NTA Level 5 • Semester 1 • PST05104

Pharmacodynamics of Macrolides

Pharmacology and Therapeutics • Source Session/Topic 21

Full source-text version: all educational wording from the extracted learning source is retained; only presenter/tutor metadata and web-layout noise are removed, while formatting is improved for readability.

Session 21: Pharmacodynamics of Macrolides

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 Macrolide

Describe drug interactions associated with Macrolides

Describe side effects of Macrolides

Describe contraindications of Macrolides

Resources Needed:

Flip charts, marker pens, and masking tape

Black/white board and chalk/whiteboard markers

Computer and LCD projector

SESSION OVERVIEW

Activity/

Step

Time

Activity/

Content

Step

Time

Content

Step

Time

Method

Content

Method

05 minutes

Presentation

Introduction, Learning Tasks

45 minutes

Presentation/

Mechanism of Action of Macrolides

45 minutes

Buzzing

Mechanism of Action of Macrolides

Buzzing

20 minutes

Presentation/

Drug Interactions Associated With Macrolides

20 minutes

brainstorming

Drug Interactions Associated With Macrolides

brainstorming

20 minutes

Presentation

Side Effects of Macrolides

20 minutes

Presentation/

Contraindications of Macrolides

20 minutes

Brainstorming

Contraindications of Macrolides

Brainstorming

05 minutes

Presentation

Key Points

05 minutes

Presentation

Evaluation

PST 05104 Pharmacology & Therapeutics

170

NTA Level 5 Semester 1 Facilitator Guide

PST 05104 Pharmacology & Therapeutics 171 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 Macrolides (45 minutes)

Activity: Buzzing (5 minutes)

ASK students to pair up and buzz on the following question for 2 minutes

• How do Macrolides 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

Macrolides

The macrolides bind irreversibly to a site on the 50s subunit of the bacterial ribosome, thus inhibiting the translocation steps of protein synthesis.

The binding site is either identical to or in close proximity to that for lincomycin, clindamycin, and chloramphenicol. Inhibition of protein synthesis does not typically kill bacteria cells, so these agents are generally bacteriostatic, but in high concentrations they can be bactericidal.

Macrolides are phagocytosed by macrophages, which is a benefit because WBCs preferentially travel to sites of infection, thereby theoretically delivering the drug to the site at which it is needed.

Mechanisms of Resistance:

o Modification of the RSU binding site either by chromosomal mutation or through methylation via methylase greatly decreases the efficacy of macrolides; bacterial methylase can be produced constitutively (all the time) or can be induced.

o Reduced intracellular concentrations are found within the bacterium, through either reduced permeability of cell membrane to macrolides or, probably more important, increased efflux of macrolides via active pumps.

o A third, and maybe least prominent, method of resistance is through the production of esterases that hydrolyze macrolides; this is more common with gram-negative enteric bacteria (bacteria that colonize the GI tract).

PST 05104 Pharmacology & Therapeutics 172 NTA Level 5 Semester 1 Facilitator Guide

Cross-resistance is complete among all macrolides; if a bacterium is resistant to one, it will be resistant to all others in this class.

STEP 3: Drug Interactions Associated with Macrolides (20 minutes)

Activity: Brainstorming (5 minutes)

Ask students to brainstorm on the following question:

What are drug interactions associated with Macrolides drugs?

ALLOW few students to respond

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below Macrolides

Erythromycin

o Erythromycin metabolites inhibit cytochrome P450 enzymes and, thus, increase the serum concentrations of numerous drugs, including theophylline, warfarin, cyclosporine, and methylprednisolone.

o Erythromycin also increases serum concentrations of oral digoxin by increasing its bioavailability.

o Erythromycin and some antibiotics eliminate a species of intestinal flora that ordinarily inactivates digoxin, thus leading to a greater reabsorption of digoxin from the enterohepatic circulation.

o Erythromycin and clarithromycin are significant CYP450 enzyme inhibitors and are metabolized by the liver. Drug interactions with other CYP450 inhibitors should be monitored.

Azithromycin

o Because it has a 15-member (not 14-member) lactone ring, azithromycin does not inactivate cytochrome P450 enzymes and, therefore, is free of the drug interactions that occur with erythromycin and clarithromycin.

o Erythromycin is unstable in gastric acid and therefore must be administered with salts or esters or via enteric-coated tablets when administered orally.

o The addition of a methyl group to erythromycin creates clarithromycin, and the addition of methylated nitrogen to erythromycin creates azithromycin; both are stable in gastric acid and very well absorbed orally.

o Because of the long duration of action of azithromycin, a 5-day, oral, once-a-day

course for most sensitive infections is considered a treatment of adequate duration.

PST 05104 Pharmacology & Therapeutics 173 NTA Level 5 Semester 1 Facilitator Guide

STEP 4: Side Effects of Macrolides (20 minutes)

Macrolides

Erythromycin

o GI: Significant GI upset because of increased gut motility

o Acute cholestatic hepatitis: Likely hypersensitivity-related, this side effect can lead to fever, jaundice, and impaired liver function.

o Abdominal pain, especially right upper quadrant pain, should lead to the suspicion of liver involvement.

Azithromycin

o These agents are better tolerated but can also cause liver impairment.

STEP 5: Contraindications of Macrolides (20 minutes)

Activity: Brainstorming (5 minutes)

Ask students to brainstorm on the following question:

What are the contraindications of Macrolides? ALLOW few students to respond?

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

Macrolides

Previous liver complications with a macrolide are likely to recur and therefore should be considered a contraindication to macrolide use.

STEP 6: Key Points (5 minutes)

Macrolides target protein synthesis in bacteria

Newer macrolides are devoid of disadvantages of erythromycin

Erythromycin is a potent enzyme inhibitor

STEP 7: Evaluation (5 minutes)

What is the mechanism of action of macrolides?

What are drug interactions associated with erythromycin?

PST 05104 Pharmacology & Therapeutics 174 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.

Robert L. Talbert, Gary C. Yee, Gary R. Matzke, Barbara G. Wells, L. Michael. (2014). Pharmacotherapy: A Pathophysiologic Approach (9th ed.). New York, McGraw-Hill Education.

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 175 NTA Level 5 Semester 1 Facilitator Guide

← Previous Topic Next Topic →View all Pharmacology and Therapeutics topics Open Complete Full Notes

PDF / OFFLINE NOTES

Unataka kutumiwa notes hizi kupitia WhatsApp?Kwa notes zilizopangiliwa vizuri kwa kusoma offline au PDF, bonyeza kitufe hapa chini. Ujumbe wenye Level, Semester, Module na Topic utaandaliwa moja kwa moja.TUMIWA NOTES WHATSAPP

WhatsApp: 255620339260