Summary of drugs that are used against malaria, amoebics and helminths

1. M.A.A.Al-Maqrashi
Drug Name & Chemical
Classification
Target
Stage
MOA
Pharmacokinetics &
Characteristics
A.EAnti-malarialDrug
[Quinolines]
[4-aminoquinoline]
Chloroquine
Liver &
Erythrocytic
Schizont
- Traversing the hepatic/erythrocytic and
plasmodial membranes
- Protonated in the acidic food vacuole [it is
weak base]→ion trapping inside the
vacuole
- specifically binds to heme, preventing its
polymerization to hemozoin.
- increased pH and the accumulation of
heme → oxidative damage to the
phospholipid membranes → leading to
lysis of both the parasite and the host
cell.
- Well-absorbed orally
- Very large Vd
- Concentrates in RBC,
liver, spleen, kidney,
lung, retina, and WBC.
- Crosses BBB & placenta
- Long t0.5(3-10 ds.)
- Hepatic metabolism
- Drug & its metabolites
appear in urine
Esp. At high doses:
- GI upset.
- Skin:
[rash, pruritus, discolored nail
beds & mm, exacerbates
psoriasis.]
- Eye:
[Blurred vision, opacities,
retinopathy.]
- CVS:
[Prolonged QT interval.]
- CNS: [Neuropsychiatric.]
[4-
methanolquinoline]
Mefloquine
Erythrocytic
Schizont
- Well-absorbed orally.
- Well-distributed & concentrated in tissues.
- Long t0.5(20 ds.).
- Hepatic metabolism & Bile excretion
- Arrhythmia:
[esp. + quinine or quinidine]
- Neuropsychiatric
[4-
methanolquinoline]
quinine
quinidine
Erythrocytic
Schizont
- interferes with heme polymerization,
resulting in death of the erythrocytic form
of the plasmodial parasite.
- Well-absorbed orally.
- Slow IV
- must dilute if IM.
- Well-distributed.
- Hepatic metabolism
- renal excretion.
- Cinchonism:
[syndrome causing nausea,
vomiting, tinnitus, and vertigo →
reversible]
- Aplastic & G6PD deficiency
hemolytic anemia
[must suspend the treatment]
- Quinine: Blackwater fever:
[hemolysis & hemoglobinuria.]
- Quinidine: prolonged QT
interval, ↓ BP,
thrombophlebitis.
[Following IV administration]
- Mild oxytocic:
[but used for severe P.
falciparum during pregnancy.]
- Visual & auditory problems.
- Hypoglycemia.
- Hypersensitivity.

2. M.A.A.Al-Maqrashi
Anti-malarialDrug
[Quinolines]
[8-aminoquinoline]
Primaquine
-Hypnoxoite
- Liver
Schizont
-
Gametocyte
- metabolites of primaquine are believed to
act as oxidants that are responsible for the
schizonticidal action
- Well-absorbed orally
- Hepatic metabolism
- minimal renal excretion
- Avoided in pregnancy
- GI upset
- headache.
- Hemolytic Anemia &
methemoglbinemia:
[Strong oxidizing agent in G6PD
deficiency pts]
Rare, serious:
- aplastic anemia
- Arrhythmias.
[Artemisinins]
Artemisinin
Dihydro-artemisinin
Artesunate
artemether
-
Erythrocytic
Schizont
-
Gametocyte
- production of free radicals resulting
- Covalently bind to and damage specific
malarial proteins & mitochondria
- Artemisinin: insoluble & orally
- Derivatives are more soluble with better efficacy:
- Dihydroartemisinin [active metabolite]: water-soluble; oral.
- Artesunate: water-soluble; oral, rectal, IM, IV.
- Artemether: lipid-soluble; oral, rectal, IM.
- Short t0.5 (< hr.).
- Hepatic metabolism
- Bile excretion.
- Artemisinin-based Combination Therapy [ACT]:
↑ Spectrum, Tolerability & Efficacy
↓ Relapse & Resistance.
- Some ACT Preparations:
- Artemether + lumefantrine [Coartem]
- Lumefantrine an antimalarial drug.
- Used in combination with artemether "co-artemether".
- Has a much longer t1/2.
- Artesunate + [Coartem OR Mefloquine OR Atovaquone-
proguanil OR Doxycycline]
[THFA synthesis
inhibitors]
Sulfadoxine
Pyrimethamine
proguanil
Erythrocytic
Schizont
- Sulfadoxine: inhibit dihydropteroate
synthetase
- Pyrimethamine & proguanil: inhibit
dihydrofolater reductase
- Well-absorbed orally.
- Sulfadoxine: long t0.5 [6-7 ds.]
- Pyrimethamine: long t0.5 [3-5 ds.].
- Proguanil: a prodrug: short t0.5 [5 hrs.]
- Sulfadoxine-pyrimethamine:
- fixed-dose combination [Fansidar]
- Synergism → sequential blockade.
- Atovaquone-proguanil:
- [Malarone] → synergism:
- ↑ Duration of action compared to proguanil alone.
- ↑ Efficacy & ↓ resistance compared to atovaquone
alone.

