B7 Pharmacology Exam 1 100% PASS

Description of Malaria - paras inf by Plasmodium spp (P. falcip, P. vivax, P. ovale, P. malariae, P. knowlesi) by Anopheles mosq vector not aff by paras - complex life cyc incl erythro stage (want to prev this stage, causes clin illness) & exo￾erythro stage (dormant in liv as hypnozoites) transm in regs near equat temps >68F Non-Pharm Prevention of Malaria - - travs to endem regs receive chemo-proph dep on who, where, when trav going, what style trav, trip dur - NO proph regimen compl effec --> comb w/ pers prot meas (ie. repellant, long sleeves+pants, mosq-free sleeping, bed nets) - can be more severe in preg wom incr risk adv preg outc --> CDC rec avoid preg trav b/c INCR SUSC to P. flacip inf by decr Bc imm Examples of Drugs for Malaria Prevention - - Atovaqone/Proquanil - Chloroquine - Doxycycline - Mefloquine - Primaquine - Tafenoquine MOA, Indications, AEs, CIs, DIs, Clinical Pearls of Atovaquone/Proguanil - - MOA = Atov sel inhib mitoch e- transp erythro+exoerythro stages stopping P. from making energy; Prog metab to active cycloguanil inhib DHFR pyrim synth disr paras DNA synth - Indics = uncomplic malar treat+proph of P. FALCIP+VIVAX - AEs = common prur, GI disturb, elev LFTs; serious neutrop, pancytop, hep, liv fail - CIs = proph in ren impair CrCl<30; only for treatm max 3d if benef>risk - DIs = Warf --> incr INR so mon; Rifamycins --> incr metab decr antimal effic; live chol vacc (get before starting Atov) - Pearls = good for last min travs (1-2d prior to trip); well-tol, take w/ food/milk optim absorp+decr GI up; **AVOID Atov in preg**; **TOC for peds>5kg** MOA, Indications, AEs, CIs, DIs, Clinical Pearls of Chloroquine - - MOA = prev heme biocryst w/ buildup causing paras tox - Indics = uncompl malaria treat+proph; also non-intest amebic inf & off-lab for sarcoidosis - AEs = common prur, blur vis, GI disturb; serious CV, SJS, TEN, hypogly, hemol anem, anaph, seiz, mac/ret disord esp from LT high-dose ther; **hemol anem most in G6PD def pts** - DIs = QTc prol ags (ie. antipsychs, azole antifungs, antiarr, FQ abx, TMP/SMX) decr absorp; Cimetidine --> chloroq tox (agit, seiz, card arr); Mg/Ca antac --> decr chloroq gut absorp; Mefloq --> convul, EKG abnorms, card arr; Rabies+Chol vaccs decr AB resp; Proguanil --> mouth ulcers - Pearls = NOT good for last min travel (start 1-2w prior); DO NOT use in Chlorq/Mefloq resis areas; give weekly so GOOD for longer trips; Hydroxychloroq (RA) as proph; **SAFE in preg** B7 Pharmacology Exam 1 MOA, Indications, AEs, CIs, DIs, Clinical Pearls of Doxycycline - - MOA = tetracyc inhib 30S ribos subun halt RNA transc intef w/ bac+paras prot synth - Indics = malar treat adjunct, malar proph esp in areas high prev MDR P. falcip - AEs = common photosens --> wear sunscr/prot clothing; serious exfol rash, hepatotox, C. diff assoc diarr (CDAD) - DIs = di-/trival cations chelation; PCN decr effic; MXT incr tox; live chol vacc decr imm resp; retinoids (ie. isoretinoin) - Pearls = inexpensive; GOOD for last min trav (start 1-2d prior); **prev Rickettsial dis & leptospirosis**; no add med if taking chron for acne; **DO NOT use for preg women** MOA, Indications, AEs, CIs, DIs, Clinical Pearls of Mefloquine - - MOA = P. schizonticide