NTA Level 5 • Semester 1 • PST05104

Pharmacodynamics of Antituberculosis Drugs

Pharmacology and Therapeutics • Source Session/Topic 39

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 39: Pharmacodynamics of Antituberculosis Drugs

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 Antituberculosis Drugs

Describe drug interactions associated with Antituberculosis Drugs

Describe side effects of Antituberculosis Drugs

Describe contraindications of Antituberculosis Drugs

Flip charts, marker pens, and masking tape

Black/white board and chalk/whiteboard markers

Computer and projector

SESSION OVERVIEW

Step

Time

Activity/

Content

Step

Time

Activity/

Content

Step

Time

Method

Content

Method

05 minutes

Presentation

Introduction, Learning Tasks

45 minutes

Presentation

Mechanism of Action of Antituberculosis

45 minutes

Presentation

Drugs

20 minutes

Presentation/

Drug Interactions Associated With

20 minutes

brainstorming

Antituberculosis Drugs

brainstorming

Antituberculosis Drugs

20 minutes

Presentation

Side Effects of Antituberculosis Drugs

20 minutes

Presentation/

Contraindications of Antituberculosis Drugs

20 minutes

Brainstorming

Contraindications of Antituberculosis Drugs

Brainstorming

05 minutes

Presentation

Key Points

PST 05104 Pharmacology & Therapeutics

308

NTA Level 5 Semester 1 Facilitator Guide

05 minutes

Presentation

Evaluation

PST 05104 Pharmacology & Therapeutics 309 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 Antituberculosis Drugs (45 minutes)

Activity: Buzzing (5 minutes)

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

How do Antituberculosis Drugs 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

Isoniazid

Isoniazid inhibits synthesis of mycolic acids, which are essential components of mycobacterial cell walls.

Isoniazid is a prodrug that is activated by KatG, the mycobacterial catalase-peroxidase.

The activated form of isoniazid forms a covalent complex with an acyl carrier protein (AcpM) and KasA, a beta-ketoacyl carrier protein synthetase, which blocks mycolic acid synthesis and kills the cell.

Rifampin

Rifampin binds to the β subunit of bacterial DNA-dependent RNA polymerase and thereby inhibits RNA synthesis

Human RNA polymerase does not bind rifampin and is not inhibited by it.

Rifampin is bactericidal for mycobacteria.

It can kill organisms that are poorly accessible to many other drugs, such as intracellular organisms and those sequestered in abscesses and lung cavities

Ethambutol

Ethambutol inhibits mycobacterial arabinosyl transferases, which are encoded by the embCAB operon.

Arabinosyl transferases are involved in the polymerization reaction of arabinoglycan, an essential component of the mycobacterial cell wall.

PST 05104 Pharmacology & Therapeutics 310 NTA Level 5 Semester 1 Facilitator Guide

Pyrazinamide

Pyrazinamide is converted to pyrazinoic acid—the active form of the drug—by mycobacterial pyrazinamidase, which is encoded by pncA .

The specific drug target is unknown, but pyrazinoic acid disrupts mycobacterial cell membrane metabolism and transport functions.

STEP 3: Drug Interactions Associated with Antituberculosis Drugs (20 minutes)

Activity: Brainstorming (5 minutes)

Ask students to brainstorm on the following question:

What are drug interactions associated with antituberculosis drugs?

ALLOW few students to respond

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

There is no serious interaction between ant tuberculosis drugs and other drugs except that rifampicin reduces plasma concentration of digoxin

Absorption of isoniazid is reduced by antacids,

Hepatotoxic of isoniazid is potentiated by general anaesthesia and its CNS toxicity is increased by cycloserine

Pyrazinamide antagonizes effect of probenecid

STEP 4: Side Effects of Antituberculosis Drugs (20 minutes)

Side effects and adverse effects of antituberculosis drugs include:

Rifampicin

o Occasional adverse effects include rashes, thrombocytopenia, and nephritis. It may cause cholestatic jaundice and occasionally hepatitis

o Rifampin commonly causes light-chain proteinuria

Isoniazid side effects are dose related

o They occur in high dose and may include nausea, vomiting, constipation, dry mouth; peripheral neuritis with high doses (pyridoxine prophylaxis, see notes above), optic neuritis, convulsions, psychotic episodes and vertigo

Pyrazinamide

o Major adverse effects of pyrazinamide include hepatotoxicity, nausea, vomiting, drug fever, and hyperuricemia

o Hyperuricemia may provoke acute gouty arthritis

PST 05104 Pharmacology & Therapeutics 311 NTA Level 5 Semester 1 Facilitator Guide

Ethambutol; the most common serious adverse event is retro bulbar neuritis, resulting in loss of visual acuity and red-green color blindness

Streptomycin is ototoxic and nephrotoxic

o Vertigo and hearing loss are the most common side effects and may be permanent. o Toxicity is dose-related, and the risk is increased in the elderly

o Toxicity can be reduced by limiting therapy to no more than 6 months whenever possible

STEP 5: Contraindications of Antituberculosis Drugs (20 minutes)

Activity: Brainstorming (5 minutes)

Ask students to brainstorm on the following question:

What are the contraindications of Antituberculosis Drugs? ALLOW few students to respond?

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

Rifampicin is contraindicated to patient with jaundice

Isoniazid is contraindicated to patient with drug induced liver disease

Pyrazinamide is contraindicated to patient with Hepatic disorders

o Patients or their careers should be told how to recognize signs of liver disorder, and advised to discontinue treatment and seek immediate medical attention if symptoms such as persistent nausea, vomiting, malaise or jaundice develop

Ethambutol is contraindicated in optic neuritis and poor vision

Streptomycin is contraindicated to patient with mythenia gravis

Cycloserine is contraindicated to patient with epilepsy, depression, severe anxiety, psychotic states, alcohol dependence and acute porphyria

PST 05104 Pharmacology & Therapeutics 312 NTA Level 5 Semester 1 Facilitator Guide

STEP 6: Key Points (5 minutes)

Isoniazid (INH), rifampin (or other rifamycin), pyrazinamide and ethambutol are the four first-line agents for treatment of tuberculosis

In practice, therapy is initiated with a four-drug regimen of isoniazid, rifampin, and pyrazinamide plus ethambutol

The incidence and severity of untoward reactions to isoniazid are related to dosage and duration of administration.

STEP 7: Evaluation (5 minutes)

What are the mechanisms of antituberculosis drugs?

What are the drug interactions of action of antituberculosis drugs?

What are the side effects of antituberculosis drugs?

PST 05104 Pharmacology & Therapeutics 313 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.

PST 05104 Pharmacology & Therapeutics 314 NTA Level 5 Semester 1 Facilitator Guide

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