volume of blood pumped by the heart. By the pulse rate, we can, to some extent, separate out syndromic hypertension, hypertension associated with damage primarily to the kidneys.By listening to the carotid arteries, listening to the abdominal aorta, renal arteries, vertebral arteries, in severe stenosis, you can hear the corresponding noises and already direct the diagnostic search in a narrower direction.

Olga Beklemishcheva: But this division of different types of hypertension somehow affects the treatment that is prescribed? That is, if, say, I have the cause of arterial hypertension in the vessels of the brain or in the vessels of the heart, will I be given different drugs to lower the pressure or the same, but in different dosages?

Segelman: The fact is that if a person’s arterial hypertension, for example, is associated with a narrowing of the carotid artery or with a narrowing of the renal artery, this can and should be copied, and there are brilliant surgeons who do this, and the person does not will have to take antihypertensive drugs, the person will be cured.Therefore it is important. If for some reason the operation is impossible or the patient refuses, then largely similar drugs are prescribed, maybe in different doses, in different combinations, but the drugs are close.

Olga Beklemishcheva: And what kind of drugs are these?

Segelman: Well, there are a lot of drugs.

Olga Beklemishcheva: By groups.

Segelman: By groups, probably, first of all, we need to talk about the so-called beta-blockers, beta-blockers.These are drugs that reduce the effect on the cardiovascular system of adrenaline in a certain part, in terms of beta receptors. This is of great importance not only for the treatment of arterial hypertension, but also for the prevention of cardiac complications, especially sudden death. They have their own specific indications, their specific contraindications, these are very important drugs. The second large group of drugs are angiotensin-converting enzyme inhibitors. This is the well-known captopril, enalapril, in Russia it is widely known under the name enap or the generic name of the drug, the first company to release renitek and other drugs in this group.The continuation of the same line is angiotensin antagonists, these are similar drugs, they act in the same direction, only more modern.

Olga Beklemishcheva: And in what direction do they act exactly? It is understood that beta blockers reduce the action of adrenaline, which is inevitably released in a stressful situation. And what are these doing?

Segelman: If the so-called ACE inhibitors – they block renin, then these block angiotensin, angiotensin is a further product of the work of renin, so this is one chain.

Olga Beklemishcheva: At different stages.

Segelman: At different stages. Therefore, they act, in general, on the same circuit. It’s just that angiotensin receptor antagonists are deprived of one side effect of inhibitors, let’s say that enalapril is, first of all, the most common drug, they do not give such a side complication as a cough that occurs in several percent of patients. But this is an effective drug. There are other drugs, well-known calcium antagonists, this is nifedipine, this is amlodipine, good drugs, effective, which are also indicated in certain groups of patients.The last of the commonly used drugs, perhaps, should have been called the first and second, these are diuretics, this is primarily hypothiazide, widely known, which is largely a reference drug, and with which the effect of other drugs is compared, well, other drugs that are similar to him. The existing other drugs are centrally acting, the well-known clonidine in Russia, the lesser-known physiotens drugs. These are alpha-blockers, are used less often, but they are effective drugs.And I must say that often the qualifications of a doctor are visible in the way they use these spare drugs.

Olga Beklemishcheva: And what does the qualification that manifested itself in the use of spare drugs mean? A good doctor does what?

Segelman: A good doctor tries to solve several problems with one drug. If a person, for example, has a bad sleep or a person has a tendency to a rapid pulse and at the same time arterial hypertension, then beta-blockers can be given to him, but if a beta-blocker for some reason is not very indicated, well, for example, a person has a problem with lungs, with bronchi, then maybe it is better to give him fiziotens or clonidine.Clonidine (or clonidine – its international name) is a drug, of course, somewhat outdated and having one very unpleasant effect – it is very difficult to leave it by starting to take clonidine, it must be taken constantly and clonidine must be removed slowly and gradually.

Olga Beklemishcheva: And now Alexey Kuznetsov will introduce you to the news from Evgeny Muslin.

Alexey Kuznetsov: The 16th World AIDS Conference will take place in Toronto this August, in which 20,000 specialists will take part.The conference, with a record number of participants, is timed to coincide with the 25th anniversary of the first diagnoses of a deadly disease and will discuss the most effective methods of preventing and treating AIDS. The previous such conference in Bangkok was attended by 17 thousand people.

“The goal of the 2006 conference is to accelerate the pace of research, radically expand access to proven drugs and prevention of new infections, and help prolong the lives of people who have already developed AIDS,” said Elena Gail, President of the International AIDS Association. …“We must mobilize all the resources available to us and mobilize our collective will to successfully translate the accumulated scientific knowledge and experience into effective programs to curb the immunodeficiency virus,” Mrs. Gail concluded her speech.

