NTA Level 5 • Semester 1 • PST05104

Pharmacodynamics of Hypnotics and Anxiolytics

Pharmacology and Therapeutics • Source Session/Topic 29

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 29: Pharmacodynamics of Hypnotics and Anxiolytics

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 Hypnotics and Anxiolytics

Describe drug interactions associated with Hypnotics and Anxiolytics

Describe side effects of Hypnotics and Anxiolytics

Describe contraindications of Hypnotics and Anxiolytics

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

05 minutes

Presentation

Introduction, Learning Tasks

45 minutes

Presentation/

Mechanism of Action of Hypnotics and

45 minutes

Buzzing

Anxiolytics

Buzzing

Anxiolytics

20 minutes

Presentation/

Drug Interactions Associated With Hypnotics

20 minutes

brainstorming

and Anxiolytics

brainstorming

and Anxiolytics

20 minutes

Presentation

Side Effects of Hypnotics and Anxiolytics

20 minutes

Presentation/

Contraindications of Hypnotics and

20 minutes

Brainstorming

Anxiolytics

Brainstorming

Anxiolytics

PST 05104 Pharmacology & Therapeutics

225

NTA Level 5 Semester 1 Facilitator Guide

05 minutes

Presentation

Key Points

05 minutes

Presentation

Evaluation

PST 05104 Pharmacology & Therapeutics 226 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 Hypnotics and Anxiolytics (45 minutes)

Activity: Buzzing (5 minutes)

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

How do hypnotics and anxiolytics 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 Hypnotics and Anxiolytics

The distinction between hypnotics and anxiolytics is rather arbitrary, and the same classes of drugs are used for both purposes.

Compounds with a short half-life tend to be used as hypnotics, because they cause less ‗hangover‘ effects; longer half-life drugs tend to be used as anxiolytics, since a longer duration of action is generally desirable in this setting.

Benzodiazepines

o These drugs are anxiolytic, anticonvulsant muscle relaxants that induce sleepiness; they remain drugs of choice for the pharmacological treatment of insomnia and anxiety.

o Clonazepam is believed to be more anticonvulsant than other members of the group at equi-sedating doses.

o Benzodiazepines target the GABA receptors (GABA is the major inhibitory neurotransmitter in the CNS). Binding of BZDs to this BZD binding site at GABA enhances the effects of GABA at the GABAA receptor.

o Binding of GABA triggers the opening the Cl- channel resulting in hyperpolarization pushing the postsynaptic neuron further from the threshold. This result to an increase in suppressing action potential generation thus increased hyperpolarization-induced neuronal inhibition.

o The clinical effects of BZDs correlate well with GABA receptor binding affinity.

o BZDs are unable to activate the GABAA receptor on their own; therefore BZDs have no pharmacologic effects on the Cl− channel when GABA is absent.

PST 05104 Pharmacology & Therapeutics 227 NTA Level 5 Semester 1 Facilitator Guide

The Actions of BDZ are:

Reduction of anxiety: At low doses, the benzodiazepines are anxiolytic. They are thought to reduce anxiety by selectively inhibiting neuronal circuits in the limbic system of the brain.

Sedative and hypnotic actions: All of the benzodiazepines used to treat anxiety have some sedative properties. At higher doses, certain benzodiazepines produce hypnosis (artificially-produced sleep).

Anticonvulsant action: Several of the benzodiazepines have anticonvulsant activity and are used to treat epilepsy and other seizure disorders.

Muscle relaxant effect: The benzodiazepines relax the spasticity of skeletal muscle, probably by increasing presynaptic inhibition in the spinal cord.

Zolpidem

o Although the hypnotic zolpidem is not a benzodiazepine, it acts on a subset of the benzodiazepine receptor family.

o The difference with BDZ: Zolpidem has no anticonvulsant or muscle relaxing properties. It shows no withdrawal effects, exhibits minimal rebound insomnia and little or no tolerance occurs with prolonged use.

Buspirone

o Buspirone is useful in the treatment of generalized anxiety disorders and has an

efficacy comparable to the benzodiazepines.

o The actions of buspirone appear to be mediated by serotonin (5-HTlA) receptors,

although other receptors could be involved, since buspirone displays some affinity for DA2 doparnine receptors and 5-HT2 serotonin receptors. The mode of action thus differs from that of the benzodiazepines.

o Difference with BDZ: Buspirone lacks anticonvulsant and muscle-relaxant properties of the benzodiazepines and causes only minimal sedation.

o Dependence is unlikely.

o Buspirone has the disadvantage of a slow onset of action.

Hydroxyzine

o Hydroxyzine is an antihistamine with antiemetic activity.

o It has a low tendency for habituation; thus it is useful for patients with anxiety, who have a history of drug abuse. It is also often used for sedation prior to dental procedures or surgery.