for erythro stage; elim t1/2 13-30d - Indics = uncomplic P. FALCIP+VIVAX proph/treat; Chloroq-resis P. falcip - AEs = common brady, GI disturbs, dizz, neuro/psych AEs; serious prol QTc interv, seiz, suicidality - CIs = quinine/quinidine hypersens; prophyl in pts w/ convul disords, psych conds (ie. depr, anx, psych, schiz) --> wors psych sx by crossing BBB - DIs = quinine, QTc prol ags (many CI), CYP3A4 inhibs b/c Mefloq metab by 3A4 - Pearls = take weekly so good for longer trip; **RESIS so not rec for SE As inf**; **CAN be used in preg**; NOT REC for pts w/ card cond disords, seiz disords, psych conds MOA, Indications, AEs, CIs, DIs, Clinical Pearls of Primaquine - - MOA = tiss shizonticide erad dev+lat exoerythro shiz in liv; erad hypnoz in "rad cure" P. OVALE+VIVAX - Indics = malar relapse prev; off-lab for proph - AEs = **BBW physic should compl famil themselves w/ compl conts leaflets before Rx primaq phosph**; common GI; serious hemol anem, leukop, metHgbemia (rare w/ malar treat) - DIs = pot hemol drugs & BM myel els depressants - Pearls = most effec for P. VIVAX PREV; good for last in travs+shorter trips b/c take 1- 2d before/7d after; **MUST test for G6PD def prior**; led to discov of G6PD def Description & Sx of Hemolytic Anemia - acq iatrog/inher incr RBC destr - G6PD = NADP+ to NADPH; only RBC def ag oxid stress so decr RBC lifesp if G6PD def; XL mut w/ def by decr in vivo enz stab, decr enz activ so accel RBC aging; maybe P. falcip resis - precip Hgb drop --> weak, fatigue, pallor, dyp; jaund+dark ur by hgburia progr to ARF - incr MCV+MCH, bili, LDH, decr-decr haptogl MOA, Indications, AEs, CIs, DIs of Tafenoquine - - MOA = anti-hyponoz activ, also ag eythro forms+gametos - Indics = P. VIVAX >/=16y/o for prophyl, treat, RADICAL cure; prophyl but NOT treat for P. FALCIP - AEs = common dizz, GI, HA, Hgb decr; severe hemol anem, psych exac - DIs = incr levs metformin, plat chemo comps **REQUIRES G6PD def screen prior** B7 Pharmacology Exam 1 Atovaqone/Proguanil for Malaria Prophylaxis - - taken DAILY - Start 1-2d before entering mal-end area - Stop 7d after leaving mal-end area Chloroquine for Malaria Prophylaxis - - Taken WEEKLY - Start 1-2w before entering mal-end area - Stop 4w after leaving mal-end area Doxycycline for Malaria Prophylaxis - - Taken DAILY - Start 1-2d before entering mal-end area - Stop 4w after leaving mal-end area Mefloquine for Malaria Prophylaxis - - Taken WEEKLY - Start 2w before entering mal-end area - Stop 4w after leaving mal-end area Primaquine for Malaria Prophylaxis - - Taken DAILY - Start 1-2d before entering mal-end area - Stop 7d after leaving mal-end area Tafenoquine for Malaria Prophylaxis - - Taken WEEKLY - Start 3d before entering mal-end area - Stop 7d(1x dose) after leaving mal-end area What to use for Malaria Prophylaxis in Chloroquine-SENSITIVE Areas - - Chloroq/Hydroxychloroq - Atov/Proguan - Doxy - Mefloq esp in PREG - Tafenoq - Primaq where P. vivax >90% causative org What to use for Malaria Prophylaxis in Chloroquine RESISTANT Areas - - Atov-Proguan - Doxy - Mefloq esp in PREG unless resis prev - Primaq when P. viv caus org >90% cases - Tafenoq Alternatives for Malaria Prophylaxis - - Pyrimethamine = NOT 1st line, may be cost