Ch 3. Drug Action Flashcards
Dicobalt edetate uses
Chelates cyanide ions and may be used in cyanide poisoning or following a potentially toxic dose of sodium nitroprusside.
Uses of y-cyclodextrin
Sugammadex- chelates selectively rocuronium, reversal of deeper blocks.
What’s the purpose of voltage gated ions?
Involved in the conduction of electrical impulses in excitable tissues such as muscle and nerve.
What are examples of voltage gated ions?
Local anaesthetics- block Na channel
Calcium channels in smooth muscle
Anti-arrhythmics block in myocardial ion channels etc
What is a receptor?
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.
What are the classes of receptors?
Classed by mechanism:
- Altered ion permeability
- Production of intermediate messengers
- Regulation of gene transcription
What types of ion channels are there?
- Pentameric family
- Ionotropic glutamate
- Ionotropic purinergic
What is the structure of the pentameric ion channel? What is an example?
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)
Ionotropic glutamate: eg receptors and drugs that interfere with action
What is glutamate?
NMDA, AMPA, Kainate (ligand gated ions). Ketamine, Xenon and nitrous oxide are non-competitive inhibitors.
Glutamate is an excitatory neurotransmitter in the CNS.
What receptor is most commonly involved in production of an intermediate messenger?
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
What does G-protein do?
Binds GDP to GTP
how is cAMP formed?
Adenylyl Cyclades catalysed the formation of cAMP.
how is cAMP regulated?
Formed under regulation of G-proteins and broken down by the action of phosphodiesterase.
What is clinical significance of phosphodiesterase?
Family of 5 isoenzymes, PGE3 Most important in the heart.
PGE inhibitors such as theophylline, enoximone, milronone.
What drugs can increase cAMP levels? Clinical effects
B-adrenergic agonist or non-adrenergic ionotrope like glucagon.
= positive ionotropy.
What acts through membrane guanylyl Cyclades?
ANP (increases cGMP through actions with membrane bound receptors with intrinsic guanylyl Cyclase)
Nitric oxide
What acts via membrane tyrosine kinase?
Insulin and growth factor, platelet derived growth factor
What hormones work by regulating gene transcription?
Steroids and thyroid hormones. Binding of hormone to ligand gated transcription factors; to alter the expression of dna: mRNA.
MR and GR receptors
What is ED 50?
The dose of drug producing 50% of the maximum response.
Features if a full agonist?
- high affinity
- high intrinsic activity (1)
Partial agonist features?
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.
Inverse agonist?
Binds to a receptor and exerts the opposite effect of the endogenous agonist.
Eg Ketanserin at 5HT2c receptors
