Ch 3. Drug Action

Question 1

Dicobalt edetate uses

Answer 1

Chelates cyanide ions and may be used in cyanide poisoning or following a potentially toxic dose of sodium nitroprusside.

Question 2

Uses of y-cyclodextrin

Answer 2

Sugammadex- chelates selectively rocuronium, reversal of deeper blocks.

Question 3

What’s the purpose of voltage gated ions?

Answer 3

Involved in the conduction of electrical impulses in excitable tissues such as muscle and nerve.

Question 4

What are examples of voltage gated ions?

Answer 4

Local anaesthetics- block Na channel

Calcium channels in smooth muscle

Anti-arrhythmics block in myocardial ion channels etc

Question 5

What is a receptor?

Answer 5

A protein, often integral to a membrane, containing a region which a natural ligand binds specifically to bring about a response.

Generally protein or glycoproteins.

Question 6

What are the classes of receptors?

Answer 6

Classed by mechanism:

1. Altered ion permeability
2. Production of intermediate messengers
3. Regulation of gene transcription

Question 7

What types of ion channels are there?

Answer 7

1. Pentameric family
2. Ionotropic glutamate
3. Ionotropic purinergic

Question 8

What is the structure of the pentameric ion channel? What is an example?

Answer 8

5 membrane spanning subunits- 2 alpha
- 1 beta, epsilon, delta

Eg. Nicotinic
Acetylcholine binds to the two alpha subunits, causes rapid flux of Na causing membrane depolarisation.

Other: GABA receptor, 5HT-3 (serotonin)

Question 9

Ionotropic glutamate: eg receptors and drugs that interfere with action

What is glutamate?

Answer 9

NMDA, AMPA, Kainate (ligand gated ions). Ketamine, Xenon and nitrous oxide are non-competitive inhibitors.

Glutamate is an excitatory neurotransmitter in the CNS.

Question 10

What receptor is most commonly involved in production of an intermediate messenger?

Answer 10

G-protein coupled receptors

• 7 helical regions that traverse membrane
• heterotrimeric
• ligand binds extracellulary and this makes likelihood of coupling and therefore activating an intermediate messenger at the expense of GTP.
• produces signal amplification

Question 11

What does G-protein do?

Answer 11

Binds GDP to GTP

Question 12

how is cAMP formed?

Answer 12

Adenylyl Cyclades catalysed the formation of cAMP.

Question 13

how is cAMP regulated?

Answer 13

Formed under regulation of G-proteins and broken down by the action of phosphodiesterase.

Question 14

What is clinical significance of phosphodiesterase?

Answer 14

Family of 5 isoenzymes, PGE3 Most important in the heart.

PGE inhibitors such as theophylline, enoximone, milronone.

Question 15

What drugs can increase cAMP levels? Clinical effects

Answer 15

B-adrenergic agonist or non-adrenergic ionotrope like glucagon.

= positive ionotropy.

Question 16

What acts through membrane guanylyl Cyclades?

Answer 16

ANP (increases cGMP through actions with membrane bound receptors with intrinsic guanylyl Cyclase)

Nitric oxide

Question 17

What acts via membrane tyrosine kinase?

Answer 17

Insulin and growth factor, platelet derived growth factor

Question 18

What hormones work by regulating gene transcription?

Answer 18

Steroids and thyroid hormones. Binding of hormone to ligand gated transcription factors; to alter the expression of dna: mRNA.

MR and GR receptors

Question 19

What is ED 50?

Answer 19

The dose of drug producing 50% of the maximum response.

Question 20

Features if a full agonist?

Answer 20

• high affinity

- high intrinsic activity (1)

Question 21

Partial agonist features?

Answer 21

Occupies receptors and produces submaximal effect, intrinsic activity less than 1.

Eg. Buprenorphine.

Can be agonists and antagonists
Antagonists if used with a full agonist.

Question 22

Inverse agonist?

Answer 22

Binds to a receptor and exerts the opposite effect of the endogenous agonist.

Eg Ketanserin at 5HT2c receptors