Sulfamethoxazole-Trimethoprim Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing

Uses

This medication is a combination of two antibiotics: sulfamethoxazole and trimethoprim. It is used to treat a wide variety of bacterial infections (such as middle ear, urine, respiratory, and intestinal infections). It is also used to prevent and treat a certain type of pneumonia (pneumocystis-type).This medication should not be used by children less than 2 months of age due to the risk of serious side effects.This medication treats only certain types of infections. It will not work for viral infections (such as flu). Unnecessary use or misuse of any antibiotic can lead to its decreased effectiveness.

How to use sulfamethoxazole-trimethoprim oral

Take this medication by mouth, as directed by your doctor, with a full glass of water (8 ounces / 240 milliliters). If stomach upset occurs, take with food or milk. Drink plenty of fluids while taking this medication to lower the unlikely risk of kidney stones forming, unless your doctor advises you otherwise. Dosage is based on your medical condition and response to treatment.

For the best effect, take this antibiotic at evenly spaced times. To help you remember, take this medication at the same time(s) every day.

Continue to take this medication until the full prescribed amount is finished, even if symptoms disappear after a few days. Stopping it too early may allow bacteria to continue to grow, which may result in a relapse of the infection.

Tell your doctor if your condition lasts or gets worse.

Side Effects

Nausea, vomiting, diarrhea, and loss of appetite may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.

Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: muscle weakness, mental/mood changes, signs of kidney problems (such as change in the amount of urine, blood in the urine), extreme drowsiness, signs of low blood sugar (such as sudden sweating, shaking, fast heartbeat, hunger, blurred vision, dizziness, or tingling hands/feet).

Get medical help right away if you have any very serious side effects, including: headache that doesn’t go away, neck stiffness, seizures, slow/irregular heartbeat.

This medication may rarely cause serious (possibly fatal) allergic reactions and other side effects such as a severe peeling skin rash (such as Stevens-Johnson syndrome), blood disorders (such as agranulocytosis, aplastic anemia), liver damage, or lung injury. If you notice any of the following, get medical help right away: sore throat or fever that doesn’t go away, cough that doesn’t go away, nausea/vomiting that doesn’t stop, skin rash/blisters, itching/swelling (especially of the face/tongue/throat), new or worsening lymph node swelling, paleness, joint pain/aches, trouble breathing, easy bleeding/bruising, yellowing eyes or skin, unusual fatigue, dark urine.

This medication may rarely cause a severe intestinal condition due to a bacteria called C. difficile. This condition may occur during treatment or weeks to months after treatment has stopped. Tell your doctor right away if you develop: diarrhea that doesn’t stop, abdominal or stomach pain/cramping, blood/mucus in your stool.

If you have these symptoms, do not use anti-diarrhea or opioid products because they may make symptoms worse.

Use of this medication for prolonged or repeated periods may result in oral thrush or a new yeast infection. Contact your doctor if you notice white patches in your mouth, a change in vaginal discharge, or other new symptoms.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US – Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.

In Canada – Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Precautions

Before taking this medication, tell your doctor or pharmacist if you are allergic to sulfamethoxazole or trimethoprim; or to sulfa medications; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, liver disease, certain blood disorders (such as porphyria, anemia due to folate vitamin deficiency), history of blood disorders caused by trimethoprim or sulfa medications, vitamin deficiency (folate or folic acid), severe allergies, asthma, decreased bone marrow function (bone marrow suppression), a certain metabolic disorder (G6PD deficiency), underactive thyroid, mineral imbalances (such as high level of potassium or low level of sodium in the blood).

This medication may cause live bacterial vaccines (such as typhoid vaccine) to not work well. Tell your health care professional that you are using this medication before having any immunizations/vaccinations.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

This medication may make you more sensitive to the sun. Limit your time in the sun. Avoid tanning booths and sunlamps. Use sunscreen and wear protective clothing when outdoors. Get medical help right away if you get sunburned or have skin blisters/redness.

If you have diabetes, this product may affect your blood sugar. Check your blood sugar regularly as directed and share the results with your doctor. Tell your doctor right away if you have symptoms of low blood sugar (see Side Effects section). Your doctor may need to adjust your diabetes medication, exercise program, or diet.

Older adults may be more sensitive to the side effects of this drug, especially skin reactions, blood disorders, easy bleeding/bruising, and a high potassium blood level.

Patients with AIDS may be more sensitive to the side effects of this drug, especially skin reactions, fever, and blood disorders.

Tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant while using sulfamethoxazole/trimethoprim. This medication may harm an unborn baby. If you become pregnant, talk to your doctor right away about the risks and benefits of this medication.

