Pharmacology: Antimicrobials (Tuberculosis)

Front 1

BCG: Use?

Back 1

(1) Protection up to 7-10 years from EXTRA pulmonary TB
(2) Beneficial effect on superficial bladder cancer

Front 2

BCG: Contra?

Back 2

Immunodeficient patients

Front 3

BCG: Epidemiology?

Back 3

Mass vaccination w/ BCG inappropriate if incidence rate less than 1% b/c of cost and interference w/ PPD

Front 4

Tuberculosis:
General treatment strategies?
1st line agents?
2nd line?
Other?

Back 4

General treatment strategies: Multidrug to prevent resistance, Active should be hospitalized and started w/ 4 anti-microbial agents

1st Line:
(1) Isoniazid (2) Rifampin (3) Ethambutol (4) Streptomycin [aminglycoside] (5) Pyrazinamide

2nd Line:
(1) Ethionamide [Izoniazide alt]
(2) Para-amino-salicyclic acid [Ethambutol alt in <5yo] (3) Amikacin & Capreomycin [aminglycoside alt to streptomycin]
(4) Cycloserine

Others:
(1) 2nd gen fluoroquinolones [cipro-, o-floxacin] & Spar-floxacin [3rd gen] --> MTB, MAC

Front 5

Isoniazid: Use?

Back 5

(1) 1st line therapy in latent TB treatment in individuals vulnerable to miliary and meningial TB
(2) TB prophylaxis in IC
(3) Close contact with ACTIVE TB

Front 6

1ST LINE TB DRUG
Isoniazid:
Route?
Distribution?
Elimination?

Back 6

Route: Well absorbed orally but inhibited by antacids

Distribution: Gets into CNS

Elimination: Isoniazid is prodrug activated by mycobacterium to INH, which is metabolized by acetylation [jap, chinese, and eskimo acetylate 5X faster] and then excreted by kidneys

Front 7

1ST LINE TB DRUG
Isoniazid:
MOA/PD?
Resistance?

Back 7

MOA/PD: Converted to INH by bacteria which inhibits mycolic acid [stage 1 cell wall] synthesis, Works both intra & extracellularly

Resistance:
(1) High: KatG gene activates isoniazid to INH [mutation reduces activation]
(2) Low: inhA codes for INH target reduce effects on cell wall synthesis

Front 8

1ST LINE TB DRUG
Isoniazid: AE?

Back 8

Inhibits pyridoxal phosphate [B6] kinase which causes: Effects can be reduced w/ B6 treatment
(1) Peripheral neuritis
(2) Hepatotoxicity [<2%] in elderly b/c of INH conversion to hydrazine [toxic]
(3) Hemolysis [in G6PD]
(4) Drug induced SLE

Front 9

Isoniazid: DI?

Back 9

1ST LINE TB DRUG
(1) Inhibits metabolism of phenytoin and warfarin
(2) MAOI so causes tyramine reaction

Front 10

Rifampin:
Others subtypes?
Use?

Back 10

1ST LINE TB DRUG
Other subtypes: Rifabutin, Rifapentine

Use:
Rifampin --> (1) 1st line therapy in active MTB (2) Latent MTB in INH intolerant (3) Atypical mycobacterium (4) ML (5) Meningocccal and staphylococcal carriers (6) Prophylaxis in exposure to meningeal H. influenzae (7) Enhance effects of amphotericin B in systemic fungal infection (8) Doxycycline + Rifampin are used in brucellosis
Rifabutin --> Better MAC activity and good in HIV b/c less interaction w/ HAART, x-resistance +ve
Rifapentine --> Longer acting than rifampin but, x-resistance +ve

Front 11

Rifampin:
MOA/PD?
Resistance?

Back 11

1ST LINE TB DRUG
MOA/PD: Inhibits DNA dependent RNA pol, Effective against both intra & extracellular

Resistance:
(1) High: KatG gene activates isoniazid to INH [mutation reduces activation]
(2) Low: inhA codes for INH target reduce effects on cell wall synthesis

Front 12

Rifampin: AE?

Back 12

1ST LINE TB DRUG
(1) Hepatotoxicity
(2) Body fluids colored red
(3) Flu-like syndrome [fever, chills, GI irritation, skin rash]

Front 13

Rifampin: DI?

Back 13

1ST LINE TB DRUG
Induces CYP450 and enhances elimination of many drugs

Front 14

Ethambutol: Use?

Back 14

1st line therapy in tuberculosis

Front 15

Ethambutol:
Route?
Distribution?
Elimination?

Back 15

1ST LINE TB DRUG
Route: Oral well absorbed

Distribution: Gets in CNS

Elimination: UNCHANGED in urine

Front 16

Ethambutol:
MOA/PD?
Resistance?

Back 16

1ST LINE TB DRUG
MOA/PD:
(1) Inhibits arabinosyl transferase and blocks arabinogalactan [cell wall]
(2) Inhibits nucleic acids

Resistance: emb gene mutation

Front 17

Ethambutol: AE?

Back 17

1ST LINE TB DRUG
(1) Decreased visual acuity & optic neuritis [dose dependent and reversible]
(2) Loss of ability to differentiate red from green
(3) Neurotoxicity
(4) May interfere w/ uric acid secretion [gouty attack]

Front 18

Ethambutol:
Contra?
Alternative?

