Drug-receptor interactions Flashcards
Drug
Chemical substance that interacts with a biological system to produce a physiological effect
Drug target sites
ALL PROTEINS
- where the drugs interact and bind
- specific target sites for different drugs
- Receptors
- Ion channels
- Transport systems
- Enzymes
Drug target sites (receptors)
- typically proteins within cell membranes for easy accessibility (steroid receptor exception)
- neurotransmitter or hormone activation
- defined by agonist or antagonist actions
- agonists and antagonists are specific to receptors
- 4 receptor families (defined according to different structures and signal transduction systems such as G-protein coupled, ion channel etc)
- examples of drug interaction include acetylcholine (agonist) and atropine (selective antagonist of muscarinic ACh receptors)
Drug target sites (ion channels)
- selective pores in cell membrane allowing the transfer of ions down electrochemical gradients (lipid bilayer impermeability to ions)
- 2 ion channel types differentiated according to gating mechanism (voltage-sensitive such as VSCC opened by changing membrane potential and receptor-linked such as nAChR which sees a conformational change in the receptor)
- nAChR is excitatory so ACh binds, stimulates it, conformational change of receptor occurs and cation channel is opened to allow sodium ion influx
- in receptor-linked, drugs interact with ion channels rather than receptor binding site
- examples of drugs include local anaesthetics (interact with VSSC to block sodium ion influx and reduce propagation of action potentials) and calcium channel blockers (block VSCC)
Drug target sites (transport systems)
- transport against concentration gradients (glucose, ions, neurotransmitters etc)
- specificity for certain species
- not receptors, just for movement
- can inactivate neurotransmitters
- transport system examples include sodium/potassium -ATPase and NA ‘uptake 1’
- examples of drugs include tricyclic anti-depressants (TCAs used for clinical depression by interacting with noradrenaline uptake) and cardiac glycosides (cardiac stimulants)
Drug target sites (enzymes)
-catalytic proteins which increase reaction rates but don’t change reaction (increase efficiency)
Drug interactions include:
- enzyme inhibitors (eg: anticholinesterases such as neostigmine which increases synaptic ACh levels)
- false substrates (eg: methyldopa->competitive inhibition)
- prodrugs (eg: chloral hydrate=metabolised to trichloroethanol to be useful/effective as active drug)
Drug-receptor interactions
- drugs can be agonists (binds to receptor to stimulate response)-> eg: acetylcholine, nicotine etc
- drugs can be antagonists (binds to receptor and inhibits it so no response/activity)->eg: atropine, hexamethonium etc
- drugs can also be described as having full or partial agonistic effects (full agonist has maximal potency and partial agonist has some antagonist activity)
Antagonists
-affinity but no efficacy
Receptor antagonist types:
- competitive
- irreversible
Receptor antagonist types (competitive)
- binds to same site on receptor as agonist
- surmountable response (can be overcome by higher concentrations of agonist)
- shifts dose-response curve right
- examples include atropine and propranolol
Receptor antagonist types (irreversible)
- binds tightly with covalent forces at same site as agonist or at different site
- insurmountable response at different site (cannot be overcome as not competing with agonist)
- example includes hexamethonium
Potency of a drug
Depends on:
- affinity
- efficacy (‘intrinsic activity’)
Non-specific drug actions
Drugs produce responses to physicochemical properties
Examples:
- antacids (physiochemical of being a basic substance can reduce stomach acidity)
- osmotic purgatives (draw water from rest of body into gut to soften stool and enable bowel movement)
Plasma protein binding
-binding of drugs to plasma proteins but response not generated so not target site (inactive drug reservoir formed)
Full agonist
-generates maximal agonist response from a receptor
Dose-response curve:
Partial agonist
- can never generate a maximal agonist response from a receptor (50-75% of full effect)
- agonists in own right but are antagonistic if administered with full agonists
Dose-response curve:
