Pharm Winter quarter - antimicrobials

• Isonaizid
• Rifampin
• Pyrazinamide
• Ethambuine
• Rifabutin
• Rifapentine

• Cycloserine
• p-Aminosalicylic acid
• Eethionamide
• Amikacin
• Kanamycin
• Capreomycin
• Levofloxacin
• Moxifloxacin
• Streptomycin
• Linezolid

Multi-drug resistant TB

Resistant to isoniazid and rifampin

Extensively drug-resistant M. tuberculosis

Resistant to isoniazid, rifampin, fluoroquinolones, and aminoglycosides and/or capreomycin

TB - #1 for latent

• bactericidal against actively growing
• bacteriostatic against nonreplicating organisms
• inhibits mycolic acid synthesis
• hepatic metabolism

TOX: hepatotox, neurotox (tx: pyridoxine), also fever, rash, drug-induced lupus

TB

• lots of drug interactions (induces p450)
• bactericidal against actively replicating M. tb
• inh RNA pol

TOX: Hepatitis, flushing, fever, pruritis, flu-like, red body fluids

TB

=Rifampin with less p450 activation - used with protease inhibitors in AIDS pts

Tox: polymyalgia, pseudojaundice, uveitis

TB

Rifampin with longer half life

Short course anti-TB

bactericidal

Tox: n/v, hepatotox, polyarthralgia

TB

bacteriostatic - inh arabinosyl transferase (cell wall)

Tox: optic neuritis (can be irrev), hyperuricemia

2nd line TB

polypeptide antibiotic. inh protein syn

Tox: hearing loss, tinnitus, dec renal f

2nd line TB

Blocks folate syn

Tox: crystalluria, GI intol, lupus-like

2nd line TB

Inh cell wall syn. Crosses BBB.

Tox: periph neuropathy, CNS dysf

2nd line TB

Bacteriostatic

Tox: GI, psych

• Streptomycin
• Gentamicin
• Amikacin
• Neomycin
• Kanamycin

• Water soluble (don't cross BBB well)
• Active against aerobic and faculative gram negative incl enterobacteria, pseudomonas, haemophilus
• Synergistic
• Cross placenta
• Tox: neuromuscular blockage, ototox!! nephrotox

Aminoglycoside

TB, Yersinia

Aminocyclitol (no glycosidic bonds)

Gonorrhea

Aminoglycoside

Part of bowel prep before GI surgery

• Tetracyclines
• Macrolides
• Clindamycin
• Chloramphenicol
• Streptogram
• Oxazolidinones

Protein synthesis inhibitors

• bacteriostatic, 30s
• acne, rickettsial, chlamydia, mycoplasma, cholera, lyme, mycobacterium marinum
• renal excretion
• tox: tooth hypoplasia, GI, hepatotox, renal, vertigo, photosen
• don't take with milk, dilantin, barbiturates

Tetracycline protein syn inh

no renal excretion, good for kidney failure

• Erythromycin
• Clarithromycin
• Azithromycin

• Binds 50s
• Gram positive, good for penallergic pts
• Tox: GI common, phlebitis, cholestatic hepatitis, transient hearing loss

• Macrolide protein syn inh
• destroyed by gastric acid

• Macrolide protein syn inh
• Better against strep and staph than erythromycin
• Less toxic, take less often

• Macrolide protein syn inh
• Less active than erythromycin against strep and staph
• Better at H. flu, Salmonella/campylobacter, chlamydia STDs
• Least often dosing

• Prot syn inh
• Binds 50s
• Very active against anaerobic bacteria and gram positive cocci, toxoplasmosis
• Tox: diarrhea, pseudomembranous colitis

• Prot syn inh
• Binds 50s
• Gram positive and negative, anaerobes, rickettsia (not staph, pseudomonas)
• Tox!! Bone marrow suppression (reversible), aplastic anemia (irrev on first dose)

• Prot syn inh
• Binds 50s
• Gram pos/neg, (includes staph, strep, enterococci, corynebacteriu, listeria)