Back 18

1ST LINE TB DRUG
Contra: Not recommended in children under 5

Alternative: Para-aminosalicyclic acid [PAS]

Front 19

Pyrazinamide: Use?

Back 19

1st line TB drug in ACTIVE infection

Front 20

Pyrazinamide:
Route?
Distribution?
Environment of activity?
Elimination?

Back 20

1ST LINE TB DRUG
Route: Good oral

Distribution: CNS also

Environment of activity: Active in acidic environments w/ effects up to 2mo if inflammation is present

Elimination: Toxicity goes up in hepatic or renal dysfunction

Front 21

Pyrazinamide: AE?

Back 21

1ST LINE TB DRUG
(1) Hepatotoxicity
(2) PPP --> Porphyria, Polyarthralgia, Photosensitivity
(3) GI Irritation, Skin rashes

Front 22

Ethionamide:
Use?
MOA/PD?

Back 22

Use: 2nd line TB drug

MOA/PD: Similar action to INH [mycolic acid synth inhibitor so stage 1 cell wall synth inhib] but no x-resistance w/ INH

Front 23

Ethionamide:
Route?
Distribution?

Back 23

2ND LINE TB DRUG
Route: Oral good

Distribution: Gets to CNS

Front 24

Ethionamide: AE?

Back 24

2ND LINE TB DRUG
Neurotoxic leading to:
(1) Mental disturbances
(2) Impotence

Front 25

Para aminosalicyclic acid [PAS]:
Use?
Alternative to?

Back 25

Use: 2nd line TB drug

Alternative to: Ethambutol in children < 5yo

Front 26

Para aminosalicyclic acid [PAS]:
Distribution?
MOA/PD?

Back 26

2ND LINE TB DRUG
Distribution: NO CNS

MOA/PD: Blocks dihydropterate synthase [folic acid synth inhibitor]

Front 27

Para aminosalicyclic acid [PAS]: AE?

Back 27

2ND LINE TB DRUG
(1) GI disturbance & pain in large doses
(2) Hypersensitivity
(3) Renal, thyroid, and liver dysfunctions

Front 28

Cycloserine: Use?

Back 28

(1) 2nd line TB drug [strains resistant to INH, streptomycin, & PAS]
(2) MAC often susceptible
(3) 2nd line against CNS nocardia [sulfa drugs 1st]

Front 29

Cycloserine:
Route?
Distribution?
Elimination?

Back 29

2ND LINE TB DRUG
Route: Oral good

Distribution: CSF good

Elimination: 50% excreted from kidneys unchanged

Front 30

Cycloserine: AE?

Back 30

2ND LINE TB DRUG
(1) Psychosis, C/I seizures Peripheral neuropathy, Convulsions
(2) Delirium, Confusion, Headache, Tremors

Front 31

Cycloserine: MOA/PD?

Back 31

2ND LINE TB DRUG
Inhibits conversion of L-alanine to D-form and linkage of D-form through inhibition of alanine racemase [cell wall stage 1 inhibitor]

Front 32

Dapsone/Acedapsone:Use?

Back 32

DOC's in leprocy:
(1) Acedapsone --> Repository form of dapsone & can also be as alternate in PCP infection in AIDS pts.

Front 33

Dapsone/Acedapsone:
AE?
AE treatment/alternatives?

Back 33

DOC IN LEPROCY
AE:
(1) Lepra rxn [Erythma nodosum leprosum, similar to Jarisch-Herxeimer rxn]
(2) Hemolytic anemia in G6PD, Peripheral neuritis, GI irritation, Drug-induced lupus

AE treatment/alternatives: Lepra rxn alternatives/treatments
(1) Clofazamine is alternative [antileprotic and anti-inflammatory effects]
(2) Chloroquine, thalidomide, & corticosteroids in serious cases

Front 34

Clofazimine: Use?

Back 34

2nd line therapy for ML in dapsone resistant, lepra rxn, combination treatment, & pts. that cannot tolerate dapsone

Front 35

Clofazimine: AE?

Back 35

2nd LINE IN LEPROCY
(1) Eosinophilic enteritis [GI irritation]
(2) DISCOLORATION of the skin

Front 36

Amithiozone: Use?

Back 36

2nd line therapy [dapsone alternate] in ML, but resistance fairly common hence only used in combo w/ other anti-leprosy drugs

Front 37

Stremptomycin:
Main use?
Back-up drug for?
Combination therapy?
Spectrum?
AE specific in long term use?

Back 37

AMINOGLYCOSIDE ANTIBIOTIC
Main Use:
(1) 1st line drug against advanced TB [best alternate is amikacin followed by capreomycin]
(2) Plague & tularemia

Back-up drug for: Brucellosis

Combination therapy: Very effective w/ Pen G in enterococcal infections

Spectrum: Differs from other aminoglycosides in that NOT very effective against gram -ve rods

AE specific in long term use? Optic nerve dysfunction

Front 38

Prophylaxis of MAC in AIDS?

Back 38

Azithromycin & Clarithromycin [macrolides w/ long half lives]

Front 39

Leprosy: Drugs used in order?

Back 39

(1) Dapsone & acedapsone
(2) Clofazimine
(3) Rifampin
(4) Amithiozone
(5) Minocycline [3rd gen tetracycline]
(6) Ofloxacin [2nd gen flouroquinolone]