prohib so not widely avail; taken once weekly - Sulfadoxine/Pyrimethamine = NOT 1st line, taken once weekly for those trav to chloroq resis areas w/ allergs to pref proph; if take in this case, bring one dose treatment along just in case - Dapsone = off-lab w/ effic in peds; G6PD def screen req+freq CBCs during init B7 Pharmacology Exam 1 Anti-Malarials for Treatment of HIV-opportunistic Infections - - Pyrimethamine for Toxo+PJP - Sulfadoxine/Pyrinmethamine for congen Toxo - Dapsone for PJP proph+treat Description & Mechanisms of Resistance to Anti-Malarials - - resis most prob w/ P. FALCIP & incr w/ P. VIV - not all drug fail by paras resis but fail may facil resis dev - app through spont gen muts & following sel pressure by drug by rem stab after drug regim remov (ie. endem resis) - Mechs of Resis = Chloroq --> efflux lim accum req for heme polym; Atov --> sing pt mut cyt b, lim by proguan/tetracyc use; Dapsone --> fol synth enz muts Presentation of Uncomplicated Malaria Illness - - incub 7-30d, shorter w/ P. falcip & longer w/ P. malar; longer incub w/ P. ov+viv esp w/ proph b/c dorm liv stage - 3-stage "malar attacks" w/ cold (shiv), hot (fev, HA, vom), sweating (nl temp return, fatigue) stages every 2nd-3rd day - sim to cold/flu/comm inf esp where malar not endem Presentation of Complicated (Severe) Malaria Illness - **MED EMERG** most by P. FALCIP - pref IV ther - serious org fail, bl/metab abnorms incl cer malar (impair consc, seiz, coma, neuro sx), sev anem, hgburia, ARDS, coag abnorms, low BP+CV coll, ac ren fail, hyperparas w/ >5% RBC inf, metab acid, hypogly (also by quinine) Overview of Malaria Treatment - - dep on dis sev/clin status, species, area of acquis (drug susc prediction) - CDC Malar hotline 24/7 for consultation - preg pt treat diff than not preg - if dev desp chemoproph --> DO NOT use chemoproph ag in treat reg b/c already exp to this drug so may dev resis - Peds regimens = wt-based dose but same drugs as adults EXCEPT **NO DOXY if <8y/o & NO TAFENOQ if <16y/o** How to Treat Uncomplicated P. falciparum/unknown spp in Non-Pregnant Adults & Children (CHLOROQ resis/unknown resistance) - - Artemether/Lumefantrine - Atov/Proguan = PREF in peds - Quinine+one of: Doxy, tetracyc, clinda - Mefloq = less pref b/c psych effs **Doxy/tetracyc NOT in kids<8y/o** How to Treat Uncomplicated P. Falciparum in Pregnancy (CHLOROQ resis/unknown resistance) - - Quinine+Clinda - Mefloq - Aremether-lumefantrine in 2nd+3rd trims B7 Pharmacology Exam 1 How to Treat Uncomplicated P. vivax in Non-Pregnant Adults & Children (CHLOROQ resis/unknown resistance) - - Quinine + Doxy OR Tetracyc + primaq - Atov/proguan + primaq - Mefloq + Primaq - Tafenoq **only in kids>16y/o** How to treat Uncomplicated P. vivax in Pregnancy (CHLOROQ resis/unknown resistance) - - compl treatm regim as dir - Chloroq prophyl dur preg - Primaq/Tafenoq after deliv unless G6PD def How to treat Uncomplicated P. falciparum/malariae/unknown spp in Non-Pregnant Adults & Children (CHLOROQ SENS area) - chloroq or hydroxychloroa How to treat Uncomplicated P. vivax & P. ovale in Non-Pregnant Adults & Children (CHLOROQ SENS area) - Chloroq/hydroxychloroq then add Primaq/Rafenoq unless G6PD def **Tafenoq only in kids>16y/o** How to