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Antituberculosis & Antihelmintics Flashcards

1
Q

characteristics of LATENT TB INFECTION?

A
  • TB bacilli live dormant inside lung, do not cause destruction of organs
  • no signs/symptoms of disease
  • not infectious
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2
Q

characteristics of TB DISEASE

A
  • TB bacilli progressively invade and damage a part (or parts) of the body
  • signs/symptoms of disease appear
  • can be infectious
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3
Q

signs/symptoms of TB?

A
  • cough > 3 wks
  • extreme tiredness
  • weight loss
  • sweating at night
  • fever
  • no appetite
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4
Q

how is TB spread?

A
  • by droplet nuclei

- expelled when an INFECTIOUS person w/ TB sneezes, speaks, sings, or coughs

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5
Q

bacteria of TB?

A
  • Mycobacterium tuberculosis
  • acid-fast bacteria
  • slow generation time (15-20 hrs)
  • facultative intracellular parasite, usu of macrophages
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6
Q

list of first line drugs for TB?

A
  • Isoniazid
  • Rifampin
  • Pyrazinamide
  • Ethambutol
  • Streptomycin
  • Rifabutin
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7
Q

list of second line drugs for TB?

A
  • Cycloserine
  • p-aminosalicylic acid
  • Ethionamide
  • Amikacin or kanamycin
  • Capreomycin
  • Fluoroquinolones
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8
Q

which drugs should be administered for first line treatment of ACTIVE, drug-sensitive TB?

A
  • Isoniazid
  • Rifampin
  • Pyrazinamide
  • Ethambutol
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9
Q

why treat active TB with all four first line TB agents?

A
  • treats disease & helps reduce Mtb drug resistance

- reduces transmission rates in first 2 months

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10
Q

which drugs can be used as monotherapy in latent TB disease?

A
  • Isoniazid

- Rifampin

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11
Q

mechanism of ISONIAZID (INH, Nydrazid)?

A
  • inhibits biosynthesis of MYCOLIC ACID

- prodrug that required KatG

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12
Q

therapeutic use of Isoniazid (INH)?

A
  • can be prophylaxis (alone) - but can cause liver damage (must weigh benefits of prophylaxis vs. risks of INH associated hepatitis, esp in pts > 35 y.o.
  • w/ active TB always use w/ Rif, EMB, PZA
  • can reach intracellular bacilli
  • bacteriostatic, when given w/ Rif = bactericidal
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13
Q

pharmacokinetics of Isoniazid (INH)?

A
  • ORAL
  • GI absorption good
  • METABOLISM BY ACETYLATION (liver) inactivates drug
  • metabolic rate depends on individuals - some “rapid” and some ““slow” metabolizers
  • half of whites/blacks = “slow”, many eskimos/native americans/asians = “rapid”
  • excretion via urine
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14
Q

toxicities of Isoniazid (INH)?

A
  • HEPATITIS, abnormal liver tests, jaundice 2.5%
  • CNS stimulation/convulsions, insomnia, restlessness, psychic episodes
  • peripheral neuritis in slow acetylators
  • headache, vertigo
  • HEMOLYSIS in ppl w/ G6PD
  • constipation, diff micturition, orthostation hypotension, eosinophilia, albuminuria, skin rashes, allergy, bone marrow depression, liver damage
  • lupus like syndrome (HIP drugs - hydrazine, INH, procainamide)
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15
Q

mechanisms Rifampin (Rimactane)?

A
  • group of structurally similar complex macrocyclic antibiotics
  • inhibits DNA DEPENDENT RNA POLYMERASE
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15
Q

mechanisms Rifampin (Rimactane)?

A
  • group of structurally similar complex macrocyclic antibiotics
  • inhibits DNA DEPENDENT RNA POLYMERASE
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16
Q

toxicities of Rifampin?

A
  • not serious
  • GI upset - nausea, vomiting, cramps, epigastric pain, diarrhea, headache, dizziness
  • hypersensitivity or allergy
  • HEPATIC ENZYME INDUCTION - cytochrome P450 interactions can enhance metabolism of endogenous substrates, incl adrenal hormones, thyroid hormones, vit D, HAART
  • imparts harmless ORANGE color to urine, sweat, tears, contact lenses
  • decreases effectiveness of birth control - induces liver metabolism of progestins
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16
Q

Rifampin use?

