Rifampicin + Isoniazid + Ethambutol Pharmacology

Rifampicin + Isoniazid + Ethambutol

About Rifampicin + Isoniazid + Ethambutol
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Mechanism of Action of Rifampicin + Isoniazid + Ethambutol
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Pharmacokinets of Rifampicin + Isoniazid + Ethambutol
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Onset of Action for Rifampicin + Isoniazid + Ethambutol
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Duration of Action for Rifampicin + Isoniazid + Ethambutol
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Half Life of Rifampicin + Isoniazid + Ethambutol
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Side Effects of Rifampicin + Isoniazid + Ethambutol
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Contra-indications of Rifampicin + Isoniazid + Ethambutol
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Special Precautions while taking Rifampicin + Isoniazid + Ethambutol
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Pregnancy Related Information
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Old Age Related Information
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Breast Feeding Related Information
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Children Related Information
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Indications for Rifampicin + Isoniazid + Ethambutol
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Interactions for Rifampicin + Isoniazid + Ethambutol
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Typical Dosage for Rifampicin + Isoniazid + Ethambutol
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Schedule of Rifampicin + Isoniazid + Ethambutol
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Storage Requirements for Rifampicin + Isoniazid + Ethambutol
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Effects of Missed Dosage of Rifampicin + Isoniazid + Ethambutol
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Effects of Overdose of Rifampicin + Isoniazid + Ethambutol
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Rifampicin

About Rifampicin
Rifamycin derivative, Antituberculosis antibiotic.
Mechanism of Action of Rifampicin
Rifampicin is primarily bactericidal and has some bacteriostatic properties also. It acts by inhibiting DNA dependent RNA polymerase and thus stopping the expression of bacterial genes.M.tuberculosis requires DNA dependent RNA polymerase enzyme for the synthesis of RNA and protein. Without this enzyme bacteria cannot reproduce and they die.

Pharmacokinets of Rifampicin
Absorption: Well absorbed orally, Distribution: Widely distributed, Metabolism: Metabolized in liver in to active desacetyl Rifampicin Excretion: Excreted mainly in bile & some extend in urine
Onset of Action for Rifampicin
N/A
Duration of Action for Rifampicin
24 hours
Half Life of Rifampicin
2 - 5 hour
Side Effects of Rifampicin
1. Nausea
2. Vomiting
3. Epigastric distress
4. Anorexia
5. Pseudo membranous colitis
6. Acute renal failure
7. Hepato toxicity
8. Eosinophilia
9. Thrombocytopenia
10. Urticaria
11. Rash
12. Pruritis
13. Purpura
14. Shock
15. Headache
16. Drowsiness
17. Visual disturbance
18. Thrombophlebitis
19. Menstrual problems
Contra-indications of Rifampicin
1.Hypersensitivity to the drug
2.Hepatic impairment
3.Jaundice
4.Biliary obstruction
5.Porphyria
6.As I.M. or S.C. injection
Special Precautions while taking Rifampicin
Renal impairment:
Use with caution
Hepatic impairment:
Use with caution
Other precautions:
1.Use with caution in alcoholics
2.Use with caution in malnourished individuals
3.Stop the drug use in Purpura & Thrombocytopenia
Pregnancy Related Information
Use with caution
Old Age Related Information
Use with caution
Breast Feeding Related Information
Use with caution
Children Related Information
Above 5 years: May be used
Neonates: Contraindicated
Indications for Rifampicin
1. Leprosy
2. Tuberculosis
3. Prophylaxis of meningococcal carriers
4. Prophylaxis of H. influenzae
Interactions for Rifampicin
Rifampicin by inducing the hepatic microsomal enzymes may reduce the efficacy of the following drugs: Acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, chloramphenicol, clofibrate. Oral contraceptives, corticosteroids, cyclosporine, digitoxin, disopyramide, beta blockers oestrogens, hydantoins, mexiletine, quinidine, sulfones, sulphonylureas, theophylline, verapamil.
Halothane: Hepatotoxicity and hepatic encephalopathy.
Isoniazid: Higher incidence of hepatotoxicity than with either agent alone.
Ketoconazole: Treatment failure of either ketoconazole or rifampicin.
Food: Interferes with absorption of rifampicin, therefore it should be taken on empty stomach.
Lab tests: Inhibits standard assays for serum folate and vitamin B12 (riboflavin). Transient abnormalities in liver function tests, reduced excretion of contrast media used for visualization of gall bladder.

