Prof. Hanan Hagar Dr Ishfaq Bukhari Pharmacology Department Medical College Treatment of dysentery...
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Transcript of Prof. Hanan Hagar Dr Ishfaq Bukhari Pharmacology Department Medical College Treatment of dysentery...
Prof. Hanan HagarProf. Hanan HagarDr Ishfaq BukhariDr Ishfaq Bukhari
Pharmacology DepartmentPharmacology DepartmentMedical CollegeMedical College
Treatment of dysentery and Treatment of dysentery and amebiasisamebiasis
ObjectivesObjectives
To understand different causes of dysentery. To describe different classes of drugs used in treatment of
both bacillary dysentery and amebic dysentery. To be able to describe actions, side effects of drugs for
treating bacillary dysentery. To understand the pharmacokinetics, actions, clinical
applications and side effects of antiamebic drugs. To be able to differentiate between three types of antiamebic
drugs luminal amebicides, tissue amebicide and mixed amebicides.
DysenteryDysentery
Dysentery:Dysentery: is an inflammatory disorder of the is an inflammatory disorder of the intestine, that results in severe intestine, that results in severe diarrheadiarrhea containing containing mucusmucus and/or and/or bloodblood in the in the fecesfeces with with feverfever and and abdominal pain.abdominal pain.
Causes of DysenteryCauses of Dysentery
The two most common causes are:The two most common causes are: Amebic dysentery Amebic dysentery (protozoal infection mainly by (protozoal infection mainly by
Entameba Histolytica).Entameba Histolytica). Bacillary dysentery Bacillary dysentery (bacterial infection mainly (bacterial infection mainly
by shigella).by shigella).
Treatment of DysenteryTreatment of Dysentery
Maintain Maintain fluid intakefluid intake using oral rehydration using oral rehydration therapy or Intravenous fluid therapy.therapy or Intravenous fluid therapy.
Antimicrobial agentsAntimicrobial agents should not be given untill should not be given untill stool analysis is done (emperic therapy should stool analysis is done (emperic therapy should be started after sample of stool taken for be started after sample of stool taken for analysis).analysis).
AmebiasisAmebiasis
Amebiasis is a protozoal infection of the Amebiasis is a protozoal infection of the intestinal tract that occurs due to ingestion of intestinal tract that occurs due to ingestion of foods or water contaminated with foods or water contaminated with cysts ofcysts of Entameba HistolyticaEntameba Histolytica..
The patients show varying degree of illness The patients show varying degree of illness from no symptoms to mild diarrhea to severe from no symptoms to mild diarrhea to severe dysentery.dysentery.
Clinical presentationsClinical presentations
Asymptomatic intestinal infectionAsymptomatic intestinal infection (Carriers, passing cysts in stool)(Carriers, passing cysts in stool) Mild to moderate intestinal disease Mild to moderate intestinal disease (colitis)(colitis) Severe intestinal infection Severe intestinal infection (amoebic dysentery)(amoebic dysentery) Ameboma Ameboma (localized granulomatous lesion of (localized granulomatous lesion of
colon)colon).. Hepatic abscess, and other extra-intestinal Hepatic abscess, and other extra-intestinal
diseases.diseases.
Life Cycle
1. Cysts ingestion in contaminated food or water.
2. Liberation of trophozoites in the colon.
3. Invasion & penetration of intestinal wall.
4. Multiplication of trophozoites within colon wall.
5. Systemic invasion to liver.
6. Cyst formation in rectum and excretion in feces.
ANTIAMEBIC DRUGSANTIAMEBIC DRUGS
▪▪ Luminal Amebicides Luminal Amebicides
▪ ▪ Tissue or systemic amebicides (not Tissue or systemic amebicides (not commonly used)commonly used)
▪▪
Luminal amebicidesLuminal amebicides
Acts on the parasites in the lumen of the bowel.Acts on the parasites in the lumen of the bowel. used for treatment of asymptomatic amebiasis used for treatment of asymptomatic amebiasis
(carriers).(carriers).
IncludeInclude Diloxanide furoateDiloxanide furoate IodoquinolIodoquinol AntibioticsAntibiotics
- Paromomycin - Paromomycin
Tissue or systemic amebicidesTissue or systemic amebicides
acts on ameba in the intestinal wall and liver (or any acts on ameba in the intestinal wall and liver (or any other extra-intestinal tissue).other extra-intestinal tissue).
