Antimycobacterial drugs؟
Rifampin Isonazide Pyrazine.amide Ethambutol Streptomycin
Cycloserine
Dapson
Kanamycin
Drugs for Tuberculosis?
RIPES
What is the MOA of antituberculotix?
what does it depends on?
- Bactericidal or Bacteriostatic
- depending on drug concentration and strain susceptibility
Isoniazid MOA?
- Inhibits the synthesis of mycolic acids (cell walls)
- it is bactericidal for actively growing tubercle bacilli, but is less effective against dormants
Isonazid PharmacoKinetix?
- absorption: well absorbed orally
- metabolism: Liver (acetylation)
- 1/2 life:
*slow acetylators 3–4 h
*fast acetylators 60–90m
(for equivalent therapeutic effects fast acetylators require higher dosage)
Isonazide clinical uses?
- most important drug used in tuberculosis - component of most drug combination regimens
- treats of latent infection
- Prophylaxis
Isonazide Toxicity?
- peripheral neuritis
- restlessness
- muscle twitching
- insomnia
- RARE hepatotoxic ( jaundice, and hepatitis)
- inhibit the hepatic metabolism of drugs (eg, carbamazepine, phenytoin, warfarin)
- Hemolysis in G6PDH deficiency
- Lupus-like syndrome
Rifampin MOA?
- bactericidal
- inhibits DNA-dependent RNApolymerase
- if the drug is used alone, Resistance develops rapidly (changes in drug sensitivity of the polymerase)
Rifampin PharmacoKinetix?
- absorption: well absorbed orally
- distribution: most body tissues (even CNS)
- metabolism: partially metabolized in the liver (enterohepatic cycling)
- Elimination: feces (free drug and metabolites)
Rifampin clinical uses?
- always used in combination with other drugs when treating tuberculosis.
- used as the sole drug in treatment of latent tuberculosis
- in INH-intolerant patients or prophylaxis for INH-resistant strains
- with dapson: In leprosy it is given monthly –> delays the emergence of resistance to dapsone.
- with vancomycin: against MRSA or PRSP
- meningococcal and staphylococcal carrier states
Rifampin Toxicity?
- Rifampin colors sweat, urine and tears orange
- light-chain proteinuria
- impair Ab responses
- skin rashes
- thrombocytopenia
- nephritis
- liver dysfunction
- induces liver drug-metabolizing enzymes
- enhances the elimination rate of many drugs (anticonvulsants, contraceptive steroids, cyclosporine, ketoconazole, methadone, terbinafine, and warfarin)
Ethambutol MOA?
- inhibits arabinogalactan synthesis
(cell walls) - if used alone, resistance develops rapidly
Etham butol PharmacoKinetix?
- absorption: well absorbed orally
- distribution: to most tissues (also CNS)
- elimination: unchanged in the urine
In renal impairment dose reduction is necessary
Ethambutol Clinical use?
- tuberculosis
- always given in combination with other drugs
Ethambutol Toxicity?
- dose-dependent visual disturbances (regress when the drug is stopped)
- headache, confusion, peripheral neuritis.
- hyperuricemia
Pyrazinamide MOA?
- MOA is not known :)
- its bacteriostatic
- Resistance develops rapidly when the drug is used alone
Pyrazinamide PharmacoKinetix?
- absorbtion: orally
- distribution:most body tissues (also CNS)
- metabolism: Liver.
- Elimination: urine (drug and metabolite)
The plasma half-life of pyrazinamide is increased in hepatic or renal failure
Pyrazinamide Clincal use?
short-course treatment regimens with other antituberculous drugs.
Pyrazinamide Toxicity?
- 40% of patients develop nongouty polyarthralgia
- Hyperuricemia (asymptomatic)
- myalgia
- G.I. irritation
- maculopapular rash
- hepatic dysfunction
- porphyria and photosensitivity reactions.
should be avoided in pregnancy
Streptomycin?
- Aminoglycoside used frequently against strains of M tuberculosis resistant to other drugs
- principally used in drug combinations for the treatment of life-threatening tuberculous diseases
Streptomycin pharmacodynamic and pharmacokinetic?
similar to those of other aminoglycosides
streptomycin uses?
- meningitis
- miliary dissemination
- severe organ tuberculosis
cycloserine?
drug of limited use because of its toxicity:
- peripheral neuropathy
- CNS dysfunction
Antitubercular standard Drug Regimens
- For empiric treatment of pulmonary TB:
initial 3-drug regimen of RIP recommended - If the organisms are fully susceptible
(and HIV negative) –> pyrazinamide can be discontinued after 2m and treatment continued for 4m with a 2-drug regimen!
