antimicrobial viral, protozoan, fungi and helmitnhics

AntimicrobialViral, Protozoan, Fungi

and Helmitnhicsand Helmitnhics

Dr. Deepak Kumar Gupta

Anti-Viral Drugs

• Viruses are obligate intracellular parasites.

• Their replication depends primarily on synthetic processes of the host cell.

• Therefore, to be effective, antiviral agents must either block viral entry into or exit from the cell or be active block viral entry into or exit from the cell or be active inside the host cell.

• Antiviral therapy is now available for herpesviruses, hepatitis C virus (HCV), hepatitis B virus (HBV), papillomavirus, influenza, and human immunodeficiency virus (HIV).

• Common property of being virustatic; active only against replicating viruses and do not affect latent virus.

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Major sites of antiviral drug action


Classification

• Anti herpes: Idoxuridine, acyclovir, valacyclovir, famciclovir, ganciclovir, foscarnet.

• Anti retrovirus – Nucleoside reverse transcriptase inhibitor NRTI:

Zidovudine AZT, Didanosine, zalcitabine, abacavirZidovudine AZT, Didanosine, zalcitabine, abacavir– Nonnucleoside reverse transcriptase inhibitors

NNRTI: nevirapine, efavirenz, delavirdine.– Protease inhibitors: Ritonavir, indinavir, nelfinavir,

lopinavir

• Anti influenza: Amanatadine rimantadine• Non selective: Ribavirin Lamivudine adefovir

dipdvoxil interferon α


ACYCLOVIR

• An acyclic guanosine derivative with clinical activity against HSV-1, HSV-2, and VZV.

• 10 times more potent against HSV-1 and HSV-2 than against VZV.2 than against VZV.

• Requires three phosphorylation steps for activation

– Firstly converts to the monophosphate derivative by the virus specified thymidine kinase.

– Then to the di- and tri-phosphate compounds by host cell enzymes


Mechanism of action of antiherpesagents


Pharmacology• bioavailability of oral acyclovir is low (15–20%) and is

unaffected by food.• intravenous formulation is available• Topical formulations produce high concentrations in herpetic

lesions.• half-life is 2.5–3 hours in patients with

normal renal function and 20 hours in patients with anuria.• half-life is 2.5–3 hours in patients with

normal renal function and 20 hours in patients with anuria.• Resistance to acyclovir can develop in HSV or VZV through

alteration in either the viral thymidine kinase or the DNApolymerase,

• clinically resistant infections have been reported inimmunocompromised hosts


Clinical Use

• First episodes of HSV oral acyclovir shortens the duration of – Symptoms by approx. 2 days, – Time to healing by 4 days, – Duration of viral shedding by 7 days

• Recurrent HSV, the time course is shortened by 1–2 • Recurrent HSV, the time course is shortened by 1–2 days.

• Decreases the frequency of symptomatic recurrences and of asymptomatic viral shedding

• VZV is less susceptible to acyclovir than HSV, higher doses are required.

• 400 mg twice daily: may reduce the plasma viral load of HIV-1 and the risk of HIV-associated disease


Side Effect

• generally well tolerated

• Nausea, diarrhea, and headache have occasionally been reported.

• Intravenous infusion may be associated with • Intravenous infusion may be associated with reversible renal toxicity or or neurologic effects.

• High doses of acyclovir causes chromosomal damage and testicular atrophy in rats


ACYCLOVIR


Other Anti-Herpetic


Anti retrovirus


Anti-Fungal DrugsAnti-Fungal Drugs


Introduction• Human fungal infections have increased

dramatically in incidence and severity in recent years,

• Mainly to advances in treatment, the HIV epidemic, and increasing use of broad-spectrum antimicrobial therapy.therapy.

• For many years, amphotericin B was the only efficacious antifungal drug available for systemic use.

• While highly effective in many serious infections, it is also quite toxic.