Over the past decade, antiretroviral therapy has dramatically reduced the death rate of AIDS patients. Unfortunately, the vast majority of the more than 40 million people around the globe who are infected with the deadly virus still do not have adequate access to treatment, the organizers of the Toronto conference said, which plans to review and discuss more than 12,000 scientific papers and messages.

International AIDS Conferences are held every two years by an independent International Association of Specialists with over 10,000 members in 132 countries.

Canadian neurologist Neil Cashman, sponsored by the Canadian National Institutes of Health, said that he and his team have developed the first simple blood tests to diagnose brain diseases such as Alzheimer’s, Parkinson’s, and Creutzfeldt-Jakob disease, the human version of cow rabies. …

“If we do not encounter unforeseen complications,” says Dr. Kashman, “new tests will be able to be introduced into clinical practice in 2-4 years.”

These tests will make it possible to confidently diagnose brain diseases in the early stages of the disease, when the action of medications may be more effective, whereas now attending physicians are forced to rely on cumbersome and unreliable methods of testing a person’s memory and mental abilities or resort to complex types of transillumination.And still, a reliable diagnosis of such diseases, occurring mainly inside the cranium, is still possible only after the death of the patient, since for this it is necessary to examine a piece of the brain under a microscope.

The number of obese children will increase substantially worldwide by 2010. “We are witnessing a global epidemic of sedentary lifestyles and the proliferation of fast food fatty foods that is affecting almost all countries,” said Dr. Philip James, chairman of the International Commission on Fighting Obesity.

This process, which has been going on for a long time in North America and Europe, has now spread to the Middle East and Southeast Asia. According to experts, even in China by 2010 every fifth child will suffer from obesity.

According to experts, the consequences of childhood obesity will be catastrophic for world health. As children grow up, they will increasingly suffer from heart disease, strokes and diabetes. “They could be the first generation with a shorter life expectancy than their parents,” says Manchester-based British surgeon Dr. Philip Thomas.”A wave of heart disease and strokes is just about to sweep through public health,” says Brian McCrindle, a Canadian pediatric obesity specialist, Toronto-based pediatrician professor.

Many doctors are convinced that, first of all, it is necessary to urgently and legally ban all advertising of low-quality instant food in order to reduce its destructive effect on children.

Olga Beklemishcheva: Well, and we return to our topic. We already have calls from listeners.Let’s first answer, and then we will continue our conversation about clonidine. The first to call was Yuri from Moscow.

Listener: I had a hemorrhage in my eye, I felt bad, and in the office I started to bleed from my nose. The doctor said, “What is your pressure?” “I have the usual – 110 to 70, all the time hypotension.” “Well, it means you have craniocerebral pressure, but the fact that you are bleeding is you have to thank fate. But the eye is a symptom. ” How to determine – the pressure gauge shows 110 to 70, and the head is bo-bo?

Segelman: The fact is that hemorrhage in the eye, in the sclera of the eye, nosebleeds occur with arterial hypertension, but there are many other diseases.Obviously, if you have really normal blood pressure, then you are suffering from some other medical condition, not related to arterial hypertension, which caused these symptoms.

Olga Beklemishcheva: And, of course, you need to be examined further. The next listener is Grigory Khrisanfovich from Moscow.

Listener: Dear Doctor Viktor Solomonovich, an invalid of the Patriotic War is speaking to you. I am 84 years old. In the Battle of Stalingrad, I commanded a company, I was twice seriously wounded, a severe head injury, a number of other wounds, and so on, and so on.But nevertheless, during the war, although my father received a notice of my death, the doctors cured me in difficult winter conditions. After the war, I suffered three heart attacks, including a transmural one. I lay in Krasnogorsk several times, the last time I was in intensive care for 15 days. So, I have hypertension all the time. You say, there, 120 by 80, my minimum is 140, or rather, sometimes 180-190 at 100, 120 and so on. And the doctors give me kapoten, anaprilin, nitro-angry and nothing else. Please tell me how you can reduce it, because I often have headaches and so on?

Segelman: I said that there are clinical cases, exceptions, when we set ourselves the goal of reducing the pressure not necessarily to 120 and 70.If a person has chronic cerebrovascular accident and this cannot be controlled, there are no conditions, there are contraindications, then sometimes we choose large numbers as target pressure, maybe 140 is normal for you, maybe even 150. As for which drugs : captopril, kapoten is an excellent drug. Its only feature is that it must be taken at least three times, and preferably four times a day. The same is about anaprilin, it must be taken at least three times a day.Now, if you take captopril every six hours, every eight hours, or every six hours also anaprilin, well, you need to see what your blood pressure will be, how you will feel. In difficult situations like yours, sometimes the pressure needs to be reduced in steps. Reduce by 10 – 15 millimeters and let the vessels get used to. Reducing your blood pressure is, of course, a difficult task, you need to meet with you again, on the radio, so I cannot say, outline the whole program of your treatment for you.