Used for treatment of systemic form of the Used for treatment of systemic form of the disease (intestinal wall infection or liver disease (intestinal wall infection or liver abscesses).abscesses).
IncludeInclude Emetine Emetine DehydroemetineDehydroemetine Chloroquine (Chloroquine (liver onlyliver only))
Mixed amoebicidesMixed amoebicides
Effective against both luminal and systemic forms Effective against both luminal and systemic forms of the disease. Although luminal concentration is of the disease. Although luminal concentration is too low for single drug-treatment.too low for single drug-treatment.
IncludeInclude MetronidazoleMetronidazole TinidazoleTinidazole
METRONIDAZOLEMETRONIDAZOLE
Mixed amoebicide.Mixed amoebicide. Drug of choice for treating Drug of choice for treating amebic infections (intestinal &amebic infections (intestinal & Extra-intestinal).Extra-intestinal). Acts on trophozoites.Acts on trophozoites. Has no effect on cysts.Has no effect on cysts. Metronidazole inhibits DNA replication.Metronidazole inhibits DNA replication.
PharmacokineticsPharmacokinetics Given orally or IV.Given orally or IV. Absorption is rapid and complete.Absorption is rapid and complete.▪ ▪ Due to rapid absorption from GIT, Due to rapid absorption from GIT, not reliably not reliably
effective against luminal parasites.effective against luminal parasites. Wide distribution to all tissues and body fluids Wide distribution to all tissues and body fluids
(CSF, saliva, milk).(CSF, saliva, milk). Metabolized in liver by mixed function oxidase Metabolized in liver by mixed function oxidase
followed by glucuronidation (consider drug followed by glucuronidation (consider drug interactions).interactions).
Excreted in urine.Excreted in urine. Clearance is decreased in liver impairmentClearance is decreased in liver impairment
Clinical UsesClinical Uses Extra-luminal amoebiasis: is the drug of choice in all Extra-luminal amoebiasis: is the drug of choice in all
tissue amebiasis tissue amebiasis ((should be combined with luminal should be combined with luminal amebicideamebicide).).
Giardiasis (cause by G. lamblia & common in Giardiasis (cause by G. lamblia & common in children) children)
Broad spectrum of anaerobic bacteria e.g.,Broad spectrum of anaerobic bacteria e.g., Helicobacter pylori infection (eradication therapy)Helicobacter pylori infection (eradication therapy) Pseudo-membranous colitis Pseudo-membranous colitis (Clostridium difficile).(Clostridium difficile). Dental infectionDental infection
Adverse effectsAdverse effects
GIT:GIT: Dry mouth, metallic taste Dry mouth, metallic taste Nausea, vomitingNausea, vomiting Oral Thrush (Moniliasis, yeast infection).Oral Thrush (Moniliasis, yeast infection).CNS: Neurotoxicological effectCNS: Neurotoxicological effect Insomnia, dizzinessInsomnia, dizziness peripheral neuropathy, paresthesiaperipheral neuropathy, paresthesia encephalopathy, convulsion (encephalopathy, convulsion (IV infusion, rareIV infusion, rare).).Dysuria,Dysuria, dark urine. dark urine.NeutropeniaNeutropeniaDisulfiram-like effectDisulfiram-like effect if taken with alcohol (hot if taken with alcohol (hot
flushes, nausea, vomiting).flushes, nausea, vomiting).
Disulfiram like -effect Disulfiram like -effect
When metronidazole is given with alcohol abdominal When metronidazole is given with alcohol abdominal distress, nausea, vomiting, flushing, or headache, distress, nausea, vomiting, flushing, or headache, tachycardia, hyperventilationtachycardia, hyperventilation alcohol alcohol aldehyde aldehyde dehydrogenase dehydrogenasedehydrogenase dehydrogenase
EthanolEthanol AcetaldehydeAcetaldehyde AcetateAcetate
Metronidazole inhibits this enzyme
Drug interactions:Drug interactions: Enzyme inhibitors Enzyme inhibitors (cimetidine, ketoconazole)(cimetidine, ketoconazole) increase duration of action of metronidazoleincrease duration of action of metronidazole Inducers Inducers (phenytoin and phenobarbitone).(phenytoin and phenobarbitone).
decrease duration of action of metronidazoledecrease duration of action of metronidazole
Metronidazole inhibits CYP family 2C9 & 3A4 Metronidazole inhibits CYP family 2C9 & 3A4 so so increases anticoagulant effect of warfarin.increases anticoagulant effect of warfarin. Increases lithium toxicity.Increases lithium toxicity.
