Antimicrobials

When a drug stops the growth of the bacterial colony by inhibiting a step the the metabolism of the drug, but does not actually kill the bacteria.

Forms a plateau in the bacterial colony numbers.

• We're ECSTaTiC about bacteriostatics
• Erythromycin Clindamycin Sulfamethoxazole Trimethoprim Tetracyclines Chloramphenicol

When a drug actually kills the bacteria so that the number of bacteria dramatically decreases after administration of the drug

• Very Finely Proficient At Cell Murder
• Vancomycin Fluoroquinolones Penicillin Aminoglycosides Cephalosporins Metronidazole

• Penicillin
• ampicillin
• ticarcillin
• pipericillin
• imipenem
• aztreonam
• cephalosporins

• Bacitracin
• Vancomycin

Polymixins

• Sulfonamides
• Trimethoprim

Fluoroquinolones

Rifampin

• Chloramphenicol
• macrolides
• clindamycin
• streptogramins (quinupristin, dalfopristin)
• linezolid

• Aminoglycosides
• Tetracylcines

• General considerations: can enhance activity if beta-lactamase inhibiitors (clavulanic acid, sulbactam), synergy w/ aminoglycosides against pseudomonal and enterococcal species
• Pharmacokinetics: eliminated by active tubular secretion that can be blocked by probenecid, dose needs to be reduced with renal dysfn
• Side effecets: hypersensitivity - types I-IV, urticarial skin rash common, but severe anaphylaxis reactions are possible, assume complete cross-allergenicity btw individual penicillins, Jarish-Herxheimer rxn when treating syphilis

• Characteristics: Pen G (IV), Pen V (PO)
• Prototype beta-lactam antibiotics
• Mechanism:
• 1. binds to penicillin-binding proteins
• 2. blocks transpeptidase cross-linking of cell wall
• 3. Activate autolytic enzymes
• Spectrum: narrow
• Clinical use: bacteriocidal for gram + cocci, gram + rods, gram - cocci and spirochetes, treponema pallium, not penicillase resistant
• Toxicity: hypersensitivity reactions, hemolytic anemia
• Benzathing penicillin G: respository form (half life of 2 weeks)

• Mechanism:
• 1. binds to penicillin-binding proteins
• 2. blocks transpeptidase cross-linking of cell wall
• 3. activates autolytic enzymes
• Spectrum: very narrow
• Clinical use: s. aureus (except for MRSA; resistant bc of altered PBP-target site)
• Toxicity: hypersensitivity reactions, methicillin causes interstitial nephritis
• Elimination: in bile

Use NAF (naficillin) for STAPH

• Mechanism:
• 1. binds to penicillin-binding proteins
• 2. blocks transpeptidase cross-linking of cell wall
• 3. activates autolytic enzymes
• Spectrum: broad: Also combine with clavulanic acid (penicillinase inhibitor) to enhance spectrum
• Clinical use: extended spectrum penicillin- certain gram + (not staph) and gram - rods, borrelia burgdorferi (amox), h pylori (amox)
• Toxicity: hypersensitivity reactions, amipicillin rash; pseudomembranous colitis, GI distress
• Elimination: undergoes enterohepatic cycling, but excreted by kidney

AMPed up on penicillin

• Coverage: ampicillin/amoxicillin HELPS kill enterococci
• Haemophilus influenze
• E coli
• Listeria monocytogenes (amp)
• Proteus mirabilis
• Salmonella
• Enterococci

• Mechanism:
• 1. binds to penicillin-binding proteins
• 2. blocks transpeptidase cross-linking of cell wall
• 3. activates autolytic enzymes
• Spectrum: extended spectrum
• Clinical use: pseudomonas spp. gram -ve rods, susceptible to penicillinase; use with clavulanic acid (beta-lactamase inhibitor)
• Toxicity: hypersensitivity reactions