• Relatively non-toxic azole drugs and the echinocandins


Classification

• Anitbiotics– Polyenes: Amphotericin B, Nystatin, Hamycin, Natamycin,– Heterocyclic: Benzofuran, Griesofulvin

• Anitmetabolite Flucytosine 5-FC • Azoles – Imidazoles– Imidazoles

• Topical: clotrimazole, Econazole, Miconazole, Oxiconazole• Systemic: Ketoconazole

– Triazoles (Systemic): Fluconazole, itraconazole, voriconazole

• Allylamine: terbinafine• Other topical agents: Tolnaftate, undecylenic acid,

benzoic acid, quiniodochlor


Mechanism Of Action


AMPHOTERICIN B

• Amphoteric polyene macrolide• Nearly insoluble in water– Therefore prepared as a colloidal suspension of

amphotericin B and sodium desoxycholate for i.v.– i.v. 0.6 mg/kg/d - results in average blood levels of – i.v. 0.6 mg/kg/d - results in average blood levels of

0.3–1 mcg/mL

• Poorly absorbed from the gastrointestinaltract. – Oral amphotericin B is thus effective only on fungi

within the lumen of the tract– Cannot be used for treatment of systemic disease.


AMPHOTERICIN B• Exploits the difference in lipid composition of fungal

(Ergosterol) and mammalian cell membranes (cholestrol)

• Antifungal Activity– Broadest spectrum of action

– Clinically significant yeasts,

– including Candida albicans and Cryptococcus neoformans;

– Endemic mycoses: Histoplasma capsulatum, Blastomycesdermatitidis, and Coccidioides immitis

– Pathogenic molds: Aspergillus fumigatus and theagents of mucormycosis

– Candida lusitaniae and Pseudallescheria boydii display intrinsic amphotericin B resistance


AMPHOTERICIN B: Clinical Uses

• useful agent for nearly all life-threateningmycotic infections

• Often used as the initial induction regimen to rapidly reduce fungal burden

• Replaced by one of the newer azole drugs• Replaced by one of the newer azole drugs• Adverse Effect– Infusion-related: nearly universal and consist of fever,

chills, muscle spasms, vomiting, headache, and hypotension.

– Renal toxicity: prolonged administration (> 4 g cumulative dose)


AZOLES

• Synthetic compounds that can be classified as either– Imidazoles

• Topical: clotrimazole, Econazole, Miconazole, Oxiconazole

• Systemic: Ketoconazole

– Triazoles (Systemic): Fluconazole, itraconazole, – Triazoles (Systemic): Fluconazole, itraconazole, voriconazole

• Reduction of ergosterol synthesis by inhibition of fungal cytochrome P450enzymes

• Greater affinity for fungal than for human cytochromeP450 enzymes


AZOLES: Clinical Uses, Adverse Effects

• Broad spectrum– Candida, C neoformans, – Endemic mycoses: blastomycosis, coccidioidomycosis,

histoplasmosis– dermatophytes, – itraconazole and voriconazole, even Aspergillus infections.– itraconazole and voriconazole, even Aspergillus infections.

• Useful in the treatment of intrinsically amphotericin-resistant organisms such as Pseudallescheria boydii

• Azoles are relatively nontoxic, minor gastrointestinal upset.

• Cause abnormalities in liver enzymes and, very rarely, clinical hepatitis


AZOLES

• KETOCONAZOLE– first oral azole introduced into clinical use– Higher affinity to human cytochrome P450 – use has been

limited to topical use only

• ITRACONAZOLEavailable in oral and intravenous formulations and– available in oral and intravenous formulations andis used at a dosage of 100–400 mg/d.

– reduced bioavailability of itraconazole when taken with rifamycins

– choice for treatment of disease due to the dimorphic fungiHistoplasma, Blastomyces, and Sporothrix.

– used extensively in the treatment of dermatophytoses and onychomycosis.


