C2 Flashcards
Antimycobacterial drugs؟
1st line :
Rifampin
Isonazide
Pyrazine.amide
Ethambutol
2nd line :
Streptomycin
Cycloserine
Kanamycin
leprosy drugs :
Dapson
clofazimine
rifampin
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?
is it effective for dormant or growing bacilli?
- 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)
inhibits CYP450
Isonazide clinical uses?
- most important drug used in tuberculosis - component of most drug combination regimens
- treats of latent infection
- Prophylaxis
Isonazide Toxicity?
- peripheral neuritis
- insomnia
- muscle twitching
- inhibit the hepatic metabolism of drugs (eg, carbamazepine, phenytoin, warfarin)
- 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:خرا feces (free drug and metabolites)
inducer of CYP450
Rifampin clinical uses?
- always in combination with others
- solo: latent tuberculosis
- in INH-intolerant patients or prophylaxis for INH-resistant strains
- with dapson: leprosy
(given monthly –> delays the emergence of resistance to dapsone) - with vancomycin: against MRSA or PRSP
- meningococcal and staphylococcal carrier states
Rifampin Toxicity?
- colors sweat, urine and tears orange
- Rashes
- thrombocytopenia
- proteinuria
- 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?
- visual disturbances
- 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)
Pyrazinamid avooooid in PPPPregnancy
Pyrazinamide Clincal use?
short-course treatment in combo with others
Pyrazinamide Toxicity?
- non gout polyarthralgia (40% of patients)
- Hyperuricemia (asymptomatic)
- myalgia
- maculopapular rash
- G.I. irritation
- hepatic dysfunction
- photosensitivity
- should be avoided in pregnancy*
Streptomycin?
- Aminoglycoside (Protein synthesis inhibitor)
- Against resistant M tuberculosis strains
- principally used in combos for life-threatening tuberculous diseases:
meningitis
miliary dissemination
severe organ tuberculosis
Streptomycin pharmacodynamic and pharmacokinetic?
similar to those of other aminoglycosides
streptomycin uses?
- meningitis
- miliary dissemination
- severe organ tuberculosis
-resistant TB, used in combo regimens
cycloserine?
MOA
INDICATION
SE
cell wall active inhibitor ( inhibits peptidoglycan synthesis)
- TB resistant to 1st line agent
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!
Antitubercular Drug Alternative regimens?
- fully susceptible organisms:
1. RI 9m,
2. RE 18m
3. Intermittent (2 or 3/week) high-dose 4-drug regimens
Antitubercular Drug Regimens Resistance?
- If resistance to Isonszide is > 4% –> the initial drug regimen should include ethambutol or streptomycin.
- Tuberculosis resistant only to isonazide (most common) –> 6m with a regimen of RPE/S
- Multidrug-resistant organisms (both Isonazide + Rifampin) –> 3 or more drugs for a period 18m (including 12m after sputum cultures become negative!)
Drug for Leprosy?
Dapson
What about Dapson?
- DiAmino.diPhenyl.SulfONe) most active drug against M.Leprae.
- it is recommended that the drug be used in combinations with Rifampin +/or Clofazimine (resistance)
Dapson MOA?
inhibition of folic acid synthesis.
Dapson PharmacoKinetix?
- absorption: oral administration
- Distribution: most tissues
- metabolism: Liver (enterohepatic cycling)
- elimination: urine
Dapson Toxicity?
- G.I. irritation
- Fever
- Skin rashes
- methemoglobinemia