TCP Takes Care of Pseudomonas

• Mechanism: B-lactam drugs that inhibit cell wall synthesis but are less susceptible to penicillinases, bacteriosidal
• Clinical use:
• 1st generation
• - cefazolin, cephalexin
• - gram + cocci
• - PEcK: Proteus mirabilis, E Coli, Klebsiella
• - surgical prophylaxis
• - no CNS entry
• 2nd generation
• - cefoxitin, cefaclor, cefuroxime
• - gram + cocci, some anaerobes
• - HEN PEcKs: Haemophilus influenzae, Enterobacter aerogenes, Neisseria, Proteus mirabilis, E Coli, Klebsiella pneumoniae, Serratia marcencens
• - CNS entry
• - resistant to most beta-lactamases
• 3rd generation:
• - ceftriaxone, cefotaxime, ceftazidime
• - serious gram - infections resistant to other B-lactams, meningitis (most penetrate the BBB) & sepsis
• - Ex: ceftazidime for pseudomonas
• - Ex: ceftrizxone for gonorrhea
• - most enter CNS (not cefoperazone)
• 4th generation
• - cefepime
• - gram -ve (pseudomonas) and gram + (wider spectrum)
• - resistant to most beta lactamases
• - enters CNS
• -Toxicity: hypersensitivity rx, cross hypersensitivity w/ penicillins, nephrotoxicity of aminoglycosides are increased, disulfiram-like rxn w/ ETOH, + COOMBS test
• if PCN allergy: for gram + use macrolide, for gram - use aztreonam

• Mechanism: monobactram resistant to B-lactamases, inhibits cell wall synthesis (binds to PBP3), synergistic w/ aminoglycosides, no cross-allergenicity w/ penicillins
• Clinical use: Gram -ve rods, Klebsiella, pseudomonas, serratia, no activity against gram +ve or anaerobes
• used in penicillin-allergeic pts and renal insufficiency pts who cannot tolerate aminoglycosides
• Toxicity: usually nontoxic, occasional GI upset, no crossreactivity w/ PCN or cephalosporins
• Administration: IV

• Mechanism:
• Imipenum: broad spectrum, B-lactamase-resistant carbapenem, always administered with cilastatin (inhibitor of renal dihydropeptidase I) to decrease inactivation in the renal tubules
• Clinical use: Gram + cocci, gram - rods, and anaerobes.
• DOC for Enterobacter
• Significant side effects limit use to life-threatening infections, or after other drugs have failed.
• Meropenem, reduced risk of seizures & is stable to dihydropeptidase I
• Toxicity: GI distress, skin rash, CNS (toxicity - seizures), @ hi plasma levels
• Elimination: renal

w/ imipenem "the kill is LASTIN' with ciLASTIN"

• Mechanism: inhibits cell wall mucopeptide formation by binding D-ala D-ala portion of the cell wall precursors, bacteriocidal, resistance occurs w/ amino acid change of D-ala D-ala to D-ala D-lac, doesn't interfere w/ PBPs
• Clinical use: used for serious, gram +ve multidrug-resistant organisms like s. aureus and c. diff (pseudomembranous colitis)
• Toxicity: Nephrotoxicity, Ototoxicity, Thrombophlebitis, diffuse flushing, Red Man Syndrome. (can largerly be prevented by pretreatment w/ antihistamines and slow infusion rate), well tolerated
• Resistance: VRSA, VRE strains
• PK: IV and PO (not absorbed) in colitis, most enters tissues, renal elimination
• Well tolerated in generatl does NOT have many problems

• 30S: Buy AT 30
• A = Aminoglycosides (streptomycin, gentamycin, tobramycin, amikacin) [bacteriocidal]
• T = Tetracyclines [bacteriostatic]

• 50S: CCELL (sell) at 50
• C = Chloramphenicol [bacteriostatic]
• C = Clindamycin [bacteriostatic]
• E = Erythromycin [bacteriorstatic]
• L = Lindcomycin [bacteriostatic]
• L = Linezolid [variable]

