Test 3: Wk11: 5 Anti- Tuberculosis Drugs - Allman Flashcards
(145 cards)
1
Q
can pts with latent TB spread TB to others
A
no
2
Q
MDR TB
A
resistant to at least INH and RIF
3
Q
pts with resistance to Rifampin alone
A
better prognosis than MDR strains however at increased risk of tx failure/ addition resistance
4
Q
XDR TB
A
extensive drug resistance
Resistant to INF and RIF plus FQN and at least one of the three injectable drugs
5
Q
Life cycle of TB
A
- Active M tuberculosis
- Macrophage
- Walled off by macrophage
- Leukocytes
- Granuloma
- Active M tuberculosis
6
Q
Prolonged treatment is required for successful eradication
A
Typically 6 months for routine Pulmonary TB Tx
7
Q
TB Pericarditis and Meningitis
A
Initial adjunctive corticosteroid therapy with dexamethasone should be given for 6 weeks for ptns with TB Meningitis
Initial adjunctive corticosteroid therapy should not be routinely used; reserved for only selected ptns
8
Q
ART CD4 <50/mm3
A
Start ART within first 2 weeks of TB treatment
9
Q
CD4 >50/mm3
A
Start ART by 8-12 weeks of TB treatment
10
Q
TB meningitis tx
A
TB meningitis = Do NOT start before 8 10 weeks of TB treatment
11
Q
pts w/ HIV and TB have increased risk of
A
developing paradoxical worsening of sx and clinical manifestations of TB
12
Q
Immune Reconstitution Inflammatory Syndrome IRIS
A
in HIV pts rxns develop as a consequence of reconstitution of immune responsiveness brought on by ART
13
Q
Signs of IRIS may include (7)
A
High fevers
Worsening respiratory symptoms
Increase in size and inflammation of involved lymph nodes, new lymphadenopathy,
Expanding central nervous system (CNS) lesions,
Worsening of pulmonary parenchymal infiltrations
New or increasing pleural effusions
Development of intra abdominal or retroperitoneal abscesses
14
Q
Starting ART within 2 weeks after starting tuberculosis therapy have higher
rates of — than those who start between 8 12 weeks
A
IRIS
15
Q
does development of IRIS worsen treatment outcomes for either TB or HIV infection
A
no
16
Q
IRIS may cause
A
severe or fatal neurological complications
17
Q
Intensive Phase of TB tx
A
2 months (knocking down the volume)
18
Q
Continuation Phase of TB tx
A
4 months (de escalate)
19
Q
Dosing Guidelines
A
Daily dosing
Twice or Thrice weekly dosing
20
Q
TB therapy requires
A
Requires Directly Observed Therapy (DOT)
21
Q
4 first line agents for TB
A
isoniazid
Ethambutol
Pyrazinamide
Rifampin
22
Q
Isoniazid function
A
inhibits cell wall synthesis
23
Q
Ethambutol function
A
inhibits cell wall synthesis
24
Q
Pyrazinamide function
A
direct target unclear
disrupts plasma membrane
disrupts energy metabolism
25
Rifampin function
inhibits RNA synthesis
26
3 Major Rifamycins
Rifampin
Rifabutin
Rifapentine
27
Rifampin
| Mechanism of Action
inhibits DNA dependent RNA pol - suppression of initiation of chain formation in RNA Synthesis
28
Rifampin bactericidal function
Bactericidal: kills slow growing mycobacteria present within
| macrophages and in caseating granulomas
29
Rifampin is active against
Active against some gram positive and gram negative bacteria.
(Reserved for TB, except in very rare
30
Rifampin Combination therapy with
INH
31
Rifampin Distribution
Widely distributed; excellent tissue distribution
CNS, tuberculosis abscesses, and intracellular sites
32
Rifampin Metabolism
Primarily metabolized by deacetylation
Autoinduction of metabolism occurs
Maximal induction at ~ 6 doses, whether given daily or twice weekly
33
Rifampin
| Adverse Effects
Transient elevation in serum transaminases
Hepatotoxicity (rare)
GI upset (frequent)
Hypersensitivity (rare)
Discoloration of bodily fluids
34
what drug causes orange discoloration of sweat tears and urine
Rifampin
35
Rifampin Hepatotoxicity
Risk factors: alcoholics with preexisting liver disease.
Augmented when combined with INH
36
Rifampin
| Hypersensitivity (rare)
Flushing, fever, pruritus
Systemic flu like syndrome
Thrombocytopenia
37
Rifampin
| Drug Interactions
Proliferation of the smooth endoplasmic reticulum in
hepatocytes
Results in an increase in cytochrome p 450 (CP450) activity.
