Pharm 9-12

mhewett's version from 2016-06-28 17:38

Chapter 9 Antiviral Drugs (4-3)

Question Answer
Amantadineimpairs uncoating of the virus by binding to influenza A's M2 matrix protein; must be used within 48 hours of symptom onset.
Interferoninhibits viral RNA translation and induces MHC1 expression, increasing macrophage sensitivity towards and ability to eradicate virally infected cells. SE include flue like sx and debilitating neuropsych problems. DOC in monotherapy for chronic HBV or acute HCV
Ribavirinmimics GTP and gets involved with transcription process, blocking viral mRNA synthesis. DOC combo for chronic HCV is ribavirin + sofobuvir (+ interferon alternitavely)
Acyclovirmimics GTP causing DNA synthesis inhibition. Selective for herpesviridae family that contains viral thymidine kinase (HSV1, HSV2, VZV, EBV --> NOT CMV!!) Penetrates BBB. DOC for HSV1,2. Valacyclovir is similar but longer T1/2.
GanciclovirMoA is like acyclovir but does NOT need viral thymidine kinase. DOC for CMV retinitis. SE bone marrow suppression --> neutropenia or aplastic anemia.
AZT (zidovudine)An NRTI - all become converted to nucleotides and all inhibit viral DNA synthesis. Has good BBB penetration. Treats HIV.
Protease Inhibitorsinhibits cleavage of "giant" protein HIV cuts apart to have functional components. They are antiretroviral drugs used for HIV. (saquinavir, ritonavir, indinavir, nelfinavir, fosamprenavir)
NNRTIsdirectly inhibits reverse transcriptase; used for HIV. (nevirapine, delavirdine, efavirenz)
Fusion InhibitorsBinds to gp41 to prevent viral fusion between the HIV virion and the cell's membrane. Increases risk for bacterial pneumonia. SE insomnia, HA, nausea. Growing resistance. (enfuvirtide)
Integrase Inhibitorsinhibits HIV viral integrase enzyme preventing integration and insertion of HIV DNA into human DNA.
Chemokine co-receptor antagonists (CCR5 Antagonists)blocks the CCR5 co receptor on WBCs targeted by HIV thus preventing entry of virus into cell. Used in HIV1 that has MDR or in tx-naive pts. (maraviroc) - extremely hepatotoxic
Neuraminidase InhibitorsTx of influenza A and B. Inhibits influenza virus neuraminidase. Used for prophylaxis of close conteacts and can cause diarrhea, nausea, and neuropsychiatric events. (zanamivir, oseltamivir)
FoscarnetInhibits DNA polymerase and reverse transcriptase. Alternative to ganciclovir in tx of CMV. Tx of acyclovir-resistant HSV. Effective against HIV (not part of HIV HAART). Nephrotoxic.
Valganciclovirused in combo w/ ganciclovir for CMV retinitis. Causes myelosuppresion
Trifluridineaka trifluorothymidine. Inhibits viral DNA synthesis. It does not require viral thymidine kinase so active against HSV. DOC for herpes keratitis.
CidofovirDOC for smallpox and severe adenovirus infections. Can also be used for CMV retinitis. Extremely nephrotoxic and can cause Fanconi syndrome. Teratogenic.
SofosbuvirUsed in combo with ribavirin as DOC for chronic Hep C. Leads to 90% cure rate. Inhibits RNA polymerase.

Chapter 10 Antifungal Drugs (5-3)

Question Answer
What is the MOA of imidazoles?interacts with fungal p450, blocking demethylation of lanosterol to ergosterol (necessary in healthy fungal cell membranes)
FluconazoleDOC for most fungal infections; DOC for thrush (candidiasis), non-disseminated coccidioidomycosis, cryptococcal infections
MiconazoleDOC vaginal candidiasis; topical
Clotrimazoletopical; oropharyngeal candidiasis
Itraconazolebroad spec; for resistant/severe/life-threatening systemic fungal infections; DOC for blastomycosis, histoplasmosis, cutaneous sporotrichosis
Posaconazolealt for mucormycosis
VoriconazoleDOC for aspergillus, Scedosporium apiospermum; can cause severe skin rxns, photosensitivity, ehpatotoxicity, commonly visual change; caution w/ OCPs
Ketoconazole is DOC fortinea versicolor
Amphotericin B MOA & DOCMOA - binds to ergosterol --> forms pore --> severe electrolyte imbalances --> fungal death; crosses placenta; nephrotoxic
DOC for disseminated coccidioidomycosis, mucormycoses, fusarioses; combo DOC for cryptococcal meningitis (with flucytosine)
Nystatintopical; vaginal candidiasis in HIV +
GriseofulvinMOA - interacts with microtubules to disrupt mitotic spindles; accumulates in keratin; alt for tinea
5-flucytosine (5FC) MOAMOA - nucleoside analog inhibiting DNA synthesis; combo DOC for cryptococcal meningitis (w/ amphotericin); can cause bone marrow suppression
TerbinafineDOC - onychomycosis, tinea capitis
MOA - inhibits squalene epoxidase (needed for ergosterol synthesis)
SE - severe hepatitis
Butenafine MOA & DOCMOA - inhibits squalene epoxidase (not oral, it's a topical cream) so limits toxicity
DOC - all tinea except capitis
Allylamines SEhepatotoxic
Griseofulvin SEhepatotoxic, teratogenic, induces P450, disulfiram like rxn with alcohol, photosensitivity rash w/ sunlight
Flucytosine SEleucopenia, thrombocytopenia, aplastic anemia
Nystatin SEtoxic if given systemically (this is why it is topical)
Amphotericin SEnephrotoxic (causing hypokalemia, anemia, hypotension, neuro effects). decrease SE w/ lipid-based or liposomal amphotericin
Imidazoles SEhepatotoxic