A
  • to treat pulmonary TB in combo with other TB drugs
  • oral
  • can be used to treat latent TB (bactericidal)
  • effective against MTB - most like INH
  • effective against leprosy
  • inhibits growth of G+ cocci, some G- microbes (E coli, pseudomonas, proteus, klebsiella), chlamydia, pox virus
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17
Q

toxicities of Rifampin?

A
  • not serious
  • GI upset - nausea, vomiting, cramps, epigastric pain, diarrhea, headache, dizziness
  • hypersensitivity or allergy
  • HEPATIC ENZYME INDUCTION - cytochrome P450 interactions can enhance metabolism of endogenous substrates, incl adrenal hormones, thyroid hormones, vit D, HAART
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17
Q

toxicities of Rifampin?

A
  • not serious
  • GI upset - nausea, vomiting, cramps, epigastric pain, diarrhea, headache, dizziness
  • hypersensitivity or allergy
  • HEPATIC ENZYME INDUCTION - cytochrome P450 interactions can enhance metabolism of endogenous substrates, incl adrenal hormones, thyroid hormones, vit D, HAART
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18
Q

mechanisms Rifampin (Rimactane)?

A
  • group of structurally similar complex macrocyclic antibiotics
  • inhibits DNA DEPENDENT RNA POLYMERASE
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19
Q

Ethambutol is not recommended for which group of ppl?

A

in children below age 13 - bc of adverse effects on vision, phys exam should include ophthalmoscopy, finger perimetry, and testing of color discrimination

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20
Q

toxicities of Rifampin?

A
  • not serious
  • GI upset - nausea, vomiting, cramps, epigastric pain, diarrhea, headache, dizziness
  • hypersensitivity or allergy
  • HEPATIC ENZYME INDUCTION - cytochrome P450 interactions can enhance metabolism of endogenous substrates, incl adrenal hormones, thyroid hormones, vit D, HAART
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21
Q

for which group of individuals is Rifampin NOT recommended?

