Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
55 Cards in this Set
- Front
- Back
|
Why are mycobacterial infections difficult to treat?
|
Slow growing
Dormant and resistant to diff drugs Lipid rich mycovacterial cell wall - impermeable to many agents Intracellular pathogens - inaccessible to drugs Notorious for developing resistance and drug combinations are needed. |
|
|
Why do we need more than 1 drug to treat mycobacteria?
|
Mutations are present in 1 bacillus in 10^6/lesions in 10^8 bacillus.
probability that bacillus is resistant to both drugs is 10^12..so in early phases of treatment when there is heavy bacterial load, four drugs are used..In late phases, only two drugs are used |
|
|
Drugs used in first line for TB treatment -
|
Isoniazid
Rifampin Pyrazinamide - reduces therapy duration to 6mo Ethambutol - for coverage against resistant mycobacterial |
|
|
Characteristic of first line Anti-TB drugs -
|
All are bactericidal except Ethambutol
Relatively less toxic Effective in combination |
|
|
Second line Anti-TB drugs -
|
Cycloserine
Ethionamide Kanamycin Capreomycin Para-amino salicylic acid Streptomycin |
|
|
Char of second line Anti-TB drugs -
|
More toxic, less tolerated
Reserved for treatment to drug resistance TB |
|
|
Isoniazid -
MOA - |
bioactivated by katG( catalase)
inhibits enzymes for mycolic acid synthesis and mycobacterial cell walls Resistance assoc with deletion in katG gene |
|
|
Pharmacokinetics for Isoniazid-
|
Oral
Tmax - 1-2 hrs Metabolized in Liver and Excreted in urine Acetylation (metabolized) diffes in population - chinese rapidly, israeli -s slow |
|
|
Adverse effects of INH -
|
Hepatitis
Neuropathy Vit B6 deficiency Pyridoxine given prophylactically to pts to prevent neuropathy as well if it develops Inhibits metabolism of phenytoin - potentiates s/e of this drug |
|
|
Rifampin
MOA - |
Blocks transcriptase
Inhibits bacterial DNA dependent RNA polymerase by binding to the beta subunit and inhibits RNA synthesis Bactericidal |
|
|
Pharmacology for Rifampin -
|
Orally - well absorbed
T1/2 - 2-5.5 hrs Metabolized in liver |
|
|
Adverse effects of Rifampin -
|
Abdominal discomfort and fever
Skin eruptions and hepatitis Increase excretion of contraceptives Urine - reddish color Contacts - rosy red color..advise pts before prescribing |
|
|
Contraindication of Rifampin in pts -
|
HIV infected individuals - as Rifampin increases metabolism of PI
Instead give Rifabutin |
|
|
Pyrazinamide
MOA |
Converted to pyrazinoic acid - active drug by bactericidal enzyme pyrazinamidase
Active at low pH - so can be active in lysosomes where mycobacteria could be residing More active against intracellular bacilli bactericidal |
|
|
Pharmaco -
|
same as Rifampin
Orally, liver, urine |
|
|
Adverse effects of Pyrazinamide -
|
Hep
Hyperuricemia gout Arthralgia, fever, skin rash |
|
|
What levels should be monitored in Pyrazinamide
|
SGOT
Serum glutamate oxaloacetic transaminase acid levels (released when liver or heart damaged) |
|
|
Ethambutol
MOA |
Inhibits arabinosyl transferase involved in bacterial cell wall synthesis
bacteriostatic |
|
|
Pharmaco of Ethambutol -
|
T1/2 10-15 hrs
Well distributed in most tissues including CNS can be used for tuberculosis meningitis Excreted mostly unchanged in urine |
|
|
Ethambutol
Adverse effects |
Optic neuritis in loss of visual acuity - and red green blindness
Peripheral neuritis HEadache Skin rash Precaution - monthly tests for visual acuity |
|
|
Who is ethambutol contra-indicated in?
|
Small children - can't tell if they are going color blind
|
|
|
When should one use second line tb drugs?