• Sulfonamides
• DHFR inh (Trimethoprim, Pyrimethamine)
• Quinolones (--floxacins)

• Nucleic acid inh
• PABA analog; can't make folate and need to
• Gram neg, gram pos, actinomyces, chlamydia, plasmodia, toxoplasma, nocardia, PCP, malaria, listeria
• Tox: crystalluria, hemolytic anemia, pg-kernicterus, rash, diarrhea, nv

• Sulfamethoxazole
• Sulfadoxine
• Sulfisoxazole
• Sulfadiazine
• Salicylazosulfapyridine (Azulfidine)

• Nalidixic acid
• Ciprofloxacin
• Levofloxacin = levoquin

• Quinolone nucleic acid inhibitor
• Inh DNA gyrase
• gram neg incl pseudomonas, some mycobacteria, many gram positive (not for anaerobes)

• Quinolone nucleic acid inh
• Inh DNA gyrase
• Better than cipro against strep
• Used for legionella, mycoplasma, strep pneumo, diarrhea

• Penicillin
• Cephalosporins
• Monobactam
• Carbapenems
• Glycopeptide - Vancomycin
• Lipopeptide - Daptomycin

• Penicillin G
• Penicillinase resistant - oxacillin, methicillin, nafcillin, dicloxacillin
• Ampicillin/Amoxicillin
• Piperacillin

Active against gram-neg (H. flu, E.coli, Proteus)

• Penicillin deriv
• Activity against gram neg

• 5% pts
• skin rashes (not IgE), anaphylaxis

• Use with penicillins to enhance activity
• Ciavulanic acid, sulbactam, tazobactam

• Transpeptidase inhibitor
• 1st gen: strep and staph, some gram neg (E coli, klebsiella)
• 2nd gen: more gram neg
• 3rd gen: most gram neg (incl pseudomonas)
• 4th gen: gram neg and pos

• Cephalexin
• Cefazolin

• Cefuroxime
• Cefaclor
• Ceftoxitin
• Cefotetan

• Cefotaxime
• Ceftriaxone
• Ceftazidime

Cefepime

• Aztreonam
• Aerobic gram-neg

• Imipenem (with cilastin)
• Meropenem
• Ertapenem

• Glycopeptide - not a beta-lactam
• Inhibits transglycosylation
• Active against all gram positives
• Bad oral abs, so works to swallow for c. difficile
• Tox: ototox, nephrotox

• Polymyxin B and Colistin
• cell membrane disruption
• MDR gram neg bacilli (actinobacter)
• Tox: nephrotox, neurotox

• Lipopeptide (not beta lactam)
• Cell membrane disruption, changes memb V
• Tox: myositis

• Topical only antibiotic
• rarely causes hypersensitivity

• Artemisinin derivative+other active agent
• Quinine+doxycycline/clinamycin, mefloquine
• Atovaquone-proguanil

• Atovaquone-proguanil
• For P. falciparum

Chloroquine+primaquine (for hypnozoites)

Chloroquine

• Malaria - inhibits parasitic heme polymerase that protects parasite from toxic metabolite
• Quinine
• Quinidine
• Chloroquine
• Mefloquine
• Amodiaquine
• Primaquine

Malaria

• For severe malaria, eg chloroquine-resistant P falciparum. Fo babesiosis
• Tox: GI, cinchonism (tinnitus, HA, nausea, blurry vision), hypotension

Malaria

• For all kinds, falciparum forms resistance
• Tox: well tol, HA, dizziness, blurry vision, GI

Malaria

• For all kinds, prophylactic
• Tox: GI, neuropsych (avoid w quinine, beta blockers, seizures, psych disorders)

Malaria (toxoplasmosis)

• Exoerythrocytic/hepatic forms of parasite
• Tox: well tol (ex pts w G6PD or methemoglobinemia)

• Malaria
• Most potent, saving for emergencies
• Tox: minimal, GI, inc LFT

• Proguanil
• Pyrimethamine

• Malaria
• Inhibits plasmodial DHFR
• Kills erythrocytic forms

• Malaria (PCP, toxoplasmosis)
• Inhibits plasmodial DHFR
• Tox: BMS

• Malaria (babesiosis, PCP, toxoplasmosis)
• (usually with proguanil in malarone)
• Tox: GI, fever, rash, HA, insomnia