• Drugs: Gentamicin, Neomycin, Amikacin, Tobraycin, Streptomycin
• Mechanism: bacteriocidal; inhibition formation fo the inital complex and cause misreading of mRNA, requires O2 for uptake and thus is ineffective against anaerobes
• Clinical use: severe gram - rod infections, synergistic w/ B-lactam abx, Neomycin is used for bowel surgery
• Toxicity: Nephrotoxicity (especially when used w/ cephalosporins), Ototoxicity (especially when used with loop diuretics), Teratogen
• PK: polar, not well absorbed orally, low Vd, renal elimination

• "Mean" GNATS canNOT kill anaerobes
• amiNOglycosides:
• N = need O = oxygen
• N = nephrotoxicity O = ototoxicity

• Drugs: Tetracycline, doxycycline, demeclocycline, minocycline
• Mechanism: bacteriostatic, binds to the 30S and prevents attachment of aminoacyl-tRNA; limited CNS penetration
• Elimination: doxycycline is fecally elminated and can't be used in renal failure
• Absorption into gut is inhibited by milk, antacids, or Fe-containing compounds
• Clinical use: Vibrio cholera, Acne, Chlamydia, Ureaplasma, Urealyticum, Mycoplasma pneumonia, Tulermia, H. pylori, Borrelia burgorferi (Lyme disease) Rickettsia
• VACUUM THe BedRoom
• Toxicity: GI distress, dicolouration of teeth, inhibition of long bone growth in children, photosensitivity, CONTRAINDICATED IN PREGNANCY

• more activity overall than tetracyline HCL
• special use: prostatitis - reaches high levels in the prostatic fluid

in saliva and tears at high concentrations, uses in meningococcal carrier states

More use in SIADH by blocking the ADH recpetor function in the collecting ducts

• Drugs: Erythromycin, azithromycin, clarithromycin
• Mechanism: inhibit protein synthesis by blocking translocation of the ribosomal subunit, bacteriostatic
• Clinical use: URI, pneumonias, STD (gram + cocci), streptococcal infections in patients that are allergic to PCN, mycoplasma, legionella, chlamydia, neisseria, campylobacter jeuni, MAC, h. pylori
• Toxicity: prolongs QT interval (especially erythromycin), GI discomfort (most common cause of noncompliance, due to motilin receptor activation), acute cholestatic hepatitis, eosinophilia, skin rash, increases the [ ] of theophyllines & oral anticoagulants, reversible deafness @ hi doses
• PK: inhibit P450

• Mechanism: inhibits 50S peptidyltransferase activity, bacteriostatic
• Clinical use: meningitis (h. influenzae, neisseria meningititids, strep. pneumo) conservative use owing to toxicity
• Toxicity: anemia (dose dep), aplastic anemia (dose indep), Gray Baby Syndrome (in preme bc they lack the liver UDP-glucuronyl transferase)
• PK: PO, good tissue distribution (into CSF too!), hepatic glucuronidation (dose reduction needed in liver failure and neonates), inhibition of CYP450

• Mechanism: blocks peptide bond formation at 50S ribosomal subunit, bacteriostatic, not a macrolide
• Clinical use: treats anaerobic infections (bacteroides fragilis, clostridium perfringes), narrow spectrum gram + cocci (including community MRSA), osteomyelitis (bc it concentrates in bone)
• Toxicity: pseudomembranous colitis (c. diff overgrowth), fever, diarrhea

treats anaerobes above the diaphragm

• Mechanism: inhibit formation of intiial complex in bacterial translation systems by preventing formation of N-formylmethionyl-ribosome-mRNA complex
• Spectrum: tx of VRSA, VRE, drug resistant pneumococci
• Side effects: bone marrow suppression (platelets)

Mechanism: several: binding to sites on 50S subunit, prevent the interaction of amino-acyl-tRNA w/ acceptor site, stimulate it dissociation from ternary compplex, decreases the release of completed polypeptide by blicking its extrusion

