Antituberculosis & Antihelmintics Flashcards Preview

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Flashcards in Antituberculosis & Antihelmintics Deck (79):
1

characteristics of LATENT TB INFECTION?

- TB bacilli live dormant inside lung, do not cause destruction of organs
- no signs/symptoms of disease
- not infectious

2

characteristics of TB DISEASE

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

3

signs/symptoms of TB?

- cough > 3 wks
- extreme tiredness
- weight loss
- sweating at night
- fever
- no appetite

4

how is TB spread?

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

5

bacteria of TB?

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

6

list of first line drugs for TB?

- Isoniazid
- Rifampin
- Pyrazinamide
- Ethambutol
- Streptomycin
- Rifabutin

7

list of second line drugs for TB?

- Cycloserine
- p-aminosalicylic acid
- Ethionamide
- Amikacin or kanamycin
- Capreomycin
- Fluoroquinolones

8

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

- Isoniazid
- Rifampin
- Pyrazinamide
- Ethambutol

9

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

- treats disease & helps reduce Mtb drug resistance
- reduces transmission rates in first 2 months

10

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

- Isoniazid
- Rifampin

11

mechanism of ISONIAZID (INH, Nydrazid)?

- inhibits biosynthesis of MYCOLIC ACID
- prodrug that required KatG

12

therapeutic use of Isoniazid (INH)?

- 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

13

pharmacokinetics of Isoniazid (INH)?

- 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

14

toxicities of Isoniazid (INH)?

- 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)

15

mechanisms Rifampin (Rimactane)?

- group of structurally similar complex macrocyclic antibiotics
- inhibits DNA DEPENDENT RNA POLYMERASE

15

mechanisms Rifampin (Rimactane)?

- group of structurally similar complex macrocyclic antibiotics
- inhibits DNA DEPENDENT RNA POLYMERASE

16

toxicities of Rifampin?

- 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

16

Rifampin use?

- 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

17

toxicities of Rifampin?

- 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

17

toxicities of Rifampin?

- 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

18

mechanisms Rifampin (Rimactane)?

- group of structurally similar complex macrocyclic antibiotics
- inhibits DNA DEPENDENT RNA POLYMERASE

19

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

20

toxicities of Rifampin?

- 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

21

for which group of individuals is Rifampin NOT recommended?

HIV treated individuals

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