Pharmacology 3 - Mechanisms of Drug Action Flashcards
List the types of drug antagonism and describe them
- Receptor blockade (competitive/irreversible)
- Physiological antagonism (drugs interact with different receptors to have an opposite effect in the same tissue)
- Chemical antagonism (interaction of two drugs in solution)
- Pharmacokinetic antagonism (the antagonist reduces the concentration of another (active) drug at the site of action by decreased absorption, increased metabolism or increased excretion. Dose needs to be adjusted, for example with barbituates and warfarin)
Give an example of drugs that act as receptor blockades
Local anaesthetics
Give an example of drugs that perform physiological antagonism
- Noradrenaline causes vasoconstriction using noradrenaline receptors
- Histamine causes vasodilation but uses histamine receptor
Give an example of a drug that performs chemical antagonism
Dimercaprol makes heavy metal complexes in solution (acting as a chelating agent), which are more easily secreted than lead (or other heavy metals)
Define drug tolerance
A gradual decrease in responsiveness to a drug with repeated administration
List the factors in drug tolerance
- Pharmacokinetic factors (increased rate of metabolism)
- Loss of receptors (by membrane endocytosis or receptor down-regulation)
- Change in receptors (desensitisation leading to conformational change)
- Exhaustion of mediator stores
- Physiological adaptation (homeostatic responses/ tolerance to drug side effects)
Give an example of drugs where tolerance is affected by pharmacokinetic factors
Barbiturates and alcohol
Give an example of receptors that are down-regulated resulting in drug tolerance
B-adrenoreceptors
Give another name for receptor up-regulation
Denervation supersensitivity
Give an example of receptors that have a conformational change causing drug tolerance
Nicotinic acetylcholine receptors at NMJ
Give a example of a drug where tolerance is caused by exhaustion of mediator stores
Amphetamine - causes release of noradrenaline, therefore there is less noradrenaline to release upon frequent use
List the 4 main types of receptors.
- Type 1 - Ion channel-linked
- Type 2 - G-protein-coupled receptors
- Type 3 - Kinase-linked (protein phosphorylation)
- Type 4 - Intracellular steroid type receptors
Compare the responses of ion channel-linked receptors, GPCRs, Kinase linked and intracellular steroid type receptors
- Ion channel linked are fast (m secs)
- GPCR are slow (secs)
- Kinase-linked slower (mins)
- Intracellular steriod type are slowest (hours)
List examples of ion chanel-linked receptors
- Nicotinic acetylcholine receptors
- GABAa
Give an example of G-protein coupled receptors
B1-adrenoreceptors (heart)
Give an example of molecules that bind to intracellular steriod type receptors, and describe their functions
- Steroids/thyroid hormones
- Regulate DNA transcription
Give examples of molecules that bind to kinase-linked receptors
Insulin/growth factors
How are the types of receptors differentiated?
- Molecular structure
- Signal transduction systems
Define use-dependency in relation to local anaesthetics
The more active the tissue is, the more ion channels open and therefore a local anaesthetic has a greater chance to bind to the inside of the ion channel and have greater effect.
