3 - Mechanisms of Drug Action Flashcards
Which is correct?
- A partial agonist will always have a higher efficacy than a full agonist
- Agonists have higher affinities than antagonists
- Full agonists that are selective for a given receptor will have the same efficacy
- Antagonists possess better efficacy than their respective agonists
- Competitive antagonists will preferentially occupy the relevant receptor in the presence of an agonist
- Full agonists that are selective for a given receptor will have the same efficacy
A drug acting as a inhibitor at a particular drug target site prevents the removal of neurotransmitter from the synapse. Which type of drug target is this drug acting on?
- Receptor
- Voltage sensitive ion channel
- Receptor linked ion channel
- Transport protein
- Non-proteinaceous target
- Transport protein
What is the key property of an antagonist?
Affinity but NO efficacy
What are the two types of antagonist?
Competitive - Same site, surmountable, D-R curve to right e.g. atropine, propranolol
Irreversible - Tightly or at a different site, insurmountable e.g. hexamethonium
What is ‘drug antagonism’?
When drugs are co-administered and one diminishes the effect of the other.
What are the causes of ‘drug antagonism’?
- Receptor Blockade - receptor antagonist, competitive or irreversible*
- Physiological Antagonism - different receptors which cause opposite effects in the same tissue e.g. NorA and histamine for BP
- Chemical Antagonism - Interaction of drugs in solution e.g. dimercaprol as a chelating agent
- Pharmacokinetic Antagonism - one antagonist may reduce concentration of the active drug at the site of action by decreasing absorption, increasing metabolism, increasing excretion**
*use dependency for ion channels - the more active a tissue is, the more effective an ion channel will be as the drug can only work when the channel is open. Therefore local anaesthetics bind selectively to actively firing fibres to a certain degree.
**e.g. barbiturates are enzyme inducers over the long term and speed up the metabolism of some other drugs
What is tolerance?
The gradual decrease in responsiveness to a drug with repeated administration (days/weeks) e.g. benzodiazepines (Valium)
What are the causes of tolerance?
- Pharmacokinetic factors - increased rate of metabolism, enzyme inducers e.g. barbiturates, alcohol
- Loss of receptors - cells don’t like repeated stimulation, receptor “down-regulation” via membrane endocytosis e.g. b adrenoceptors*
- Change in receptors - receptor desensitization via conformational change e.g. nAChR at NMJ
- Exhaustion of mediator stores e.g. amphetamine, acts by entering cell via uptake, binding to vesicles and causing exocytosis of NorA (loss of endogenous NorA stores)
- Physiological adaptation - Homeostatic responses e.g. BP, antihypertensives. However, helpful in developing tolerance to side effects; disappear after continuous use
*N.B. receptor “up-regulation”
(denervation supersensitivity)
How are receptors classified?
They are classified based on their molecular structure and signal transduction system.
What are the types of receptors?
4 types
Type 1 [ionotropic, ligand gated] - ion channel linked, ms, nAChR; GABA a, depolarisation, 4 or 5 subunits w/ 4 TM segments; subunits join to form receptor
Type 2 [metabotropic] - G-protein coupled, secs, b1 adrenoceptor, secondary messengers, 7 TM segments
Type 3 - kinase-linked, mins, insulin; growth factor, protein phosphorylation, catalytic domain e.g. protein phosphorylation
Type 4 [nuclear] - intracellular steroid, hrs, steroids; thyroid hormones, regulate DNA transcription, DNA binding domain (“zinc fingers”)
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?
- Competitive receptor blockade
- Physiological antagonism
- Chemical antagonism
- Pharmacokinetic antagonism
- Irreversible receptor blockade
- Chemical antagonism
Tolerance to the euphoric effects of drugs of abuse (e.g. heroin and cocaine) can occur after repeated use. Which form of tolerance would not involve any change in the cells that mediate the euphoric effects?
- Receptor desensitisation
- Receptor down-regulation
- Exhaustion of mediator stores
- Receptor up-regulation
- Increased metabolic degradation
- Increased metabolic degradation