AZOLES: FLUCONAZOLE• high degree of water solubility and good cerebrospinal

fluid penetration. • Comparatibly higher oral bioavailability and less drug

interactions • Oral and intravenous formulations and is used at a dosage

of 100–800 mg/d.of 100–800 mg/d.• Azole of choice in the treatment and secondary prophylaxis

of cryptococcal meningitis• Equivalent to amphotericin B in treatment of candidemia in

ICU patients with normal WBC counts.• Commonly used for the treatment of mucocutaneous

candidiasis. • Prophylactic use: reduce fungal disease in bone marrow

transplant recipients and AIDS patients,


Summary: Antifungal


Anti-Protozoan Drugs: AntimalarialDrug

• Four species of plasmodium typically cause human malaria: Plasmodium falciparum,P vivax, P malariae, and P vivax, P malariae, and P ovale.

• Drug resistance is an important therapeutic problem, most notablywith P falciparum.


Life Cycle of Protozoan

• An anopheline mosquito inoculates plasmodium sporozoites to initiate human infection

• Then it invade liver cells, and exoerythrocyticstage tissue schizonts mature in the liver.

• Merozoites are subsequently released from the • Merozoites are subsequently released from the liver and invade erythrocytes

• Only erythrocytic parasites cause clinical illness.• Sexual stage gametocytes also develop in

erythrocytes before being taken up by mosquitoes


Drug Principle

• In P falciparum and P malariae infection, only one cycle of liver cell invasion and multiplication occurs, and liver infection ceases spontaneously in less than 4 weeks

• Treatment that eliminates erythrocytic parasites will cure these infections.

• In P vivax and P ovale infections, a dormant hepatic stage - hypnozoite, is not eradicated by most drugs

• Subsequent relapses can therefore occur after therapy directed against erythrocytic parasites.

• Eradication of both erythrocytic and hepatic parasites is required to cure these infections

• It usually requires two or more drugswww.facebook.com/notesdental

Classification: Antimalarial Drug

– 4-aminoquinolines: chloroquine amodilaquinepiperaquine

– Quiniline methanol: mefloquine– Cinchona extracted: Quinine quinidine– Biguanides: Proguanil, chlorproguanil– Biguanides: Proguanil, chlorproguanil– Diaminopyrimidines: pyrimethamine– 8-aminoquinoline: primaquine, bulaquine– Sulfonamides: Sulfadoxine, Sulfamethopyrazine ,Dapsone– Tetracyclines: Tetracylcines, doxycyclines– Sesquiterpine lactones: artesunate, artemether, arteether– Amino alcohols: halofantrine, lumefantrine– Mannich base: pyronaridine– Napthoquinone: Atovaquone


Classification: Antimalarial Drug

• It can also be classified on the basis of action

– tissue schizonticides

– blood schizonticides

– gametocides– gametocides


CHLOROQUINE

• drug of choice for both treatment andchemoprophylaxis of malaria since the 1940s

• Usefulness against P falciparum has been seriously compromised by drug resistance

Chemistry & Pharmacokinetics• Chemistry & Pharmacokinetics– synthetic 4-aminoquinoline phosphate salt for oral use

– rapidly and almost completely absorbed from the gastrointestinal tract,

– Reaches maximum plasma concentrations in about 3 hours


Pharmacokinetics

• Rapidly distributed to the tissues.• large apparent volume of distribution of 100–

1000 L/kg and is slowly released from tissuesand metabolized.

• Principally excreted in the urine with an initial • Principally excreted in the urine with an initial half-life of 3–5 days

• Antimalarial Action & Resistance– Highly effective blood schizonticide– Moderately effective against gametocytes of P vivax, P

ovale, and P malariae but not against those ofP falciparum.


Treatment

• drug of choice in the treatment of nonfalciparum and sensitive falciparum malaria

• rapidly terminates fever (in 24–48 hours) and clears parasitemia (in 48–72 hours)

• replaced by other drugs, principallyartemisinin-basedartemisinin-based

• does not eliminate dormant liver forms of P vivaxand P ovale,

• primaquine must be added for the radical cure of these species.

