Antimicrobials - antifungals/ anthelmintic Flashcards
1
Q
Polyenes include
A
Amphotericin B
Nystatin
2
Q
Echinocandins include
A
Caspofungin
3
Q
Azoles include
A
Clotrimazole
Ketoconazole
Fluconazole
itraconazole
posaconazole
voriconazole
4
Q
Allylamines include
A
terbinafine
5
Q
MOA of amphotericin B
A
IV - disrupts the fungal cell wall synthesis binding to sterols, leading to the formation of pores in the cell membrane, causing K+ to leak out of cell resulting in cell death
6
Q
What is Amphotericin B used to treat
A
severe invasive fungal infections - systemic
wide spectrum - widest of all antifungals
last resort - hard for people to tolerate
7
Q
Amphotericin B onset of action?
A
rapid; not dependent on organisms growth rate
8
Q
Amphotericin B kidney affects
A
nephrotoxicity - vasoconstrictive effect on the afferent renal arterioles, GFR usually returns to normal after cessation of medication
renal tubular acidosis
9
Q
Amphotericin B adverse reactions
A
fever and rigors
premedicate with acetaminophen and/or diphenhydramine recommended
N/V
anemia
phlebitis
10
Q
Flucytosine (5-FC) MOA
A
inhibits thymidylate synthesis and incorporates into fungal RNA disrupting nucleic acid and protein synthesis
Resistance can occur when fungi decrease level of enzymes targeted
11
Q
Flucytosine is not used as
A
monotherapy; used in combo with amphotericin B or itraconazole
12
Q
Flucytosine and Amphotericin B are used together for treatment in
A
systemic mycoses and meningitis caused by cryptococcus and candida spp.
13
Q
Flucytosine and itraconazole are used together for treatment in
A
chromoblastomycosis infections
14
Q
when using flucytosine you need to _____ adjust in _____ impairment
A
dose , renal
15
Q
flucytosine adverse reactions
A
reversible neutropenia, thrombocytopenia (lab draws everyday)
dose related bone marrow suppression
reversible hepatic dysfunction
GI upset, N/V, diarrhea - m/c
16
Q
The azoles are broken up into two different subgroups
A
imidazoles
triazoles
17
Q
drugs included in the imidazole group
A
ketoconazole
miconazole
clotrimazole
more potent, usually topical, too toxic to be used systemically
18
Q
drugs included in the triazoles group
A
fluconazole
itraconazole
voriconazole
posaconazole
less potent, usually IV, more systemic sx
19
Q
the imidazoles MOA
A
inhibit C-14 alpha-demethylase (CYP450) which disrupts membrane structure
20
Q
miconazole and clotrimazole are both ______ to be used _____
A
too toxic
systemically
21
Q
Ketoconazole can be used _____
A
systemically
22
Q
Ketoconazole should not be used with
A
Amphotericin B
23
Q
Ketoconazole requires _________ for dissolution and absorption
A
gastric acid
24
Q
Antacids and H2 histamine receptor blockers or PPI’s impair absorption of
A
ketoconazole
25
Ketoconazole adverse reactions
CYP450
gynecomastia, decreased libido, menstrual irregularities
26
Contraindications of ketoconazole
pregancy
27
the triazoles MOA
inhibits synthesis of cell membrane via the fungal CYP450, however does not interfere with the mammalian CYP450 enzymes involved in other steroid hormones - no endocrine side effects
28
Fluconazole indications
candida, cryptococcus neoformans, coccidiomycosis
29
Fluconazole does not depend on _______ for absorption
gastric acid
30
Fluconazole does penetrate the
CSF
31
Adverse reactions of fluconazole
N/V, rashes, alopecia, hepatitis
32
Contraindications Fluconazole
pregnancy - teratogenic
33
Itraconazole indications
histoplasmosis, blastomycosis and sporotrichosis
34
Itraconazole does require
gastric acid for absorption, no IV formulation
35
Itraconazole does not