This drug passes into breast milk. While there have been no reports of harm to healthy infants, this drug may have undesirable effects on infants who are ill or premature or have certain disorders (jaundice, high blood levels of bilirubin, G6PD deficiency). Breast-feeding is not recommended for infants with these conditions. Consult your doctor before breast-feeding.

Interactions

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor’s approval.

Some products that may interact with this drug include: “blood thinners” (such as warfarin), dofetilide, methenamine, methotrexate.

This product may interfere with certain laboratory tests, possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this product.

Does sulfamethoxazole-trimethoprim oral interact with other drugs you are taking?

Enter your medication into the WebMD interaction checker

Overdose

If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe nausea/vomiting/diarrhea, severe dizziness or drowsiness, mental/mood changes.

Do not share this medication with others.

This medication has been prescribed for your current condition only. Do not use it later for another infection unless your doctor tells you to.

If taking this medication for a long time, lab and/or medical tests (such as complete blood count, kidney function, potassium blood level, cultures) should be done while you are taking this medication. Keep all medical and lab appointments. Consult your doctor for more details.

If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

Images

sulfamethoxazole 800 mg-trimethoprim 160 mg tablet

Color: whiteShape: ovalImprint: H 49

This medicine is a white, oval, scored, tablet imprinted with “H 49”.

sulfamethoxazole 400 mg-trimethoprim 80 mg tablet

Color: whiteShape: roundImprint: IP 271

This medicine is a white, oval, scored, tablet imprinted with “H 49”.

sulfamethoxazole 400 mg-trimethoprim 80 mg tablet

Color: whiteShape: roundImprint: H 48

This medicine is a white, oval, scored, tablet imprinted with “H 49”.

sulfamethoxazole 800 mg-trimethoprim 160 mg tablet

Color: whiteShape: ovalImprint: MP 85

This medicine is a white, oval, scored, tablet imprinted with “H 49”.

sulfamethoxazole 800 mg-trimethoprim 160 mg tablet

Color: whiteShape: oblongImprint: VP 120

This medicine is a white, oval, scored, tablet imprinted with “H 49”.

sulfamethoxazole 800 mg-trimethoprim 160 mg tablet

Color: whiteShape: ovalImprint: IP 272

This medicine is a white, oval, scored, tablet imprinted with “H 49”.

sulfamethoxazole 400 mg-trimethoprim 80 mg tablet

Color: whiteShape: roundImprint: MP 81

This medicine is a white, oval, scored, tablet imprinted with “H 49”.

Selected from data included with permission and copyrighted by First Databank, Inc. This copyrighted material has been downloaded from a licensed data provider and is not for distribution, except as may be authorized by the applicable terms of use.

CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.

Sulfamethoxazole/Trimethoprim | VCA Animal Hospital

What is sulfamethoxazole/trimethoprim?

Sulfamethoxazole/trimethoprim (brand names: Co-trimoxazole®, Primsol®, Bactrim®, Sulfatrim®, Novo-Trimel®, Septra®) is a potentiated sulfonamide antibiotic/antimicrobial used to treat certain infections such as bladder and prostate infections, Nocardia infections, or parasitic infections.

Its use in cats, dogs, birds, reptiles, and small mammals to treat infections is ‘off label’ or ‘extra label’. Many drugs are commonly prescribed for off label use in veterinary medicine. In these instances, follow your veterinarian’s directions and cautions very carefully as their directions may be significantly different from those on the label.

How is sulfamethoxazole/trimethoprim given?

Sulfamethoxazole/trimethoprim is given by mouth with or without food in the form of a tablet or liquid suspension or solution. If your pet vomits or acts sick after receiving the medication on an empty stomach, give the next dose with a meal or treat. The liquid suspension should be shaken well before use and does not need to be refrigerated.

There is also an injectable form that is used in exotic pets and given in the muscle or under the skin.

Allow free choice access to water, as pets should not be allowed to become dehydrated while on this medication.

This medication will take effect quickly, in about 1 to 2 hours, but visible effects may take a few days to be observed.

People with allergies to sulfa compounds should avoid handling this medication or should use gloves while administering this medication.

What if I miss giving my pet the medication?

If you miss a dose and it is not within 6 hours of the next scheduled dose, give the missed dose when you remember and then continue with the regular dosing schedule. If you miss a dose and it is within 6 hours of the next dose, give the missed dose, skip the dose when you remember, skip the next dose, and then return to the regular dosing schedule. Never give your pet two doses at once or give extra doses.