• Chloroquine (28d)
• Malarone (7d)
• Mefloquine (28d)
• Doxycycline (28d)
• Primaquine (not used much)

• Trimethoprim/sulfamethoxazole (Bactrim)
• Atovaquone
• Clindamycin+primaquine
• Pentamidine
• Dapsone

• PCP (Trypanosomiasis, leishmaniasis)
• IV
• Inh nucleic acid, protein, phospholipid syn
• Tox: 50% have rxn: hypotension, tachycardia, nv, flushing

• PCP
• Sulfone - inh dihydropteroate synthase
• Tox: fever, hemolytic anemia, methemoglobinemia, BMS

• Clindamycin+quinine
• Atovaquone+azithromycin

• Pyrimethamine+sulfonamide
• Trimethoprim-sulfamethoxazole for prophylaxis
• Or Dapsone+pyrimethamine
• Or Atovaquone

Stibogluconate Na, miltefosine, amphotericin B, pentamidine

Nifurtimox, Benznidazole, Pentamidine, Suramin

• Leishmaniasis
• Tox: myalgia, nv, diarrhea, arrhythmias

• Metronidazole
• Tinidazole

• Asx: Iodoquinol, paromomycin
• Invasive: Metronidazole+iodoquinol/paromomycin

Tinidazole, nitazoxanide

Trimethoprim-sulfamethoxazole

Trimethoprim-sulfamethoxazole

Albendazole, fumagillin

Nitazoxanide

• Anti-parasitic
• Ex: metronidazole, tinidazole
• Mech- free radicals
• Tox: HA, n, dry mouth, metallic taste, peripheral neuropathy, neutropenia

Anaerobic/microaerophilic bacteria, entamoeba histolytica, giardia, trichomonas vaginalis, dracunculus medinensis

Giardia - single dose, trichomonas vaginalis, entamoeba

Metronidazole

Mebendazole

Albendazole

Mebendazole

• Diethylcarbamazine (DEC)
• Ivermectin

Ivermectin

Albendazole/Mebendazole - single does, repeat in 2 weeks

• Albendazole or mebendazole
• Inh microtubule polymerizations

• Nematodes: capillaria, necator americanus, toxocara, ancylostoma, trichinella, taenia solium
• Well tol

• Opens glutamate gated cl channels
• well tolerated
• Onchocerca volvulus, strongyloides stercoral

Praziquantel, Albendazole

Albendazole

Schistosomiasis, intestinal flukes, paragonomiasis

Triclabendazole, bithionol, praziquantel

• Permethrin (lice, crabs, scabies)
• Malathion=Nix (lice)
• Crotamiton (scabies)
• Lindane (scabies)

• Anti-fungal
• Amphotericin B
• Nystatin

• Anti-fungal
• Amphoterrible
• Binds ergosterol, makes holes
• Tox: renal, intra renal vasospasms(reversible, dose dep), anemia (low epo)

• Anti-fungal
• binds ergosterol
• poor absorpsion
• Tox: major-so only topical

• Antifungal - antimetabolite
• De-am to 5UTP, blocks fungal DNA/RNA syn
• Oral only
• Use for Cryptococcal meningitis (w AmB)
• Tox: myelosuppression, hepatitis

• Antifungal
• Inh lanosterol demethylase
• p450
• Imidazoles: ketoconazole, clotrimazole, miconazole
• Triazoles: fluconazole, itraconazole, voriconazole, posaconazole

• Antifungal - imidazole
• Requires low gastric pH
• Oral and topical
• Use: tinea, prostate ca
• Tox: gynecomastia, oligospermia, mpotence, menstrual irreg, alopecia