A

HIV treated individuals

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22
mechanism of ETHAMBUTOL (Myambutol)?
- inhibits ARABINOSYL TRANSFERASES involved in synthesis of arabinogalactan - bacteriostatic
23
pharmacokinetics of ethambutol?
- given in combo w/ INH, Rif, PZA for active disease - bacteriostatic - oral, well absorbed, gets into CNS - renal elimination - excreted in feces & urine - dose adjustment needed in renal failure
24
toxicities of Ethambutol?
- DECREASE VISUAL ACUITY AND LOSS OF GREEN-RED PERCEPTION - usu reversible when discontinuing drug - allergy, GI distress, numbness, joint pain, peripheral neuritis - w/ renal insufficiency give smaller dose
25
Ethambutol is not recommended for which group of ppl?
in children below age 13 - bc of adverse effects on vision, phys exam should include ophthalmoscopy, finger perimetry, and testing of color discrimination
26
w/ HIV individuals, which drug replaces Rifampin for active TB drug combo?
RIfabutin bc less potent inducer of P450 enzymes | - has become first line drug
27
second line antiTb agents & method of admin?
- Cycloserine = oral, bacteriostatic - p-aminosalicylic acid = oral, bacteriostatic - Ethionamide = oral, bacteriostatic - Amikacin or kanamycin = IM, bactericidal - Capreomycin = IM, bactericidal - Fluoroquinolones = oral or IV, bactericidal - Rifapentine = analog of Rifampin *lower potency or greater toxicity
28
side effects of Pyrazinamide?
- hyperuricemia - not gouty polyarthralgia - HEPATIC DYSFUNCTION - myalgia - GI irritation - porphyria - photosensitivity
29
why is Pyrazinamide a critical first line drug?
responsible for reducing therapy to the current standard of 6 months (instead of 9-12 months)
30
info about Streptomycin?
- protein synthesis inhibitor (30S ribosome) - bactericidal - parenteral, limited tissue penetration, cell penetration poor, therefore good for extracellular Mtb - renal excretion (filtration), dose adjustment needed w/ renal failure - dose related toxicity: OTOTOXICITY, NEPHROTOXICITY - renewed interest in drug w/ increase in MDR, XDR
31
info about Rifabutin (Mycobutin)?
- inhibits DNA dependent RNA polymerase - bactericidal - oral, well absorbed, enterohepatic cycling - metabolites ORANGE COLORED
32
w/ HIV individuals, which drug replaces Rifampin for active TB drug combo?
RIfabutin bc less potent inducer of P450 enzymes | - has become first line drug
33
second line antiTb agents & method of admin?
- Cycloserine = oral, bacteriostatic - p-aminosalicylic acid = oral, bacteriostatic - Ethionamide = oral, bacteriostatic - Amikacin or kanamycin = IM, bactericidal - Capreomycin = IM, bactericidal - Fluoroquinolones = oral or IV, bactericidal - Rifapentine = analog of Rifampin
34
mechanism of fluoriquinolones?
- sec line tb drug | - MDR Mtb (all first line)
35
mechanism of action p-aminosalicylic acid?
- sec line tb drug | - folic acid synthesis inhibitor
36
mechanism of action ethionamide?
- sec line tb drug | - inhibits peptide synthesis
37
mechanism of action cycloserine?
- sec line tb drug - ICWS - analog of D-ala
38
XDR TB resistant to which meds?
INH, Rif, fluoroquinolones, usu kanamycin/capreomycin/amikamycin
39
mechanism of action kanamycin/amikacin?
- sec line tb drug - aminoglycoside - MDR Mtb
40
mechanism of fluoriquinolones?
- sec line tb drug | - MDR Mtb (all first line)
41
treatment of MAC?
1. clarithromycin or azithromycin 2. ethambutol 3. third oral drug (rifabutin, clofazimine, rifampin (if no HIV), cipro) *can add IV amikacin in some cases if resistance to clarithromycin
42
define: XDR TB
extensively multidrug resistant TB
43
MDR TB resistant to which meds?
INH, Rif
44
XDR TB resistant to which meds?
INH, Rif, fluoroquinolones, usu kanamycin/capreomycin/amikamycin
45
how is mycobacterium avium complex (MAC) transmitted?
- soil, water, birds | - common environmental pathogen, infection following inhalation or swallowing bacterial
46
characteristics of MAC?
- intrinsically resistant to anti-TB and antimicrobials - treatment w/ 2 or 3 antimicrobials for 12 months - co-infection w/ HIV common (20-30%)
47
treatment of MAC?
1. clarithromycin or azithromycin 2. ethambutol 3. third oral drug (rifabutin, clofazimine, rifampin (if no HIV), cipro) *can add IV amikacin in some cases if resistance to clarithromycin
48
toxicity of dapsone?
- nausea, vomiting, headache, dizziness - dose related hemolysis - methemoglobinemia, leukopenia, agranulocytosis, allergic derm, sometimes exfoliative derm, - w/ liver damage.. fever - peripheral neuritis - nasal obstruction improves 3-6 months
49
why treat leprosy w/ multi drug therapy?
- treatment w/ only one drug will lead to resistance | - treatment w/ dapsone or another mono therapy = unethical practice
50
treatment of leprosy?
- PB leprosy patients = 1-5 patches get rifampin & dapsone | - MB leprosy patients = > 5 patches get rifampin, dapsone & clofazimine
51
which is most widely used drug to treat leprosy?
dapsone - also cheapest
52
mechanism of action of DAPSONE?
- similar to sulfonamides - PABA antagonistic - interferes w/ nutrition of m. leprae - interferes w/ folic acid synthesis
53
admin/absorption/fate of dapsone?
- ORAL - GI absorption almost complete & rapid - excretion slow