Example: If dosing at 8AM and 8PM, and you forget the 8AM dose and remember at 11AM, give it at 11AM, then again at 8PM, then at 8AM the following morning. If you forget the 8AM dose and remember at 3PM, give it at 3PM, skip the 8PM dose, and give it at 8AM the following morning.

Are there any potential side effects?

Common side effects in dogs include a decreased appetite, vomiting, and diarrhea. Possible serious side effects include keratoconjunctivitis sicca (dry eye), acute liver inflammation characterized by yellowing of the skin/eyes, fever, hemolytic anemia, urticaria (hives), polyarthritis, facial swelling, increased drinking and urination, and cholestasis (gall bladder attack).

Less common side effects include inducing hypothyroidism (low thyroid levels), allergic reactions including anaphylaxis and immune reactions, anemia (low red blood cells) and low white blood cells. Rarely, it can cause severe and massive liver damage. There is suspicion it may cause pancreatic inflammation, but this has not been definitively shown.

In cats, a decreased appetite or increased salivation is common. More severe side effects include low white blood cells and low red blood cells. In rabbits, low tear production/dry eye is possible.

In all species, an increased risk of urinary crystals, blood in the urine, and urinary obstruction are possible.

This short-acting medication should stop working within 24 hours, although effects can be longer in pets with liver or kidney disease.

Are there any risk factors for this medication?

Sulfamethoxazole/trimethoprim should not be used in dogs with liver tissue damage, blood cell problems, dogs that are dehydrated or at an increased risk for urinary stones, or those allergic to sulfonamides. It should be used cautiously in Doberman Pinschers as they may be more susceptible to adverse side effects. It should be used with caution in pets with liver or kidney disease; old, sick, or debilitated pet; or pets with a folate deficiency. Sulfamethoxazole/trimethoprim should be used cautiously in pregnant and nursing pets, and should not be used in are near the end of their pregnancy.

Are there any drug interactions I should be aware of?

The following medications should be used with caution when given with sulfamethoxazole/trimethoprim: amantadine, antacids, cyclosporine, digoxin, thiazide diuretics, oral hypoglycemic agents, methotrexate, phenytoin, tricyclic antidepressants, warfarin, potassium supplements, potassium-sparing drugs, and pyrimethamine.

Be sure to tell your veterinarian about any medications (including vitamins, supplements, or herbal therapies) that your pet is taking.

Is there any monitoring that needs to be done with this medication?

Your pet should be monitored for adverse side effects. For prolonged therapy, your veterinarian will recommend baseline and ongoing complete blood counts and tear tests. A baseline, and ongoing thyroid function test may also need to be monitored. Your veterinarian may monitor your pet to be sure that the medication is working.

How do I store sulfamethoxazole/trimethoprim?

Follow the storage directions as instructed by the manufacturer. Otherwise, store all products at room temperature at 20°-25°C (68°-77°F). Do not allow the medication to freeze and keep in a tightly sealed container.

What should I do in case of emergency?

If you suspect an overdose or an adverse reaction to the medication, call your veterinary office immediately. If they are not available, follow their directions in contacting an emergency facility.

90,000 Mononeuropathies in adults. Clinical guidelines.

Contents

Keywords

• Cranial neuropathies

• Neuropathy of the oculomotor nerve

• Trigeminal neuropathy

• Abducens neuropathy

• Neuropathy of the facial nerve

• Mononeuropathies

• Carpal tunnel syndrome

• Pronator tunnel syndrome

• Cubital tunnel syndrome

• Fibular tunnel syndrome

• Spiral canal syndrome

• Therapy program

• Evaluation of the effect of ongoing therapy

• Criteria for assessing the quality of medical care

List of abbreviations

CT – computed tomography

MN – mononeuropathy

MRI – magnetic resonance imaging

CRT – excitation propagation velocity

ultrasound – ultrasound

ENMG – electroneuromyography

Terms and definitions

• Condition – changes in the body arising from
  with the influence of pathogenic and (or) physiological factors and requiring
  providing medical care;

• Instrumental diagnostics – diagnostics using various devices, devices and instruments for examining a patient.

• Level of evidence – reflects the degree of confidence that the found effect of the application of medical intervention is true.

• Strength of recommendations
  – reflects not only the degree of confidence in the reliability of the effect
  intervention, but also the degree of confidence that following
  recommendations will do more good than harm in a particular situation.

• Working group – two or more people of the same or
  different professions working together and in concert to
  creating clinical guidelines, and having overall responsibility for
  the results of this work.

• Syndrome is a set of symptoms with common etiology and pathogenesis.

• Surgery is an invasive procedure that can be used to diagnose and/or treat disease.

• Surgical treatment is a method of treating diseases by separating and connecting tissues during a surgical operation.

