Pharmacodynamics of Drugs for Amoebiasis
Session 24: Pharmacodynamics of Drugs for Amoebiasis
Total Session Time: 120 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Describe mechanism of action of Drugs for Amoebiasis
Describe drug interactions associated with Drugs for Amoebiasis
Describe side effects of Drugs for Amoebiasis
Describe contraindications of Drugs for Amoebiasis
Resources Needed:
Flip charts, marker pens, and masking tape
Black/white board and chalk/whiteboard markers
Computer and LCD projector
SESSION OVERVIEW
Step
Time
Activity/
Content
Step
Time
Activity/
Content
Step
Time
Method
Content
Method
Method
1
1
05 minutes
05 minutes
Presentation
Introduction, Learning Tasks
Introduction, Learning Tasks
2
2
45 minutes
45 minutes
Presentation/
Mechanism of Action of Drugs for
Mechanism of Action of Drugs for
2
2
45 minutes
45 minutes
Buzzing
Amoebiasis
Amoebiasis
Buzzing
Amoebiasis
Amoebiasis
3
3
20 minutes
20 minutes
Presentation/
Drug Interactions Associated With Drugs for
Drug Interactions Associated With Drugs for
3
3
20 minutes
20 minutes
brainstorming
Amoebiasis
Amoebiasis
brainstorming
Amoebiasis
Amoebiasis
4
4
20 minutes
20 minutes
Presentation
Side Effects of Drugs for Amoebiasis
Side Effects of Drugs for Amoebiasis
5
5
20 minutes
20 minutes
Presentation/
Contraindications of Drugs for Amoebiasis
Contraindications of Drugs for Amoebiasis
5
5
20 minutes
20 minutes
Brainstorming
Contraindications of Drugs for Amoebiasis
Contraindications of Drugs for Amoebiasis
Brainstorming
6
6
05 minutes
05 minutes
Presentation
Key Points
Key Points
7
7
05 minutes
05 minutes
Presentation
Evaluation
Evaluation
PST 05104 Pharmacology & Therapeutics 188 NTA Level 5 Semester 1 Facilitator Guide
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify
ASK students if they have any questions before continuing.
STEP 2: Mechanism of Action of Drugs for Amoebiasis (45 minutes)
Activity: Buzzing (5 minutes)
ASK students to pair up and buzz on the following question for 2 minutes
How do Drugs for Amoebiasis produce their pharmacological effects?
ALLOW few pairs to respond and let other pairs add on points not mentioned
WRITE their response on the flip chart/board
CLARIFY and SUMMARIZE by using the content below Tissue Amoebicides
Nitroimidazoles amoebicides (Metronidazole, tinidazole and ornidazole).
Nitroimidazoles are chemically reduced by ferredoxin and the reduction products are responsible for killing the parasite.
Entamoeba lacks a functional Krebs cycle and oxidative phosphorylation
Metronidazole is a prodrug. The nitrogen group must be reduced (addition of electron) before the chemical obtains its anti-infective function.
It is reduced by a nitro reductase enzyme called a ferredoxin (an iron- and sulfur-containing enzyme).
The extra nitrogen side chain is reduced in this reaction.
With aerobic bacteria the electron transport chain does not require these special enzymes because oxygen is the terminal electron acceptor; therefore the prodrug is
not converted to the active form of the drug.
However, with anaerobic bacteria, with which oxygen is absent, these special enzymes are present.
Therefore metronidazole is not activated with aerobic bacteria but is particularly
effective against anaerobic bacteria.
Reduction of the prodrug metronidazole results in the production of toxic products (hydroxylamine) and other free radicals that damage DNA.
Their bactericidal, activity is limited to anaerobic bacteria and protozoa. Metronidazole kills trophozoites of E. histolytica in intestine and tissue but does not eradicate cysts from intestines.
PST 05104 Pharmacology & Therapeutics 189 NTA Level 5 Semester 1 Facilitator Guide
Emetines (Emetine and dihydroemetine).
o The drugs cause an irreversible block of protein synthesis by inhibiting movement of the ribosome along messenger RNA.
o They have a direct lethal action to trophozoites.
Chloroquine
o Is active principally against amoeba in the liver
Luminal Amoebicides
Dichloracetamides (Diloxanide furoate, clefamide, teclozan, etofanide) o Mechanism is still unknown
Halogenated hydroxyquinolines ( Iodoquinol, Clioquinol)
Mechanism is unknown
Luminal amoebicide; acts primarily in bowel lumen since it is poorly absorbed.