• Chemoprophylaxis• Amebic Liver Abscess: reaches high liver concentrations

and may be used for amebic abscesses


Adverse Effects

• very well tolerated, even with prolongeduse

• Nausea, vomiting, abdominal pain, headache, anorexia, malaise, blurring of vision, and anorexia, malaise, blurring of vision, and urticaria are uncommon

• Dosing after meals may reduce some adverse effects.


Contraindications & Cautions

• Psoriasis or porphyria: may precipitate acute attacks of these diseases

• retinal or visual field abnormalities or myopathy• history of liver disease or neurologic or

hematologic disorders. hematologic disorders. • antidiarrheal agent kaolin and calcium- and

magnesium-containing antacids interfere with theabsorption of chloroquine and should not be co-administered with the drug.

• safe in pregnancy and for young children


ARTEMISININ & ITS DERIVATIVES

• Artemisinin: sesquiterpene lactone endoperoxide- active component of an herbal medicine (China for over 2000 years)

• Artesunate: water-soluble; useful for oral, intravenous, intramuscular, and rectal intravenous, intramuscular, and rectal administration

• Artemether: lipid-soluble; useful for oral,intramuscular, and rectal administration

• Dihydroartemisinin: water-soluble; useful for oral administration


Chemistry & Pharmacokinetics

• Rapidly absorbed, with peak plasma levels occurring in 1–2 hours

• half-lives of 1–3 hours after oral administrationadministration

• Artemisinin, artesunate, and artemetherare rapidly metabolized to the active metabolite dihydroartemisinin.


Antimalarial Action & Resistance

• Artemisinin monotherapy for the treatment of uncomplicated malaria is now strongly discouraged

• Rather, co-formulated artemisinin-based combination therapies are recommended toimprove efficacy– oral combination regimen Coartem– oral combination regimen Coartem

(artemetherlumefantrine)

• Prevent the selection of artemisinin-resistantparasites

• Rapidly acting blood schizonticides against all human malaria parasites

• No effect on hepatic stages


Clinical Uses

• Standard for treatment of uncomplicated falciparum malaria.

• WHO recommends five • WHO recommends five artemisinin-based combinations for the treatment of uncomplicated falciparum malaria


Adverse Effects & Cautions

• Generally very well tolerated• Rare serious toxicities include neutropenia,

anemia, hemolysis, elevated liver enzymes, and allergic reactions.

• Although cytotoxic to embryo in lab animal, its • Although cytotoxic to embryo in lab animal, its used in pregnancy due to significant risk of malaria– WHO recommendation for treatment of severe

malaria during pregnancy – i.v artesunate or quinine: first trimester– i.v artesunate: second and third trimesters


QUININE & QUINIDINE

• Important therapies for falciparum malaria

– especially severe disease

– Resistance is uncommon – Resistance is uncommon but may be increasing

• Derived from the bark of the cinchona tree


Pharmacology

• Rapidly absorbed orally

• Reaches peak plasma levels in 1–3 hours

• Widely distributed in body tissues

• Pharmacokinetics of quinine varies among • Pharmacokinetics of quinine varies among populations– Individuals with malaria develop higher plasma levels

of the drug and has higher plasma half life than healthy controls,

• Primarily metabolized in the liver and excreted in the urine


Antimalarial Action

• Rapid-acting, highly effective blood schizonticide against the four species of human malaria parasites

• Gametocidal against P vivax• Gametocidal against P vivaxand P ovale but not P falciparum.

• Not active against liver stage parasites

• mechanism of action of quinine is unknown.