treat Uncomplicated P. malariae & P. knowlesi in Non-Pregnant Adults & Children (CHLOROQ SENS area) - chloroq/hydroxychloroq How to treat Uncomplicated P. falciparum/malariae/unknown spp in Pregnancy (CHLOROQ SENS area) - Chloroq/Hydroxychloroq How to treat Uncomplicated P. vivax & P. ovale in Pregnancy (CHLOROQ SENS area) - - compl treatm reg as directed - Chloroq proph dur preg - Primaq/Tafenoq after deliv unless G6PD def How to treat Uncomplicated P. malariae & P. knowlesi in Pregnancy (CHLOROQ SENS area) - Chloroq/Hydroxychloroq How to treat Complicated Malaria of any Species in Non-Pregnant Adults & Children - Artesunate followed by one of: - Artemether-lumefantrine - Atov-prog - Quinine+Doxy or clinda - Mefloq (LAST LINE b/c AEs) How to treat Complicated Malaria of any Species in Pregnancy - Artesunate followed by one of: - Clinda - Mefloq B7 Pharmacology Exam 1 MOA, Indications, AEs, CIs, DIs, Clinical Pearls of Artemether/Lumefantrine - - MOA = inhib paras nuc ac+prot synth of erythro stage --> resis can occur to lumefant but artemether shown to mitig this in vivo - Indics = uncomlic P. FALCIP - AEs = overall well-tol; common palps, GI, arthralg, myalg, asthenia, sleep disord; serious **delayed hemol** (may need transfus), prol QTc interv, splenomeg, hepatomeg - CIs = strong 3A4 inhib drugs (rifampin, carbamaz, phenyt); **CAUTION in cardiac conds arryth/sev HD** - DIs = 3A4 inhibs (ie. ketocon, primidone), QTc prol drugs (ie. antipsychs, antiarryth, - azole antifungs, FQs), decr effic w/ 3A4 inds, red lumefantrine levs+effic w/ Mefloq, card effs w/ 2D6 subs (ie. TCAs, flecainide) - Pearls = give w/ food incr abs+decr GI disturb; no dose adj in ren/hep insuff but ens benef>risk in sev impair MOA, Indications, AEs, CIs, DIs, Clinical Pearls of Quinine sulfate - - MOA = inhib nuc ac+prot synth, inhib glycol, bind hemazoin aff erythros - Indics = uncomplic P. FALCIP+VIVAX; babesiosis; off-lab adjunct for chron leuk, labor ind, leg cramp prophylaxis (**BBW use for treat/prev nocturn leg cramps can res in ser+life-threat hemat rxns, risk>benefs**) - AEs = common dermatitis, blur vis; serious CV+hemat effs, cinchonism, ototox, HUS, ren fail - CIs = G6PD def, mefloq hypersens by cross-sensit, myasth grav (exac), op neuritis, prol QTc - DIs = QTc prol drugs; decr effic w/ rifamp+carbamaz; incr quinine w/ Ritonavir; digitialis tox w/ digox; decr abs w/ Mg/Al antacs - Pearls = hypogly monitoring esp in preg); incr adv drug rxns in mild-mod hep impair MOA, Indications, AEs of Artesunate - - MOA = free O2 rad prod interf w/ paras func; derived from Sweet Wormwood (artemisia annua) - Indics = **TOC for COMPLIC** Malaria; in seq w/ one of: artem+lumef, atov-prog, quin+doxy/clinda, mefloq - AEs = common n/v, dizz, anorex; serious neutrop, anem, hemol, elev LFTs, ?neuro tox (likely from malar itself not treatment) **benef of treatment>risk in preg** MOA, Indications, AEs, DIs of Clindamycin for Malaria - - MOA = inhib 50S rib subun inhib prot synth - Indics = **pref in PREG (quinine+clinda) for uncomplic illness & complic illness as seq w/ artesunate** - AEs = common rash, GI, diarr; serious C. diff diarr, exfol rash, hepatotox - DIs = DO NOT use w/ erythromycin b/c antag antimic effs, live cholera vacc