1. Summary

1.1 Definition

usually associated with damage to one motor, sensory
or mixed nerves. In cases of involvement in the pathological process
symmetrical or some other nerve, or nerves speak of
“multiple MN”. Clinical symptoms of the disease are manifested by a violation
functions of one of the cranial nerves or long nerves of the limbs
[4,12].

1.2 Etiology and pathogenesis

diseases that differ in etiology and pathogenetic mechanisms
to create a clear description of the etiology and pathogenesis of MR is sufficient
challenging task. Basically, the pathogenetic mechanisms of MN are associated either with
toxic or compressive effect on the peripheral nerve,
leading to a violation of its function expressed to a greater or lesser extent
degree, which subsequently determines the strategy and tactics of treatment.

1.4 ICD-10 coding

G58 – Other mononeuropathy

G56 – Upper limb mononeuropathy

G5 7 – Mononeuropathies of the lower limb

h59. 0 – Paralysis of the 3rd (oculomotor) nerve

h59.2 – Paralysis of the 6th (abducens) nerve.

2. Diagnosis

Because
a single scale for assessing motor, pain, sensory or
there are no trophic disorders in patients with various forms of MR,
or if it exists for one of the forms, then it cannot be applied to
everything else, the basis of diagnosis is a thorough analysis
neurological status of patients.

2.1 Complaints and anamnesis

• Recommended to obtain data on availability or
  absence of neurological symptoms associated with impaired function
  particular nerve, such as muscle weakness,
  sensitivity, trophic disorders and muscle atrophy [5,12].

Level of persuasiveness – A (level of certainty – 2b)

Level of persuasiveness – B (level of certainty – 3)

Level of persuasiveness – B (level of confidence – 3)

Comments: extremely rare
isolated lesion of the motor portion of the nerve, passing through the
the third branch of the nerve, which innervates several muscles of the bottom
oral cavity.

Level of credibility – C (level of confidence – 3)

2.2 Instrumental diagnostics

Level of evidence – A (level of evidence – 2a)

Comments: variety of clinical forms of MN
selectivity and uneven involvement in the pathological process
different muscle groups does not imply the concept of “standard
research”. Thus, in case of cranial MR, electromyographic studies
are limited only to the study of the parameters of the M-response and latent
time of the facial nerve, comparing these indicators on the affected and
healthy side. On the other hand, when examining MNs of long nerves
limbs, there is a certain algorithm for conducting
electromyographic study

Level of credibility – B (level of confidence – 2b)

Comments:
informative in the assessment of cranial MNs, in particular, the location
compression of the facial nerve inside the canal passing in the mastoid
process of the skull, as well as the orbits in case of cranial MN, manifested
oculomotor disorders

Level of credibility – C (level of credibility – 3)

Comments:
structure of peripheral nerves and change in standard characteristics in
depending on the zone of expected compression.

3. Treatment

Save
relevance of various methods of treatment of MN, drug and
surgical. Each of the methods has specific goals and is
the most appropriate at a particular stage of the development of the disease. Important
emphasize that the variety of clinical forms of MN: features of age,
the nature of the course, determine the strategy and tactics of treatment.

3.1 Conservative treatment

• Recommended anticholinesterase drugs:
  neostigmine methyl sulfate** 15 mg tablets twice daily or
  subcutaneous injections of 1.0 ml of a 0.05% solution 1 – 2 times a day;
  galantamine** in the form of subcutaneous injections of 10 mg 1% solution 1-2 times a day
  a day or in tablets of 10 mg, 2 tons 3 times a day [4,10,11].

Level of persuasiveness – B (level of certainty – 2b)

Level of persuasiveness – A (level of evidence – 2b)

Level of persuasiveness – A (level of evidence – 2a)

Comments: especially effective s early
terms of treatment of patients with MN and can be used as local injections in
zone of supposed nerve compression, at a dose of 4 – 8 mg in the form of 3 – 5
introductions. Also, glucocorticoid drugs can be prescribed for
scheme every other day, once in the morning. The dose of the drug in patients
with MN on average is determined at the rate of 0.5 mg per 1 kg of body weight.
Given the effect of glucocorticoid drugs on the autonomic nervous
system (palpitations, tachycardia, sweating), the first dose of the drug
is half the dose. Then, if well tolerated,
switch to a therapeutic dose. The duration of treatment is
about 2 weeks, so the effectiveness of therapy is evaluated after 6 – 8
drug intake. Upon reaching the effect and improving the condition of patients,
as well as in its absence, the dose of the drug is gradually reduced by 4
– 5 mg per dose, up to complete withdrawal .

