NTA Level 5 • Semester 1 • PST05104

Pharmacodynamics of General Anaesthetics

Pharmacology and Therapeutics • Source Session/Topic 38

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Session 38: Pharmacodynamics of General Anaesthetics

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 General Anaesthetics

Describe drug interactions associated with General Anaesthetics

Describe side effects of General Anaesthetics

Describe contraindications of General Anaesthetics

Resources Needed:

Flip charts, marker pens, and masking tape

Black/white board and chalk/whiteboard markers

Computer and LCD projector

Handout 38.1. Side Effects of Inhalation Anaesthetics

SESSION OVERVIEW

Step

Time

Activity/

Content

Step

Time

Activity/

Content

Step

Time

Method

Content

Method

05 minutes

Presentation

Introduction, Learning Tasks

40 minutes

Presentation

Mechanism of Action of General

40 minutes

Presentation

Anaesthetics

15 minutes

Presentation/

Drug Interactions Associated With General

15 minutes

brainstorming

Anaesthetics

brainstorming

Anaesthetics

15minutes

Presentation

Side Effects of General Anaesthetics

15minutes

Presentation/

Contraindications of General Anaesthetics

15minutes

Brainstorming

Contraindications of General Anaesthetics

Brainstorming

05 minutes

Presentation

Key Points

05 minutes

Presentation

Evaluation

10 minutes

Presentation

Assignment

PST 05104 Pharmacology & Therapeutics 300 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 General Anaesthetics (40minutes)

Activity: Buzzing (5 minutes)

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

How do general anaesthetics 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

General Anaesthetics are the drugs which produce reversible loss of all sensation and consciousness, or simply, a drug that brings about a reversible loss of consciousness

General Anaesthetics are generally administered by an anesthesiologist in order to induce or maintain general anesthesia to facilitate surgery

General anaesthetics are mainly inhalation or intravenous as shown in the table below;

Inhalation:

Intravenous:

Gas:

Inducing agents:

e.g Nitrous Oxide

•

Thiopentone,

•

Methohexitone sodium,

•

propofol

•

etomidate

Volatile liquids:

Benzodiazepines (slower acting):

•

Ether

•

Diazepam

•

Halothane

•

Lorazepam

•

Enflurane

•

Midazolam

•

Isoflurane

•

Desflurane

•

Sevoflurane

Dissociative anaesthesia:

e.g Ketamine

Neurolept analgesia:

e.g. Fentanyl

PST 05104 Pharmacology & Therapeutics

301

NTA Level 5 Semester 1 Facilitator Guide

Major targets of General Anaesthetics is ligand gated ion channels GABA-A, Cl¯ channel receptors which are found throughout the CNS

Normally, GABA-A receptor mediates the effects of gamma-amino butyric acid (GABA), the major inhibitory neurotransmitter in the brain

When a general anaesthetic binds to this receptor, it causes conformational changes leading to opening of central pore and passing down of Cl- along concentration gradient

The result is inhibitory effect which reduces the activity of neurones

Therefore, General Anaesthetics bind with these channels and cause opening and potentiation of these inhibitory channels leading to inhibition and anaesthesia

Fig 38. 2 Structure of GABAA receptor

STEP 3: Drug Interactions Associated with General Anaesthetics (15minutes)

Activity: Brainstorming (5 minutes)

Ask students to brainstorm on the following question:

What are drug interactions associated with general anaesthetics drugs?

ALLOW few students to respond

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

PST 05104 Pharmacology & Therapeutics 302 NTA Level 5 Semester 1 Facilitator Guide

Adrenergic Neurone Blockers: enhanced hypotensive effect when general anaesthetics given with Adrenergic Neurone Blockers

Alpha-blockers: enhanced hypotensive effect when general anaesthetics given with Alpha-Blockers

Aminophylline: increased risk of convulsions when Ketamine given with Aminophylline

Analgesics: metabolism of etomidate inhibited by Fentanyl (consider reducing dose of etomidate);

effects of thiopental possibly enhanced by Aspirin;

effects of intravenous general anaesthetics and volatile liquid general anaesthetics possibly enhanced by Opioid Analgesics

Angiotensin-II Receptor Antagonists: enhanced hypotensive effect when general anaesthetics given with Angiotensin-II Receptor Antagonists

STEP 4: Side Effects of Local Anaesthetics (15minutes)

The side effects of General Anaesthetics are as indicated in the tables below;

Table 28.1; Intravenous Anaesthetic Agents

Drug

Speed of induction and

Main unwanted effect(s)