penetrate CSF well
36
adverse reactions itraconazole
N/V, rash, HA, HTN, hypokalemia, edema, chronic therapy can cause alopecia, rarely hepatitis
37
Itraconazole drug-drug interactions
warfarin, statins, phenytoin
38
Contraindications itraconazole
teratogenic
39
Black box warning itraconazole
do not use for onychomycosis in pts with evidence of CHF or history of CHF
40
Caspofungin MOA
inhibits B(1,3)-D-glucan synthase, an enzyme involved in fungal cell wall synthesis
41
Caspofungin indication
invasive aspergillus infection (2nd line)
candidal infections
azole resistant Candida esophagitis
42
Caspofungin adverse drug reactions
histamine reaction with infusion
drug-drug interactions (cyclosporine, tacrolimus, rifampin)
CNS penetration is poor
43
Nystatin MOA
binds to ergosterol; similar mechanism to amphotericin B
too toxic for systemic use - never IV
44
Nystatin is not absorbed in
the GI tract
45
Nystatin is available in
powder, ointment, cream or suspension
46
Drug that is excellent for swish and spit or swish and swallow
topical use for skin and/or vaginal infections
Nystatin
47
Griseofulvin MOA
inhibits mitosis - accumulates in keratin containing tissues
48
Griseofulvin indications
dermatophytic nail infections
49
Griseofulvin treatment is required for how long
6-12 months
50
Griseofulvin should be avoided with
alcohol
increases rate of metabolism of other drugs including anticoagulants
CYP450 enzymes
51
Terbinafine MOA
inhibits cell wall synthesis by inhibiting fungal squalene epoxidase - decreases synthesis of ergosterol
accumulates in skin, nails and fat
52
Terbinafine contraindicated
nursing mothers - accumulates in breast milk
53
Terbinafine adverse reactions
hepatotoxicity - LFTs at baseline
54
antiprotozoal drugs include
trimethoprim - sulfamethoxazole
metronidazole
55
antihelmintic drugs include
albendazole
pyrantel pamoate
ivermectin
praziquantel
56
Metronidazole MOA
activated by anaerobes to metabolites that damage DNA leading to cell death
57
Metronidazole indications
amebiasis
giardiasis
trichomoniasis
(anaerobic bacterial infections)
58
Metronidazole adverse reactions
GI upset
metallic taste
seizures
neuropathy
?disulfiram effect with alcohol (sudden desire to vomit)
59
Metronidazole contraindications
pregnancy
breastfeeding
recent use of disulfiram
60
trimethoprim - sulfamethoxazole MOA
synergistic blockade of folate pathway, leads to inhibition of thymidine synthesis
61
trimethoprim - sulfamethoxazole avoid in pts with
renal disease
62
trimethoprim - sulfamethoxazole contraindications
newborns and pregnancy
63
trimethoprim - sulfamethoxazole adverse effects
rash
SJS
bone marrow suppression
anemia
renal impairment
hepatotoxicity
64
Ascaris lumbrioides (nematodes) treatment
albendazole
65
Trichuris trichuria (nematodes) treatment
albendazole
66
Enterobius vermicularis (nematodes) treatment
albendazole
67
Necator americanus (nematodes) treatment
albendazole
68
Strongyloides stercoralis (nematodes) treatment
ivermectin
albendazole - 2nd line
69
Onchocerca volvulus (nematodes) treatment
ivermectin
70
cestodes (tapeworms) treatment
taenia solium (pork)
taenia saginata (beef)
praziquantel
71
trematodes (flukes) treatment
schistosoma ssp
clonorchis sinensis
praziquantel
72
albendazole MOA
binds to the microtubules in intestinal and tegmental worms and larvae; impaired glucose uptake --> glycogen depletion --> degeneration of ER and mitochondria, release of lysosomes, and depletion of ATP/ energy causing worm death
73
albendazole adverse reactions
HA
elevated LFTs
rare = GI
alopecia
rare = liver failure, myelosuppression, seizures
