Enzyme Inhibitors and Inducers
Session 7: Enzyme Inhibitors and Inducers
Total Session Time: 120 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Describe Enzyme induction
Describe Enzyme inhibition
Describe role of enzyme induction and inhibition
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
Activity/
Content
Step
Time
Method
Content
Method
Method
1
1
05 minutes
05 minutes
Presentation
Introduction, Learning Tasks
Introduction, Learning Tasks
2
2
30 minutes
30 minutes
Presentation/
Enzyme Inducers
Enzyme Inducers
2
2
30 minutes
30 minutes
Buzzing
Enzyme Inducers
Enzyme Inducers
Buzzing
Presentation/
3
3
45 minutes
45 minutes
Small Group
Enzyme Inhibitors
Enzyme Inhibitors
Discussion
4
4
30 minutes
30 minutes
Presentation
Clinical Importance of Enzyme Induction and
Clinical Importance of Enzyme Induction and
4
4
30 minutes
30 minutes
Brainstorming
Inhibition
Inhibition
Brainstorming
Inhibition
Inhibition
5
5
05 minutes
05 minutes
Presentation
Key Points
Key Points
6
6
05 minutes
05 minutes
Presentation
Evaluation
Evaluation
PST 05104 Pharmacology & Therapeutics 52 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 objectives and clarify
ASK students if they have any questions before continuing.
STEP 2: Description of Enzyme Induction (30 minutes)
Activity: Buzzing (5 minutes)
ASK students to pair up and buzz on the following question for 2 minutes
How does enzyme induction occur?
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
As discussed in the earlier session on metabolism of drugs, Cytochrome P-450 Enzymes Cytochrome (CYP450) enzymes are responsible for metabolism of endogenous or exogenous substrates.
There are at least 40 CYP450 enzymes but the most common isozymes are 3A4, 2D6, 2C9 and 2C19, and 1A2.
Clinically significant drug interactions arise from either induction or inhibition of these enzymes.
Enzyme induction:
A number of drugs increase the activity of microsomal oxidase and conjugating systems when administered repeatedly.
The effect is referred to as induction and is the result of increased synthesis of microsomal enzymes
An inducer stimulates increased production of a CYP450 enzyme.
Enzyme induction can increase drug toxicity and may reduce drug effectiveness (drug interaction).
Drugs which induce cytochrome P450 enzyme system significantly include: o Rifampicin, ethanol and Carbamazepine
o Drinks and herbal plants may also induce the cytochrome 450 isoenzyme a good example being St. John‘s wort and nicotine (smoking).
PST 05104 Pharmacology & Therapeutics 53 NTA Level 5 Semester 1 Facilitator Guide
STEP 3: Enzyme Inhibition (45Minutes)
Activity: Brainstorming (5 minutes)
Ask students to brainstorm on the following question:
How does enzyme inhibition occur?
ALLOW few students to respond
WRITE their responses on the flip chart/ board
CLARIFY and SUMMARISE by using the content below
Inhibition of a CYP450 enzyme will result in increased levels of a substrate (drug) that is metabolized by that enzyme.
Inhibition may be either competitive or allosteric:
Competitive inhibition
Two drugs are metabolized by the same enzyme system, and one of the drugs binds more readily to the enzyme, resulting in the inhibition of metabolism of the other drug.
Example: Erythromycin and atorvastatin are both metabolized by CYP3A4.
o Erythromycin is also a CYP3A4 inhibitor; therefore it inhibits the metabolism of atorvastatin.
Allosteric (non-competitive) inhibition
A drug inhibits an enzyme that it itself is not metabolized by.
This inhibition occurs at an allosteric site (i.e., not at the site where the substrates bind).
Drugs which inhibit cytochrome P450 enzyme system significantly include:
Cimetidine,
Omeprazole,
Quinolone antibiotics,
Amiodarone,
Antipsychotics,
Antihistamines,
Antifungal drugs,
Fluvastatin,
Isoniazid,
Macrolide antibiotics
Drinks and herbal plants may also inhibit the cytochrome 450 isoenzyme a good example being grapefruit juice and red wine.
PST 05104 Pharmacology & Therapeutics 54 NTA Level 5 Semester 1 Facilitator Guide
STEP 4: Clinical Importance of Enzyme Induction (30minutes)
Enzyme inhibition:
It may lead to drug-drug interaction due to increased plasma concentration of active drug (substrate) which its metabolism has been inhibited resulting in increased biologic activity (or toxicity) of the drug.
Prodrugs require metabolic enzymes for transformation to an active (or more active) metabolite.
Therefore enzyme inhibitor would lead to a reduction in levels of active drug, in turn reducing the biologic activity of the drug.
Enzyme induction
It may lead to drug-drug interaction whereby the plasma concentration of active drug (substrate) which its metabolism has been increased will be sub-optimal, which might result in reduced biologic activity of the drug, perhaps leading to therapeutic failure.
However, for drugs having toxic metabolites, enzyme induction may exacerbate metabolite-mediated toxicity because more and more toxic metabolited will be formed.
For prodrug enzyme induction may accelerate the formation of active drug, , leading to an exaggerated effect and toxicity
STEP 5: Key Points (5 minutes)
Induction or inhibition of metabolizing enzyme has a clinical importance.
Concomitant administration of known significant inducers or inhibitors with other drugs may result to drug interactions
The most common isozymes most likely to be inhibited or induced are 3A4, 2D6, 2C9 2C19 and 1A2.
STEP 6: Evaluation (5 minutes)
What types of drugs are known to be enzyme inducers?
What is the importance of enzyme inhibition?
What is the consequence of enzyme induction on a pro drug?
PST 05104 Pharmacology & Therapeutics 55 NTA Level 5 Semester 1 Facilitator Guide
References
Katzung, B. G. (2018). Basic and clinical pharmacology. New York: Mcgraw Hill Education.
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 56 NTA Level 5 Semester 1 Facilitator Guide
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