C.2 Flashcards
Antimycobacterial
Isoniazid,
Rifampin,
Pyrazinamide,
Ethambutol,
Streptomycin,
Kanamycin,
Cycloserine,
Dapsone
Antitubercolotic drugs 1st line
Isoniazid (INH), Rifampin (RA), Pyrazinamide (PZA), Ethambutol (ETB), Streptomycin
Antitubercolotic drugs 2nd line
Ethionamide, Cycloserine, Paraaminosalicylic acid (PAS), Kanamycin, Amikacin, Capreomycin, Fluoroquinolons, Rifabutin, Linezolid, Bedaquiline, Delamanid
Isoniazid
MOA: inhibits synthesis of mycolic acid;
-Bactericidal for actively growing bacteria,
-Bacteriostatic for dormant bacteria;
Pharmacokinetics: prodrug, well absorbed p.o, i.v administration is also possible, excellent tissue distribution, it is acetylated in the liver (T1/2=1h in case of fast and T1/2=3h in case of slow acetylators);
SEs:
-Hepatotoxicity (more common in rapid acetylators),
-neurologic problems (more common in slow acetylators)- peripheral neuritis, paresthesias (rarely headache, memory loss, psychosis, seizures). peripheral neuritis is due to B6 deficiency (INH binds B6 and blocks the metabolite formation which is a coenzyme of various enzymes)
Rifampin
Bactericidal;
MOA: inhibits RNA polymerase;
Spectrum: M.tuberculosis, M.leprae, N. meningitidis, H.influenza, Pox virus;
Pharmacokinetics: well absorbed p.o, good distribution (incl. phagocytic cells, abscesses, lung cavities), hepatic metabolism (accelerates its own metabolism);
SEs: hepatotoxicity (enzyme elevation, rarely hepatitis), orange discoloration of urine, tears and sweat, rarely neurologic problems;
IND: mainly in combination!, most effective antiTB, leprosy (in combo with Dapsone and Clofazimine), in monotherapy for the prophylaxis of contact in meningococci, H. influenza infections, highly resistant staphylococci infections (endocarditis, osteomyelitis - in combo with ciprofloxacine);
Interactions: strong enzyme inducer, CYP3A4, CYP1A2, CYP2C9, CYP2C19, CYP2D6. accelerates its own metabolism
Pyrazinamide
Bactericidal;
MOA: Pyrazinoic acid is formed inhibits CoA synthesis;
SEs: hepatotoxcity, Hyperurecimia, drug fever;
IND: only act against M.tuberculosis;
ROA: p.o (1.5-2gX1/day);
Extra: resistance may develop
Ethambutol
Bacteriostatic;
MOA: inhibits arabinozil-transferase (→inhibits bacterial cell wall synthesis);
Pharmacokinetics: well absorbed p.o (alcohol decreases abs.);
IND: acts against Mycobacteria only;
SEs: retrobulbar neuritis (impairment of visual sharpness, red green color blindness), rarely- nausea, joint pain, headache, allergy;
Dosage: 15-25mg/kg X1/day p.o
Streptomycin
Bactericidal;
MOA: protein synthesis inhibitor (30S subunit), Aminoglycoside abx;
Spectrum: Zoonosis (Francisella), M.tuberculosis, not effective against IC bactaria, acts against free mycobacteria ONLY;
Pharmacokinetics: only parentral administarion (i.m), does NOT enter CNS, ALWAYS filtered by the kidneys (NOT metabolized at ALL);
SEs: particularly ototoxicity, nephrotoxcity, teratogenic;
Resistance: M avium and kansasii
Kanamycin
MOA: Aminoglycoside, protein synthesis inhibitor (30S ribosomal subunit);
IND: multiresistant TB, atypical mycobacteria;
SEs: Ototoxicity, Nephrotoxic, teratogenic; Extra: mainly used in cases of streptomycin resistance
Cycloserine
MOA: cell wall synthesis inhibitor D-ala analogue;
SEs: severe CNS SEs (tremor, acute psychosis (treated with pyridoxin), seizures), peripheral neuropathy, depression
Dapsone
MOA: folic acid synthesis inhibitor;
IND: leprosy; Extra: commonly used in combo with rifampin;
SEs: hemolysis (in G6PD), methemoglobinemia, erythema nodosum, GI SEs
Optic neuritis
inflammation or demyelination of the optic nerve
aminoglyosides administered only parenterally
if someone has liver failure the liver cannot reduce ammonia, and bacteria are the 1st agents to produce ammonia in the body.
Antituberculotics: Therapeutical specificities
- Actively growing bacterial: Isoniazid (INH)
- Dormant bacteria: Rifampin (RA), Pyrazinamide (PZA), Ethambutol (ETB)
- Time of treatment: 6months-2years
- Therapeutical protocols: INH+RA+PZA+ETB- first 2 months, then INH+RA- 4 months afterwards