74
albendazole contraindications
pregn
75
Pyrantel Pamoate (OTC) MOA
causes release of acetylcholine and inhibits cholinesterase - acts as a neuromuscular blocker, spastic paralysis, release of the helminths
76
Pyrantel Pamoate adverse reactions
rare HA, dizziness, GI distress
77
Praziquantel MOA
increases cell permeability to Ca2+ in schistosomes --> strong contractions and paralysis of worm musculature which leads to detachment, dislodgement and death
78
Praziquantel adverse reactions
abdominal pain, dizziness, drowsiness
79
Ivermectin MOA
binds and activates glutamate - gated chloride channels in invertebrate nerve and muscle cells --> hyperpolarization and death of helminth
does not cross BBB
80
Ivermectin adverse reactions
nephrotoxicity (CNS depression, ataxia)
81
Ivermectin contraindications
preg, meningitis
82
Neuraminidase inhibitors include:
oseltamivir
83
MOA oseltamivir
inhibitors of neuraminidase (enzyme that is essential for cleaving the virus from the host cell and allowing spreading of the virus from cell to cell)
84
Anti-influenza agents - neuraminidase inhibitors
oseltamivir (PO) - active against flu A and B
85
How to administer Oseltamivir for flu
24-48 hrs on sx onset to decrease course of disease by 1-2 days
decreases viral load
also used for prophylaxis
86
How is oseltamivir metabolized and where
active orally as a prodrug and hydrolyzed by the liver to its active form
87
Oseltamivir needs to be dose adjusted for
renal impairment
88
SE of oseltamivir
N/V
recommended to take with food to minimize
89
Antivirals against Herpes virus
acyclovir and derivatives
foscarnet
90
MOA Acyclovir
Guanosine analogs, inhibits transcription
Activated by viral thymidine kinase (TK) - activated in infected cells
AcyclcoGTP inhibits viral DNA polymerase by chain termination
91
Acyclovir spectrum of activity
herpes simplex 1 & 2 viruses (not effective against latent virus)
varicella-zoster virus
92
Acyclovir metabolism
renal metabolism
93
Acyclovir dose adjustment for
renal impairment
94
Acyclovir adverse effects
well tolerated
mild GI upset
nephrotoxicity and neurotoxicity
95
To overcome poor bioavailability of Acyclovir, _______ was developed
valacyclovir
96
Acyclovir has poor ________ and requires ________ dosing
Bioavailability
frequent
97
Valacyclovir is a
prodrug
98
How is Valacyclovir metabolized
hydrolyzed by first pass enzymes in the intestine and liver (99% conversion rate to acyclovir)
99
Valacyclovir is more ______ than Acyclovir
expensive
100
Valacyclovir has the same SE as Acyclovir but _____ is more common
HA
101
Famciclovir overcomes ________ of penciclovir
poor bioavailability
102
How is Famciclovir metabolized
metabolized to penciclovir which requires phosphorylation by viral thymindine kinase in infected cells to become active
103
Famciclovir MOA
selectively inhibits viral DNA polymerase by chain termination
104
Herpes Agent Foscarnet MOA
directly inhibits DNA polymerase (does NOT require activation by viral kinase)
reversibly blocks the pyrophosphate binding site of viral DNA polymerase
105
Foscarnet is a inorganic
pyrophosphate analog
106
Foscarnet is used for treatment
of immunocompromised patients with cytomegalovirus (CMV) retinitis and mucocutaneous acyclovir-resistant HSV and VZN infections
107
IV acyclovir can
crystalize in the renal tubules causing renal dysfunction (obstructive crystalline nephropathy)
108
Foscarnet is only given in ____ form
IV
109
Foscarnet toxicity
requires dose adjustment in renal impairment
GI effects
electrolyte abnormalities (arrhythmias)
nephrotoxicity - reversible, worse when combined with other nephrotoxic agents