• Recommended antioxidants. Antioxidant
  properties of alpha-lipoic acid preparations give rise to the use
  them in patients with MN. Alpha lipoic acid preparations contribute to
  activation of mitochondrial synthesis. In addition, they reduce
  the severity of oxidative stress in patients, by reducing the content
  in the blood of free radicals that damage cellular and
  mitochondrial membranes during ischemia. Treatment should start with
  intravenous drip in the amount of 600 – 900 mg/day with
  further transition to oral administration in the same dosage [4,10].

• Level of persuasiveness – B (level of certainty – 2b)

  3.2 Surgical treatment

Level of credibility – A (level of evidence – 2a)

Comments: the main clinical symptom
determining the expediency of surgical treatment is the appearance
muscle atrophy. Another indirect sign is the absence
the effect of the conservative treatment methods performed. However, how
show the results of neuroimaging and electromyographic
studies, the data of these studies can be based on
determining the need for earlier nerve decompression.
Most often, surgical treatment is used for cubital and
carpal tunnel MN, much less often with fibullar syndrome and
Guyon’s canal syndrome.

3. 3 Other treatment

Level of confidence – B (level of evidence – 3)

• Recommended use of therapeutic masks, splints and
  other orthopedic devices that contribute to compensation and
  correction of emerging movement disorders [4,12].

Level of credibility – C (level of confidence – 3)

6. Additional information affecting the course and outcome of the disease

Additional information affecting the course and outcome of the disease

Summarizing the above, it should be emphasized that the correct diagnosis
and timely appointment of adequate methods of treatment leads to
compensation of movement disorders in more than 80% of patients
mononeuropathies.

Criteria for assessing the quality of medical care

References

1. Ebenbichler G. R., Resch K.L., Nicolakis P., Weisinger G.F., Uhl F.,
   Ghanem A.H., Fialka V// Ultrasound treatment for treating carpal tunnel
   syndrome: randomized ‘swam’ controlled trial// 1998. – BMJ 316. –
   R.731-735.

2. O’Connor D., Marshall S., Massy-Westroop N. Non-surgical treatment
   (other than steroid injection) for carpal tunnel syndrome// Cochrane
   Database Syst. Rev. – 2003. – V.1. CD003219.

3. Page M.J., O’Connor D., Pitt V., Massy-Westroop N. Therapeutic
   ultrasound for carpal tunnel syndrome// Cochrane Database Syst. Rev. –
   2012. – V.1. CD009601.

4. Campbell W.W. Evaluation and management of peripheral nerve injury// Clin. neurophysiol. – 2008. – V.119. – R.1951-1965.

5. Dvali L., Mackinnon S. Nerve repair, grafting and nerve transfers// Clin. Plast. Surg. – 2003. -V. 30. – R.203-221.

6. Millesi H., Rath T., Reihsner R., Zoch G. Microsurgical neurolysis:
   its anatomical and physiological basis and its classificanion//
   microsurgery. – 1993.-V.14(7). – R.430-439.

7. Berlit P. Isolated and combined pareses of cranial nerves III, IY and
   YI. A retrospective study of 412 patients.// J. Neurol. sci. – 1991. –
   V.103. – R.10-15.

8. Chadwick D. The cranial nerves and special senses// In Walton J.
   (ed.) Brains diseases of the nervous system. Oxford University 1993. –
   Press Oxford. – R.76-126.

9. Garsia-Rivera C.A., Zhou D., Allahyari P et al.// Miller-Fisher
   syndrome: MRI findings. Neurology. – 2001. – V.57. – R.1755-1769.

10. Grisold W., Vass A. Neuromuscular complications/ /Handb. Clin. Neurol. – 2012. -V.105. – R.781-803.

11. Keane J.R. Fourth nerve palsy: historical review and study of 215 patients. Neurology. 1993/43. – R.2439-2443.

12. Kline L.B., Hoyt W.F. The Tolosa Hunt Syndrome //J. Neurol. neurosurgery. Psychiatry. – 2001. – V.71. – R.577-582.

13. Love S. , Coakham H.B. Trigeminal neuralgia Pathology and pathogenesis // Brain. -2001. – V.124. – R.2347-2360.

14. Newsom-Davis J., Thomas P.K., Spalding J.M.K Diseases of the ninth,
    tenth, eleventh and twelfth cranial nerves/ In Dyck P.J, Thomas P.K.,
    Bunge R. (eds) Peripheral neuropathy // WB Saunders Philadelphia. –
    1984. – R.1337-1350.

15. Park K.S., Chung J.M., Jeon B.S et al. Unilateral trigeminal
    mandibular motor neuropathy caused by tumor in the foramen ovale// J.
    Clin. Neurol. – 2006. -V.2. – R.194-197.