Since active only against intraluminal form of amoebiasis, used to eradicate cysts of E. histolytica after treatment of invasive disease.
Antibiotics
Tetracyclines– these affect luminal amoebae indirectly- tetracyclines inhibit the
bacterial associates of amoebae (E.histolytica).
Paromomycin- an effective directly acting amoebicide
Erythromycin has direct amoebicidal action but cannot be used alone.
STEP 3: Drug Interactions Associated with Drugs for Amoebiasis (20 minutes)
Activity: Brainstorming (5 minutes)
Ask students to brainstorm on the following question:
What are drug interactions associated with drugs for amoebiasis?
ALLOW few students to respond
WRITE their responses on the flip chart/ board
CLARIFY and SUMMARISE by using the content below
Nitroimidazoles amoebicides (Metronidazole, tinidazole and ornidazole).
Metronidazole elimination is accelerated by simultaneous use of phenytoin and phenobarbital which are CYP450 enzyme inducers.
Metronidazole clearance is decreased by cimetidine which is an enzyme inhibitor.
PST 05104 Pharmacology & Therapeutics 190 NTA Level 5 Semester 1 Facilitator Guide
Metronidazole potentiates coumarin type of anticoagulants.
Metronidazole can have a disulfuram-like effect: ingestion with alcohol can lead to severe nausea and vomiting.
This results from inhibition of the enzyme acetaldehyde dehydrogenase, leading to increased levels of acetaldehyde, which are toxic.
STEP 4: Side Effects of Drugs for Amoebiasis (20 minutes)
The following areSide and adverse effects;
Metronidazole
o Metallic taste: common, harmless
o CNS toxicity: rare, manifests as ataxia, encephalopathy, or seizure.
STEP 5: Contraindications of Drugs for Amoebiasis (20 minutes)
Activity: Brainstorming (5 minutes)
Ask students to brainstorm on the following question:
What are the contraindications of drugs for amoebiasis? ALLOW few students to respond?
WRITE their responses on the flip chart/ board
CLARIFY and SUMMARISE by using the content below Contraindications include;
Metronidazole
o Ethanol: Metronidazole can have a disulfuram-like effect: ingestion with alcohol can lead to severe nausea and vomiting.
o This results from inhibition of the enzyme acetaldehyde dehydrogenase, leading to increased levels of acetaldehyde, which are toxic.
o Pregnancy (first trimester in particular): Metronidazole causes tumour growth in laboratory rats and readily crosses the placenta.
o It should be used only in extreme situations in pregnancy, after risks have been weighed against benefits.
STEP 6: Key Points (5 minutes)
Metronidazole is not recommended during pregnancy
Tinidazole have similar mechanism to metronidazole
STEP 7: Evaluation (5 minutes)
What are drugs used in treatment of amoebiasis?
What is the mechanism of action for metronidazole?
How does bacterial resistance to metronidazole develop?
PST 05104 Pharmacology & Therapeutics 191 NTA Level 5 Semester 1 Facilitator Guide
Santos, R. R., Rang, H. P., Dale, M. M., Ritter, J. M., & Flower, R. J. (2007). Rang & Dale Farmacologia. Rio de Janeiro: Elsevier.
Tripathi, K. (2018). Essentials of Medical Pharmacology. Place of publication not identified:
Jaypee Brothers Medical P.
Ministry of Health and Social Welfare. (2013). Standard Treatment Guidelines & National Essential Medicines List Tanzania Mainland (4th ed.). Dar es salaam, Tanzania government printers.
Sally S.R, Jeanne C.S. (2000). Introductory Clinical Pharmacology (6th ed) New York, Lippincott Williams and Wilkins.
School of Pharmaceutical sciences. (2011).Tanzania Pharmaceutical Handbook (2nd ed.).
Dar es Salaam, ARDHI University press.
The Royal Pharmaceutical Society of Great Britain. (2007). Martindale, the Extra Pharmacopoeia (5TH ed). London, pharmaceutical press.
The Royal Pharmaceutical Society of Great Britain. 2009. British National Formulary (59th ed). London, BMJ Group and RPS Publishing.
PST 05104 Pharmacology & Therapeutics 192 NTA Level 5 Semester 1 Facilitator Guide
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