A Powerpoint presentation on. ANTI-MALARIAL DRUGS Dr Farah Manger,Dr.Prashant,MD www.pharmacology4students.com Drprashant.editor@gmail.com A Powerpoint presentation on. ANTI-MALARIAL DRUGS Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com INTRODUCTION TYPES OF MALARIA AND THEIR CAUSES MALARIA IS CAUSED BY 4 SPECIES OF PROTOZOAL PARASITES PLASMODIUM VIVAX PLASMODIUM OVALE PLASMODIUM FALCIPARUM PLASMODIUM MALARIAE MALARIA IS CAUSED BY FOUR SPECIES OF MALARIAL PARASITES Dr Prashant's www.pharmacology4students.com

LIFE CYCLE OF MALARIAL PARASITE Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com MALARIAL PARASITES EXHIBIT A COMPLEX LIFE CYCLE THEY HAVE ALTERNATING CYCLE OF ASEXUAL DIVISION (SCHIZONY) IN HUMANS SEXUAL DEVELOPMENT (SPOROGONY) OCCURS IN FEMALE MOSQUITOES. Dr Prashant's www.pharmacology4students.com

ANTIMALARIAL DRUGS CLASSIFICATION 4-AMINOQUINOLONES CHLOROQUINE AMODIAQUINE QUINOLINE METHANOL MEFLOQUINE

Dr Prashant's www.pharmacology4students.com ACRIDINE MEPACRINE CINCHONA ALKALOID QUININE BIGUANIDES ROGUANIL DIAMINOPYRAMIDINES PYRIMETHAMINE Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com 8-AMINOQUINOLONES PRIMAQUINE BULAQUINE SULFONAMIDES AND SULFONES SULFODOXINE SULFAMETHOPYRAZINE DAPSONE TETRACYCLINES TETRACYCLINE DOXYCYCLINE Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com SESQUITERPINE LACTONES ARTESUNATE ARTEMETHER ARTEETHER PHENANTHRENE METHANOL HALOFANTRENE NAPTHOQUINONE ATIVAQUONE Dr Prashant's www.pharmacology4students.com

