Mechanism of drug action Flashcards
What are 4 types of drug antagonism?
Receptor blockade
Physiological antagonism
Chemical antagonism
Pharmocokinetic antagonism
What is a physiological antagonism?
Drugs interact with different receptors causing opposite effects in same tissue eg NA and histamine on BP
What is a receptor blockade
Block receptors, can be a competitive or irreversible antagonist
What is a pharmacokinetic antagonism?
Antagonist decreases the concentration of the active drug at the side of action by decreasing the absorption /increasing metabolism/ excretion of the drug
What is drug tolerance
Gradual decrease in responsiveness to drug with repeated administration eg benzodiazepines
What are factors that lead to drug tolerance (5)
Pharmacokinetic factors Loss of receptors Change in receptors Exhaustion of mediator stores Physiological adaption
What is an example of a pharmacokinetic factor that leads to drug tolerance
An increase in rate of metabolism eg barbituates or alcohol
What is an example of a loss of receptors leading to drug tolerance
Membrane endocytosis - receptor down regulation (beta adrenoceptors)
What is the up regulation of receptors also called?
Denervation supersensitivity
What is an example of a change in receptors leading to drug tolerance
Receptor desensitization - conformational change eg nAChR at NMJ
What is an example of an exhaustion of mediator stores that leads to drug tolerance
Amphetamines
What is an example of a physiological adaption that leads to drug tolerance
Homeostatic response - tolerance to drug side effects
What are the 4 types of receptor families?
Ion channel linked receptor
G protein coupled receptors
Kinase linked type
Intracellular steroid type receptor
What is the response rate of an ion channel linked receptor and what are examples?
Fast responses - m secs
nAChR or GABA A
What is the response rate of a G protein coupled receptor and what are examples?
Slower responses - secs
Beta 1 adrenoceptors in the heart
What is the response rate of a kinase linked type receptor and what are examples?
Mins
Insulin/Growth Factors
What is the response rate of an intracellular steroid type receptor and what are examples? What do they do?
Hrs
Steroid/thyroid hormones
Regulate DNA transcription
Where is the location of the 4 main types of receptors?
Type 1-3 are found in the membrane and type 4 - the ones that control gene transcription are found intracellularly
What are the different types of effectors in receptors?
Type 1 - Channel
Type 2 - Enzyme or channel
Type 3 - Enzyme
Type 4 - Gene transcription
What are the different types of coupling in receptors?
Type 1 - Direct
Type 2 - G protein
Type 3 - Direct
Type 4 - Via DNA
A 4 year old girl is bitten by a Tiger snake whilst holidaying in Australia. An anti-venom (harvested antibodies) is administered. Which form of antagonism is utilised by the anti-venom?
A: Competitive receptor blockade B: Physiological antagonism C: Chemical antagonism D: Pharmacokinetic antagonism E: Irreversible receptor blockade
C
Tolerance to the euphoric effects of drugs of abuse (e.g. heroin & cocaine) can occur after repeated use. Which form of tolerance would not involve any change in the cells that mediate the euphoric effects? A: Receptor desensitisation B: Receptor down-regulation C: Exhaustion of mediator stores D: Receptor up-regulation E: Increased metabolic degradation
E
What is ‘use dependency’ of an ion channel blocker?
The more that the tissue is used, the more active the tissue is, the more active the ion channel is therefore if blocked then will cause a more complete response faster (more effective)
What is chemical antagonism?
Interaction of drugs in solution - where drugs can negate the effects of each other eg dimercaperol reduces toxicity of heavy metals by forming complexes