|
In case of resistance to first line agents
In case of failure of clinical response to conv therapy Serious treatment limiting adverse drug reaction |
|
|
Streptomycin
|
Inhibits bacterial protein synthesis
Interferes with initiation complex of protein formation and also causes misreading - which results in incorporation of incorrect aa and nonfunctional proteins |
|
|
Pharm for streptomycin -
|
Not absorbed orally, given IV
Distributed in most of tissues Very low intracellular concentrations Excreted unchanged |
|
|
Adverse reactions of strep -
|
Ototoxicity
Vestibular dysfunction (patients fall in dark room) Auditory disturbances Renal injury Precautions - routine audiometry |
|
|
Paramino salicylic acid
MOA |
Competes with PABA for mycobacterial dihydropteroate synthetase (folate biosynthesis)
Bacteriostatic |
|
|
Pharmaco for Paramino salicylic acid -
|
Absorbed orally
Liver -> urine t1/2 - 1 hr |
|
|
Adverse effects of PAS
|
Hypersensitivty
HEP N/V/D - abdo pain PAS used less frequently now as other drugs are well tolerated |
|
|
Ethionamide
MOA - |
Related to INH and blocks synthesis of mycolic acids
|
|
|
Pharmaco -
|
orally
liver - > ethionamide sulphoxide t1/2 - 2h |
|
|
Ethionamide
Adv effects - |
Hepatotoxicity
Neurological symptoms pyridoxine can lessen neuro sx |
|
|
Clofazimine
MOA |
Inhibits bacterial DNA synthesis
|
|
|
Pharmaco -
|
Orally
Concentrates in RES and slowly released from it Metabolized into several inactive metabolites Excreted mainly in feces T1/2 10 days |
|
|
Clofazimine
Adverse effects - |
GI disturbances
drug accumulates in tissues and causes patients to develop red brown skin color Discoloration of urine and feces as well |
|
|
MOA of cycloserine -
|
acts by inhibiting cell wall synthesis - poor efficacy and adverse effects
|
|
|
MOA of Fluroquinolones -
|
Inhibits topoisomerase II
Moxifloxacin is most active against M tuberculosis and is useful for drug resistant TB - widely used to treat atypical mycobacterium infections |
|
|
Principles of anti-tb treatment -
|
Develop spontaneous resistance to drugs
Treatment with single drug will select resistant population Use of two drugs or more prevents resistance |
|
|
Standard treatment regimens for pulmonary tb
|
Initial phase of 2 months daily -
INH, RIF, PZA or INH, RIF, PZA, EMB Sterilizing phase - 4 months daily or 3 times a week INH, RIF |
|
|
Who is preventive chemotherapy for?
|
Individuals with positive tuberculin test
Contacts of infectious cases of TB INH monotherapy for 6 mos |
|
|
Reasons for failure of TB regimen
|
Unsatisfactory regimens (# of drugs/dosages) or duration of therapy
non compliance with treatment Resistance of M. tuberculosis to drugs |
|
|
What is DOT
|
Directly Observed Therapy
Non-compliance leads to treatment failure, development of drug resistance and spreading of MDR bacilli Supervised therapy has more success rate |
|
|
What is Leprosy (Hansen's disease)
|
Chronic infectious disease caused by M. Leprae
Affects skin, peripheral nerves, mucose of URT, and eyes |
|
|
M. leprae char -
|
gram positive rod
waxy coat only stains with carbol-fuchsin stain and not with traditional gram stain |
|
|
Where does M. leprae grow
|
Feet of mice and Armadillos -
Obligate intracellular parasites Lacks many necessary genes for independent survival |
|
|
Early Tuberculoid form of Leprosy (Paucibacillary)
|
One or more hypopigmented skin macules and anesthetic patches
Lost skin sensations - due to peripheral nerve damage (cellular infiltration of neural sheath - onion skin appearance) Thickening of auricular nerve on neck of patient |
|
|
Late Tuberculoid Leprosy
|
Total deformity
Loss of extremities |
|
|
Multibacillary Lepromatous
|
Symmetrical skin lesions
Nodules Plaques Thickened Dermis Frequent involvement of nasal mucosa - resulting in nasal congestion Gynecomastia Loss of sensation in regions with skin lesions.. blindness as dz advances |
|
|
Advanced Lepromatous Leprosy can also result in -
|
Leonine faces
Loss of eyebrows Partial collapse of nose with heavy bacterial load Reservoirs for infection |
|
|
Techniques used to identify Leprosy infections -
|
Biopsy from nodule
PCR |
|
|
Treatment for Leprosy -
|
MDT consists of -
MB -Rifampin, Clofazamine, Dapsone PB - Rifampin, and Dapsone |
|
|
Dapsone
MOA |
Inhibits folate synthesis
Excreted in bile - reabsorbed from intestine - excreted in ruine |
|
|
S/e with Dapsone
|
Well tolerated
GI disturbances Rash - skin Exfoliative dermatitis |
|
|
T/x of Leprosy drug dosage
|
Rifampin - once a month (red color urine after intake)
Clofazamine - daily; brownish black discoloration and dryness of skin Dapsone - rashes and exfoliative dermatitis |
|
|
Who should dapsone be not given to?
|
Pts who are allergic to sulfa drugs
|
|
|
Atypical Mycobacteria -
|
Nontuberculous bacteria
Not communicable M Avium - most imp in AIDS pts T/x Azithro Ethambutol Rifabutin Flouroquinolones |
