Antiparasitic Agents

Mechanism Target Adverse effects Miscellaneous

ANTIHELMINTIC AGENTS : Nematodes
Benzimidazoles - Anti-microtubule - Albendazole : - well tolerated - poorly absorbed
- Albendazole = impaired cell devision, › intestinal nematodes - increase absorption with fatty meal
- Mebenazole motility, cytoplasmic transport › Strongyloides 2nd line - Albendazole : metabolized to active
(glucose uptake) › Cutaneous, Visceral metabolite + well distribute to
- bind to ß-tubulin of nematodes larva migrans tissues/CSF
= ovicidal + larvicidal › Cysticercosis (ใ ้คู่กับ - Mebendazole : metabolized to
- bind to ß-tubulin of larval corticosteroids, ฆ่าเฉพาะ viable cyst) inactive metabolite
cestodes › Hydatid disease
= disrupt intrigity of protoscolex - Mebendazole :
› intestinal nematodes
Ivermectin -
- Activate Cl channel of GABA - Strongyloides 1st line - well tolerated - Good, rapid absorption
receptor, Glutamate-gated Cl - - cutaneous larva migrans - host Inflammatory - High Vd
channel (specific to nematodes) - Microfilariacidal (ฆ่า response to dying - P-gp substrate (ไม่เข้า BBB)
= Hyperpolarize flaccid adult worms ไม่ได้) microfilariae - Metabolited to inactive metabolite
paralysis, pharyngeal paralysis › Onchocerciasis 1st line
(inhibit feeding) › Lymphatic filariasis
- = Expulsion from intestine
Diethylcarbamazine - Immobilization, Alteration of - Lymphatic filariasis - host reaction to - Good, rapid absorption
(DEC) surface structure of microfilariae (drug of choice) protein release from - Rapidly distributed to tissue
› micro = rapidly killed dying parasites - Excreted unchanged form in urine
› adult = slowly killed - N/V, anorexia fever - selective, mass drug administration
** C/I Onchocerciasis headache, dizziness,
(River blindness) muscle/joint pain
- limited effect by
Antihistamine

ANTIHELMINTIC AGENTS : Tapeworm

Niclosamide - Inhibit oxidative phosphoryla- - Intestinal tapeworms - infrequent, mild - Poorly absorbed
tion = Interfere energy production (เฉพาะ adult) and transient GI - Alcohol increase absorption
in tapeworms ** T. solium : ใ ้ fast- irritation ( แต่ต้องการใ e้ ffectในGI ดังนั้น ้ามกิน)
- destroy scolex and segments of acting laxative ex. MgSO4
tapeworms ร่วมด้วย
Praziquantel - increase calcium influx Mature/larval stage of - infrequent, mild - Good, rapid absorption
= spastic paralysis - Trematodes and transient GI - High Vd, cross BBB
- Cestodes irritation, malaise - CYP 450 substrate (metabolized to
› intestinal tapeworms headache dizziness inactive metabolite)
› cysticercosis fever rash - Corticosteroid decrease drug level
› Hydatid disease
** C/I ocular cysticercosis
Doxycycline - Slowly eliminated Wolbachia - Filariasis - ไม่ใช้รัก า filariasis เดี่ยว ๆ ต้องใช้
(endosymbiotic bact. of filarial ร่วมกับยาอื่น
nematodes) = microfilaricidal
- long term sterility of female
macrofilariae
ANTIPROTOZOAL AGENTS : Non-antimalarial
Nitromidazoles - DNA synthesis inhibitor - bacteria - GI disturbances, - Well, rapid absorption
- Metronidazole Ferridoxin donate e- reactive › anaerobe, microaerophillic headache, dizziness - High Vd, cross BBB
- Tinidazole nitro anion inhibit DNA - Protozoa (ไม่ฆ่า cyst) (Tinidazole: fewer, milder) - Tinidazole = longer half-life
synthesis cell death › Amebiasis (doc) - reddish-brown - Metronidazole : CYP450 substrate
› Trichomoniasis (doc) urine
› Giardiasis (doc) - Disulfram-like
reaction
Co-trimoxazole - Antimetabolites : block neucleic - Protozoa Bone .folic folinic
marrom vd De :
( Trimethoprim - acid synthesis › Cystoisosporiasis (doc)
Sulfonamides) › Trimethoprim: competitive › Cyclosporiasis (doc) suppression
** IV form inhibitor of dihydrofolate - Fungus
Tnp -
smy
reductase › Pneumocystis
› Sulfonamides: competitive pneumonia (PCP) (doc)
inhibitor of dihydroteroate foxoplasma
synthase
Pyrimethamine - act against tachyzoites but not - Toxoplasmosis (doc) - Dose-related bone - Well absorption
bradyzoite - Cystoisosporiasis marrow suppression - High Vd, cross BBB
- PCP decreased by - Sulfadiazine = Synergist effect
- Malaria Folinic acid - Immunocompromised ต้องใ ้ 2°
(Leucovorin) prophylaxis (Co-trimoxazole) เผื่อ
bradyzoite แตกออกมาอีก
ANTIPROTOZOAL AGENTS : Antimalarial
Quinine - inhibit heme detoxification Blood schizont 2nd line - Cinchonism: visual,
** IV form (Heme FPPIX Hemozoin) - severe malaria hearing disturbance,
- Mechanism of resistance: - uncomplicated PF headache nausea
mutation in pfcrt, pfmdr1 - Hyperinsulinemic
(transporter ที่ food vacuole) hypoglycemia
** P. falciparum = high resistance - Arrhythmia (QT
prolong)
- Vasodilation
- Hypersensitivity
reaction: less freqeunt
Chloroquine - inhibit heme detoxification Blood schizont 1st line - low doses : well - Well, rapid absorption
i
(Heme FPPIX Hemozoin) - uncomplicated non-PF tolerated, pruritis - Widely distribution (RBC,Brain)
⑤@
mmmmm