Typical Dosage for Rifampicin
Adults: 0.45gm to 0.6gm single dose
Children: 10 to 20 mg/kg/day
Leprosy: 600mg orally once monthly
Pulmonary tuberculosis:
Adults: 600mg/day orally or I.V. as a single dose
Children: 10 to 20 mg/kg/day orally or I.V.as a single dose
Meningococcal infections:
600mg 12 hourly for two days
Children (1 to 2 years): 10 mg/kg
Children (below 1 year): 5mg/kg for two days

Schedule of Rifampicin
H
Storage Requirements for Rifampicin
Store in a cool dry place.Protect from heat and light.Keep out of the reach of children.
Effects of Missed Dosage of Rifampicin
Take the missed dose as soon as noticed and if it is the time for next dose then skip the missed dose. Continue the regular schedule. Do not double the dose.
Effects of Overdose of Rifampicin
Treatment includes Gastric lavage, administration of activated charcoal, forced diuresis & bile drainage etc.

Isoniazid

About Isoniazid
Hydrazine derivative, Antitubercular Agent.
Mechanism of Action of Isoniazid
Isoniazid is a bactericidal drug. I t inhibits the mycolic acid synthesis which is essential for the cell wall formation. It also inhibits DNA, RNA and protein synthesis and cell metabolism. As the results of these bacterial death occurs.
Pharmacokinets of Isoniazid
Absorption: It is rapidly absorbed after oral administration.Distribution: It is very widely distributed in the body.Metabolism: It undergoes metabolism in the liver.Excretion:It is mainly excreted through urine and small amount excreted through bile, breast milk, sputum and saliva.
Onset of Action for Isoniazid
1 - 2 days
Duration of Action for Isoniazid
1 day
Half Life of Isoniazid
1 - 4 hour
Side Effects of Isoniazid
1. Nausea
2 .Vomiting
3. Gastric upset
4. Peripheral neuritis
5. Optic neuritis
6. Atrophy
7. Paresthesia
8. Allergy
9. Fever
10.Rash
11.Malaise
12.Lymph adenopathy
13.Jaundice
Contra-indications of Isoniazid
1. Hypersensitivity to Isoniazide
2. Drug induced hepatic disease
Special Precautions while taking Isoniazid
1.Renal impairment
2.Hepatic impairment
3.Alcoholism
4.Epilepsy
Pregnancy Related Information
Contraindicated
Old Age Related Information
Use with caution
Breast Feeding Related Information
Use with caution
Children Related Information
May be used
NEONATES: may be used
Indications for Isoniazid
1.Tuberculosis (pulmonary &extra pulmonary)
Interactions for Isoniazid
Alcohol: Regular ingestion of alcohol is associated with higher incidence of INH-related hepatitis.
Aluminium Salts: Oral absorption of INH reduced leading to decreased serum levels.
Oral anticoagulants: Efficacy of oral anticoagulants increased.
Benzodiazepines: Activity of benzodiazepines that undergo oxidative metabolism is possibly increased.
Carbamazepine: Isoniazid hepatotoxicity & carbamazepine toxicity may occur from concurrent use.
Cycloserine: Increased cycloserine related CNS side effects, especially dizziness.
Disulfiram: Acute behavioural and co-ordination changes.
Enflurane: High output renal failure may occur.
Halothane: Hepatotoxicity and hepatic encephalopathy.
Hydantoins: Serum hydantoin levels increased leading to enhanced pharmacological and toxic effects.
Ketoconazole: Serum concentrations of ketoconazole decreased possibly leading to resistance to antifungal treatment.
Rifampicin: Higher incidence of hepatotoxicity than with either agent alone.
Food: Interaction with tyramine-containing foods since INH has MAOI activity.
Exaggerated response (headache, palpitation, sweating, hypotension, flushing, itching) to foods containing histamine (tuna, sauerkraut juice, yeast extract).

