Pharm: Drugs for Non-Bacterial Infections

life cycle of a virus

1. attachment of virus to host cell

2. release of the virus's genes into host cell

3. replication and assembly of new viral components

4. release of viral components into a new host cell

drugs used to treat AIDS are part of a regimen known as

highly active antiretroviral therapy (HAART)

what is the one major issue with the HAART drugs?

high degree of non-adherence to the drug regimen

drug combinations for HAART include 3 drugs from _____ different classes

2

if treatment for HAART is started from more than one class and therapy fails, what is the disadvantage?

cross-resistance to one or more of the remaining drugs in these classes of drugs is likely

most common combination of antiretrovirals

two NRTI paired with one of the following: NNRTI, PI, or II

what signs should point clinicians to suspect resistance to the ARV drugs?

tiredness

development of opportunistic infections

high plasma viremia

virus detection in sexual organs and secretions

how is HIV-induced immune system damage measured?

CD4 + T-cell counts

in what case would ART therapy be initiated in a person with HIV?

symptomatic disease, decreasing CD4 T-cell counts, and a high viral load

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

abacavir

emtricitabine

lamivudine

zidovudine

tenofovir

what is the MC NRTI?

lamivudine/zidovudine

NRTI adverse reactions

rash, abdominal pain, diarrhea, nausea, anorexia, hepatitis, lactic acidosis, back pain, myopathy, headache, dizziness, depression, dream disorder

what is an adverse reaction of tenofovir?

renal failure

abacavir adverse reactions

hepatomegaly, hypotension, hypersensitivity

Lamivudine adverse reactions

anemia, neutropenia

Tenofovir adverse reactions

decreased bone mineral density, hypercholesterolemia, renal failure

Zidovudine adverse reactions

anemia, leukopenia

before initiation NRTI therapy, all patients should be tested for

chronic Hep B

Protease Inhibitors (PI)

atazanavir

fosamprenavir

ritonavir

darunavir

Lopinavir

Lopinavir/Ritonavir

Protease inhibitors MOA

bind to an active site that inhibits the virus from processes viral precursors critical to the maturation of the HIV virus

PIs are metabolized in the liver by the

CYP450 system

Protease inhibitors (PI) adverse reactions

rash, SJS, diarrhea, nausea, vomiting, hyperlipidemia, thrombocytopenia, exacerbation of diabetes, lipodystrophy, headache

which PI is used as a booster?

Ritonavir

Protease inhibitors could cause serious life-threatening adverse events if taken with the following medications:

sedative hypnotics

triazolam

midazolam

antiarrhythmics

Protease inhibitors are pH dependent; therefore, which medications will decrease the absorption of PIs?

PPIs, H2 blockers, antacids

contraindication for PIs

concomitant use with drugs that are highly dependent on CYP34A for clearance

important patient education for PIs

GI intolerance is likely to occur

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

efavirenz

etravirine

rilpivirine

NNRTIs adverse reactions

skin rash, nausea, vomiting, diarrhea, increased liver enzymes, headache, fatigue, depression

Efavirenz adverse reaction

hypoesthesia

NNRTIs interactions

antihistamines

sedative hypnotics

antiarrhythmics

CCBs

amphetamines

skin rash associated with NNRTIs usually occur within the first 28 days of treatment; as a class, patients must be monitored for:

steven johnsons syndrome

when should Efavirenz be taken?

at bedtime

Integrase inhibitors

Raltegravir

Elvitegravir

Dolutegravir

Bictegravir

An appropriate HIV treatment regimen:

bictegravir/emtricitabine/tenofovir

Integrase inhibitors MOA

inhibits strand transfer step of HIV-1 DNA integration

integrase inhibitors adverse reactions

pruritus, hyperglycemia, diarrhea, abdominal pain, flatulence, vomiting, nausea, increase in LFTs, neutropenia, leukopenia, insomnia, suicidal ideation, depression

if a patient is using an II and taking antacids, the II should be taken

2 hours before antacid use or 6 hours after antacid use

CCR5 antagonist

Maraviroc

Maraviroc MOA

prevent HIV-1 from entering and infection immune cells by blocking CCR5 cell-surface receptor

fusion inhibitor (FI)

enfuvirtide

treatment for viral herpes is most effective when initiated within ______ hours after rash onset

72

antivirals for treating viral herpes

acyclovir, ganciclovir, valacyclovir

which antiviral for herpes is used topically?

penciclovir

Antivirals for herpes adverse reactions

rash, urticaria, nausea, diarrhea, headache, malaise, increase in SCr

be cautious with antivirals in patients who have

renal impairment

antivirals for treating influenza

Oseltamivir (Tamiflu)

rimantadine

zanamivir

Baloxavir

which antiviral is only effective in the treatment of Flu A?