16. Richards B.W., Jones F.R.I., Young B.R. Causes and predictions in 4278
    cases of paralysis of oculomotor, trochlear and abducens cranial nerve//
    Am. J. Ophtalmol. – 1992. – V.113. – R.489-496.

17. Thomas P.K., Maths C.J. Diseases of the ninth, tenth, eleventh and
    twelfth cranial nerves // In Dyck P.J, Thomas P.K., Griffin J.P, Low
    P.A., Poduslo J.F. (eds.) Peripheral neuropathy // WB Saunders
    Philadelphia. – 1993. – Р.867-885.

Appendix A1. The composition of the working group

1. Sanadze Alexander Georgievich, head of the outpatient office for
   patients with myasthenia gravis GBUZ “City Clinical Hospital No. 51 DZM”, MD, professor. Member
   All-Russian Society of Neurologists.
2. Sidnev Dmitry Vladimirovich, outpatient neurologist
   for patients with myasthenia gravis GBUZ “City Clinical Hospital No. 51 DZM”, MD Member of the All-Russian
   Society of Neurologists.

Conflict of interest: none

Annex A2. Methodology for the development of clinical guidelines

Target audience of these clinical guidelines:

1. Neurologists, therapists, general practitioners;
2. Medical students, residents, graduate students;
3. Teachers, researchers.

Table A1 – Levels of evidence

Table A2 – Strength levels of recommendations

Procedure for updating clinical guidelines – revision once every 3 years.

Appendix A3. Related Documents

These Clinical Practice Guidelines have been developed in accordance with the following regulations:

1. Order of the Ministry of Health of Russia dated July 7, 2015 N 422an “On approval of criteria

evaluation of the quality of medical care”.

Appendix B. Patient management algorithms

Side effects that appear with long-term use of levodopa drugs – Center for Extrapyramidal and Cognitive Disorders

For about 50 years, levodopa has remained the most effective treatment for Parkinson’s disease ( L-DOPA – levorotary isomer of the amino acid deoxyphenylalanine). In terms of effectiveness, it is ahead of any other anti-Parkinsonian drug and even neurosurgical intervention. It provides the most guaranteed anti-Parkinsonian effect, causing improvement in almost 100% of patients with Parkinson’s disease. Not a single patient with Parkinson’s disease who seeks to maximize the period of his active life can avoid its intake. Levodopa is considered the “gold standard” for the treatment of Parkinson’s disease. It increases the life expectancy of patients. To date, there are no convincing data on the neurotoxic effect of levodopa. Moreover, the ability of small doses of levodopa to exert a neuroprotective effect cannot be ruled out.

​

After oral administration, levodopa enters the brain and is converted by functioning nerve cells into dopamine, compensating for its deficiency. Modern drugs (such as Nakom or Madopar) contain a combination of levodopa with an inhibitor of the enzyme DOPA-decarboxylase, which blocks the metabolism of levodopa in peripheral tissues, resulting in a large part of levodopa reaching the brain and reducing the likelihood of side effects associated with the peripheral action of the drug. In the early stages of Parkinson’s disease, even small doses of levodopa often have a significant effect, almost completely eliminating the symptoms of parkinsonism. Unfortunately, a few years after the start of treatment with levodopa in a significant proportion of patients, the reaction to the drug changes: the duration of the action of a single dose decreases, violent movements (dyskinesias) appear.

​

The patient takes the prescribed single dose of levodopa, it begins to act after 40 minutes – the patient begins the “on” period, characterized by a decrease in the symptoms of parkinsonism, and after 3-4 hours, and subsequently even faster – after 2- 2.5 hours – the effect of the drug weakens – a period of “off” begins with a decrease in motor activity. Sometimes “on” and “off” are accompanied by involuntary (violent) movements of a different nature. During the day there are also stiffenings when walking, when for a few seconds or minutes the patient cannot move. For patients with this disorder, turning or passing through a relatively narrow doorway may be particularly difficult. Fluctuations in motor activity, which are possible in a wide range – from excessive motor activity at the peak of the dose to a sharp weakening of motor capabilities during the “off” period, are called motor fluctuations in the medical literature.

There are several types of motor fluctuations. The phenomenon of “exhaustion” of the end of the dose is characterized by a gradual predictable partial return of the symptoms of parkinsonism by the end of the next dose of levodopa. Many patients, as the effect of a single dose of levodopa wears off, also note depression of mood, anxiety, sweating, palpitations, increased pain, etc. (“non-motor fluctuations”).

