Flashcards in PDA anti-everything else Deck (166):
What increases risk for TB?
socioeconic very low
TB-endemic area travel or immigration
What are the challeges of antimycobacterial therapy?
difficult to kill
vunerable to -cidal drugs only when metabolically active
small population semi-dormant
slow growth-hampers identification/susceptibility
spontaneous resistance requires multi-drug therapy
What are the side effects of isoniazid?
improved with pyridoxine and vitamin B6 admin
What drugs are first line TB drugs?
What is isoniazid mechanism of action?
inhibits synthesis of mycolic acid by targeting the enoyl acyl carrier protein reductase
activated by catalse peroxidase
cidal for actively growin bacilli
What is resistance to isoniazid?
very high up to 25% in some cities, spontaneous resistance
What is isoniazid use?
primary TB drug most important; given in combination
Tx active TB given in combination
can be given alone for latent TB
What are the side effects of RIfampin?
Hepatotoxicity and inducer of multiple CYPs
orange-red color of body secretions
What is the mechanism of action of Ethambutol?
interferes with arabinosyl transferase blocking cell wall syntehsis
Tuberculostatic and enhances the permeability for drugs
What are the side effects of ethambutol?
well-distributed generally well tolerated but causes optic neuritis
decreased visual acuity or loss of ability to differentiate red-green
What is mechanism of action of pyrazinamide?
blocks mycolic acid syntehsis by inhibiting fatty acid synthase I, -cidal
Pyrazinamide is particulary useful for TB with what involvement?
CNS involvement because of distribution
What are the adverse effects of Pyrazinamide?
hepatic damage, adds to hepatotoxicity of other drugs
What is the mechanism of streptomycin?
aminoglycoside, binds to several ribisomal sites and cause mRNA misreading
usually reserved for most serious forms of TB
What are the side effects of streptomycin?
and ototoxciity efecting both balance and hearing
What does tx of short-course uncomplicated TB requrie?
isoniazid plus rifampin plus pyrazinamide for the first two months
How does one treat disseminated TB?
isoniazid plus rifampin for 9 mos-2yrs and others for first two months
Why use simultaneous 4 or more drugs?
disseminated disease, meningitis, known exposures to drug-resistant strains, severe pulmonary disease
How does one treat XDR TB?
5 or more drug treatments at once
What are atypical mycobacterial infections?
MAC= m. avium intracellulare complex
among most frequent opportunistic infections in AIDS
less fatal than TB
What does rifabutin do/ mechanism of action?
prophylaxis of MAC
similar to Rifampin but less severe side effects
What is clarithromycin used to treat with regards to mycobacteria?
tx of MAC in AIds patients and MAC prophylaxis
What is dapsone sued to treat?
leprosy and pneumocystis jiroveci in AIDs pats
What is the mechanism of action of Dapsone?
structural analog of para-aminobenzoic acid; inhibits syntehsis of folic acid
What are the side effects of Dapsone?
What is teh mechanism of Clofazimine?
mechanism poorly understood; somehow binds to DNA and interferest with growth
What is Clofazimine used to treat?
What are the adverse side effects of Clofazimine?
GI problems and red-brown pigmentation of eyes and skin
What drugs are used to treat leprosy?
Clofazimine, Dapsone and Rifampin
What is amphotericin B used to treat?
effecctive broad spectrum anti-fingal for most systemic myoces; esp those that are life-threatening
Gold-standard for anti-fungal effectiveness
What is the mechanism of action of amphotericin B?
Binds to ergosterol; very lipophilic
Why is hte total cumulative dose of Amphotericin important?
permanent renal toxicitiy is related to the total cumulative dose
What is the side effects of amphotericin?
fever, nausea, vomiting, headache, chills
hypotension, hypokalemia, tachypnea
90% will show non-permanent renal toxicity
reversble hypochromic, normocytic anemia
cnS side effects
What flucytosine (5-FC) used to treat?
serious infections of candida and crytpococcus
used in conjunction wiht amphotericin
What si the mechanism of action of flucytosine?
inhibits thymidylate synthetase and thus DNA syntehsis
incorporated in RNA in place of Uracil
fungal cytosine deaminase activates it
What are the side effects of flucytosine?
may accumulate in renal insufficiency and dangerous in bone marrow suppresion
elevated hepatic enzymes
What are the two antifungal classes for serious infections?
imidazole and triazole
What are the mechanism of actions of imidazole and triazoles?
inhibits 14-alpha-sterol demethylase a fungal cytochrom p450 that conferst lanosterol to ergosterol
inhibits ergosterol syntehsis
SLOW onset of action
What is fluconazole used to treat?
