C2

Question 1

Antimycobacterial drugs؟

Answer 1

1st line :
 Rifampin
   Isonazide
    Pyrazine.amide
     Ethambutol

2nd line :
Streptomycin
Cycloserine
Kanamycin

leprosy drugs :
Dapson
clofazimine
rifampin

Question 2

Drugs for Tuberculosis?

Answer 2

RIPES

Question 3

What is the MOA of antituberculotix?

what does it depends on?

Answer 3

• Bactericidal or Bacteriostatic

- depending on drug concentration and strain susceptibility

Question 4

Isoniazid MOA?

is it effective for dormant or growing bacilli?

Answer 4

• Inhibits the synthesis of mycolic acids (cell walls)

- it is bactericidal for actively growing tubercle bacilli, but is less effective against dormants

Question 5

Isonazid PharmacoKinetix?

Answer 5

• 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

Question 6

Isonazide clinical uses?

Answer 6

• most important drug used in tuberculosis - component of most drug combination regimens
• treats of latent infection
• Prophylaxis

Question 7

Isonazide Toxicity?

Answer 7

• peripheral neuritis
• insomnia
• muscle twitching
• inhibit the hepatic metabolism of drugs (eg, carbamazepine, phenytoin, warfarin)
• Lupus-like syndrome

Question 8

Rifampin MOA?

Answer 8

• bactericidal
• inhibits DNA-dependent RNApolymerase
• if the drug is used alone, Resistance develops rapidly (changes in drug sensitivity of the polymerase)

Question 9

Rifampin PharmacoKinetix?

Answer 9

• 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

Question 10

Rifampin clinical uses?

Answer 10

• 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

Question 11

Rifampin Toxicity?

Answer 11

• 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)

Question 12

Ethambutol MOA?

Answer 12

• inhibits arabinogalactan synthesis
  (cell walls)
• if used alone, resistance develops rapidly

Question 13

Etham butol PharmacoKinetix?

Answer 13

• absorption: well absorbed orally
• distribution: to most tissues (also CNS)
• elimination: unchanged in the urine

In renal impairment dose reduction is necessary

Question 14

Ethambutol Clinical use?

Answer 14

• tuberculosis

- always given in combination with other drugs

Question 15

Ethambutol Toxicity?

Answer 15

• visual disturbances
• headache, confusion, peripheral neuritis.
• hyperuricemia

Question 16

Pyrazinamide MOA?

Answer 16

• MOA is not known :)
• its bacteriostatic
• Resistance develops rapidly when the drug is used alone

Question 17

Pyrazinamide PharmacoKinetix?

Answer 17

• absorbtion: orally
• distribution:most body tissues (also CNS)
• metabolism: Liver.
• Elimination: urine (drug and metabolite)

Pyrazinamid avooooid in PPPPregnancy

Question 18

Pyrazinamide Clincal use?

Answer 18

short-course treatment in combo with others

Question 19

Pyrazinamide Toxicity?

Answer 19

• non gout polyarthralgia (40% of patients)
• Hyperuricemia (asymptomatic)
• myalgia
• maculopapular rash
• G.I. irritation
• hepatic dysfunction
• photosensitivity
• should be avoided in pregnancy*

Question 20

Streptomycin?

Answer 20

• Aminoglycoside (Protein synthesis inhibitor)
• Against resistant M tuberculosis strains
• principally used in combos for life-threatening tuberculous diseases:
  meningitis
  miliary dissemination
  severe organ tuberculosis

Question 21

Streptomycin pharmacodynamic and pharmacokinetic?

Answer 21

similar to those of other aminoglycosides

Question 22

streptomycin uses?

Answer 22

• meningitis
• miliary dissemination
• severe organ tuberculosis

-resistant TB, used in combo regimens

Question 23

cycloserine?
MOA
INDICATION
SE

Answer 23

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

Question 24

Antitubercular standard Drug Regimens

Answer 24

• 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!

Question 25

Antitubercular Drug Alternative regimens?

Answer 25

- fully susceptible organisms: 1. RI 9m, 2. RE 18m 3. Intermittent (2 or 3/week) high-dose 4-drug regimens

Question 26

Antitubercular Drug Regimens Resistance?

Answer 26

- 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!)

Question 27

Drug for Leprosy?

Answer 27

Dapson

Question 28

What about Dapson?

Answer 28

- DiAmino.diPhenyl.SulfONe) most active drug against M.Leprae. - it is recommended that the drug be used in combinations with Rifampin +/or Clofazimine (resistance)

Question 29

Dapson MOA?

Answer 29

inhibition of folic acid synthesis.

Question 30

Dapson PharmacoKinetix?

Answer 30

- absorption: oral administration - Distribution: most tissues - metabolism: Liver (enterohepatic cycling) - elimination: urine

Question 31

Dapson Toxicity?

Answer 31

- G.I. irritation - Fever - Skin rashes - methemoglobinemia