• Drugs: polymyxin B, polymyxin E
• Mechanism: bind to cell membranes of bacteria and disrupts the osmotic properties
• Characteritics: polymyxins are cationic, basic proteins that act like detergents
• Clinical use: resistant gram -ve infections
• Toxicity: neurotoxicity, acute renal tubular necrosis

MYXins MIX up the membrane

• Drugs: Sulfamethoxazole SMX), sulfisoxazole, sulfadiazine
• Mechanism: PABA antimetaboltes inhibit dihydropteroate synthesase, bacteriostatic
• Clinal use: gram +, gram -, nocardia, chlamydia, toxo, p. jiroveci simple UTI (triple sulfa or SMX), sulfonamides alone not used much due to resistance, sulfasalazine: uclerative colitis, RA, + Ag in burns
• Toxicity: hypersensitivity reactions, hemolysis of G6PD deficient, nephrotoxicity (tubulointerstital nephritis), photosensitivity, kernicterus in infants, displaces other drugs from albumin (ie warfarin)
• PK: hepatically acetylated (conjugation), renal excreted metabolites cause crystalluria, high protien binding

• Mechanism: inhibits dihydrofolate reductase, bacteriorstatic
• Clinical use: combined w/ sulfonamides (TMP-SMX), sequentially blocks folate synthesis, combination used for recurrent UTI infections, shigella, salmonella, pneumocystis jiroveci pneumonia
• Toxicity: megaloblastic anemia, leukopenia, granulocytopenia (may alleviate with supplemental folinic acid)

TMP = Treats the bone Marrow Poorly

if pts don't tolerate sulfa they can't be given any of the sulfa drugs including: sulfasalazine, sulfonylureas, thiazide diurectics, acetazolamide, or furosemide

• Drugs: ciprofloxacin, norfloxacin, ofloxacin, sparfloxacin, moxifloxacin, etc. naldixic acid (a quinolone)
• Mechanism: inhibits DNA gyrase (topoisomerase II & IV), bactericidal, can't take with antacids (Fe/Ca limit absorption)
• Clinical use: gram - rods of urinary tract or GI tract (including pseudomonas), neisseria, some gram +ve, PID, STD, UTI
• Toxicity: GI upset, superinfections, skin rash, headache, dizziness, CONTRAINDICATED IN PREGNANCY and CHILDREN bc animal studies show cartilage damage, tendonitis, tendon ruptures in adults, leg cramps and myalgias in kids
• PK: reanl elmilation (inhibited by probenecid)

fluoroquinoLONES hurts the attachment to BONES

• Mechanism: forms toxic metabolites in the bacterial cell that damages DNA, bactericidal, antiprotozoal
• Clinical: Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, Aanaerobes (bacteroides, clostridium), triple therapy for h. Pylori (metronidazole + bismuth + amoxacillin/tetracycline)
• Toxicity: disulfiram-like rxn w/ ETOH; headache, metallic taste

• GET GAP on the Metro!
• Anaerobic infections below the diaphragm

Get BaCk on the Metro, G!

• Mechanism: inhibits DNA-dep RNA polymerase
• Clinical use: mycobacterium tuberculosis delays resistnace to dapsone when used for leprosy, meningococcal prophylaxis & chemoprophylaxis in children with h. flu type B exposure
• Toxicity: minor hepatotoxicity, drug interactions (increased P-450), orange body fluids (nonhazardous)

• Treponema: PenG (+benzamine to last longer), may try to desensitize
• Gonorrhea: ceftriaxone (3rd gen ceph) -ax drugs
• Chlamydia: macrolides or tetracyclines
• Trichamonas: macrolides

• Listeria: ampicillin, + -ax if young/elderly
• Neonatal or elderly meningitis: ampicillin + -ax drug
• Meningitis: adult/empiric -ax drug (give an axe to the head
• UTI, PJP, community aquired MRSA: TMP-SMX
• Hospital aquired MRSA: vancomycin
• Empiric treatment for pneumonia: -penums
• Pneumonia: macrolide
• (causes: typical - strep pneumo, atypical mycoplasma, listeria)
• Most broad abx: meropenum, amipenum-should be comebined with cilastatin to prevent amipenum toxicity NOT A STATIN!
• Gram -: -ax drugs, fluoroquinolones
• Gram +: vanco