Chapter 11 Anti-Parasitic Drugs (5-3)

Question Answer
What are protozoa?one-celled animals
What are the 5 species that cause malaria?Plasmodium - vivax, ovale, malariae, falciparum, knowlesi
Which species is primarily chloroquine resistant?Plasmodium falciparum
In addition to normal malaria tx, pts with P vivax or ovale must also be treated with what and why?primaquine bc they form hypnozoites in the liver (want to prevent recurrence at later date)
Malaria prophylaxis DOC in areas that are chloroquine sensitivechloroquine; when pregnant - chloroquine
Malaria prophylaxis DOC in areas that are chloroquine resistantatovaquone/proguanil; pregnant - mefloquine
doxycyclineMOA - protein synthesis inhibitor
SE - discolors developing teeth, bones
CI - children < 8 , pregnant
mefloquineSE - MI when used in combo with other quinines; also causes drug-induced psychosis or seizures; other is retinal damage and G6PD exacerbation
CI - generalized anxiety, seizure, schizophrenia, other pscyh, major depressive disorder
MOA - like chloroquine but also effective in chlorquine resistant P falciparum
atovaquoneMOA - ubiquinone analog; selectively inhibits protozoan's mitochondrial ETC limiting ATP synthesis
SE - teratogenic
chloroquineMOA - poisons organisms, physical destruction, starvation, inhibits DNA synthesis; crosses BBB and placenta
Tx of chloroquine sensitive specieschloroquine; pregnant - chloroquine
Tx of chloroquine resistant speciesquinine + doxycycline/tetracycline/clindamycin; pregnant - quinine + clindamycin
Tx of malaria d/t chloroquine resistantquinine + doxycycline/tetracycline + primaquine; pregnant - quinine
Tx of malaria d/t P vivax/ovalemalaria tx + primaquine; pregnant - no primaquine
4 ways chloroquine kills malarial organisms1) transforms heme into toxin (Plasmodia eat heme so they get poisoned)
2) forms complexes that lyse Plasmodia and RBCs that contain Plasmodia
3) alkalizes Plasmodia food vacuole (needs to be acidic to digest so organism starves)
4) inhibits Plasmodia DNA synthesis
quinineSE - cinchonism (tinnitus, photophobia, mental dullness, depression, confusion, HA, nausea)
MOA - inhibits Plasmodial DNA synthesis
primaquineprevents malaria relapse by killing organisms in liver; prevents gametocyte formation --> prevents spread to other ppl/animals
artemethercombo w/ lumefantrine; schizonticides (effective against erythrocytic stage) and gametocides
MOA - interacts w/ heme in Plasmodium's food vacuole generating toxic ROS --> causes inhibition of nucleic acid and protein synthesis; inhibits COX 3 in CNS decreasing pain and fever
SE - arthralgia, HA, nausea, recrudescence
metronidazoleDOC for trichomoniasis, amoebiasis
MOA - electron acceptor
SE - disulfiram-like rxn in those who ingest alcohol; makes urine dark; occasionally paresthesias, peripheral neuropathy, seizures
tinidazoleDOC for giardiasis
stibogluconateMOA - inhibits glycolysis
DOC - cutaneous leishmaniasis
suraminMOA - reacts with metabolic enzymes like G6PD --> cellular destruction; does not cross BBB
DOC - early stage East African sleeping sickness
CI - renal or liver disease
SE - pruritis, fever
pentamidineDOC - early stage West African sleeping sickness
MOA - inhibits topoisomerase
SE - nephrotoxic, pancreatitis, hypotension
melarsoprolDOC - late stage East African sleeping sickness
MOA - reacts with SH groups rendering enzymes non functional; penetrates bbb
SE - fatal neurotoxicity, severe hypersensitivity rxns, significant GI problems if pt is not fasting; dec neurotoxicity by giving prednisone; can also cause Jarisch-Herxheimer rxns
What are Jarisch-Herxheimer rxns?when large number of microorganisms die in body during abx therapy --> toxins released in quantities larger than liver and kidney can handle --> causes increase in TNF alpha, IL6, other cytokines --> results in fever, myalgia, HA, chills
eflornithineDOC - late stage West African sleeping sickness
MOA - inhibitor of ornithine decarboxylase; limits polyamine production causing decreased cellular growth and proliferation
benznidazole, nifurtimoxDOC - Chagas disease
MOA - creates ROS that destroy enzymes
nitazoxanideDOC - cryptosporidiosis, giardiasis
MOA - prodrug that inhibits electron transport mechanism of the organism starving it of ATP
trimethoprim-sulfamethoxazoleDOC - Pneumocystis jiroveci, cyclospora cayetanensis, prophylaxis for toxoplasma encephalitis
MOA - inhibits folate manufacture and use, inhibiting DNA synthesis
SE - megaloblastic anemia
amphotericin BDOC - amoeba (naegleria fowleri)
MOA - binds to ergosterol; creates a pore through which K leaks out
What are helminths?parasitic worms - flatworms (platyhelminthes) and roundworms (nematodes)
What are the 2 types of flatworms?cestodes (tapeworms), trematodes (flukes)
praziquantelDOC - flatworms
MOA - increases cestode cell membrane permeability to calcium ions causing worms to undergo a tetanic like contraction that paralyzes them; also prevents adenosine uptake by the worms
SE - drowsiness
albendazole, mebendazoleDOC - roundworm infections
MOA - binds to tubulin in cells of roundworms preventing microtubule formation
CI - pregnant, teratogenic
ivermectinDOC - strongyloides stercoralis (roundworm)
MOA - opens voltage gated chloride channels causing flaccid paralysis of helminthic muscles and neurologic inhibition
SE - mild but can cause Mazzotti reaction (massive eosinophil degranulation resulting in severe lesions at site of worm death).
diethylcarbamizine (DEC)DOC - (combo w/ doxy) wuchereria bancrofti
MOA - inhibits metabolism of arachidonic acid in filarial organisms (long thread like worms)
SE - pruritis and other T1 hypersensitivity reactions, can cause Mazzotti rxn, teratogenic
triclabendazoleDOC -Fasciola infection
MOA - transtegumentary absorption acusing microtubular destruction resulting in fluke paralysis and inhibition of release of proteolytic enzymes needed for survival
what are ectoparasites?live on surface of human body and include lice, scabies, fly larvae
permethrinDOC - infestation of head lice or pubic lice, infestation with scabies
MOA - inhibits transmission of nerve impulses resulting in rapid and permanent paralysis
malathion or permethrin powderfor bedding/clothing of pts with body lice
What is myiasis?infestation of tissues by the larvae (maggots) of flies; they lay eggs in wounds and other exposed (urogenital, eyes, nose, ears); cutaneous myiasis is treated by occluding the opening (punctum). Lack of O2 will force larvae to migrate closer to opening for manual removal