Olga Beklemishcheva: Indeed, after all, a sharp decrease in pressure in vessels that are already accustomed to high pressure, it can turn out to be dangerous.

Segelman: In general, it is believed that even with a hypertensive crisis, when there is a threat of stroke … A hypertensive crisis is almost always a brain damage, encephalopathy. We shouldn’t quickly reduce the pressure by more than 20%, of course. There is a complex game of vessels – a person constantly changes his position, his head drops, rises, a person sits down, lies down, walks, stands, so if a person has 240, say, and 120 during a crisis, then he does not need to reduce the pressure to norms, this is wrong.

Olga Beklemishcheva: Returning to the conversation about clonidine, this is a rather old drug. At one time, clonidine was even somewhat arrogantly rejected and it was said that it was too old a drug, that you, dear Russian doctors, were stuck, you need to switch to new ones. But you are now saying that in certain cases, clonidine is justified. And I know, for example, my relative who has been on clonidine for many years, and, at a very respectable age of a lady, she is already 93, although the pressure is consistently high, nevertheless, the safety of functions and a sufficient quality of life is observed on clonidine.How can this situation be explained? Here are new drugs, old drugs, some are better than old ones, some are better with new ones, how to figure it out?

Segelman: First, you need to immediately separate clonidine from adelfan. Adelfan is a completely different group of drugs, there are two main active ingredients, this is hypothiazide, which I spoke about, this is an effective drug and there are no complaints about its effectiveness. The second main active drug is reserpine. This is a serious drug, but it is really outdated because it has a lot of side effects, so Adelfan is definitely a going away drug.Clonidine preparations – there is now a new generation of these drugs. The so-called physiotens is widely known, the Hungarian albarel is less known, and related preparations. They are more modern, they work better, they are more effective, they are less dangerous if canceled quickly. These are drugs that remain relevant. Clonidine, in addition to the fact that its cancellation is very dangerous, because of simply organizational things, it cannot be put on the open sale, since it has some other qualities, it is often used for criminal purposes, therefore prescribing clonidine is a difficult task, special recipes are needed, maybe be, therefore, treatment with them is still somewhat difficult.Therefore, take drugs physiotens, drug albarel, these are good drugs, they are moderately effective, in serious cases, as a rule, you already have to give them up. But with benign hypertension, people can take them with good effect for many years.

Olga Beklemishcheva: And so you said: for many years … I would like to draw the attention of our listeners to the fact that therapy for arterial hypertension is lifelong, that is, if you have been prescribed this drug, you cannot quit it.So, Viktor Solomonovich?

Segelman: Yes. A very correct word “life”. If arterial hypertension, hypertension has already begun, we do not know how to cure it, no one can cure it anywhere. Even if we leave the stressful situation, if we become, I don’t know, foresters in the Siberian taiga, then, obviously, the pressure will decrease somewhat, but arterial hypertension will remain. Therefore, patients should receive treatment for life. In addition, there are drugs, the withdrawal of which is very dangerous.We have already talked about the danger of canceling clonidine, the sudden cancellation of beta-blockers is very dangerous. These are the well-known atenolol, anaprilin, the lesser known metoprolol in different brand names. Beta blockers also cannot be canceled immediately without careful monitoring.

Olga Beklemishcheva: And I really want to draw the attention of our listeners to what Dr. Segelman said. This is the general opinion of the entire medical community. Only 5% of people with arterial hypertension are treated correctly.Many, unfortunately, take great liberties in the order of the use of drugs, in replacement, sometimes it seems to them that they feel good, and they stop drinking. This cannot be done, it is very dangerous. So, Viktor Solomonovich?

Segelman: Certainly. These words about the intoxication of the body with drugs, about saturation, I do not want to get used to drugs … It’s amazing to hear such expressions.

Olga Beklemishcheva: What the doctor ordered should be drunk exactly as he ordered.And the next listener is Leonid Isaakovich from Moscow.

Listener: My blood pressure is 125 to 60, sometimes it is 125 to 55. Pulse is 50. 67 years old. Is it dangerous that my lower pressure is low? This is the first question. And second, I read in one place that older people still need to measure their pressure while lying and standing. Should I do this or not?

Segelman: Well, this is desirable, not necessary, but if you are hypotensive and tolerate it well, you’re in luck, hypotensives live longer than normatonics.

Olga Beklemishcheva: And the next listener is Elizaveta Gavrilovna from Moscow.

Listener: I also wanted to consult a doctor so famous. I rarely go to doctors very much, I hope more in the Lord. I am 83 years old. I suffered from severe hypertension. My pressure reached 220-240. I drank Enalaprin Enlaz Indian and now I drink it, but for some reason the noise in my left side of my head and in my ears never stops. What can be done?

