antiprotozoal drugs Flashcards
Classification of drugs used for the treatment of malaria
1) Tissue schizonticids act on liver forms, e.g. primaquine.
2) Blood schizonticids (suppressive therapy): Act on erythrocyte forms, prevents the clinical symptoms e.g. chloroquine, quinine.
3) gametocides kill gametocytes, e.g. primaquine
4) prophylactic therapy.
Chloroquine (supressive) Mechanism Kinetics- 3 Indications- 3 +special ADverse effects: 4 Contraindications: 2
Mechanism of action: blood schizonticid – inhibits heme-polymerase, inhibits the inactivation of heme into hemozoin → heme accumulates → toxic for the protozoons
Pharmacokinetics:
well absorbed orally
accumulates in the tissues- goes through CNS and placenta
elimination half life 4 days
Clinical indications:
1) suppressive therapy
2) prophylaxis
* ** P. falciparum is commonly resistant
3) Rheumatoid arthritis
Adverse effects: few – pruritus, GI symptoms, visual disturbances (rare, due to retina- and cornea deposits). Hemolysis in G6PD deficient
persons.
Cinchona alkaloid, quinine and quinidine MEchanism? Administartion- 2 Clinical indications- 4 adverse effects:3.
Mechanism of action:
Exact mechanism of action is unknown.
Pharmacokinetics:
well absorbed orally
Parental (I.V. Slow) (in severe Falciparum).
Clinical indications:
1) blood schizonticid (last theraputical option for P. Falciparum).
2) gametocid againts P. vivax and P. ovale).
3) - Not for profilaxis due to its toxicity
4) - Babesiosis
Adverse effects:
1) Quinine intoxication (cinchonism) – vomit, diarrhoeia, visual and hearing disturbances (vertigo, tinitus),
This usually does require stoppage of medication.
2) Worse symptoms are QT prolongation, hemolysis (leading to thrombocytopenia and leukopenia) are worse outcomes-> STOP medication.
3) overdose – cardiotoxicity
Mefloquine Mechanism- 1 Kinetics: 1. Clinical indication 4 adverse: 2 contra- 3
Exact mechanism of action is unknown
Pharmacokinetics: orally.
Clinical indications:
1) blood schizonticid (effective in most cases of resistance).
2) profilaxis if resistant to chloroquine.
3) gametocid.
4) therapy of uncomplicated malaria in combination with Artesunat
adverse: GI and central symptoms (depression and other psychosis, hallucination).
contraindication: not with psychiatric disorders, epilepsy or quinines.
Primaquine
Mechanism?
Kinetics- 1
Indications: 4
adverse: 3
Exact mechanism of action is unknown.
Pharmacokinetics: oral.
Clinical indications:
1) : tissue schizonticid for all types of plasmodium strains.
2) Radical cure of acute Vivax and Ovale malaria (works on the liver form, dormant?).
2) Prophylaxis.
3) gametocid (no transmission).
4) pneumocystis jiroveci infection (in combination
with clindamycine)
Adverse effects:
well tolerated; in higher doses GI side effects, very
rarely leukocytopenia, methemoglobinaemia, hypersensitive reaction
**According to book this is the only drug working on OVALE And VIVAX in the liver form.
Halofantrine Works on? Mechanism? Pharmacokinetics: Clinical indications: 1 toxicityAdverse effects: 4
Mechanism of action: Unknown mechanism of action.
Pharmacokinetics: good oral absorbtion.
Clinical indications: blood schizonticid for all plasmodium forms.
rarely used because of its toxicity
Adverse effects: GI, rashes, pruritus, arrhythmia, impulse conduction disturbances!
Lumefantrine
Characteristic?
Indicated /w
Similar to Halofantrine with less side effects.
Indicated in combination with arthemeter for the treatment of not complicated P. falciparum malaria
Sulfadoxine + pyrimethamine
What mechanism?
CLinical indication-2
(inhibitors of folate synthesis)
Clinical indications:
- In case of Chloroquine resistancy, treatment of uncomplicated malaria
- P. falciparum is commonly resistant
Proguanil (Folate synthesis inhibitor):
Mechanism
Proguanil:
- its active metabolite inhibits the bifunctional dihydrofolate (FH2 reductase inhibitor)
reductase thymidylate synthase → inhibits DNA synthesis.
atovaquone- 2
Atovaquone:
- inhibits mitochondrial functions
- tissue and blood schizonticid
Atovaquone + proguanil = ?
Indication
Atovaquone + proguanil = Malaron
Clinical indications:
atovaquone + proguanil → for treatment and prophylaxis in case of known chloroquine resistancy (P.
falciparum is usually susceptible)
which antibiotics can you use?
tetracyclins, clindamycin, azithromycin
artemisinin (natural compound- NOBEL prize) and its derivatives: 4 who does it work on? Mechanism? admin? 3 Indication? in combo with? adverse effects?
Derivatives: arthemeter, artemotil, artesunat, dihydroartemisinin
Antimalarial effect: blood schizonticid (fast effect).
They might act through production of free radicals.
Pharmacokinetics: possible ways of administration: orally, i.v., i.m
Clinical indications: often used for the treatment of uncomplicated falciparum malaria in combination (!) •Artesunate-mefloquine
•Artemether-lumefantrine
Adverse effects: well tolerated (!), most common GI side effects