Barbiturates

o Barbiturates have been used as mild sedatives to relieve anxiety, nervous tension, and insomnia. Most have been replaced by the benzodiazepines.

o Details on mechanism of action, side effects, drug interactions and contraindications of barbiturates are shown in Session 34(Pharmacodynamics of Anticonvulsants).

PST 05104 Pharmacology & Therapeutics 228 NTA Level 5 Semester 1 Facilitator Guide

STEP 3: Drug Interactions Associated with Hypnotics and Anxiolytics (20 minutes)

Activity: Brainstorming (5 minutes)

Ask students to brainstorm on the following question:

What are drug interactions associated with hypnotics and anxiolytics drugs?

ALLOW few students to respond

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below The drug interaction of hypnotics and anxiolytics include;

Benzodiazepines

o Pharmacodynamic interactions with other centrally acting drugs are common, whereas pharmacokinetic interactions are not.

o Pharmacodynamic interactions include potentiation of the sedative actions of alcohol, histamine (H1) antagonists and other hypnotics.

o SSRI‘s and oral contraceptives decrease metabolism of BDZs.

STEP 4: Side Effects of Hypnotics and Anxiolytic (20 minutes)

The side effects of Hypnotics and Anxiolytics include;

Benzodiazepines

o Psychological and physical-dependence-on benzodiazepines can develop if high doses of the drug are given over a prolonged period. Abrupt discontinuation of-the benzodiazepines results in withdraw symptoms, including confusion, anxiety, agitation, restlessness, insomnia, and tension.

o Because of the long half-lives of some of the benzodiazepines, withdrawal symptoms may not occur until a number of days after discontinuation of therapy.

o Benzodiazepines with a short elimination half-life, such as triazolam, induce more

abrupt and severe withdrawal reactions than those seen with drugs that are slowly eliminated, such as flurazepam.

o In general, Benzodiazepines short half-life like lorazepam short-term use is associated with intense withdrawal phenomena and dependence than those with long half-life.

Flumazenil is a benzodiazepine antagonist. It can be used to reverse benzodiazepine

sedation.

It is short acting, so sedation may return. It can cause nausea, flushing, anxiety and fits, so is not routinely used in benzodiazepine overdose which seldom causes severe adverse outcome.

PST 05104 Pharmacology & Therapeutics 229 NTA Level 5 Semester 1 Facilitator Guide

Amnesia—the impaired ability to remember—may be a desired effect for medical procedures.

Respiratory depression may be seen at higher doses and can lead to respiratory

acidosis, particularly in those with chronic obstructive pulmonary disease (COPD).

Decreased blood pressure, increased heart rate: These cardiovascular effects are seen at higher doses and are likely mediated by a decrease in vascular resistance (midazolam) or cardiac output (diazepam).

Daytime sedation: This is a continuation of the intended therapeutic effect of BZDs. The extent of sedation is largely a function of the half-life and frequency of use.

Disinhibition may occur.

Drowsiness and confusion: These effects are the two most common side effects of the

benzodiazepines; Ataxia occurs at high doses and precludes activities that require fine motor coordination, such as driving an automobile.

Cognitive impairment (decreased long-term recall and acquisition of new knowledge) can occur with use of benzodiazepines.

Triazolam, the benzodiazepine with the most rapid elimination, often shows a rapid development of tolerance, early morning insomnia and daytime anxiety, along with amnesia and confusion.

Zolpidem

Adverse effects of zolpidem include nightmares, agitation, headache, gastrointestinal upset, dizziness, and daytime drowsiness.

Buspirone

The frequency of adverse effects is low, the most common effects being headaches, dizziness, nervousness, and lightheadness.

Sedation and psychomotor and cognitive dysfunction are minimal, and dependence is unlikely.

STEP 5: Contraindications of Hypnotics and Anxiolytics (20 minutes)

Activity: Brainstorming (5 minutes)

Ask students to brainstorm on the following question:

What are the contraindications of Hypnotics and Anxiolytics Drugs? ALLOW few students to respond?

WRITE their responses on the flip chart/ board

CLARIFY and SUMMARISE by using the content below

Contraindications of Hypnotics and Anxiolytics include;

Benzodiazepines

o Addiction to other drugs or past history of BZD addiction is a contraindication.

PST 05104 Pharmacology & Therapeutics 230 NTA Level 5 Semester 1 Facilitator Guide

Sleep apnea: Patients with central or obstructive sleep apnea have abnormal respiratory centers and may be at risk for exacerbations of sleep apnea if given sedatives of any type.

STEP 6: Key Points (5 minutes)

Flumazenil is a benzodiazepine antagonist. It can be used to reverse benzodiazepine sedation.

It is a dose which determines the anxiolytic and sedative hypnotic effect of drugs used.

Benzodiazepines have other indications than anxiolytic effects.

STEP 7: Evaluation (5 minutes)

What is the mechanism of action of benzodiazepines in controlling anxiety

What are adverse effects of benzodiazepines?

What is the mechanism of action of Buspirone

PST 05104 Pharmacology & Therapeutics 231 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 232 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