Candida many sites including CNS and urinary; some albican and glabrata but not krusei
excreted in urine so good for urinary
What is itraconazole ussed to treat?
Blastomyces, histoplasma, candida esophogause and oropharynx
more albican and glabatra some krusei
What is voriconazole used to treat?
aspergillus with some CNS coverage
Fusarium, Scedosporium, Candida-->covers most species but not for urinary candida infections
What drug is superior to amphotericin for invasive aspergillus?
What azole has best CNS penetration?
What are the side effects common to -azoles?
mild hepatotoxicity; discontinue with onset of liver dysfunciton
CYP3A and 2C inhibitors
What is the major contraindication of itraconazole?
other drugs that are metabolized by CYP3A4; and potential for serious CV events
What azole has lowest incidence of hepatotoxicity?
What unusal side effects do voriconazole have?
visual disturbance and photosensitive component to rash
What anti-fungals target the cell wall?
What is Caspofungin used to treat?
Candida with wide coverage
What is mechanism of action fo capsofungin?
inhibits fungal cell wall ysntehsis by noncompetively blocking syntehsis of Beta-D-glucan in filamentous fungi
No cross resistance mechanisms
What are the side effects fo capsofungin?
phlebitis at injection site
some pulm edema but generally well tolerated
Fluconazole is used to treat what other than serious infections?
superficial fungi; often one oral dose all thats required
miconazole is used to treat what?
creams/suppositories to treat vaginal infections
What is clotrimazole used to treat?
candida; topical use
Nystatin is what mechanism of action?
similar to amphotericin B
What is nystatin used to treat?
superficial fungi; for -azole resistant strains
topical use for candida and GI tract
What are the side effects fo Nystatin?
Some GI side effects but topical well toleratied
What is natamycin used for?
opthalmic infections by fungal infectionss
What is mechanism of action of natamycin?
similar to amphotericin B; too toxic for systemic
What are used for topical treatment of dermatophytes?
What is mechanism of action of tolnaftate?
likely inhibits fungal ergosterol syntehsis
few toxic reactions topical only
What is ciclopriox used for?
approved topical tx for mild to moderate fungal nail infections
What is the ciclopirox mechanism of action?
inhibits metal-depndent fungal enzymes by metal chelation is the believed mechanism
What are the oral preapartions of dermatophyte used for?
severe dermatophyte infections
those that are resistant
What is terbinafine used for?
12-week thereapy for nail infections
shorter for other dermatophytic infections
What is the mechanism of action of terbinafine?
deposits in skin and nails leadign to prolonged effect
blocks ergosterol syntehsis and causes accumulation of squame which is toxic to fungi
What are the side effects of terbinafine?
diarrhea dyspepia, GI
well tolerated in general
What is griseofulvin tx?
for recalcitrant dermatophytic infections of skin, hair, nails
tx for children esp tinea capitis
What is the mechanism of aciton of griseofulvin?
interferes wtih microtubule function
What are the side effects of griseofulvin?
contraindicated in those with porphyria and advanced liver disease
increased metabolism by CYP inducer
used in caution in those with penicillin allergies
Itraconazole is used to treat what in addition to systemic fuunals?
Inner city children are more likely to have what parasite?
What does mebendazole treat?
many of the roundworm species
kill some ova
Why does mebendazole have few systemic side effects?
What does albendazole treat?
cutaneous larval migrans
What rae hte problems with albendazole metabolism?