110
Hep B treatment
entecavir
tenofovir
lamivudine
111
Hep C treatment
Ribavirin
Ledipasvir
Sofosbuvir
112
Interferons MOA
IFNalpha2b and alpha2a: host cytokines with complex antiviral, immunomodulatory and antiproliferative activities
113
Interferons are thought to
induce gene transcription that inhibit viral RNA, increases phagocytic activity of macrophages, increase cytotoxicity of lymphocytes for target cell's
114
Interferons are given by
IV or subQ - no PO
115
Interferons may be treatment for
HBV and HCB as combination - rarely first line
116
Adverse effects of interferons
flu like sx shortly after administration
mood disorders, somnolence, confusion, wt loss, depression, seizures, autoimmune rxn... many more
117
Interferons need to be dose adjusted in
severe renal disease
118
Goal of HBV antiviral therapy
suppression of HBV DNA levels
decrease risk of liver damage
seroconversion of HBeAg+ to HBeAg-
loss of HBsAg detection
119
Chronic Hepatitis B viral infection treatment
lamivudine
entecavir
tenofovir
120
lamivudine MOA
cytosine analog works to inhibit viral DNA synthesis by inhibiting HBV DNA polymerase
121
lamivudine has good ______ absorption
PO
122
lamivudine needs to be dose adjusted for
renal impairment (if CrCl < 50)
123
Adverse effects of lamivudine
well tolerated
HA
dizziness
may cause pancreatitis
124
rare SE's of Lamivudine, Entecavir and Tenofovir
lactic acidosis
severe hepatomegaly
125
Entecavir MOA
phosphorylated to guanosine triphosphate and competes as substrate for HBV DNV polymerase thereby inhibiting the enzyme
126
Entecavir is not preferred for
lamivudine resistant strains - tenofovir is preferred
127
Entecavir is not recommended for use in
HIV-HBV co-infection without a fully suppressive anti-HIV regimen as it may select resistance to lamivudine
128
Adverse effects of Entecavir
increase ALT levels, mild GI upset, mild hyperglycemia, HA
129
Tenofovir MOA
inhibits replication of HBV by inhibiting HBV DNA polymerase (also works against HIV reverse transcriptase)
130
Tenofovir may be used
in pts who have had prior treatment or develop drug resistance - preferred if lamivudine resistance
131
Tenofovir needs to be dose adjusted for
renal impairment
132
Tenofovir adverse effects
GI effects, rash, hypercholesterolemia, decreased bone mineral density
133
Black box warning post treatment of Tenofovir
post treatment exacerbation of hepatitis
monitor hepatic function closely for at least several months in pts who discontinue anti-hep B therapy
134
Ribavirin MOA
inhibits guanine nucleotide synthesis thereby inhibiting viral transcription and RNA replication
135
Ribavirin is used in treatment for
hep C (PO) in combination with interferon
severe pediatric RSV infections
136
Serious adverse effect of Ribavirin
hemolytic anemia
137
Ledipasvir MOA
inhibits NS5A protein which plays a role in both viral replication and the assembly of the hep C virus
138
Ledipasvir is administered
PO in combination with other direct acting antivirals
139
What can decrease the absorption of Ledipasvir
increased gastric pH levels
140
Ledipasvir adverse reactions
well tolerated
$$$
141
Sofosbuvir MOA
inhibits NS5B protein which plays a role in both viral replication and assembly of the hepatitis C virus
142
Sofosbuvir administered
PO in combination formulation
143
Sofosbuvir can not be coadministered with
Amiodarone - reports of sx bradycardia and a fatal cardiac arrest
144
Ledipasvir-Sofosbuvir should be avoided in pts with
renal impairment
145
Ledipasvir-Sofosbuvir should not be coadministered with
amiodarone