• Antifungal - imidazole
• Topical only
• Use: tinea, candida vaginitis, thrush

• Antifungal - imidazole
• topical only
• use: candida vaginitis, tinea skin inf

• Antifungal - triazole
• Oral
• Leasat c450 inh of azoles
• Uses: skin, mucosal, systemic candida; cryptococcal meningitis; coccidioidomycosis; NOT aspergillus/zygomycetes
• Tox: Hepatitis, rash, alopecia

• Antifungal - triazole
• Oral, requires low gastric pH
• Uses: Candida, aspergillus, histoplasma, blastomycis, sporothrix, tinea, onychomycosis, madiera foot
• Tox: n, diarrhea, hepatitis, HTN, hypokalemia, edema

• Antifungal - triazole
• IV/oral
• Uses: candida, cryptococcus, dimorphs, ASPERGILLUS not zygomyces)
• Tox: Skin photosensitivity, visual disturbances, hepatitis

• Antifungal - triazole
• Oral (w food)
• Uses: broadest spectrum; aspergillus, zygomycetes, cadida, cryptococcus, dimorphs

• Antifungal
• Inhibit glucan synthesis (fungal cell wall)
• Less toxic than ergosterol meds
• Caspofungin, micafungin, anidulafungin

• Antifungal - echinocandin
• Inh cell wall (glycan)
• Use: candida, some aspergillus activity
• Tox: allergic rxn, rash

• Adamantanes
• Neuraminidase inhibitors
• Nucleoside analouges
• Nucleotide analogues
• Pyrophosphate analoug
• Interferons

• blocks M2 protein H+ ion channel; no RNP entry into cell nucleus
• Take within 24-48h of sx
• Tox: CNS, resistance, don't give if seizures/need to concentrate at job
• Ex: Amantadine, rimantadine

• Blocks active site of influenza neuraminidase, can't spread in resp system
• Treat influenza A/B within 48h of sx or for prophylaxis
• don't give if known hypersensitivity
• Ex: zanamivir, oseltamivir

• Ribavirin
• Acyclovir/valacyclovir
• Famciclovir
• Ganciclovir/Valganciclovir
• Entecavir
• Telbivudine

• Antiviral
• Nucleoside analog like guanosine/inoside
• Inhibits inosine monophosphate dehydrogenase
• Uses: HCV with interferon, severe resp syncytial virus
• Tox: hemolytic anemia, nausea, lethargy, HA

• Antiviral
• Triphosphorylated intracellularly by thymidine kinase to activate
• Valacyclovir is oral pro-drug
• ACV-PPP potent inhibits viral DNA pol
• Uses: HSV/VZV tx, prophylaxis against HSV/CMV
• Tox: phlebitis, reversible nephrotox (crystallizes in tubules), nv, light-headedness, diaphoresis, rash

• Antiviral
• Prodrug of penciclovir
• Uses: HSV, herpes zoster
• Tox: HA, n, fatigue. don't use if documented hypersensitivity

• Antiviral
• Acyclic analog of guanosine; valgaciclovir is prodrug
• Uses: severe CMV
• Tox: seizures if with imipenem, bone marrow suppression, don't give with documented hypersensitivity

• Antiviral
• nucleoside analogue of guanosine
• Inhibits HBV DNA pol
• Uses: chronic active HBV infection
• Tox: mild

• Antiviral
• Nucleoside analog of thymidine
• Uses: HBV infection
• Tox: myopathy, lactic acidosis

Ex: Cidofovir, adefovir dipivoxil

• Antiviral
• IV
• p450
• Tox: nephrotox, neutropenia, uveitis, alopecia, ocular hypotony

• Antiviral
• Nt reverse transcriptase inhibitor
• Oral prodrug of adefovir
• Uses: chronic active HBV
• Tox: mild nephro, HIV spikes, hypersensitivity

• Foscarnet
• Inhibits viral DNA Polymerase adn reverse transcriptase
• IV only
• Kidney excretion
• Uses: CMV, HSV, VZV, HIV, HBV
• Tox: nephrotoxicity, hypo/hypercalcemia, hypo/hyperphosphatemia, n/v, seizures, anemia, mucosal ulcerations