38
Rifampin increases metabolism of
P450
Warfarin
Theophylline
Narcotics
Oral Hypoglycemics
Steroids (oral contraceptives)
39
Rifampin
| Place in Therapy
Treatment of active TB
2nd line agent for preventative therapy
40
Rifamycin derivative.
Rifabutin (Mycobutin)
41
when is rifabutin used
when pts are receiving meds with unacceptable interactions with Rifampin or had intolerance to rifampin
42
More active than rifampin against Mycobacterium avium
| complex
Rifabutin (Mycobutin)
43
Rifabutin is used in the tx of
More active than rifampin against Mycobacterium avium
| complex (MAC)
44
Rifabutin ADRs (7)
```
Rash
GI
Arthralgias
Myalgias
Discoloration of urine/sweat/ and tears
neutropenia
hepatoxicity
```
45
Used once weekly with INH in the continuation phase of
| SPECIFIED treatment of TB
Rifapentine (Priftin)
46
Ptn must be HIV negative to use
Rifapentine (Priftin®)
47
pt must have --- to take Rifapentine
Non cavitary , drug susceptible pulmonary tuberculosis who have
negative sputum smears at completion of the initial phase of treatment
48
advantage of Rifapentine
Once weekly
49
Rifapentine ADRs
similar to RIfampin
50
Isoniazid (INH)
| Mechanism of Action
Inhibits synthesis of mycolic acid
Important constituent of mycobacterial cell walls
51
--- Actively transported into bacterium
INH
52
INH kills actively growing organisms in
the extracellular environment
53
INH inhibits
growth of formant organisms within macrophages preventing granulomas
54
INH metabolism
Primarily acetylation
55
INH important metabolite
Monoacetyl hydrazine
56
Monoacetyl hydrazine excreted
in urine or further acetylated to diacyl form or hydroxylated to electrophile intermediated
57
--- is responsible for hepatotoxic effects with INH
electrophile intermediated
58
Rates of acetylation of INH & mono acetyl hydrazine dependent on
Dependent on an individual’s phenotypic classification
59
IMH classifications
slow or rapid acetylator
60
Slow acetylators of INH may lead to
higher blood concentrations
61
Caucasians acylation of INH
equally divided fast and slow
62
Eskimos and Japanese acylation of INH
rapid
63
Egyptians acylation of INH
slow
64
INH half life in rapid acetylators
1-2 hrs
65
INH half life in slow acetylators
2-5 hrs
66
INH serum transaminase
transient elevation ~15% within first 8-12 wks of therapy
67
INH hepatotoxicity risk factors
age, liver dz,
4-8 wks of tx use rifampin
68
INH neurotoxicity
alcoholics, children, malnourished, slow acetylators
69
prevent neurotoxicity if INH
Pyridoxine (Vitamin B6)
70
hypersensitivity in INH
rare
71
Isoniazid
| Place in Therapy
Treatment of active TB
72
Preventative therapy for patients with (+) PPD
INH
73
Pyrazinamide (PZA)
| Mechanism of Action
not well documented
74
PZA bactericidal toward
dormant organisms residing in the acidic
| environment within macrophages
75
PZA metabolism
Hydrolyzed in liver to active pyrazinoic acid
76
PZA elimination
5 hydroxypyrazinoic acid ( hydroxylated pyrazinoic acid) is excreted by the kidneys.
77
PZA t 1/2
9-10hrs
78
PZA ADEs
Hepatotoxicity
hyperuricemia
GI
Hypersensitivity
79
hepatotoxicity PZA
more frequent with high dose
baseline hepatic function should be obtained
monitor for hepatitis
80
PZA hyperuricemia
decreased renal excretion of uric acid
Pyrazinoc acid competes with uric acid for elimination
81
PZA hypersensitivity
photosensitivity and rash
82
Ethambutol (ETH, EMB, Myambutol) MOA
not documents
Bacteriostatic
83
ETH pharmacokinetics
60-80% of parent compound + inactive metabolite excreted in urine
84
Ethambutol
| Adverse Effects
Optic neuritis (Retrobulbar neuritis)
85
Optic neuritis ( Retrobulbar neuritis)
Decreased visual acuity and red green color blindness.