Clinical Uses• Parenteral Dose

– quinine dihydrochloride or quinidine gluconate– administered slowly intravenously or, in a dilute solution,

intramuscularly in divided doses or by continuous intravenous infusion; • Cardiac toxicity and the relative unpredictability of its pharmacokinetics,

– Treatment should begin with a loading dose– Therapy should be changed to an effective oral agent as soon as the – Therapy should be changed to an effective oral agent as soon as the

patient has improved

• Oral Treatment– Quinine sulfate– commonly used with a second drug (most often doxycycline or in

children, clindamycin)– less effective than chloroquine against other human malarias and is

more toxic.– Babesiosis: first-line therapy, in combination with clindamycin, in

Babesia microti or other human babesial infections.


Adverse Effects

• commonly cause tinnitus, headache, nausea, dizziness, flushing, and visual disturbances –cinchonism

• Therapy should be not discontinued to mild symptoms of cinchonismsymptoms of cinchonism

• Hypersensitivity: skin rashes, urticaria, angioedema, and bronchospasm.

• Hematologic abnormalities: hemolysis (especially with G6PD deficiency), leukopenia, agranulocytosis, and thrombocytopenia


Adverse Effects

• It may also cause hypoglycemia through stimulation of insulin release;

• stimulate uterine contractions – 3rd trimester, but still drug of – 3rd trimester, but still drug of choice

• Blackwater fever: a rare severe illness with marked hemolysis and hemoglobinuriain the setting of quinine therapy for malaria.


Contraindications

• Should be discontinued if signs of severecinchonism, hemolysis, or hypersensitivity occur.

• avoided if possible in patients with underlying visual or auditory problems

• great caution in those with underlying cardiac • great caution in those with underlying cardiac abnormalities

• C/I concurrently with mefloquine

• Absorption may be blocked by aluminum containing antacids

• Quinine can raise plasma levels of warfarin and digoxin


Antiameobic• Amebiasis is infection with

Entamoeba histolytica whichcause– Asymptomatic intestinal

infection– Mild to moderate colitis, Mild to moderate colitis, – Severe intestinal infection

(dysentery), – Ameboma, – liver abscess– Other extraintestinal infections.

• The choice of drugs depends on the clinical presentation


Life Cycle of Amoeba


Classification: Antiameobic drug

• Tissue amoebicides– Intestinal/extraintestinal nitroimidazoles:

metrondiazoles ,tinidazole, secnidazole, ornidazole, satranidazole

– Alkoloids: Emetine, Dehydroemetine, Estraintestinal, Chloroquines

– Alkoloids: Emetine, Dehydroemetine, Estraintestinal, Chloroquines

• Luminal amoebicides– Amide: Diloxanide, furoate, nitazoxanide– 8-hydroxyquinolines: quiniodochlor, clioquinol,

diiodohydroxyquin– Antibiotics: Tetracycllines


Treatment of Specific Forms of Amebiasis

• Asymptomatic Intestinal Infection– treated with a luminal amebicide– Each drug eradicates carriage in about 80–90% of patients with a

single course of treatment.

• Amebic Colitis– Metronidazole plus a luminal amebicide: drug of choice.– Tetracyclines and erythromycin are alternative drugs for moderate – Tetracyclines and erythromycin are alternative drugs for moderate

colitis

• Extraintestinal Infections– metronidazole plus a luminal amebicide– 10-day course of metronidazole cures over 95% of uncomplicated liver

abscesses.– For unusual cases in which initial therapy with metronidazole has

failed, aspiration of the abscess and the addition of chloroquine to a repeat course of metronidazole should be considered.


METRONIDAZOLE & TINIDAZOLE

• a nitroimidazole

• It kills trophozoitesbut not cysts of E histolytica and effectively eradicateseffectively eradicates

• Tinidazole, another related nitroimidazole– appears to have similar

activity and a better toxicity profile than metronidazole


Pharmacology

• readily absorbed and permeate all tissues by simple diffusion.

