ANTI PROTOZOAL DRUGS

V.THIRUMALAI

LECTURER, DEPT OF PHARMACOLOGY

RVS DENTAL COLLEGE AND HOSPITAL

ANTI AMOEBIC DRUGS TISSUE AMOEBICIDES:

I.Both intestinal & extraintestinal

Nitroimidazole

• Metronidazole

• Tinidazole

• Secnidazole

• Orindazole

• Satranidazole

Alkaloid:

• Emetine, dehydroemetine

II.Extraintestinal only : Chloroquine

Cont...

LUMINAL AMOEBICIDES:

• Amide : Diloxanide Furate, Nitazoxanide

• 8-hydroxyquinolines: Quinidochlor, Diiodohydroxyquin

• Antibiotics : Tetracyclines

METRONIDAZOLE

• Metronidazole – prototype of

Nitroimidazole (1959)

• First introduced for trichomoniasis.

• Higher Amoebicidal activity and Anti

Anerobic Activity (Bacterio cidal activity)

• Antiamoebic drugs : these are the drug

which are active against the protozoan

infection especially Entamoeba histalitica .

PHARMACOKINETICS

• ABSORPTION: oral administration

• Metronidazole can also be given intravenously or by

rectal suppository.

• DISTRIBUTION: widely distributed in tissues, and

reaches serum levels of 4–6 mcg/mL after a 250-mg

oral dose.

• Penetrates well into the CSF and brain

• METABOLISM : Inliver by Oxidation &

Glucuronide conjugation and may accumulate in

hepatic insufficiency.

• EXCRETION: Urine

• PLASMA t ½ : 8 hrs.

MECHANISM OF ACTION

MET

CYTO

TOXICITY

NH –

RADICAL

ANAEROBIC ORGANISM

NITRO GROUP REDUCTION BY

REDOX PROTEINS IN ANAEROBES

DISTRUPTS ENERGY METABOLISM

OF ANAEROBES

RESISTANCE

MET

DEFICIENCY IN THE

GENERATION OF REACTIVE

NITRO RADICAL

INACTIVE STATE OF

METRONIDAZOLE

DRUG RESISTANCE

ANAEROBIC ORGANISM

ADVERSE EFFECTS

• “Disulfiram-like effect”, and patients should

be instructed to avoid alcohol

CONT....Thrombophelibitis of injected vein (if solution is not

well diluted)

CONT...

• Metallic taste, anorexia, nausea, and

abdominal cramps .

• Less frequent side effects : head ache ,

glossitis, druness of mouth, dizziness,

rashes and transient neutropenia.

• Prolonged use: peripheral neuropathy &

CNS efects

• Very high doses- seizures.

CONTRAINDICATION

• Neurological diseases

• Bloody dyscriasis

• First trimester of pregnancy (due to

mutagenic effect. But teratogenic effect not

yet proved)

• Chronic alcoholism

INTERACTIONS

• Alcohol: disulfiram like reaction

• Enzyme inducers (phenobarbitone , rifampicin) : decreases the therapeutic effects

• Cimetidine : reduce metabolism

• Warfarin : its metabolism inhibited by metronidazole

• Lithium : renal excretion decreased by metronidazole

USES- DENTISTRY

• Ulcerative gingivitis and trench mouth: active

against spirochete – fusiformbacteria complex from

the lesions and resolution of pain , bleeding ,

ulceration and halitosis within 2-3 days.

OTHER USES – MEDICAL

• Amoebiasis

• Giardiasis

• Trichomonas vaginitis

• Anaerobic infections : oral infections, post

operative infection , brain abscesses and

endocarditis.

• Pseudomembranous enterocolitis

• Helicobacter pylori: only in triple drug

combination therapy.

ANTI MALARIAL DRUGS

INTRODUCTION

• Malaria – most common protozoan infections.

Causative organism :

• Plasmodium vivax, P.ovale and p.malariae( both erythrocytic and tissue cycles).

• P.falciparum ( no tissue cycle).

DRUG CLASSIFICATION

• 4-Aminoquinolines: Chloroquine, Amodiaquine, Piperaquine.

• Quinoline-methanol: Mefloquine.

• Cinchona alkaloid: Quinine, Quinidine

• Biguanide: Proguanil (chloroguanide)

• Diaminopyrimidine: Pyrimethamine

• 8-Aminoquinalines: Primaquine

Cont...

• Sulfonamides and sulfone: Sulfadoxine, Sulfamethopyrazine, Dapsone

• Tetracylines: Doxycycline

• Sesiquiterpine lactones: Artesunate , Artemether, Arteether.

• Aminoalcohols : Halofantrine, Lumefantrine

• Naphthoquinone: Atovaquone

DRUG THERAPY Causal prophylaxis – preerythrocytic

phase ( liver )

Target is cause and clinical attack of infection.

• E.g: proguanil (P.falciparum), primaquine

Suppressive prophylaxis : Schizontocides– erythrocytic phase .

• E.g : chloroquine, mefloquine or doxycycline ( not more tan 6 weeks )

Cont...

• Intermittent preventive therapy (IPT):slufadoxine 1500mg+ pyrimethamine 75 mg single dose. 2nd and 3rd trimester in high risk of P.falciparum endemicity

• Clinical cure

• Radical cure

• Gametocidal

Cont...Clinical cure:

• Erythrocytic schizonticides to terminate episode of malarial fever.

A) Fast acting high- efficacy drugs: chloroquine, amodiaquine, quinine, mefloquine, halofantrine, lumefantrine,atovaquine, artemisinin

B) Slow acting low- efficacy drugs:

proguanil, pyremethamine, sulfonamides, tetracylcines

Cont...Radical cure :

• Exoerythrocytic ( hypnozoites)

• Total eradiation of the parasites from the patient’s body

• E.g: primaquine.

Gametocidal :

• Elimination of male and female gametsformed in the patient’s blood .

• E.g: Primaquine and artemisins

CHLOROQUINE MECHANISM OF ACTION

Drug Spectrum MOA Adverse effects

Chloroquine P.Falciparum(not in liver form)

PreventsDetoxification of heme and causes parasite death in food vacuoles

GI distress, rashes, headache toocular toxicity, methemoglobenemia, hemolyticanemia (G6PD defeciencypatients)

Primaquine Exo erythrocytic , liver lurking forms

Unclear Mild toxicity, anorexia, nausea, vomiting , cramps, hemolyticanemia and methemoglobenimia(G6PD defeciency patients )

Quinine Erythrocyticforms – only

Similar to chloroquine

Cinchonism , allergic skin rashes, hypotension, SK muscle weakness, renal damage, hemolyticanemia and methemoglobenimia(G6PD defeciency patients )

Mefloquine Erythrocyticforms – only

Similar to Chloroquine

GI distress

Drug Spectrum MOA Adverse effects

Atovaquone/proguanil

Erythrocytic & non erythrocyticforms

Inhibition of Mitelectron transport of Plasmodium / Inhibits dehydrofolatereductase in plasmodium

GI distress , enzyme level increased

Pyrimethamin,chloroquanide& trimethoprim

Erythrocytic & exoerythrocyticforms

Dehydrofolatereductaseinhibitors

Weak human dihdrofolic acid –leads to megaloblastic anemia.