3. M.A.A.Al-Maqrashi
Cont.
[Atovaquone]
- Orally
- Better with food.
- High PPB.
- Long t0.5 (2-3 ds.).
- Eliminated unchanged in bile.
Well-tolerated
Drug Name MOA
Pharmacokinetics &
Characteristics
Uses Adverse Effects
Anti-AmoebicsDrugs[Amoebicides]
Metronidazole
- Disrupts DNA
replication, TXN &
repair
- Well-absorbed orally
- distributes well
throughout body tissues
and fluids
[CSF, milk, saliva,
semen]
- Hepatic metabolism &
renal excretion.
- NOT recommended in
pregnancy & lactation.
- Mixed amebicide: Kill luminal &
tissue trophozoites
- Drug of choice for:
- tissue amoebiasis
- amoebic liver abscess
- pseudomembranous
- colitis
- giardiasis
- Oral moniliasis.
- Common:
- GI upset
[alleviated by taking it with
meals.]
- Unpleasant metallic taste
- dark urine
- Rare:
- Neurotoxicity
- Pancreatitis
Tinidazole
- Tinidazole is as effective as metronidazole, with a:
- shorter course of treatment
- more expensive.
- Alcohol consumption should be avoided during
therapy.
- Mixed amebicide: Kill luminal &
tissue trophozoites
Less toxic than Metronidazole
Dehydroemetine
- inhibits protein
synthesis by blocking
chain elongation.
- SC [better] or IM
- irritant when taken
orally
- Systemic amebicide: Kill tissue
trophozoites [intestinal wall, liver,
lung]
- Used in metronidazole
contraindication or refractoriness.
- Replaced by metronidazole ← better
safety
- NOT IV
- NOT used for > 5 days.
- Pain at the site of injection
- Cardiotoxicity

4. M.A.A.Al-Maqrashi
- NOT in young kids or pregnancy.
Cont.Amoebicides
Paromomycin
- Aminoglycoside
- not absorbed from GIT
- Luminal amebicide: Kill trophozoites
& cysts in GIT
- Alternative to metronidazole in
giardiasis.
- Occasionally:
GIT distress and diarrhea
Iodoquinol - not absorbed from GIT
- Luminal amebicide: Kill trophozoites
& cysts in GIT
- Avoid long-term use.
- GI upset [esp. diarrhea]:
[alleviated by taking it with
meals.]
- Iodine toxicity:
[dermatitis, urticaria, pruritus,
fever]
- Dose-related peripheral
neuropathy & optic neuritis.
Anti-HelminthicDrugs
Mebendazole
- inhibiting assembly of microtubules in the parasite
- irreversible blocking of glucose uptake.
- Drug of choice for nematodes.
- NOT in pregnancy.
- abdominal pain
- diarrhea
Albendazole
- inhibiting assembly of
microtubules in the
parasite
- irreversible blocking of
glucose uptake.
- Absorption is enhanced
by a high-fat meal.
- distributes widely,
including the CSF.
- extensive first-pass
metabolism → active
metabolite
- Albendazole and its
metabolites are
primarily excreted in the
bile
- Short-course (1-3 ds.) for nematodes → mild headache & nausea.
- Long-course (3ms.) for cestodes → hepatotoxicity & pancytopenia.
Praziquantel
- ↑ Ca2+
influx →
contracture and paralysis
of the parasite
- well-absorbed orally
- taken with food and not
chewed due to a bitter
taste.
- Well-distributed; CSF.
- Extensively-metabolized.
- Renal excretion.
- Drug of choice for schistosomiasis &
some cestodes.
- GI upsets
- headache
- dizziness
- malaise.

5. M.A.A.Al-Maqrashi