54
toxicity of dapsone?
- nausea, vomiting, headache, dizziness - dose related hemolysis - methemoglobinemia, leukopenia, agranulocytosis, allergic derm, sometimes exfoliative derm, - w/ liver damage.. fever - peripheral neuritis - nasal obstruction improves 3-6 months
55
thalidomide has orphan drug status for treatment of ____.
- primary brain malignancies - kaposi's sarcoma - HIV wasting syndrome - LEPROMATOUS LEPROSY - recurrent aphthous ulcers and stomatitis - TREATMENT OF MYCOBACTERIUM INFECTIONS - treatment and prevention of graft vs host dz - multiple myeloma
56
mechanism of action clofazimine?
binds preferentially to MYCOBACTERIAL DNA (GUANINE) and inhibits reproduction and growth
57
pharmacokinetics of clofazimine?
- oral admin - incompletely absorbed from GI tract - GI disturbances, hepatitis, jaundice
58
toxicities of clofazimine?
- GI DISTURBANCES - anorexia, diarrhea, nausea/vomiting, colicky/burning pain (50% pts) - skin discoloration (75-100% pts) - HEPATITIS - crystalline deposits of clofazimine seen in many tissues and organs, lower dose w/ GI upset
59
what is the DOC for moderate to severe Erythema Nodosum Leprosum (ENL)?
Thalidomide
60
contraindications of Thalidomide?
100% contraindicated in pregnant women - very teratogenic
61
thalidomide has orphan drug status for treatment of ____.
- primary brain malignancies - kaposi's sarcoma - HIV wasting syndrome - LEPROMATOUS LEPROSY - recurrent aphthous ulcers and stomatitis - TREATMENT OF MYCOBACTERIUM INFECTIONS - treatment and prevention of graft vs host dz - multiple myeloma
62
three blood flukes (shistosomes)?
- Schistosoma mansoni - Schistosoma haematobium - Schistosoma japonicum
63
three types of worms?
- roundworms (nematodes) - tapeworms (cestodes) - flukes (trematodes, shistosomes)
64
characteristics of ROUNDWORMS (nematodes)?
- non-segmented, cylindrical - infection: after ingestion of food contaminated w/ embryonic eggs - some live in blood, tissues - hookworms go in lungs
65
characteristics of TAPEWORMS (cestodes)?
- segmented, flatworm, suckers for attachment - eggs, passed in feces - larvae - may invade intestinal wall, get into bloodstream and lodge in eye/live/brain - adults - intestinal parasites - may grow to 20 ft - mild illness = abdominal discomfort, hunger, indigestion, anorexia, Vit B deficiency
66
characteristics of FLUKES (trematodes)?
- non-segmented flat worms, two suckers - eggs mature before entering humans - acquired through food or penetration of skin - mature in intestine, lung, liver - diarrhea, abdominal pain, anorexia - LIVER FLUKE - bile duct blockage, liver enlargement, URQ pain - LUNG FLUKE - cough, hemoptysis, chest pain
67
characteristics of BLOOD FLUKES (shistosomes)?
- penetrate skin in contact w/ contaminated H2O (snail intermediate host) - go through lymphatics to blood and liver - following maturation migrate into mesenteric or vesicular vein, adults mate/lay eggs - eggs pass through wall of intestine or bladder, may go to lung or liver - malaise, fever, intestinal discomfort - after eggs released - fever, abdominal pain, liver tenderness
68
three blood flukes (shistosomes)?
- Schistosoma mansoni - Schistosoma haematobium - Schistosoma japonicum
69
mechanism of anti-hemintic therapy?
interferes w/: - energy metabolism - neuromuscular coordination - microtubular function - cell permeability
70
drugs for Roundworms/nematodes?
- pyrantel pamoate (Antiminth) | - Ivermectin (Mectizan)
71
characteristics Pyrantel pamoate (antiminth)?
- oral, broad spectrum - effective against roundworm, pinworm, hookworm - neuromuscular blocking agent that causes release of Ach & inhibition of cholinesterases - results in paralysis followed by expulsion of worms - little absorbed, few effects on humans - dizziness, drowsiness, headache - available OTC
72
characteristics Ivermectin (Mectizan)?
- oral - effective against nematodes, insects, acarine parasites - DOC for filaria infestation - used for THREADWORM, roundworm, cutaneous larva migraines - PARALYZES parasite, intensifies GABA-mediated transmission of signals in peripheral nerves - minimal side effects, pruritis, tender lymph nodes, fever
73
drugs for Tapeworms (cestodes)?
Praziquantel (Biltricide)
74
drugs for Flukes (Trematodes)?
- Praziquantel (Biltricide) | - Biothionol (Bitin)
75
characteristics of Praziquantel (Biltricide)?
- oral - DOC for all shistosomes, effective against most cestodes & trematodes - thought to act by increases worm's permeability to Ca2+, results in contraction and paralysis of worm's muscles, dislodgment, death - well absorbed from GI tract - used for systemic infections - few systemic effects - nausea, vomiting, abdominal discomfort from release of dead worms' proteins - not recommended for pregnant women (possible abortion)
76
characteristics of Biothionol (Bitin)?
- given orally - absorbed from GI tract - uncouples oxidative phosphorylation - active against flukes, incl liver & lung fluke - DOC for sheep liver flukes - side effects mild - nausea, vomiting, headache, diarrhea, dizziness, urticaria, rash - rxn to antigens released from dying worms

KG - Pharmacology (8 decks)

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