| 1 TB has been plaguing humans for __ years
2 Discovered mycobacterium tuberculosis
3 Discovered Streptomycin | 1) 4000
2 Robert Koch, 1905 (Nobel Laureate)
3 Selman Waksman, 1952 (Nobel Laureate) |
| 1 In the year 1938 discovered:
2 sulfone derivative (4,4-diaminodiphenylsulfone)
treatement of leprosy
(Mycobacteriumleprae), antimalarial> too
toxic in high dosages | 1 Sulfanilamide-bacteriostatic properties
2 Dapsone |
| 1 aminoglycoside antibiotic, Waksman et al. in 1944 > modern era of anti-TB tx
2 (PAS)
3 Introduced in 1952
4 (synthetic)
5 ( semisynthetic) | 1 Streptomycin
2 P-aminosalicylic acid
3 Isoniazid
4 Ethambutol
5 Rifampin |
| 1 Can be used only for infected patients who do not have TB (latent TB infection)
2 standard medical practice
3 Choice of antiTB drugs depends on: | 1 Monotherapy
2 Combination therapy
3)
a. Location of dx (pulmonary, urogenital, GI, neural)
b. Results of susceptibility tests
c. Pattern of resistance in the locality
d. Physical condition and age of the patient
e. Toxicities of ind. agent |
| Nonpharmacologic Therapy Aim: | 1 Prevent Spread of TB
2 Return the patient to a state of normal weight and wellbeing
3 Surgery may be needed to remove destroyed lung tissue, tuberculomas and certain extrapulmonary lesions |
| 1 These drugs have high antitubercular efficacy; are used routinely
2 These drugs have either low antitubercular efficacy or higher toxicity or both;
are used as reserved drugs | 1 First Line Drugs
2 Second Line Drugs |
| 1 First Line Drugs (AntiTB) | 1 Isoniazid
2 Rifampicin
3 Pyrazinamide
4 Ethambutol
5 Streptomycin |
| Second Line Drugs (AntiTB) | 1 Para-aminosalicylic acid (PAS)
2 Kanamycin
3 Amikacin
4 Ethionamide
5 Prothionamide
6 Fluoroquinolones (Oflo, levo, moxi, Ciprofloxacin) |
| It is a prodrug and is converted into active form inside mycobacterium cell | Isoniazid ( Isonicotinic acid hydrazide, isonicotinyl hydrazide, INH) |
| Isoniazid (Isonicotinic acid hydrazide, isonicotinyl hydrazide, INH) SIDE EFFECTS: | 1 Inducer of Lupus, Inhibitor of CYTP450
2 Neuropathy (Peripheral)
3 Hepatotoxicity, Hemolysis in G6PD Deficiency |
| 1 Isoniazid is an analog of __
2 Adverse Effects of Isoniazid
3 Adverse effects happen because Isoniazid competes with __ for the enzyme __
4 Prevents Neurotoxicity even in higher doses of Isoniazid, but routine use is not mandatory.
5 Is treated with Vitamin B6 100mg / day. | 1 Pyridoxine (Vitamin B6)
- a potent anti tubercular drug
2
a) peripheral neuritis
b) Neurological manifestations: Paresthesia, Numbness, Mental disturbances, Optic neuritis, Convulsions
c) Hepatitis (potentially fatal)
- Due to Pyridoxine (Vit B6 Deficiency)
3 Pyridoxal phosphate, Apoptryptophanase
4 Vitamin B6 10 mg / day
5 Isoniazid Neurotoxicity |
| 1 Isoniazid can potentiate the adverse effects of __
2 Slow/ Fast Acetylators are particularly At risk from Isoniazid | 1 Difenin (Nystagmus, Ataxia)
- Isoniazid inhibits metabolism of Difenin
2) Slow Acetylators |
| used in combination with
other agents because
resistance develops
rapidly
must be enzymatically hydrolyzed to
Pyrazinoic acid (active form)
1st line drug for short
term treatment | Pyrazinamide (Pyrazinecarboxamide, PZA) |
| Pyrazinamide Side Effects | 1 Hepatotoxicity
2 Hyperuricemia
3 Gout like Arthralgia
4 Others: Rash, Vomiting, Anemia, Lupus, Seizures, Photodermatitis |
| active only in dividing
mycobacteria
S/E: Optic neuritis
↓ visual acuity
loss of ability to
discriminate red and
green colors | Ethambutol, (+)-2,2-ethylenediimino)-d-1-butanol
dihydrochloride, EMB |
| structural analog of isoniazid
2-substitution enhances activity in the thioisonicotamide series
used in the tx of Isoniazid-resistant TB
S/E: Gastric irritation,
hepatoxicity, peripheral
neuropathies, optic neuritis | Ethionamide , 2-Ethylthioisonicotinamide |
| acts as a competitive
inhibitor for
p-aminobenzoic acid in
folate biosynthesis
S/E: Severe gastric
irritation | Para-aminosalicylic acid (4-aminosalicylic acid) |
| basic red dye used in the treatment of leprosy (Hansen's dx), including dapsone-resistant forms
S/E: GI intolerance,
hyperpigmentation,
ichtyosis, dryness, rash,
pruritus | Clofazimine (Lamprene) |