RESPIre = Rifampin, Ethambutol, Streptomycin, Pyrazinamide, Isoniazid

• - Combination therapy is the rule
• - Primary drug combo: rifampin, ethambutol, isoniazid, pyrazinamide
• - Back up drugs: aminoglycosides (streptomycin, amidacin, kanamycin), fluoroquinolones, capreomycin (markedhearing loss), cycloserine (neurotoxic)
• - Prophylaxic tx: INH, rifampin if intolerant

dose dep retrobulbar neuritis = decreased visual acuity and redgreen discrimination

side effects: hepatitis, hyperuricemia (100% of ppl)

• Mechanism: protein synthesis inhibition
• Side Effects: deafness, vestibular dysfn, nephrotoxicity

• Mechanism: inhibits mycolic acid synthesis, prodrug that requires catalase conversion, high resistance
• Side Effects: hepatitis, peripheral neuritis (use B6), siderblasitc anemia (use B6), SLE-like sydnrome- slow acetylators

• Prophylaxis: azithromycin
• Tx: azithromycin, rifampin, ethambutol, streptomycin

• Prophylaxis: none
• Tx: Dapsone, rifampin, clofazimine

• Mechanism: binds ergosterol (unique to fungi), and tears holes in mb to allow for elyte leakage
• Clinical use: wide spread systemic mycoses (crypto, blastomyces, cocciodiodes, aspergillus, histo, candida, mucor), intrathecally for fungal meningitis, does not cross BBB
• Toxicity: Fever/chills (shake'n'bake), hypotension, nephrotoxicity (dose dep), arrhythmias, anemia (less EPO), IV phlebitis, (essentially amphoterrible!), hydration reduces nephrotoxicity, liposomal ampho reduces toxicity and Na loading (allowing less amp B to be needed)
• PK: IV slow infusion, poor CNS penetration, slow clearance (t1/2 >2 wks)weeks

• Mechanism: binds to ergosterol, tears holes in mb to allow for elyte leakage
• Toxicity: too toxic for systemic use
• Clinical use: 'swish and swallow' for oral candidiasis (thrush), topical for diaper rash or vaginal candidiasis

• Drugs: fluconazole, ketoconazole, clotrimazole, any -azole drug
• Mechanism: inhibit ergosterol synthesis at 14-alpha-demethylase (P450 enzyme), resistance if it cant be [ ] inside the cell
• Clinical use: systemic mycoses
• fluconazole: for cryptococcal meningitis in AIDS (bc it can cross the BBB)
• candida infections of all kinds
• Ketoaconazole: blastomycoeces, coccidioides, histo, candida, hypercortisolism
• Clotrimazole/miconazole for topical fungal infections
• Itraconazole/Voriconazole: DOC for balstomycoses, sporotrichoses, aspergillosis, back up drug
• Toxicity: hormone synthesis inhibition (gynecomastia), liver dysfn (inhibits CYP-450), fever/chills
• PK: PO, absorption decreased by antacids, increased itraconazole by food

• Mechanism: 5FU is formed by activated fungal cystosine deaminase that can:
• a) 5FU be incorporated into fungal RNA
• b) 5FU inhibits DNA synthesis by conversion to 5-Fd-UMP by thymidylate synthase, which decreases thymine
• Clinical use: systemic fungal infections (candida, crypto), in combo with ampB
• Toxicity: n/v/d, bone marrow suppression, enters CNS

• Mechanism: inhibits cell wall synthesis by inhibiting synthesis of B-glucan
• Clinical use: invasive aspergillosis
• Toxicity: GI upset, flushing

• Mechanism: inhibits fungal enzyme squalene epoxidase
• Clinical use: dermatophytoses (oncomycosis)
• Side effects: GI distress, rash, headahe, increased LFT = hepatoxicity

