anti protozoal and anti malarial drugs
TRANSCRIPT
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
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.
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
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.