• Intracellular concentrations rapidly approach extracellular levels

• Peak plasma concentrations are reachedin 1–3 hoursin 1–3 hours

• Protein binding of both drugs is low (10–20%); • The half-life of unchanged drug is 7.5 hours for

metronidazole and 12–14 hours for tinidazole• excreted mainly in the urine• Plasma clearance of metronidazole is decreased in

patients with impaired liver function


Clinical Uses

• Both drugs are equally effective and drug of choice of following protozoan infection

• Amebiasis– Neither drug is reliably effective against luminal parasites

and so must be used with a luminal amebicide to ensure eradication of the infectioneradication of the infection

• Giardiasis– Dosage is much lower than amebiasis – so better tolerated– Efficacy after a single treatment is about 90%

• Trichomoniasis– A single dose of 2 g is effective.– Metronidazole-resistant organisms can occur– Tinidazole may be effective against some of these resistant

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Adverse Effects• Nausea, headache, dry mouth, or a metallic taste in

the mouth occurs commonly• Taking the drug with meals lessens gastrointestinal

irritation.• nausea and vomiting can occur if taken with alcohol• The dosage should be adjusted for patients with severe • The dosage should be adjusted for patients with severe

liver or renal disease• potentiate coumarin-type anticoagulants effect• Phenytoin and phenobarbital may accelerate

elimination of the drug• Cimetidine may decrease plasma clearance. • Data on teratogenicity are inconsistent - best avoided

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Anti-Helminthics

• Multicellular organisms that infect very large numbers of humans and cause a broad range of diseases.

• Various helminthes affecting humans– Roundworm

– Hookworm– Hookworm

– Threadworm

– Guinea worm

– Whipworm

– Filaria

– Tapeworm

– Hydatid Disease


Round Worm

• Ascaris lumbricoides, which causes ascariasis

• present in the GI tract (small intestine) of 1.2–1.5 billion individuals in tropical and subtropical areas

• acquired through ingestion of • acquired through ingestion of embryonated eggs.

• Usually asymptomatic but can be complicated by several conditions, includingappendicitis, bowel perforation, cholecystitis, intestinal obstruction (large numbers),malabsorption


Anti-Helminthics: Classification• Roundworm

– 1st choice: Mebendazole, Albendazole, Pyrantel

– Alternative: Piperazine, levamisole, ivermectin

• Hookworm– 1st choice: Pyrantel,

mebendazole, albendazole

• Whipworm– 1st choice: mebendazole,

Albendazole– Alternative: albendazole

mebendazole

• Filaria– 1st choice: Diethyl

Carbamazine, ivermectinmebendazole, albendazole– Alternative: levamisole, Pyrantel

• Threadworm – 1st choice: Pyrantel,

mebendazole, albendazole, ivermectin

– Alternative: Piperazine, albendazole

• Guinea worm: Metrondiazoles

1st choice: Diethyl Carbamazine, ivermectin

– Alternative: Albendazole

• Tapeworm – 1st choice: Praziquantel

niclosamide , albendazole– Alternative: albendazole

• Hydatid Disease: albendazole, mebendazole


ALBENDAZOLE

• broad-spectrum oral antihelminthic - drug of choice

• It’s a benzimidazole carbamate• erratically absorbed (increased with a fatty meal) • then rapidly undergoes first-pass metabolism in • then rapidly undergoes first-pass metabolism in

the liver to the active metabolite albendazolesulfoxide.

• treatment of hydatid disease, cysticercosis, pinworm, hookworm infections, ascariasis, trichuriasis, and strongyloidiasis


ALBENDAZOLE

• Sulfoxide is mostly protein-bound, distributes well to tissues, and enters bile, cerebrospinal fluid, and hydatid cysts

• plasma half-life is 8–12 hours and maximum plasma concentration reaches in 3 hrsplasma concentration reaches in 3 hrs

• metabolites are excreted in the urine.• act against nematodes by inhibiting microtubule

synthesis.• Larvicidal effects in hydatid disease, cysticercosis,

ascariasis, and hookworminfection


CLINICAL USE

• administered on an empty stomach when used against intraluminal parasites but with a fatty meal when used against tissue parasites