OBJECTIVES AND USE OF ANTIMALARIAL DRUGS THE AIMS OF USING DRUGS IN A MALARIAL INFECTION ARE (a)TO PREVENT AND TREAT CLINICAL ATTACK OF MALARIA (b)TO COMPLETELY ERADICATE THE PARASITES FROM THE PATIENTS BODY (c)TO REDUCE THE HUMAN RESERVOIR OF INFECTION Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com ANTIMALARIAL THERAPY IS GIVEN IN THE FOLLOWING FORMS:- 1)CASUAL PROPHYLAXIS -IN THIS THE PREERYTHROCYTIC STAGE IS THE TARGET. -FOR THIS PURPOSE THE DRUGS THAT CAN BE GIVEN INCLUDE (a)PROGUANIL (b)PRIMAQUINE Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com 2)SUPPRESSIVE PROPHYLAXIS THE SCHIZONTOCIDES WHICH SUPPRESS THE ERYTHROCYTIC PHASE AND THUS ATTACKS OF MALARIAL FEVER CAN BE USED FOR THIS PURPOSE. THEY INCLUDE:- (a)CHLOROQUINE-300mg WEEKLY Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com (b)PROGUANIL-200mg DAILY WITH CHLOROQUINE 300mg (c)MEFLOQUINE-250mg WEEKLY (d)DOXYCYCLINE-100mg DAILY 3)CLINICAL CURE THE ERYTHROCYTIC SCHIZONTOCIDES ARE USED TOTERMINATE AN EPISODE OF MALARIAL FEVER Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com THESE ARE:- (A)FAST ACTING HIGH EFFICACY DRUGS (a)CHLOROQUINE (b)MEPACRINE (c)MEFLOQUINE (d)HALOFANTRINE (e)ATOVAQUONE (B)SLOW ACTING LOW EFFICACY DRUGS (a)PROGUANIL (b)PYRIMETHAMINE (c)SULFONAMIDES (d)TETRACYCLINES Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com SEVERE AND COMPLICATED FALCIPARUM MALARIA THIS INCLUDES P. FALCIPARUM INFECTION ATTENUATED BY:- HYPERPARASITAEMIA HYPERPYREXIA FLUID AND ELECTROLYTE IMBALANCE HYPOGLYCAEMIA CARDIOVASCULAR COLLAPSE PULMONARY OEDEMA Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com HAEMOGLOBINURIA PARENTRAL FEVER RENAL FAILURE AND CEREBLAR MALARIA TREATMENT:- PARENTRAL ADMINISTRATION(I.M/I.V) HAVE TO BE USED DRUGS GIVEN ARE:- QUININE ARTESUNATE/ARTEEMETHER CHLOROQUINE Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com RADICAL CURE A RADICAL CURATIVE IS NEEDED IN RELAPSING MALARIA WHILE IN FALCIPARUM MALARIA ADEQUATE TREATMENT OF CLINUCAL ATTACK LEAVES NO PARASITE IN THE BODY. DRUGS:- PRIMAQUINE-15mg DAILY FOR 2 WEAKS Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com CHLOROQUINE CHLOROQUINE IS A RAPIDLY ACTING SCHIZONTOCIDE. IT BELONGS TO AMINOQUINOLONES MECHANISM OF ACTION BY ACCUMULATING IN ACIDIC VESCICLES OF PARASITE AND BECAUSE OF ITS WEAKLY BASIC NATURE IT RAISES THE Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com VESCICULAR PH AND THEREBY INTERFERES WITH DEGRADATION OF HAEMOGLOBIN BY PARASITIC LYSOSOMES. RESISTANCE:- RESISTANCE TO P. FALCIPARUM IS ASSOCIATED WITH A DECREASED ABILITY OF PARASITE TOACCUMULATE CHLOROQUINE Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com PHARMACOKINETICS ROUTE- ORAL ADMINISTRATION 50% BOUND TO PLASMA PROTEIN IT IS CONCENTRATED IN LIVER,SPLEEN, KIDNEY, LUNGS, AND RETINA. ITS ACCUMULATION IN RETINA IS RESPONSIBLE FOR ITS OCULARTOXICITY. Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com ADVERSE EFFECTS PARENTRAL ADMINISTRATION CAN CAUSE HYPOTENSION, CARDIAC DEPRESSION, ARRYTHMIAS AND CNS TOXICITY. LOSS OF VISION DUE TO RETINAL DAMAGE LOSS OF HEARING RASHES PHOTOALLERGY MENTAL DISTURBANCE Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com USES:- SUPPRESSIVE PROPHYLAXIS OF ALL TYPES OF MALARIA EXCEPT THAT CAUSED BY RESISTANT P FALCIPARUM EXTRAINTESTINAL AMOEBIASIS RHEUMATOID ARTHRITIS DISCOID LUPUS ERYTHMATOSUS LEPRA REACTIONS PHOTOGENIC REACTIONS INFECTIOUS MONONUCLEOSIS Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com MEFLOQUINE INTRODUCTION:- IT IS A DRUG THAT DEALS WITH CHLOROQUINE RESISTANT P. FALCIFARUM IT HAS EMERGED FROM REINVESTIGATION OF QUINOLONE METHANOLS. Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com MECHANISM OF ACTION LIKE CHLOROQUINE IT RAISES THE INTRAVASCULAR PH. IT BINDS TO THE HAEM AND THE COMPLEX DAMAGES MEMBERANES OF THE PARASITE. RESISTANT ORGANISMS ACCUMULATE LESS MEFLOQUINE Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com PHARMACOKINETICS ORAL ABSORBTION OF MEFLOQUINE IS QUITE GOOD. HIGHLY PLASMA PROTEIN BOUND T1/2 IS 2-3 WEEKS EXTENSIVE METABOLISM OCCURS IN LIVER AND IS EXCRETED IN BILE. Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com ADVERSE EFFECTS BITTER IN TASTE NAUSEA VOMITING DIARRHOEA DIZZINESS ABDOMINAL PAIN AND SINUS BRADYCHARDIA Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com INTERACTIONS:- HALOFANTRINE OR QUINIDINE GIVEN TO PATIENTS WHO HAVE RECEIVED MEFLOQUINE CAUSE QTc LENGHTHENING AND CARDIAC ARRESTS ARE REPORTED. EXAGGERATED BRADYCHARDIA OR ARRYTHMIAS HAVE BEEN RPORTED WHEN MEFLOQUINE IS GIVEN TO PATIENTS RECEIVING B-BLOCKERS AND Ca CHANNEL BLOCKERS Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com USES:- TREATMENT OF UNCOMPLICATED FALCIPARUM MALARIA IN AREAS WITH MULTIDRUG RESISTANCE PROPHYLAXIS OF MALARIA AMONG TRAVELLERS Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com QUININE QININE IS A LEVO ROTATORY AQLKALOID OBTAINED FROM CINCHONA BARK. IT IS AN ERYTHROCYTIC SCHIZONTICIDE FOR ALL SPECIES OF PLASMODIA Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com MECHANISM OF ACTION IT GETS CONCENTRAATED IN THE ACIDIC VACUOLES OF THE BLOOD SCHIZONTS AND CAUSES PIGMENT CHANGES ALSO INHIBITS THE POLYMERIZATION OF HAEM TO HEMOZOIN FREE HEME OR HEMOZOIN COMPLEX DAMAGES PARASITE MEMBERANE AND KILLS IT. Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com PHARMACOKINETICS QUININE IS RAPIDLY ABSORBED ORALLY IT IS 70% BOUND TO PLASMA PROTEIN CSF CONCENTRATIONS ARE LOW LARGE FRACTION OF DOSE IS METABOLISED IN THE LIVER T1/2= 10-12 HRS Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com ADVERSE EFFECTS:- CINCHONISM THE SYMPTOMS ARE AS FOLLOWS:- RINGING IN EARS, NAUSEA, VOMITING, HEADACHE, MENTAL CONFUSION, VERTIGO, DIFFICULTY IN HEARING AND VISUAL DEFECTS. IN ADDITION DELIRIUM, FEVER, TACHYPNOEA, FOLLOWED BY RESPIRATORY DEPRESSION AND CYANOSIS. Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com USES:- MALARIA CEREBRAL MALARIA NOCTURNAL MUSCLE CRAMPS DIAGNOSIS OF MYASTHENIA GRAVIS SPERMICIDAL IN VAGINAL CREAMS INJECTED ALONG WITH URETHANE IT CAUSES THROMBOSIS AND FIBROSIS OF THE VARICOSE VEIN MASS Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com PYRIMETHAMINE IT IS DIRECTLY ACTING INHIBITOR OF DHFrase NOT REQUIRE CONVERSION TO A CYCLIC TRIAZINE. MECHANISM OF ACTION:- MECHANISM OF ACTION RESEMBLES PROGUANIL BUT IS MORE POTENT Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com PHARMACOKINETICS:- ABSORPTION OF PYRIMETHAMINE FROM GIT IS GOOD BUT SLOW. CONCENTRATED IN CERTAIN ORGANS LIKE LIVER, BRAIN T1/2= 4 WEEKS PROPHYLACTIC CONC REMAIN IN BLOOD FOR 2 WEEKS Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com ADVERSE EFFECTS:- OCCASIONAL NAUSEA RASHES FOLATE DEFICIENCY USES:- IN COMBINATION WITH A SULFONAMIDE IT IS USED IN TREATMENT OF MALARIA. Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com PRIMAQUINE IT IS A POOR ERYTHROCYTIC SCHIZONTOCIDE IT DIFFERS FROM ALL THE OTHER ANTIMICROBIALS IN HAVING A MARKED EFFECT ON PRIMARY AS WELL AS SECONDARY TISSUE PHASES OF MALARIAL PARASITE. Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com PHARMACOKINETICS:- READILY ABSORBED AFTER ORAL ABSORBTION OXIDISED IN LIVER PLASMA T1/2=3-6 HRS EXCRETED IN URINE WITHIN 24 HRS. Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com ADVERSE EFFECTS ABDOMINAL PAIN GI UPSET WEAKNESS OR UNEASINES DOSE RELATED HAEMOLYSIS, METHHAEMOGLOBINAEMIA, TACHYPNOEA,CYANOSIS Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com USES USED FOR RADICAL CURE OF RELAPSING MALARIA ALSO USED IN TREATMENT OF FALCIPARUM MALARIA DOSE= 15 mg DAILY FOR TWO WEAKS OTHER DRUGS INCLUDED IN THIS GROUP ARE:- BULAQUINE TETRACYCLINES Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com ARTEMESENIN DERIVATIVES ARTEMESENIN IS THE ACTIVE PRINCIPLE OF PLANT ARTEMESIA ANNUA IT IS USED IN CHINESE TRADITIONAL MEDICINE AS ‘QUINGHAOSU’ ARTEMESENIN IS POORLY SOLUBLE IN WATER AS WELL AS OIL Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com MECHANISM OF ACTION THE ENDOPEROXIDE BRIDGE IN ITS MOLECULE INTERACTS WITH HEME IN THE PARASITE IRON MEDIATED CLEAVAGE OF THE BRIDGE RELEASES A HIGHLY REACTIVE FREE RADICAL SPECIES Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com THIS BINDS TO MEMBERANE PROTEINS CAUSES LIPID PERODIXATION,DAMAGES ENDOPLASMIC RETICULUM, INHIBITS PROTEIN SYNTHESIS, AND ULTIMATELY LYSIS OF THE PARASITE. Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com PHARMACOKINETICS ARTENSUATE AND ARTEETHER ARE PRODRUGS RAPIDLY ABSORBED AND CONVERTED INTO THE ACTIVE METABOLITE DIHYDRO-ARTEMISININ T1/2 OF ARTENSUATE < 1 hr T1/2 OF ARTEETHER= 3-11 HOURS Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com ADVERSE EFFECTS NAUSEA VOMITING ABDOMINAL PAIN ITCHING ABNORMAL BLEEDING DARK URINE S-T SEGMENT CHANGES FIRST DEGREE A-V BLOCK TRANSIENT RETICULOPENIA AND LEUCOPENIA Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com INTERACTION CONCURRENT ADMINISTRATION OF ARTEMISIN COMPOUNDS WITH TERFENADINE, ASTEMIZOLE, ANTIARRYTHMATICS,TRICYCLIC ANTIDEPREEANTS AND PHENOTHIAZINES Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com USES TREATMENT OF ACUTE ATTACKS OF SEVERE FALCIFARUM MALARIA CEREBRAL MALARIA CHLOROQUINE/OTHER MULTIDRUG RESISTANT MALARIA THEIR USE FOR PROPHYLAXIS OF MALARIA IS IRRATIONAL AND NOT ALLOWED Dr Prashant's www.pharmacology4students.com

Dr Prashant's www.pharmacology4students.com i THANKING YOU Dr Prashant's www.pharmacology4students.com