​

Over time, the patient’s transition from the “on” state to the “off” state becomes more and more brief and abrupt, which is referred to as the “on-off” phenomenon.

​

Sometimes the “off” period comes on suddenly, regardless of when the drug is taken. In addition to the above fluctuations, delayed development of “on” or complete absence of “on” is possible, when taking the next dose is not accompanied by an improvement in clinical symptoms or does not occur quickly enough.

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Against the background of “turning on” (at the peak dose of levodopa), rapid “dancing” (choreiform) movements may occur, mainly involving the upper half of the body (“peak dose dyskinesia”). This is a kind of limiter, requiring the weakening of dopaminergic therapy, since increasing the dose will lead to an increase in dyskinesias. This phenomenon is based on hypersensitivity of dopamine receptors.

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Off-period dystonia is a violent, prolonged, often painful contraction of the muscles of the lower extremities, often with plantar flexion or tucking of the foot. It usually appears at night or in the morning before the next dose of the drug and decreases with longer dopaminergic stimulation, achieved by prescribing a sustained-release levodopa drug (Madopar GSS), a long-acting dopamine receptor agonist, or a combination of levodopa with a DOPA decarboxylase inhibitor and a catechol inhibitor. -Omethyltransferase entacapone (Stalevo).

y Since the risk of developing fluctuations and dyskinesias depends on the total dose of levodopa preparations, it is customary to prescribe them only with a real decrease in the patient’s functional capabilities, which interferes with his professional or daily household activity.

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In younger patients (up to 60 years of age), the fluctuations in the effect of levodopa develop faster, therefore, the moment of prescribing levodopa in this age group is tried to be delayed by starting treatment with other antiparkinsonian drugs: dopamine receptor agonists (ropinirole, pramipexole, piribedil, rotigotine) , monoamine oxidase inhibitors – rasagiline (Azilect) or selegiline (Yumex). Additionally, to enhance the effect, amantadine and an anticholinergic (especially with rest tremor) or a combination of all of these drugs can be prescribed. And only when they no longer give the desired effect and do not provide sufficient patient mobility, small doses of levodopa are added to them. However, some experts believe that excessive delay in the appointment of levodopa is not the best tactic in the management of patients, as it is often accompanied by insufficient control of symptoms. Meanwhile, adequate correction of motor functions is the main guarantee of the best long-term results of treatment.

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In the elderly, who are at lower risk of fluctuations and dyskinesias, it is common to start levodopa immediately. In this case, the minimum effective dose should be adhered to, which can be achieved by adding dopamine receptor agonists, type B monoamine oxidase inhibitors or amantadine.

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“Off” periods and dyskinesias can be excruciating for patients, and they may be tempted to relieve their condition by taking an emergency dose of levodopa or another antiparkinsonian drug. Often, in a vicious circle, this leads to an aggravation of the instability of the patient’s condition. Because of this, any changes in the treatment regimen, especially with fluctuations, should be agreed with the attending physician. Correction of fluctuations and dyskinesias is a difficult task even for an experienced specialist, and it can be solved only with close cooperation between the doctor and the patient.

The goal of adjusting the treatment regimen is to maximize the duration of the “on” period in the absence or minimal presentation of dyskinesias. Filling in a daily activity diary by the patient at 1-hour intervals can help the clinician analyze the relationship between the “off” period and dyskinesias, as well as their occurrence relative to the timing of medications.

When the duration of action of levodopa decreases (end-of-dose ‘wasting’ phenomenon), most specialists first resort to splitting the dose of levodopa (reducing the single dose with a shortening of the interval between doses of the drug) and switching from an immediate-release drug to a sustained-release drug (Madopar HSS) . In addition, the effect of levodopa can be enhanced by improving its absorption. To do this, the drug is taken at least 60 minutes before a meal and not earlier than 2 hours after a meal. In addition, they reduce protein intake during the day (amino acids formed during the breakdown of food proteins compete in the intestines with levodopa for absorption). If this does not work, one of the dopamine receptor agonists (preferably controlled-release), the catechol-O-methyltransferase inhibitor entacapone (switching to Stalevo), or a monoamine oxidase inhibitor type B must be added sequentially.

The sequence of prescribing drugs is determined individually, including taking into account the risk of side effects in each individual patient.

Freezes that develop during the “off” period respond to techniques that reduce the “off” phase. It is useful to teach the patient how to overcome freezing by walking in place, unusual dance movements, stepping over an imaginary line drawn on the patient’s path, or using a special cane with a thin metal bar that folds down at the bottom, stepping over which the patient can start moving.

