mechanism of drug action Flashcards
What is an agonist?
chemical that binds to and activates a receptor to produce a biological response
What is an antagonist?
blocks the actions of an agonist
What is a quantal response?
An all or nothing response
What are constitutively active receptors?
receptors that have a background activity even when an agonist is not present
What is the Two-State Model of Receptors?
- receptors can be active or resting
- under baseline circumstances, most receptors remain in the resting state
What are some targets for drug action?
- ion channels
- enzymes
- carrier molecules
- receptors
What are some type of receptors that are targets for drug action?
- type 1: ligand gated ion channels
- type 2: G-protein coupled receptors
- type 3: enzyme-linked and related (kinase-linked)
- type 4: nuclear ‘intracellular’ receptors
Give an example of a drug that directly interacts with ion channels?
- lidocaine can block them in nerves
- local anaesthetic
How does aspirin work on enzymes to treat pain?
- enzyme cyclo-oxygenase (COX) converts arachidonic acid into prostaglandins (PGs) which mediate pain and inflammation
- aspirin (acetyl-salicylic acid) targets COX and inhibits its activity
- reduce generation of inflammatory prostaglandins
Give an example of a ‘loop-diuretic’ drug and how does it work
- furosemide used to increase urine production by blocking Na+K+2Cl- transporter
What is GABA?
- gamma-aminobutyric acid
- predominant inhibitory neurotransmitter in the brain
How does GABA inhibit things?
- interacts with GABAa receptor on Cl- channel
- allows Cl- to enter cell
- makes depolarisation difficult
- stabilises tissue
Describe the cAMP pathway in G-protein coupled receptors?
- Gs activated (Gi does opposite)
- adenylate cyclase (AC) activated, converts ATP to cAMP
- cAMP is second messenger, causes physiological response
Describe the calcium pathway in G-protein coupled receptors?
- Gq activated
- activated phospholipase C (PLC)
- activates IP3 and DAG
- they increase Ca2+ levels
What are some examples of physiological beta 2 receptor antagonists?
- noradrenaline
- adrenaline
What is cAMP broken down by?
phosphodiesterase
Give an example of a synthetic beta 2 receptor agonist and what its for
- salbutamol
- leads to bronchodilation, good for asthma
Describe type 4 receptors (nuclear receptors)
- also called steroid hormone receptor
- normally at rest in cytosol
- move to nucleus when they bind to their ligand
- control gene expression and lead to protein synthesis
How do type 3 receptors work?
- enzyme linked receptors
- usually lead to protein phosphorylation cascade
Rank the time each type of receptor takes
- type 1 (millisceonds)
- type 2 (seconds)
- type 3 (minutes)
- type 4 (hours)
What drug helps with high blood pressure and how?
atenolol blocks beta 1 receptors to reduce blood pressure
What are the difference types of beta receptors?
- beta 1 (heart rate)
- beta 2 (bronchodilation)
- beta 3
What is receptor desensitisation?
- short term effect
- happens very quickly (days)
- involves loss of intrinsic activity of receptor complexes
What is receptor down-regulation?
- longer term effect (weeks)
- involves a loss of number of receptors from cell surface
- takes longer to recover
What are some other mechanisms for a loss of effect of a drug?
- exhaustion of mediators
- increased metabolic degradation
- physiological adaptation
What are the possible effects of drug action?
- therapeutic effects
- side effects
- adverse effects
- toxic effects
What are therapeutic effects of drug action?
drug produces the intended biological effect
What is a side effect of drug action?
- nuisance (e.g dry mouth)
- can become harmful (e.g sedation)
What is an adverse effect of drug action?
undesired effects that can be harmful (e.g allergies, anaphylactic shock)
What is a toxic effect of drug action?
- drug poisoning
- harmful, may be life threatening (e.g liver damage associated with paracetamol overdose)
Are agonists or antagonists more likely to produce unwanted effects and why?
- antagonists
- they are more likely to interact with multiple receptor types bc there are fewer constraints for molecular structure
