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RS Pharmacology

Respiratory System Pharmacology- Anti- TB

First line anti-tuberculous agents: Isoniazid (INH) Rifampin “Rifadin” or “Rimactane” Ethambutal Streptomycin Pyrazinamide Island Rivers Establish Shoddy Palms
Secondary or Second Line Drugs used as anti-tuberculous agents: Ethionamide Capreomycin Cycloserine Para-Amino-Salicylic Acid (PAS) Amikacin Flouroquinolones Linezolid Rifabutin Rifapentine Earthworms Create Creepy Pumpkins And Ferrets List Robotic Robots
Most active anti-TB drug: Isoniazid
General characteristics of Isonazid: Small molecule, water soluble, Structurally related to Pyridoxine Prodrug, activated by KatG, the mycobacterial catalase peroxidase
MOA of Isonazid: Blocks mycolic acid synthesis-consequently mycobacterial cell wall synthesis- bactericidal effect in growing TB cells Widely distributed, penetrates into macrophages Metabolized by acetylation
Resistance of Tb to Isonazid: 1 in 10^6 when used alone 1 in 10^12 when used in combination
Side effects of Isonazid use: Hepatitis-1% Anorexia N,V Jaundice Neuropathy:10-20% Neurotoxicity: Memory loss, Psychosis,Seizures Tinnitus GIT effects Interactions
Neuropathy is more likely to occur in: Slow acetylators Malnutrition AIDS Alcoholics DM Uremia Due to pyridoxine deficiency
Rifampin was isolated from: Stretomyces miditerranei
Rifampin is effective in cases of: Gram+ve and –ve bacteria Mycobacteria Enterococci Chlamydia
MOA of rifampin: Binds to the beta subunit of bacterial DNA-dependant RNA polymerase and therefore inhibits RNA synthesis Bactericidal Widely distributed Hepatic metabolism - enterohepatic recirculation
What are the clinical uses of Rifampin? TB Leprosy Meningococcal Carrier State Prophylaxis in H.influenzae. Staph osteomyelitis and valve endocarditis.
In Jordan it is available only in MOH Ministry of Health
Rifampin toxicity can cause: Orange color to secretions( tears, urine, sweat). Nephritis Rashes Hepatitis Flu-like syndrome Liver Enzyme Inducer- lower serum levels of many drugs
Uses of streptomycin: Anti-tuberculus agent. Plague Tuleremia Brucellosis Endocarditis
Streptomycin toxicity causes: Allergy: Fever, Rashes Pain, after i.m injection Vestibular toxicity---- Irreversible Nephrotoxicity
What are the Indications for Secondary or Second- Line Drugs? 1) Resistance to first –line drugs 2) Failure of clinical response to conventional therapy 3) Occurrence of serious treatment-limiting adverse drug reactions 4) When expert guidance is available to deal with the toxic effects
MOA of Ethionamide: Related to Isoniazid Blocks mycolic acid synthesis
How is Ethionamide administered? Orally
Disadvantages of taking Ethionamide: Poorly tolerated: Severe GIT irritation Neurotoxic Hepatotoxic
MOA of Capreomycin: Peptide protein synthesis inhibitor
Administration of Capreomycin via: Injection
Disadvantages of taking Capreomycin: Nephrotoxic, ototoxic Local pain and sterile abscesses may occur
MOA of Cycloserine: Inhibits cell wall synthesis
Disadvantages of taking Cycloserine: Peripheral neuropathy CNS toxicity including depression and psychotic reactions
MOA of Para-Amino-Salicylic Acid (PAS): Folate synthesis antagonist
Dosage of PAS: 8-12 gm/day
Advantages of taking PAS: Well absorbed Widely distributed, except CNS Excreted in urine
Disadvantages of taking PAS: GI toxicity Hypersensitivity reactions Crystalluria
Uses of Amikacin: Multidrug-resistant strains Atypical mycobacteria
Use of Florquinone: Combination, because resistance develops rapidly when used alone
When is Linezolid used? For multi-drug resistant strains \LAST resort
Side effects of Linezolid use: Bone marrow suppression Irreversible peripheral and optic neuropathy
MOA of Rifabutin and Rifapentine Related to Rifampin. Inhibit bacterial RNA polymerase. Both, like Rifampin, are inducers for CYP P450 enzymes. But Rifabutin is a less potent inducer
Rifabutin is indicated in place of Rifampin in the treatment of TB in HIV-infected patients receiving protease inhibitor or nonnucleoside reverse transcriptase inhibitor
Drugs used in the cases of Atypical Mycobacteria M.tuberculosis complex: Erythromycin Sulphonamides Tetracycline M.avium complex: Important and common cause of disseminated TB in late stages of AIDS Azithromycin or Clarithromycin Ethambutal & Ciprofloxacin
Stats for TB: Annually, 9 million cases recorded 5% of these are drug-resistant tuberculosis Forty-nine percent of those with XDR-TB died compared to 19 percent of patients with ordinary MDR-TB
Created by: Ulaisl



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