Rifampicin + Isoniazid + Vit B6 Pharmacology

Rifampicin + Isoniazid + Vit B6

About Rifampicin + Isoniazid + Vit B6
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Mechanism of Action of Rifampicin + Isoniazid + Vit B6
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Pharmacokinets of Rifampicin + Isoniazid + Vit B6
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Onset of Action for Rifampicin + Isoniazid + Vit B6
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Duration of Action for Rifampicin + Isoniazid + Vit B6
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Half Life of Rifampicin + Isoniazid + Vit B6
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Side Effects of Rifampicin + Isoniazid + Vit B6
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Contra-indications of Rifampicin + Isoniazid + Vit B6
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Special Precautions while taking Rifampicin + Isoniazid + Vit B6
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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 + Vit B6
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Interactions for Rifampicin + Isoniazid + Vit B6
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Typical Dosage for Rifampicin + Isoniazid + Vit B6
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Schedule of Rifampicin + Isoniazid + Vit B6
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Storage Requirements for Rifampicin + Isoniazid + Vit B6
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Effects of Missed Dosage of Rifampicin + Isoniazid + Vit B6
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Effects of Overdose of Rifampicin + Isoniazid + Vit B6
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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.

Vit B6

About Vit B6
Physiological functions: It is involved as a coenzyme (Pyridoxal phosphate) in metabolism of tryptophan, in several metabolic transformations of amino acids including transamination, decarboxylation & racemization.
Deficiency symptoms: Peripheral neuritis, seizures, stomatitis, glossitis, anaemia, seborrhea like lesions.
Mechanism of Action of Vit B6
Vitamin B6 is a collective term for Pyridoxine, Pyridoxal, Pyridoxamine and their phosphorylated derivatives such as Pyridoxine phosphate, Pyridoxal phosphate and Pyridoxamine derivatives respectively. Vitamin B6 is essential for the metabolism of amino acid, glycogen and fatty acids, for nerve functions, for the formation of red blood cells and also helps the skin healthy. Vitamin B6 is also used for the synthesis of nucleic acid, Haemoglobin, Sphingomyelin, other Sphingolipids, Serotonin, Dopamine, Noradrenaline and GABA.
Pharmacokinets of Vit B6
Absorption: Vitamin B6 is readily absorbed after oral administration.
Distribution: It is mainly distributed in the body in protein bound form. It is stored primarily in the liver and to a lesser extent muscle and brain.
Metabolism: It is metabolised in the liver
Onset of Action for Vit B6
N/A
Duration of Action for Vit B6
N/A
Half Life of Vit B6
15-20 days
Side Effects of Vit B6
1. Neuropathy
2. Unstable gait
3. Drowsiness
4. Perioral numbness
5. Paresthesia
6. Numbness of feet
7. Somnolence
8. Sensory neuropathy
9. Ataxia
Contra-indications of Vit B6
1. Hypersensitivity to Vitamin B6
Special Precautions while taking Vit B6
N/A
Pregnancy Related Information
May be used
Old Age Related Information
May be used
Breast Feeding Related Information
Use with caution
Children Related Information
Use with caution
NEONATES: Contraindicated
Indications for Vit B6
1. Vitamin B6 deficiency including inadequate diet and drug induced causes
2. Neuropathy
3. Premenstrual syndrome
4. Hyperoxaluria type 1
5. Metabolic disorder
6. Isoniazid poisoning
Interactions for Vit B6
Cycloserine, Hydralazine, Isoniazide, Oral contraceptive, Penicillamine: Increase Pyridoxine requirement.
Levodopa: Pyridoxine reverses the therapeutic effect of Levodopa.
Phenobarbital, Phenytoin: Pyridoxine decreases serum level of these anticonvulsants.
Typical Dosage for Vit B6
Adult: 10 - 20 mg / day
Dietary deficiency: 2.5 -10 mg / day for effective therapeutic response is obtained.
Maintenance dose: 2 - 5 mg / day for several weeks.
Drug induced deficiency: 100 - 200 mg / day for 3 weeks.
Maintenance dose: 25 - 100 mg / day
Neuropathy: 50 - 200 mg /day
Premenstrual syndrome: 40 - 500 mg / day
Hyperoxaluria type 1: 25 - 300 mg / day
Metabolic disorder: 100-500 mg /day.
Isoniazid poisoning: Initial dose: 1 - 4 g as IV administration, then 1 g IM every 30 minute until Pyridoxine dose is equal to the Isoniazid dose has been given.
Schedule of Vit B6
N/A
Storage Requirements for Vit B6
Store it at 15 - 30 degree C. Protect from moisture and heat.
Effects of Missed Dosage of Vit B6
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 Vit B6
Give supportive measures and symptomatic treatment. The signs of Pyridoxine overdose can be resolved by discontinuation (withdrawal) of Pyridoxine.

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