• Antiviral
• Small MW glycoproteins
• Broad spectrum against RNA/DNA viruses
• Inh viral penetration and uncoating, mRNA syn, viral protein translation
• Recombinant alpha 2a/2b for HPV, Hep B, Hep C
• Tox: flu-like sx, CNS, BMS

• Amantadine/rimantadine
• Zanamivir/Oseltamivir

• Acyclovir
• Valacyclovir
• Famciclorvir
• Cidofovir
• Foscarnet

• Ganciclovir
• Valganciclovir
• Foscarnet
• cidofovir

• Entecavir
• Telbivudine
• Tenofovir/Lamivudine/Emtricitabine
• Adefovir dipivoxil
• Interferon

• Ribavirin
• Interferon

Interferon

• CCR5 inhibitors (Maraviroc)
• Fusion inhibitors (Enfuviritide)
• NRTIs (abacavir, lamivudine, tenofovir, emtricitabine)
• NNRTIs (efavirenz)
• Integrase inhibitors (raltegravir)
• PIs (atazanavir, darunavir)

• Tenofovir + emtricitabine
• Plus efavirenz or atazanavir/ritonavir or darunavir/ritonavir or raltegravir

• Anti retroviral - CCR5 inhibitor
• blocks interactio nbtw HIV-1 gp120 and CCR5
• Useless if HIV strain uses CCR5 and CXCR4
• Tox: abdominal pain, cough, URI, allergic rxn, hepatotox, ortostatic hypotension

• Anti retroviral - fusion inhibitor
• SubQ injection
• Interferes with HIV-1 entry into cells
• Tox: local injection site rxn, more bacterial pneumonia, hypersensitivity

• Antiretroviral nucleoside reverse transcriptase inhibitors
• triphosphorylated intracellularly to active form
• Incorporated into growing viral nucleic acid - chain termination
• Tox: lactic acidosis, hepatic steatosis

• Antriretroviral
• Zidovudine (ZDV)
• Didanosine (ddl)
• Stavudine (D4T)
• Lamivudine (3TC)
• Abacavir (ABC)
• Tenofovir (TDF)
• Emtricitabine (FTC)

• Antiretroviral
• Zidovudine and lamivudine

• Antiretroviral
• Zidovudine and lamivudine and abacavir

Tenofovir and emtricitabine

Abacavir and lamivudine

• Antiretroviral
• Liver metab then kidney excrete
• Tox: Mito tox with lactic acidosis and hepatic steatosis , anemia, granulocytopenia, GI, HA, insomnia, asthenia

• Antiretroviral
• Minimal tox

• Antiretroviral
• Tox: asthenia, HA, diarrhea, n/v, flatulence, RENAL, bone loss

• Antiretroviral
• Tox: minimal, hyperpigmentation

• Q151M (can only then use Tenofovir)
• 69 insertion complex of T69S (no drugs work)
• K65R (can only then use Zidovudine)

• Antiretroviral - non-nucleoside reverse transcriptase inhibitors
• Reversible non-comp inh of HIV reverse transcriptase
• Nel and Efavirenz induce P450
• Do not use with: rifampin, sedatives, PPIs
• Mutations lead to loss of utitility of multiple drugs eg K103N
• ex: EFAVIRENZ, nevirapine, delavirdine, etravirine, rilpivirine
• Tox: skin rash, stevens-johnson syndrome, hepatotox, EFV has CNS sxs

• Antiretroviral - integrase inhibitor
• Inh catalytic activity of HIV-1 integrase
• few drug interactionsTox: muscle inflam, nv, HA, fever

• Antiretroviral
• Atazanavir*
• Darunavir*
• Saquinavir, ritonavir, indinavir, nelfinavir, fosamprenavir, lopinavir, tipranavir

• Antiretroviral
• Blocks protease cleavage of viral gag and gag-pol polyproteins making noninfectious viral particles
• Inhibits p450
• Tox: bleeding in hemophiliacs, CV effects, Fat malabsorption (buffalo hump and protease paunch), hyperlipidemia, osteonecrosis, inc DM