​Other recommendations for freezing:

• stop trying to continue driving;
• try to shift from one foot to the other;
• slightly bend your knees, lift your foot off the floor and step forward;
• count “one, two, three” or tell yourself “left-right, left-right”;
• hum a rhythmic tune;
• imagine the sound of footsteps on the pavement and raise your leg to take a step;
• try to imitate the walking of the person in front;
• if you have a problem getting through a narrow space, try to look beyond it: imagine where you will be when you pass this space.

​In cases where the transition from “on” to “off” becomes unpredictable, it is possible to return to less frequent use of relatively large doses of levodopa (“dose piling”). This will lead, on the one hand, to an increase in the period of “on” in the daytime period, when the patient needs to be active; on the other hand, the “off” period will also increase, but will move to the evening and become more predictable. Treatment of on-off fluctuations becomes more difficult when the on-period is accompanied by dyskinesias. In these cases, there may not be an unambiguously satisfactory solution, and the patient himself must decide whether to put up with hyperkinesis during the “on” or suffer from a long period of “off”. Usually patients choose the first.

​In cases where drugs fail to achieve sufficient effect, resort to stereotaxic operations (constant stimulation of certain areas in the basal ganglia) (see below). An alternative may be subcutaneous administration of apomorphine, the introduction of a gel with levodopa / carbidopa (duodopa) into the duodenum.

But sometimes it is not possible to completely get rid of motor fluctuations. Then it remains to adapt to them: you do all the things you need during the hours when you feel better, spend the rest of the hours doing activities that do not require movement: reading, watching TV, listening to the radio.

In domestic clinical practice, patients with Parkinson’s disease are often treated with drugs whose effectiveness in this disease has not been convincingly proven. Often these are the so-called “vascular drugs”, often administered intravenously by drip. Their appointment is often justified by naive and archaic ideas about the connection of Parkinson’s disease with “bad vessels of the brain”, which in most patients, even the elderly, do not suffer significantly. The positive experience of their use, if it exists, is explained by nothing more than the placebo effect.

The placebo effect is achieved by the patient’s faith in the doctor, misreported or inaccurately perceived information, the power of tradition, and sometimes the patient’s despair in the methods of classical medicine. Parkinson’s specialists are well aware that a significant proportion of patients respond well to placebo, but this effect is never sustainable. Most importantly, ineffective drugs and other treatments do not prevent adequate treatment of a disease that, if delayed, can have adverse long-term consequences.

In general, patients with Parkinson’s disease should be careful when using any medication, some of which carry the risk of worsening their condition. First of all, this applies to neuroleptics, such as haloperidol, triftazin, etaperazine, clopixol, olanzapine (Zyprexa), risperidone (Rispolept). Even such relatively mild drugs as sulpiride (Eglonil), thioridazine (Sonapax), teraligen, when taken regularly, can cause significant deterioration.

The same can be said about a number of drugs that are widely used in neurological and therapeutic practice, but can block dopamine receptors and increase the symptoms of parkinsonism: cinnarizine (including combined preparations of cinnarizine and piracetam, for example, Omaron or Phezam), metoclopramide (Cerucal), pipolfen . Iron preparations prescribed for iron deficiency anemia can reduce the effectiveness of levodopa and often require an increase in its dose.

Be careful with drugs that cause sedation, including sleeping pills, especially if they are long-acting (eg phenazepam). When using them, inform your doctor about the severity of the sedative effect, the possible increase in symptoms during the day. On the other hand, such “nootropic” drugs as piracetam or fenotropil can cause arousal in some patients.

Finally, it should be borne in mind that during surgical interventions for concomitant diseases, inhalation anesthetics are often used for anesthesia – drugs with a strong sedative effect that can cause an artificial coma, which is necessary for surgical intervention. In older people, they can cause confusion. Some surgeries can be performed under the influence of less dangerous drugs, in some conditions you can do without surgery. Ask your doctor about alternative treatments before opting for surgery.

The list of drugs that can cause deterioration in patients with Parkinson’s disease is very extensive, so it makes sense to consult a neurologist before starting a new drug on a regular basis, even if it is prescribed for a different disease.

Rapid progress in the study of the pathogenesis of Parkinson’s disease, as well as the development of the latest medical technologies (in particular, the technique of planting stem cells that can take the place of dying cells, or genetic therapy) allow us to hope that in the next decade a way will be found to significantly slow down the progression of this disease .

​To get the most out of your doctor’s visit, try these simple tips:

• Most doctors welcome information about your condition. This will help you to participate in making decisions about therapy, and you will be able to articulate your complaints more precisely.
• Make a list of questions you have with your doctor ahead of time.
• Don’t put off seeing your doctor for too long, especially if you feel your treatment is worsening or getting worse.