B7 Pharmacology Exam 1
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