Notes

recovery

Propofol

Fast onset, very fast

Cardiovascular and

•

Rapidly metabolized

recovery

respiratory depression

• Possible to use as

continuous infusion

•

Causes pain at

injection site

Thiopental

Fast (accumulation

Cardiovascular and

•

Largely replaced by

occurs, giving slow

respiratory depression

propofol

recovery)

propofol

recovery)

•

Causes pain at

'Hangover'

•

Causes pain at

'Hangover'

injection site

•

Risk of precipitating

porphyria in

susceptible patients

Etomidate

Fast onset, fairly fast

Excitatory effects during

•

Less cardiovascular

recovery

induction and recovery

and respiratory

Adrenocortical

and respiratory

Adrenocortical

depression than with

suppression

depression than with

suppression

thiopental

•

Causes pain at

injection site

Ketamine

Slow onset, after effects

•

Psychotomimetic

Produces good analgesia

common during recovery

effects following

and amnesia

effects following

recovery

•

Postoperative nausea,

vomiting and

salivation

•

Raised intracranial

pressure

Midazolam

Slower than other agents

–

Little respiratory or

cardiovascular depression

PST 05104 Pharmacology & Therapeutics

303

NTA Level 5 Semester 1

Facilitator Guide

REFER Students to Handout 38.1: Side Effects of Inhalation Anaesthetics

STEP 5: Contraindications of Local Anaesthetics (15 minutes)

Activity: Brainstorming (5 minutes)

Ask students to brainstorm on the following question:

What are the contraindications of Local Anaesthetics? ALLOW few students to respond?

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

General Anaesthetics are contraindicated in patients with;

Family history of malignant hyperthermia.

Hyperkalaemia

Low plasma-cholinesterase activity (including severe liver disease)

Major trauma.

Neurological disease involving acute wasting of major muscle.

Personal or family history of congenital myotonic disease.

Prolonged immobilisation (risk of hyperkalaemia)

STEP 6: Key Points (5 minutes)

Anaesthesia is induced with either a volatile drug given by inhalation or with an intravenously administered drug;

Propofol is the most widely used intravenous anaesthetic, and can be used for induction or maintenance of anaesthesia in adults and children

STEP 7: Evaluation (5 minutes)

What are General Anaesthetics?

What is the mechanism of action of general anaesthetics?

What are the side effects of general anaesthetics?

PST 05104 Pharmacology & Therapeutics 304 NTA Level 5 Semester 1 Facilitator Guide

STEP 8: Take HomeAssignment (10 minutes)

Activity: Take Home Assignment (5 minutes)

DIVIDE students in groups or individuals

ASK the students to work on the following Assignment

Prepare a presentation on the mechanism of action of opioid analgesics (Give examples of drugs in this pharmacological group)

ALLOCATE time for students to do the assignments and submit

REFER students to recommended reference

PST 05104 Pharmacology & Therapeutics 305 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 306 NTA Level 5 Semester 1 Facilitator Guide

Handout 20.1 Side Effects of Inhalation Anaesthetics

Table 28.2 Inhalation Anaesthetics

Drug

Speed of

Main unwanted

Notes

induction and

effect(s)

recovery

Nitrous

Fast

Few adverse effects

Good analgesic effect

oxide

Risk of anaemia (with

Low potency precludes

prolonged or repeated

use as sole anaesthetic

use)

agent-normally combined

Accumulation in

with other inhalation

gaseous cavities

agents

lsoflurane

Medium

Few adverse effects

Widely used

Possible risk of coronary

Has replaced halothane

ischemia in susceptible

patients

Sevoflurane

Fast

Few reported

Similar to desflurane

Theoretical risk of renal

toxicity owing to

fluoride

Desflurane

Fast

Respiratory tract

Used for day-case surgery

irritation, cough,

because of fast onset and

bronchospasm

recovery (comparable

with nitrous oxide)

Halothane

Medium

Hypotension

Little used nowadays

Cardiac arrhythmias

Significant metabolism to

Hepatotoxicity (with

trifluoracetate

repeated use)

Malignant hyperthermia

(rare)

Enflurane

Medium

Risk of convulsions

Has declined in use

(slight)

May induce seizures

Malignant hyperthermia

(rare)

Ether

Slow

Respiratory irritation

Now obsolete, except

Nausea and vomiting

where modern facilities

Explosion risk

are lacking

PST 05104 Pharmacology & Therapeutics 307 NTA Level 5 Semester 1 Facilitator Guide

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