• Mechanism: interferes with microtubule function; disrupts mitosis, deposits in keratine-containing tissues (ie nails)
• Clinical use: oral tx of superficial infections, inhibits dermatophytes (tinea, ringworm)
• Toxicity: teratogenic, carcinogenic, confusion, headaches, increased P450, warfarin metabolism, disulfiram-like rxn

• -avir = AIDS virus drugs
• -ivir = Influenza virus drugs
• -ovir = herpes virus drugs

• Mechanism: blocks viral penetration/uncoating (M2) protein; may buffer pH of endosome, causes release of DA from intact nerve terminals
• A man to dine takes of his coat
• Clinical use: prophylaxis and tx of influenza A, parkinson's disease
• Toxicity: ataxia, dizziness, slurred speech
• Mechanism of resistance: Mutated M2 protein, 90% of all influenza A strains are resistance, so not used
• Safer derivative: Rimandatine: fewer CNS side efects (doesn't cross BBB)
• Amantadine blocks influenza A and rubellA and causes problems in the cerebellA

• Mechanism: inhibits influenza neuroaminidase, decreases release of viral progeny, decreased penetration
• Clinical use: influenza A and B, mostly prophylaxis but may decrease by 2 - 3 days

• Mechansism: damages RNA (prevents end-capping), inhibits syntehsis of guanine nucleotides by competitively inhibiting IMP dehydrogenase
• Clinical use: RSV, chronic hep C, RSV, Lassa fever, Hantavirus
• Toxicity: hemolytic anemia, severe teratogenicity, upper airway irritation

• Mechanism: monophosphorylated by HSV/VZV thymdine kinase guanosine analg, triphosphate formed by cellular enzymes, preferentially inhibits viral DNA pol by chain termination
• Clinical use: HSV, VZV, EBC, used for HSV-induced mucocutaneous and genital lesions, encephalitis, prophylaxis in immunocompromised pts, herpes zoster should use famiciclovir, no effect on latent HSV/VZV
• Toxicity: well tolerated
• Mechanism of resistance: lack of thymidine kinase

• Mechanism: 5'-monophosphate formed by CMV viral kinase or HSV/VZV thymidine kinase, guanosine analogue, triphosphate formed by cellular kinases, preferentially inhibits viral DNA polymerase
• Clinical use: MCV, especially immunocompromised pts
• Toxicity: leukopenia, neutropenia, thrombocytopenia, renal toxicity, more toxic to host enzymes than acyclovir
• Mechanism of resistance: mutated CMV DNA pol or lack of viral kinase

• Mechanism: viral DNA polymerase inhibior that binds to the pyrophosphate-binding site of enzyme, does not require activation by viral kinase
• Clinical use: CMV retinitis in immunocompromised pts when gancyclovir fails; acyclovir-resistant HSV
• Toxocity: nephrotoxicity
• Mechanism of resistance: mutated DNA pol

FOScarnet = pyroFOSphate analogue

• Herpes (-ovir, needs to be phosphorylated)
• CMV: gancyclovir, foscarnet
• HIV: NRTI, NNRTI, -avir, protease inhibitors
• Hep C: Interferon alpha + Ribaviron

Amantadine, enfuvirtide, maraviroc

Acyclovir, foscarnet (not phosphorylated), ganciclovir (phosphoryalted)

• Foscarnet
• ribavirin

• zanamivir
• osteltamavir

• RTI: Reverse Transcriptase Inhibitors-original inhibitors of reverse transcriptases are ucleoside antimetabolites that are converted to active forms via phosphorylation ractions
• NRTI: Non Reverse Transcriptase Inhibitors-made in most combo drug regimens, used w/ protease inhibitors, highly active antiretrovial therapy (HAART) = decreased viral RNA, reversal of decline in CD4 cells, decrease opportunistic infections
• Protease inhibitors
• Fusion inhibitors

Drugs: Zidovudine (formerly AZT), didanosine (DDI), Zalcitabine (DDC), Stavudine (D4t), laivudine (3TC), abacavir

have YOU (vudine) with my nuclear (nucleosides) family?