Well distributed and causes elevated hepatic enzme
abdominal pain vomitting
What does Thiabendazole used to treat?
stronglyoides, cutaneous larva migrans
What is the mechanism of thiabendazole?
hook worm inhibits energy metabolism, mitochondrial fumarate reductase
strongyloides blocks microtubule assembly
What is mechanism of action of mebendazole?
immobilizes and kills parasites by selective microtubule damage
What is the mechanism of action of pyrantel pamoate?
depolarizing neuromucular blocker
What is pyrantel pamoate used for?
hookworm, pinworm and roundworm
OTC for pinworm
Why does pyrantel pamoate have few side effects?
poorly absorbed resulting in only mild GI side effeccts
What is praziquantel mechansim of action?
increase calcium permeability causing spastic paralysis
What is praziquantel side effects?
abdominal discomfor and nausea
What is praziquantel used for?
flukes; drug of choice for shicstosoma and some activity against other trematodes
What is praziquantel used for besides flukes?
off label for many cestodes(tapeworms)
for Taneia solium b/c also kill egss thereby avoiding cysticerosis
What is albendazole used to treat besides roundworms?
What is paromomycin sulfate used for?
3rd choice for those who can't handle other drugs for tapeworms
What are antimalarial drugs used for?
none prevent infections; only prevent progression to symptomatic infection
What is chloroquine used for?
effective for all 4 species; not effective for chloroqine sensitive strains;
What is the mechanism of action of chloroquine?
parasitic erythrocytes concetnrates teh drug 25 fold by pH dependent mechanism intoo acidic vacuoles; inhibitis heme polymerization allowing heme to accumulate to toxic levels for parasites
What malaria is mostly resistant to chloroquine?
What ar ethe side effects of chloroquine?
visual impairment with extended use but generally well tolerated
What is mfeloquine mechanism?
similar to chloroquine
What does mefloquine treat?
P. falciparum and P. vivaz
tx or prevention of malaria
What side effect does meloquine cause?
contraindicated in ppl with epilepsy or psychiatric disorders
-8% of men
What is the Atovquone and proguanil used to treat?
block and tx of chloroquine resistant P. falciparum
What is the mech of action of Atovaquone and Proguanil?
atovaquone selectively inhibits malarial electron transport and disrupts pyrimidine synthesis
proguanil disrupts folate syntehsiss preventidng pyramidine synthesis
What are the side effects of Atovquone and proguanil>
nausea, diarrhea, vomiting and rash
What is quinine?
bark of cinchona tree
What is mechanism of quinine?
mechanims similar to chloroquine
What is quinine used to treat?
blood schizonticide all four malarial parasites
severe malarial attack
What is quinine side effects?
cinchonism-headache, visual distrubance, dizziness, tinnitues
cardiac effects similar to quinidine
What is doxycycline used in addition to antibacterial?
decreases malarial syntehsis
depresses dihydroorate synthesis
What is primaquine used to treat?
kill liver hypnozoites
radical cure/terminal prophylaxis of P. vivax and ovale
Pneumocystis jiroveci pneumonia in AIDs in combination with an antibacteria
What is primaquine side effects?
hemolytic reactions in those wiht G6P dehydrogenase deficiency
What is the treatment for amebic dysentery?
metronidazole pluse either idoquinol or paromomycil sulfate
What is used to treat Giardia and Tirchomonas vaginals?
What is used to treat nitrazoxanide?
giardia and cryptosporidium parvum
What is used to treat pneumocystis jiroveci as a prophylaxis or treamnet as an alternative for intolerance of TMP/SMX?
What is amantadine used to treat?
Influenza A; reduces fever by 50%
What is the mechanism of action of Amantadine?
blocks viral uncoating by interfering with viral uncoating by interefering M2 protein the ion channel
What are the amantadine side effects?
CNS effects; confusion, slurred speach, depression, headache, hallucinations
WHat is the mechanism of action of oseltamivir?
inactive pprodrug converted to oseltamivir carobxylate competiviely inhibits neuramidiases interferres with viral release and viral pen
What is the approved use of oseltamivir?
treatment of influenza A and B; only effective if given within 48 hours of onset
What are the side effects of oseltamivir?
nausea, vomiting and diarreha
bronchitis and cough
What is mechanism of action of trifluridine?
thymidine analog interferes with DNA synthesis
What is trifluridine used for?
opthalmic use only treatment of herpes simplex type 1 and 2
Acyclovir has what mechanism of action?
inhibits herpes DNA polymerase 10-30 times more effectively than host cell DNA polymerase
occurs after it is phosphorylated
What is the intravenous acyclovir used for?
serious systemic herpes virus
What is acyclovir orally used for?
primary genital herpes
primary herpes in the mouth or face region for
What is topical acyclovir used for?