Segelman: If you have tinnitus against the background of good, decent or normal blood pressure, then you have another disease, well, we call it now beautifully – ischemic brain disease.It is necessary to do an ultrasound examination of the vessels of the brain and be treated by a neurologist with drugs such as Cavinton, gingobiloba and other drugs that improve cerebral circulation. If you find a narrowing of, say, the carotid artery, then, in spite of your generally respected age, it can be sympathetic, and then the tinnitus will certainly stop.

Olga Beklemishcheva: That is, in fact, there are quite a lot of options for treating hypertension, like any other.And here you need to maintain a certain vigilance. Often people prefer such folk methods, turning to oriental practices, and so on. In this case, this is not very good. Dr. Segelman ”border =” 0 ″ height = ”11 ″ width =” 16 ″>, please tell me how the treatment methods, say, Chinese medicine, Tibetan medicine and the academic approach of Western modern medicine in terms of arterial hypertension relate?

Segelman: You see, oriental medicine, Chinese medicine, Tibetan medicine is often very effective.Unfortunately, they often improve well-being more than they cure the disease. I met with a seemingly very effective treatment of arterial hypertension in renal patients with the methods of Tibetan medicine. The patient felt great, while his blood pressure was very high when measured, which soon ended in a vascular catastrophe. But here I would like to say something very important: unfortunately, there are very few doctors and just practicing specialists in Chinese, in oriental medicine.Unfortunately, these methods are practiced by people who quickly completed some monthly, two-week courses and quickly heal using notes. These people very often do harm by delaying the start of effective therapy. With hypertension, there is a very simple way to determine the effectiveness. This is to measure your blood pressure. If acupuncture, moxibustion and something else lower blood pressure, good.

Olga Beklemishcheva: And if it doesn’t decrease, but does the state of health improve?

Segelman: This is very bad, because one of the bad features of arterial hypertension is that the symptoms of hypertension appear late, when arterial hypertension has already caused great harm to the body.

Olga Beklemishcheva: And she will continue to do this harm if the pressure is not reduced. The same target organs – the brain, heart, kidneys – will suffer even if you don’t feel it, so vigilance, vigilance and more vigilance. And the next calls from our listeners. Natalia Vladimirovna from Moscow.

Listener: How to understand in the light of what the doctor said, this is my doctor’s prescription: a quarter of anaprilin tablet twice a day?

Segelman: You see, what’s the matter, there is a circadian rhythm of pulse, pressure.Maybe the doctor takes into account that a person’s pulse decreases at night, and if, for example, your pulse at night, for example, without drugs, is less than 60, then this is the right good prescription, taking into account your characteristics. Also, I’m talking about the general human population. Each person secretes drugs in his own way, detoxifies them in his own way, they have different ras

90,000 How effective is clonidine for anxiety?

Clonidine reduces the physical stress response in the human body by blocking adrenaline, a chemical involved in fight or flight responses.It is prescribed for several physical and mental health conditions, including anxiety, panic disorder, insomnia, and high blood pressure. Using clonidine for anxiety helps prevent physical reactions to anxiety, such as heart palpitations and high blood pressure, rather than relying on its ability to stop anxious thoughts.

There are other medications for treating anxiety and panic disorder, but many mental health professionals choose to use clonidine to treat anxiety.Unlike benzodiazepines, another class of drugs used for anxiety, clonidine does not cause physical dependence and there is little risk of dependence. Studies investigating the effectiveness of this drug as a treatment for anxiety have shown that it is far superior to placebo treatment, indicating a real effect in treating this mental disorder. Clonidine reduced anxiety attacks in most people studied, but in some cases it made anxiety symptoms worse.

When people are given clonidine for anxiety, it is usually in pill form. More severe cases of anxiety can cause a person to wear a patch with this medication, allowing it to be gradually absorbed through the skin. In a hospital setting, this drug is available in injectable form for the treatment of acute anxiety attacks.

Patients taking clonidine for anxiety should be aware of its potential side effects, usually limited to fairly harmless symptoms such as dry mouth, itching and dry skin.Some patients may experience headaches, nausea, and trouble sleeping. Occasionally, however, more serious side effects may occur that may require medical attention, such as a heart rate below 60 beats per minute, confusion, or hallucinations. Fever, light-headedness, shortness of breath, or trouble urinating are also troublesome.

More than one medication can be prescribed for anxiety, and anxiety often occurs along with other disorders.Therefore, people taking clonidine for anxiety should be aware of possible drug interactions. Benzodiazepines and other depressants, including alcohol as well as opiate pain relievers, can increase drowsiness and other effects of clonidine and can potentially be fatal when combined in high doses.