• Ascariasis, Hookworm and Pinworm • Ascariasis, Hookworm and Pinworm Infections– adults and children older than 2 years of age:

– single dose of 400 mg orally

– repeated for 2–3 days for heavy ascaris infections and in 2 weeks for pinworm infections


CLINICAL USE

• Hydatid Disease– treatment of choice for medical therapy and is a useful

adjunct to surgical removal or aspiration of cysts– more active against Echinococcus granulosus than against

E multilocularis– 400 mg twice daily with meals for 1 month or longer.– 400 mg twice daily with meals for 1 month or longer.– Daily therapy for up to 6 months has been well tolerated.

• Other Infections: drug of choice in the treatment of – Cutaneous larva migrans (400 mg daily for 3 days), – visceral larva migrans (400 mg twice daily for 5 days), – intestinal capillariasis (400 mg daily for 10 days), – microsporidial infections (400 mg twice daily for 2 weeks

or longer)


MEBENDAZOLE

• Synthetic benzimidazole• Wide spectrum of antihelminthic activity and a

low incidence of adverse effects.• 10% of orally administered mebendazole is

absorbed.absorbed.• absorbed drug is protein-bound (> 90%),• rapidly converted to inactive metabolites -

primarily during its first pass in the liver)• Plasma half-life of 2–6 hours• Excreted mostly in the urine


MEBENDAZOLE

• a portion of absorbed drug and its derivatives are excreted in the bile

• Mechanism of action inclused inhibition of microtubule synthesismicrotubule synthesis

• Efficacy of the drug varies with

– gastrointestinal transit time,

– intensity of infection,

– perhaps with the strain of parasite.


Clinical Use

• The drug kills hookworm, ascaris, and trichuriseggs.

• Pinworm infection: 100 mg once, repeated at 2 weeks.2 weeks.

• Ascariasis, trichuriasis, hookworm, and trichostrongylus infection– dosage of 100 mg twice daily for 3 days is used

for adults and for children older than 2 years of age.


Adverse Reactions, Contraindications & Cautions

• Short-term therapy for intestinal nematodes is nearly free of adverse effects.

• Mild nausea, vomiting, diarrhea, and abdominal pain• Rare side effects, usually with high-dose therapy, are

hypersensitivity reactions (rash, urticaria), agranulocytosis, alopecia, and elevation of liver enzymes.alopecia, and elevation of liver enzymes.

• teratogenic in animals and therefore contraindicated in pregnancy.

• It should be used with caution in children younger than 2 years of age because of limited experience

• Plasma levels may be decreased by concomitant use of carbamazepine or phenytoin and increased by cimetidine.

• Mebendazole should be used with caution in patients with cirrhosis


PIPERAZINE

• alternative for the treatment of ascariasis, with cure rates over 90%

• not recommended for other helminth infections• available as the hexahydrate and as a variety of

salts.salts.• readily absorbed, and maximum plasma levels

are reached in 2–4 hours• Most of the drug is excreted unchanged in the

urine in 2–6 hours,• Excretion is complete within 24 hours


PIPERAZINE

• causes paralysis of ascaris by blocking acetylcholine at the myoneural junction;

• unable to maintain their position in the host

• live worms are expelled by normal peristalsis.• live worms are expelled by normal peristalsis.

• 75 mg/kg (maximum dose, 3.5 g) orally once daily for 2 days.

• heavy infections, treatment should be continued for 3–4 days or repeated after 1 week


References

• Basic & Clinical Pharmacology Bertram G. Katzung Twelfth Edition

• Essential of medical pharmacology - K.D. Tripathi6th edition

Lippincott - Modern Pharmacology With Clinical • Lippincott - Modern Pharmacology With Clinical Applications 6E

• Color Atlas Of Pharmacology, 2Nd Ed (Lüllmann, Thieme 2000)


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antimicrobial viral, protozoan, fungi and helmitnhics

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