What are the side effects of acyclovir?
What is the mechanism of action of Famciclovir?
Prodrug activated by complex with multiple intermediates
herpes thymidine similar to acyclovir after activated
What is the use of famciclovir?
acute herpes zoster (shingles) (latent chickenpox virus)
tx and suppression of current genital herpes
What is the mechanism of penciclovir?
activated for of famciclovir but can be given straight but only topically
very similar to acyclovir
What is the use of penciclovir?
recurrent herpes of the lips and face
What is the importance of CMV in pts with HIV?
retinitis can be caused by it or GI, CNS, respiratory, adrenal
What is the mechanism of ganciclovir??
mechanism similar to acyclovir, except mono-phos. by CMV protein kinase
What is the use of ganciclovir?
CMV retinitis in AIDS pts
CMV prophylaxis for transplant pts
What are the side effects of Ganciclovir?
bone marrow suppression
What is foscarnet mechanism of action?/
inhibits CMV DNA polymerase by binding to its pyrophosphate site
doesn't requrie activation
What is Foscarrnet used for?
acyclovir-resistant herpes simplex
What are the side effects of Foscarnet?
some side effects
-higher % of side effects
What is the mechanism of action of Lamivudine?
inhibits the reverse transcriptase domain of hte hepatitis B DNA polymerase
Nucleoside analg phosphorylated by cell enzymes to active form
What is Lamivudine used to treat?
HIV and hepatitis B
What are the side effects of Lamivudine?
GI effects pretty common;
otherwise well tolerated
What is the mechanism of action of Tenofovir?
adenosine monophosphate analog
What si tenofovir used to treat?
What is the mechanism of Ribavirin?
interferes with viral mRNA synthesis
Moono-P form inhibits inosine-5' dehydrogenase and therefore GTP syntehsis
Tri-P form inhibits GTP dependent capping
What is the use of aerosol use of Ribavirin?
severe RSV infections in young children; no longer used
What are the oral capsules of Ribavirin used for?
hepatitis C in combination with PEG-interferon-alpha
What are the side effects of RIbavirin?
drug may precipitate in and clog respiratory equipment
pulmonary function deterioration
IV or oral
anemia, bone marrow suppression
What are hte alpha interferons used for?
hep B and C; used in combination with ribavarina nd boceprevir for hep C
What is the side effects fo interferon alpha?
leukopenia, bone marrow suppresion
What is hte mechanism of Boceprevir?
reversible inhibitor of NS3 protease of hepatitis C, blocks formation of infectious virus
What is Boceprevir used for?
Hep C genotype 1
What combination of drugs i the most efefctive tx for hep C genotype 1?
interferon alpha, boceprevir, ribavirin
What are the side effects of boceprevir?
bone marrow suppression
What is zidovudine?
first anti-HIV drug
What is the mechanism of action of zidovudine?
What are the side effects of Zidovudine?
bone marrow suppression
avoid drugs which inhibit glucuronyl transferase
What are the mechanism of action of other NRTIs
nucleoside analogs that must be phosphorylated
What is used to treat HIV that is an analog of lamivudine?
What is the mechanism of abacavir?
nucleoside analog inhibitor of RT
What are the side effects of abacavir?
What are the side effects associated with NRTI's?
What is the mechanism of efavirenz?
non-nucleoside reverse transcriptase inhibitor;
binds RT and disrupts teh active site
What are the side effects of Efavirenz?
CNS/ psychiatric symptoms, nightmares
What are hte toxicities common to protease inhibitors?
alterations in lipid metabolism
alters metabolism of many other drugs
What is Ritonavir used for?
used to boost levels of other protease inhibitors bc blocks their metabolism by CYP3A
What is the mechanism of action of enfuviritide?
binds to gp41 subunit of HIV glycoprotein; blocks conformational changes required for membrane fusion to CD4 cells
What are the side effects of Enfuvirtide?
local injection site reactions
What is the mechanism of Maraviroc?
CCR5 antagonist; tx of HIV-1
effective in strains resistant to other drugs
What is raltegravir used for?
tx of HIV-1 and works on virust that is resistant to other drugs