86
Optic neuritis ( Retrobulbar neuritis) reversibility
usually reversible , tim dependent with degree of impairment
87
Drug that causes eye damage
Ethambutol
88
Streptomycin MOA
aminoglycoside antibiotic
89
Streptomycin bactericidal through
inhibition of protein synthesis
90
Streptomycin inactive against
intracellular organisms; limiting activity to suppression
91
Streptomycin is used as an alternative for
Ethambutol
92
Streptomycin absorption
poor in GI
| administer IM or IV
93
Streptomycin ADEs
nephrotoxicity
impairment of 8th cranial nerve
pain at injection site/ abscess formation
94
TB drug combo Rifamate
Rifampin and Isoniazid
95
TB drug Combo Rifater
Rifampin, Isoniazid, Pyrazinamide
96
Bedaquiline MOA
inhibits mycobacterial ATP synthetase
97
Bedaquiline safety concerns
QT prolongation
| increased death potential
98
--- used for MDR only
Bedaquiline
99
6 2nd line agents
1. Para-Aminosalicylate
2. Ethionamide
3. Cycloserine
4. Capreomycin
5. Kanamycin
6. Amikacin
100
--- most widely used as anti-leprosy agent
Clofazimine (Lamprene)
101
Clofazimine ADRs
GI
Severe life threatening abdominal pain and organ damage
discoloration of skin and eyes
102
what causes organ damage with Clofazimine
crystal deposition
103
2 Macrolides
Clarithromycin and Azithromycin
104
Macrolides effectivity against TB
unlikely
105
Macrolides should be used in combination with other agents for --- tx
MAC - Mycobacterium Avium Complex
106
BCG Vaccine
attenuated hybridized strain of M bovis
107
BCG Vaccine against TB
does not appear to be effective
108
BCG Vaccine should be avoided in
Pregnant and HIV
109
BCG Vaccine side effects
prolonged ulceration at vaccine site
lymphadenitis and lupus vulgaris
110
WHO recommendations of BCG Vaccine
High risk TB and HIV+ infants with no sx
111
TB Regimens
RIPE or RIPS
112
RIPE
Rifampin
Isoniazid
Pyrazinamide
Ethambutol
113
RIPS
Rifampin
Isoniazid
Pyrazinamide
Streptomycin
114
RIPE / RIPS tx
6mos for general TB tx
115
Osteo/miliary/meningitis regimen
12-24 mos
116
Concomitant Illnesses (HIV, Hepatitis) Regimen
Treat concomitant disease states
117
Renal failure TB regimen
Avoid Streptomycin, Kanamycin, and Capreomycin
118
Children TB regimen
Avoid Ethambutol if proper assessment is not feasible
119
TB Suspected Treatment Failure
Lack of clinical progression 6 8 weeks into therapy
Add 2 new TB agents when failure suspected
Evaluate for non adherence or drug resistance
120
Leprosy Causative agent
Mycobacterium leprae (Leprosy)
121
2 major groups of Leprosy
Lepromatous widespread
Tuberculoid localized
122
can leprosy be cultured in vitro
no
123
Lepromatous Leprosy
disseminated , multibacillary , with loss of specific cell mediated immunity
124
Tuberculoid Leprosy
localized, paucibacillary , with strong cell mediated immunity)
Paucibacillary = having or made up of few
125
Leprosy transmission requires
prolonged contact and occurs directly through intact
| skin, mucous membranes, or penetrating wounds.
126
Leprosy infection leads to
Lesions
Hypopigmentation
Loss of sensation (anesthesia)
127
Leprosy dx
Based on acid fast stain and cytologic examination of affected skin and response to the lepromin skin test
128
Leprosy multidrug therapy (3 drugs)
Dapsone / Rifampin/ Clofazimine
129
how long does leprosy tx last
3-5 years
130
Dapsone MOA
competitive inhibitor of folic acid synthesis
Competitive inhibition of dihydropteroate synthase which prevents
bacterial utilization of para aminobenzoic acid
131
Dapsone is a
bacteriostatic
132
Dapsone is absorbed
rapidly and completely from the GI tract
133
Dapsone ADRs
Hypersensitivity reaction
| Fever, Malaise, Dermatitis, Jaundice
134
Dapsone hypersensitivity
sulfone syndrome
135
Dapsone Sulfone Syndrome sx occur
1-4 wks into therapy
136
Mycobacterium Avium Complex (MAC) sx
fever, night sweats, wt loss, anemia
137
MAC stands for
Mycobacterium Avium Complex
138
MAC usually occurs in
Advanced HIV pts
139
MAC tx
combination therapy
140
MAC preferred tx
Clarithromycin
Ethambutol
141
Rifampin
GI Upset, Drug Drug Interactions, Orange discoloration, Hepatotoxicity
142
Isoniazid
Neurotoxicity, Peripheral Neuropathy, Hepatotoxicity
143
PZA
GI Upset, Hyperuricemia , Hepatotoxicity
144
Ethambutol
Optic Neuritis, Children
145
Streptomycin
Neurotoxicity (8 th cranial nerve Vertigo ), Nephrotoxicity potential