• Mechanism: preferentially inhibits RT of HIV; prevents incorporation of DNA copy of viral genome into hose DNA
• Toxicity: bone marrow suppression (neutropenia, anemia), peripheral neuropathy, lactic acidosis

clinical use: when CD4 coutnts get low (~500 cells/mm³) or high viral load

Drugs: Nevirapine, Efavirenz, Delavirdine

Never Ever Deliver nucleosides

• Mechanism: perferentially inhibits the RT of HIV; prevents incorporation of DNA copy of viral genome into host DNA
• Toxicity: bone marrow suppression (neutropenia, anemia), peripheral neuropathy, rash, megaloblastic anemia (ZDV)
• (~500 cells/mm3) or high viral load

• Characteristics: nucleoside
• Mechanism: phosphorylated nonspecifically to a triphosphate = inhibits reverse transcriptase by competing with natural nucleotides, can also be incorporated into viral DNA = chain termination
• Toxicity: hematoxocity (majoy & dose limiting), headache, asthenia, myalgia, peripheral neuropathy
• Clinical use: general prophylaxis and during pregnancy to reduce fetal transmission

• Mechanism: phosphorylated nonspecifically to a triphosphate = inhibits RTase, incorporated into viral DNA = chain termination
• Toxicity: pancreatitis (major/dose limiting), peripheral neuropathy, hyperuricemia, liver dysfn

• Mechanism: aspartate protease (pol gene encoded) is a viral enzyme that cleaves precursor polypeptides in HIV pbuds to form proteins of the mature virus core, this enzyme contains dipeptide structure that is not seen in mammilian proteins: PIs bind to this protein = inhibiting the enzyme
• Resistance: via specific point mutation in pol gene = not complete resistance btw different PIs
• Clinical uses: always in combo with 2 NRTIs - Indinavir, ritonavir, saquinavir (least toxic, low oral bioavailability, predisposition to developing resistance)
• Toxicity: nephrotoxicity
• Mechanism of resistance: mutated DNA polymerase

NAVIR (never) TEASE a proTEASE

• Clinical use: in combo with ritonavir
• Side effects: crysalluria (maintain hydration)
• Genearl: sydnreom of disordered lipid and CHO metabolism w/ central adiposity and insulin resistance

• Clinical use: in combo with Indinavir
• Side effects: major drug interactions: induces CYP 1A2 and inhibits major P450 isoforms (3A4, 2D6)
• General: sydnreom of disordered lipid and CHO metabolism w/ central adiposity and insulin resistance

• Mechanism: binds tcells the gp41 subunit; inhibit confirmational chg needed for fusion with CD4 = block entry and subsequent replication
• Toxicity: hypesensitivity reactions, rxns at subcutaneous injection site, increased risk of bacterial pneumonia
• Clinical use: persisten viral replication in spite of antiretroviral therapy, used in combo w/ other drugs

Mechanism: blocks CCR5 proein on T cell surface = viral entry inhibited

• Clinical uses:
• Chloroquine-sensitive regions: Prophylaxis = chloroquine +- primaquine, back up = hydroxychloroquine, primaquine, pyrimethamine-sufladoxine
• Specifically:
• p. falciparum - chloroquine
• p. malariae - chloroquine
• p. vivax - chloroquine + primaquine
• p. ovale - chloroquine + primaquine

• Chloroquine-resistant areas:
• Prophylaxis = mefloquine, backup doxy, atovaquone-proguanil
• Tx = quinine +- doxy, clinda, pyrimethamine

Side effects: hemolytic anemia in G6PD deficiency (primaquine, quinine), cichonism (quinine)

• Most intestinal nematodes (worms)
• - Mebendazole (decreases glu uptake and decreases microtubular structure)
• - Pyrantel pamoate (NM agonist = spastic paralysis)

• Most cestodes (tapeworms) & trematoads (flukes)
• - Praziquantel (increases Ca influx, increases vacuolization)