amantadine

antivirals for influenza general adverse reaction

blurred vision, dry mouth

amantadine adverse reactions

hypotension, syncope, insomnia, delusion, anxiety, hallucinations, paranoia

Oseltamivir (Tamiflu) adverse reactions

steven-johnson syndrome, toxic epidermal necrosis

Amantadine should not be used in

pregnancy

antivirals for influenza have been shown to shorten the virus by _______ when the virus is not resistant

1-2 days

to avoid insomnia, patients should be instructed to take the antiviral

4 hours before bedtime

Antifungals classes include:

polyene macrolides

the azoles

Terbinafine

Griseofulvin

Polyene macrolides:

amphotericin B and Nystatin

Polyene macrolides MOA

binds to sterol in the fungal cell membrane (ergosterol), altering cell permeability and allowing intracellular components to leak out

clinical uses of Amphotericin B

cryptococcal meningitis in HIV patients

invasive and rapidly progressing fungal infections

visceral leishmaniasis (black fever)

nystatin clinical uses

topical fungal infections such as oral candidiasis, vaginal infections, GI and cutaneous fungal infections

Amphotericin B adverse reactions

hypotension, arrhythmias, low electrolytes, hyperglycemia, nephrotoxicity, anemia, leukopenia, thrombocytopenia, anaphylaxis, hypoxia

what combination can be used to decrease inflammation and itching associated with topical fungal infections?

nystatin + triamcinolone

______ when giving any amphotericin B formulation is common

infusion reaction

what do you need to monitor when administering amphotericin B?

CBC, renal function, electrolytes, liver function tests, as well as total dosage

the azoles:

Fluconazole

Ketoconazole

Itraconazole

clinical uses of the azoles

superficial infections by yeast

dermatophytes

invasive systemic mycoses

what topical forms are used for treatment of tinea infections?

miconazole and clotrimazole

the azoles adverse reactions

QT prolongation, GI upset, hepatotoxicity

black box warning for the azoles

hepatotoxicity

QT prolongation

Itraconazole black box warning

congestive heart failure

the azoles have many ________, so it is important to always consult a drug reference when prescribing these drugs

drug interactions

all of the azoles are metabolized by the

cytochrome P450 enzyme system

what do you need to do before prescribing any of the azoles?

liver function tests

Terbinafine is mainly used clinically for

fungal nail infections

Terbinafine adverse reactions

itching, rash, vision color changes, hepatotoxicity, cough

Griseofulvin MOA

binds to microtubules and inhibits fungal mitosis

Griseofulvin adverse reactions

photosensitivity, GI bleed, sore throat, leukopenia, granulocytopenia, mental confusion, hepatotoxicity, proteinuria, nephrosis, rash

griseofulvin interactions

oral contraceptives- increases chance of menstrual irregularities and possible pregnancy

reduces effect of warfarin

increase effects of alcohol

Griseofulvin is pregnancy category X and has resulted in cases of

conjoined twins

antiprotozoals

Metronidazole

Tinidazole

Nitazoxanide

metronidazole clinical uses

bacterial vaginosis

anaerobic infections

Nitazoxanide clinical uses

tx of diarrhea associated with Giardia and cryptosporidium, especially in children

metronidazole is often used with a _______ as a perioperative prophylactic agent in colorectal surgery

cephalosporin

antiprotozoals adverse reactions

nausea, unpleasant taste, reddish-brown or darkened urine, disulfram-like reaction

antiprotozoals contraindications

first trimester of pregnancy

lactating women

Antimalarials

end in -quine

+ quinidine and quinine

main antimalarial used

chloroquine

what medication can be used for cardioversion of atrial fibrillation/flutter to normal sinus rhythm

quinidine

quinidine overdose can lead to severe

cinchonism (manifests as headache, intestinal cramps, etc)

what antiprotozoal is used for liver involvement and post-exposure prevention for relapsing malaria?

primaquine

antimalarials adverse reactions

arrhythmias, QT prolongation, visual disturbances, abnormal dreams

if a patient needs to take a beta blocker or CCB and is on antimalarials, the patient should space the dosing by at least

12 hours after antimalarial drug

contraindications of antimalarials

history of seizures, psych disorders, cardiac abnormalities

which antimalarial is contraindicated in pregnancy?

primaquine

what 2 medications are usually appropriate for majority of helminthic infections?

mebendazole or albendazole

antihelminthics:

benzimidazoles

pyrantel pamoate

ivermectin

Benzimidazoles

Albendazole

Mebendazole

Thiabendazole

Benzimidazoles are typically used to treat

pinworm

mebendazole MOA

inhibits microtubule synthesis

Thiabendazole MOA

suppresses production of eggs and larva

Albendazole MOA

inhibits tubulin polymerization