Typical Dosage for Isoniazid
Adult: 200 - 300 mg once daily for 6 months to 24 months depending on the severity of infection
Children:5 - 10 mg / kg body weight / day for 6 months to 24 months depending on the severity of infection.
Schedule of Isoniazid
H
Storage Requirements for Isoniazid
The drug should be stored at room temperature .Keep away from heat, light and moisture. The vial should be kept at 2 - 8 degree Celsius.
Effects of Missed Dosage of Isoniazid
Take the missed dose as soon as noticed and if it is the time for next dose then skip the missed dose.Continue the regular schedule.Do not double the dose.
Effects of Overdose of Isoniazid
Give supportive measures and treatment. Control seizure by giving Diazepam. Then Pyridoxine is administered followed by gastric lavage. Acidosis can be treated with sodium bicarbonate by parenteral administration. Forced diuresis and dialysis can be done if necessary.

Ethambutol

About Ethambutol
Ethylenediamine derivative, Antitubercular Agent(Cell envelope antibiotic).
Mechanism of Action of Ethambutol
Ethambutol is a bacteriostatic drug.It inhibits arabinogalactan synthesis and interfere mycolic acid incorporation in to the cell wall.
Pharmacokinets of Ethambutol
Absorption: About 70 % of the drug is rapidly absorbed after oral administration.Distribution: It is very widely distributed in the body.Metabolism: It undergoes metabolism in the liver.Excretion:It is excreted mainly through urine and also bile and breast milk.
Onset of Action for Ethambutol
N/A
Duration of Action for Ethambutol
1 day
Half Life of Ethambutol
3 - 4 hour
Side Effects of Ethambutol
1. Optic neuritis
2. Nausea
3. Vomiting
4. Abdominal pain
5. Gastric upset
6. Headache
7. Loss of colour vision
8. Dizziness
9. Mental confusion
10. Hallucination
11. Peripheral neuritis
12. Anaphylactoid reaction
13. Dermatitis
14. Pruritis
15. Thrombocytopenia
16. Malaise
Contra-indications of Ethambutol
1. Optic neuritis
2. Hypersensitivity to Ethambutol
3. Children below 13 years
Special Precautions while taking Ethambutol
1. Renal impairment
2. Diabetic retinopathy
3. Eye inflammation
4. Gout
5. Cataract
Pregnancy Related Information
Use with caution
Old Age Related Information
N/A
Breast Feeding Related Information
Use with caution
Children Related Information
contraindicated in children below 13 year
NEONATES: contraindicated
Indications for Ethambutol
Pulmonary tuberculosis in category 1 & 2 patients
Interactions for Ethambutol
Aluminium salts: Absorption of ethambutol may be delayed or reduced.
Typical Dosage for Ethambutol
Adult: 15 - 25 mg / kg/ body weight/day depending on the condition of the disease state
Children (above 13 year): 15 - 25 mg / kg/ body weight/day depending on the condition of the disease state.
Schedule of Ethambutol
H
Storage Requirements for Ethambutol
Ethambutol should be kept in a tightly closed container at room temperature. Keep away from heat and moisture.
Effects of Missed Dosage of Ethambutol
Take the missed dose as soon as noticed and if it is the time to take the next dose then skip the missed dose.
Effects of Overdose of Ethambutol
Give supportive measures and treatment. Induce emesis or gastric lavage followed with charcoal administration.

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