Chapter 12 HIV and AIDS (6-2)

Question Answer
What does HAART mean?highly active antiretroviral therapy
What are NRTIs?mimic certain nucleosides - they get triphosphorylated and integrated into DNA molecule. (Zidovudine)
What are NNRTIs?do not mimic nucleosides - they bind directly to inhibit reverse transcriptase (Efavirenz, Nevirapine)
What are protease inhibitors?prevents viral protein products from being cleaved to form functional structures (gag-pol-env). ("-avirs")
What are fusion inhibitors?prevents fusion of HIV with outer membrane of host target cell (binds gp41). (Enfuvirtide)
What are integrase inhibitors?inhibits HIV-1 integrase, preventing integration and insertion of HIV DNA into human DNA. ("-tegra")
What are CCR5 antagonists?blocks CCR5 coreceptor located on WBCs targeted by HIV so it prevents viral entry. These are hepatotoxic, increase infection risk and malignancies, may cause systemic allergic rxns. (Maraviroc)
When should HIV therapy be started?HAART is initiated when pt is HIV + (regardless of CD4 count and cont until plasma HIV RNA remains below detectable levels.
When therapy is started, what should be used?2 NRTI + (1 NNRTI or 1 protease inhibitor or 1 integrase inhibitor)
HIV + in pregnant womenIV zidovudine should be given during labor to women with heavy viral burden (HIV RNA > 1000); c section; Right after delivery, zidovudine therapy should be initiated for any infant born to an HIV + woman regardless of viral load
GanciclovirDOC for CMV retinitis
Amphotericin B + flucytosine DOC forDOC for cryptococcal meningitis
Clarithromycin + ethambutol DOC forMycobacterium avium complex (MAC)
TMP-SMX DOC forDOC for tx/prophylaxis of pneumocystis; also DOC for prophylaxis against toxoplasmosis
bacteria make their own folate bc they have what enzyme?dihydropteroate synthetase (inhibited by sulfa abx)
Itraconazole DOC forDOC for prophylaxis of histoplasmosis; tx of mild/mod histoplasmosis
liposomal amphotericin B is DOC fortx of severe/disseminated histoplasmosis