CONTRAINDICATIONS / PRECAUTIONS:CONTRAINDICATIONS / PRECAUTIONS:
▪ ▪ Pregnancy and nursing women.Pregnancy and nursing women.
▪ ▪ Alcohol intakeAlcohol intake
▪ ▪ CNS diseasesCNS diseases
▪ ▪ Severe hepatic disease Severe hepatic disease Severe renal diseaseSevere renal disease
TinidazoleTinidazole
Tinidazole Tinidazole has similar activity but better potency than metronidazole, With longer duration of action (12-14h), a simpler dosing regimen and a better toxicity profile than metronidazole.
- Well tolerated in Children.
EmetineEmetine and dehydroemetineand dehydroemetine
Emetine Emetine is is an alkaloid derived from ipeca while an alkaloid derived from ipeca while dehydroemetinedehydroemetine is a synthetic analog, is a synthetic analog,
Both are effective against tissue trophozoites of Both are effective against tissue trophozoites of E. histolytica causing irreversible block of E. histolytica causing irreversible block of protein synthesis.protein synthesis.
Because of major toxicity concerns Because of major toxicity concerns they have they have been almost completely replaced by been almost completely replaced by metronidazolemetronidazole
Clinical UsesClinical Uses
Severe forms of amebiasis Severe forms of amebiasis acute amoebic acute amoebic dysenterydysentery dehydroemetine is preferable due to dehydroemetine is preferable due to less toxicity (3-5 days).less toxicity (3-5 days).
ChloroquineChloroquine
Anti-malarial drugAnti-malarial drug Used in combination with metronidazole or Used in combination with metronidazole or
dehydroemetine and luminal amebicide for dehydroemetine and luminal amebicide for amebic liver diseases.amebic liver diseases.
Now not commonly used in amebeasis. Now not commonly used in amebeasis.
Luminal amoebicidesLuminal amoebicides
IncludeInclude Diloxanide furoateDiloxanide furoate IodoquinolIodoquinolAntibioticsAntibiotics
- Paromomycin- Paromomycin -Tetracyclins-Tetracyclins
Diloxanide furoateDiloxanide furoate Given orally.Given orally. It splits in the intestine, most of diloxanide is It splits in the intestine, most of diloxanide is
absorbed, conjugated to form a glucoronide absorbed, conjugated to form a glucoronide which is excreted in urine (90%).which is excreted in urine (90%).
The unabsorbed diloxanide is the The unabsorbed diloxanide is the amoebicidal amoebicidal agent (10%).agent (10%).
Direct amoebicidal action against luminal formsDirect amoebicidal action against luminal formsNot active against trophozoites in intestinal wall or Not active against trophozoites in intestinal wall or extra-intestinal tissuesextra-intestinal tissues..
Mechanism of action is unknownMechanism of action is unknown
Therapeutic UsesTherapeutic Uses
Drug of choice for Drug of choice for asymptomatic intestinal asymptomatic intestinal infection (drug of choice in cysts passers). infection (drug of choice in cysts passers).
For complete eradication of amebic infections For complete eradication of amebic infections given along with tissue amebicides eg given along with tissue amebicides eg metronidazole.metronidazole.
Adverse EffectsAdverse Effects FlatulenceFlatulence Nausea, vomiting, abdominal cramps.Nausea, vomiting, abdominal cramps. No serious adverse effectsNo serious adverse effectsContraindications:Contraindications:
- Pregnancy- Pregnancy - Children (less than 2 years).- Children (less than 2 years).
Iodoquinol Iodoquinol Is given orallyIs given orally
Not absorbed (90%), excreted in feces.Not absorbed (90%), excreted in feces. 10% enter circulation, excreted as glucouronide 10% enter circulation, excreted as glucouronide
in urine.in urine. Mechanism of action is unknownMechanism of action is unknown
effective against the luminal trophozoites.effective against the luminal trophozoites.