- Mechanism of resistance: - long term, high - T1/2 = 1 – 2 months

Ai DF Psiq
mutation in pfcrt, pfmdr1 doses used in ( ะ มในไขมัน)
+ 에

autoimmune
disorder (RA,SLE) :
retinopathy
Mefloquine - inhibit heme detoxification st
Blood schizont 1 line - inhibit AchE - Well, rapid absorption
(Heme FPPIX Hemozoin) - severe malaria › GI disturbances, - Widely distribution
- Mechanism of resistance: - PF (effective against dizziness, difficult - T1/2 = 2 – 3 weeks
mutation in pfcrt, pfmdr1 chloroquine resistance PF) sleeping, anxiety, - avoid in cerebral malaria, Hx of
in combination of visual disturbance seizures
artesunate = Artimisinin › bradycardia
combination therapy - Rare: depression,
(ACT) seizure, psychosis
Piperaquine - inhibit heme detoxification Blood schizont 1st line - well tolerated - Well, rapid absorption
(Heme FPPIX Hemozoin) - severe malaria - Widely distribution
- mutated pfcrt are unable to - PF (effective against - T1/2 = 2 – 4 weeks
efflux (ขนาดใ ญ่จนขับออกไม่ได้) chloroquine resistance PF)
in combination of
dihydroartemisinin =
Artimisinin combination
therapy (ACT)
Artemisinin and - Fe2+ กระตุ้นใ ้ มู่ endoperoxide Artimisinin combination - well tolerated - Well, rapid absorption
derivatives ในยาเปลี่ยนเป็น free radicals therapy (ACT) - rarw: bone marrow - Widely distribution
- dihydroartemisinin › bind to Heme = inhibit heme › prevent recrudescense suppression - Metabolized to DHA (active
(DHA) detoxification › prevent drug resistance metabolites, short half-life)
- Artesunate: IV form › bind to protein = loss function › decrease drug toxicity - Short T1/2 : high rate of
recrudescense
- severe malaria
- uncomplicated PF CIIooog
(multidrug resistance PF)
Doxycycline - Protein synthesis inhibitor Blood schizont 2nd line CII Dpog
Daxy ③

Clindamycin - severe malaria

** IV form - uncomplicated PF
* Slow-acting used in
combination with
artesunate or quinine
Primaquine - Not well understood (May be Tissue schizont 1. generate ROS = - Well, rapid absorption
increase ROS) › chemoprophylaxis cause hemolysis - Widely distribution
Hypnozoite esp. G6PD def - Metabolized to carboxyprimaquine
› relapse prevention in 2. enhance (less effective but inducing hemolysis)
PV, PO malaris conversion of Hb to - C/I single dose: Pregnancy, Lactating
Gametocyte MetHb esp. G6PD def women, infant(<6mo)
› reduce trsnsmission in - C/I relapse prevention: Pregnancy,
PF malaria (single dose) Lactating women, infant(<6mo),
severe G6PD deficiency

NOTE: Pregnancy
- ้าม Doxycycline, Primaquine, Artesiminin
- ใ ้ weekly chloroquine suppressive prophylaxis จนกว่าจะคลอดและใ ้นมเ ร็จ แล้วจึงใ ้ primaquine เพื่อ
relapse prevention
- 1st trimester ใช้ quinine + clindamycin รัก า uncomplicated PF แทน artemisinin