UsesUses luminal amoebicide for luminal amoebicide for
asymptomatic amebiasis.asymptomatic amebiasis.
Adverse EffectsAdverse Effects GIT:GIT: Nausea, vomiting, diarrhea. Nausea, vomiting, diarrhea. Peripheral neuropathyPeripheral neuropathy including optic neuritis including optic neuritis Enlargement of the thyroid gland.Enlargement of the thyroid gland. Iodine sensitivity Iodine sensitivity interference with thyroid function tests (increase interference with thyroid function tests (increase
protein-bound serum iodine, decrease in protein-bound serum iodine, decrease in measuredmeasured ((131131I uptakeI uptake).).
Iodoquinol should be used with caution in Iodoquinol should be used with caution in patients with optic neuropathy, renal or thyroid patients with optic neuropathy, renal or thyroid disease.disease.
discontinueddiscontinued if it produces persistent diarrhea if it produces persistent diarrhea or signs of iodine toxicity or signs of iodine toxicity (dermatitis, urticaria, (dermatitis, urticaria, pruritus, fever).pruritus, fever).
Paromomycin SulphateParomomycin Sulphate
Aminoglycoside antibiotic.Aminoglycoside antibiotic. It is given orally and Not absorbed from GITIt is given orally and Not absorbed from GIT Effective against luminal forms of amebaEffective against luminal forms of ameba Has direct amebicidal action Has direct amebicidal action (causes leakage by its (causes leakage by its
action on cell membrane of parasite).action on cell membrane of parasite). Indirect killing of bacterial flora essential for Indirect killing of bacterial flora essential for
proliferation of pathogenic amoebae.proliferation of pathogenic amoebae. Use in chronic amebiasis to eliminate cysts (in Use in chronic amebiasis to eliminate cysts (in
cysts passers (cysts passers (Dilaxonide and iodoquinolol are Dilaxonide and iodoquinolol are best for this purposebest for this purpose))
Paromomycin SulphateParomomycin Sulphate
Adverse effectsAdverse effects Gastrointestinal distress and diarrhea.Gastrointestinal distress and diarrhea.PrecautionsPrecautions Severe renal diseaseSevere renal disease patients with GIT ulcerationpatients with GIT ulceration
Safe in pregnancySafe in pregnancy
TetracyclinesTetracyclines Very weak direct amoebicidal action.Very weak direct amoebicidal action. Acts mainly Acts mainly indirectly indirectly on bacterial flora.on bacterial flora. Used in severe cases of amoebic dysentery not Used in severe cases of amoebic dysentery not
responding to metronidazoleresponding to metronidazole
BacillaryBacillary dysenterydysentery
Treated by: Treated by:
• Fluoroquinolones such as ciprofloxacin • Cotrimoxazole (trimethoprim- sulfamethoxazole)• Children or patient allergic to sulpha drugs
parenetral ceftriaxone or oral cefixime (3dr gen cephalosporin) are safe and effective.
• Cotrimoxazole is commonly used in travelers diarrhea.
Ciprofloxacin
active against a variety of gram-positive and gram-negative bacteria.
block bacterial DNA synthesis. Used in treatment of 1. Bacterial diarrhoea (caused by shigella, salmonella, and E coli). 2. Urinary tract infections 3. contraindicated in preganancy and choldren under
age 18 TOXICITY: GIT, CNS and Tendon related (ciprofloxacin)
SUMMARYSUMMARY Maintain Maintain fluid fluid intakeintake (oral rehydration therapy or (oral rehydration therapy or
Intravenous fluid therapy).Intravenous fluid therapy). asymptomatic luminal amebiasis is treated by asymptomatic luminal amebiasis is treated by
luminal amebicides luminal amebicides (diloxanide furoate, or (diloxanide furoate, or paromomycin )paromomycin )..
Intestinal and extra-intestinal amebiasis is treated by Intestinal and extra-intestinal amebiasis is treated by tissue amebicides (tissue amebicides (metronidazolemetronidazole is drug of choice is drug of choice usually being given first, followed by luminal usually being given first, followed by luminal amebicides to ensure complete eradication). amebicides to ensure complete eradication).
Ciprofloxacin is the drug of choice in bacillary dysentery. In childrn and pregnancy ceftriaxone or cefixime is the choice. Cotrimoxazole is good in travelers diarrhea.