Drug Mechanisms and Receptor Interactions Flashcards
Explain the term “drug”
Chemical substance –> interaction –> physiological effect
Explain the term “drug target site”
Examples include: receptors, ion channels, transport systems and enzymes
What are the 2 types of ion channel?
Voltage-gated; receptor-linked
What is blocked by the drug lidocaine?
VGSCs
Give 2 examples of common antagonists
Atropine
Hexamethonium
What is the ‘affinity’ of a drug?
The avidity with which it seeks out and binds to receptors
What is the potency of a drug determined by?
Its affinity and efficacy
Explain the term “drug selectivity”
A drug has a preference for a specific type of receptor (but it NOT specific to it)
Describe the term “structure activity relationship”
Basis of the ‘lock and key’ analogy –> describes close relation of activity and structure of a drug, and how sensitive a drug’s pharmacokinetics are to structural changes
List the 4 main categories of drug target sites
Receptors
Ion channels
Transport proteins
Enzymes
What sort of ion channels are blocked by lidocaine?
VGSCs
Why is the Na+/K+ pump not classed as a receptor?
Does not produce a physiological response
Give an example of a drug class and its mechanism that has an ion channel as its target site
Tri-Cyclic Antidepressants (TCAs)
Slow down reuptake of NA and 5HT at the serotonin receptor
Give an example of a drug that inhibits enzymes
Anti-cholinesterases
Give an example of a drug that acts as a false substrate
Methyl-DOPA (generates methyl-NA)
Differentiate between a full and partial agonist
Full = full efficacy Partial = part efficacy
How can full agonists differ in their level of action?
Whilst they all have full efficacy they can differ in affinity
Describe the shape and relative positioning of full agonists with high affinity, full agonists with lower affinity and partial agonists on a log dose-response curve
Slightly sigmoid shape
Full agonist goes through origin
FA with lower affinity –> right, same shape
Partial agonist crosses x at same point as FAWLA but has lower gradient
Describe the shape and relative position of full agonists and partial agonists on a dose-response curve
Curve with decreasing gradient
Full agonist has higher gradient
Give an example of a competitive and an irreversible antagonist
Competitive: atropine/ propanolol
Irreversible: hexamethonium
Differentiate between log dose-response curves to a specific agonist in the absence and presence of a competitive antagonist and an irreversible antagonist
Slightly sigmoid shape
Agonist alone goes through origin
+ Comp. antagonist = curve moves right
+ irr. antagonist = moves further right and gradient reduced
Recall and summarise the 4 main types of antagonism
- Receptor blockade
- Physiological antagonism (interact with diff. receptors to have opp. effects in same tissue)
- Chemical antagonism (2 ligands interact in solution)
- Pharmacokinetic antagonism (one drug changes effect of an other)
Describe the interaction of warfarin and barbiturates
When barbiturates are administered for a long period of time, the liver enzyme that metabolises them is upregulated. This same enzyme is used to metabolise warfarin. Therefore, when warfarin is given a higher dose is required as it will be metabolised more quickly.
What is the “receptor reserve” phenomenon?
Stimulation of only a fraction of the whole receptor population apparently elicits the maximal effect achievable
List the 4 main families of receptors
1: channel-linked
2: GPCR
3: Tyrosine - Kinase-linked
4: controllers of gene transcription
Describe the structure of a type 1 (channel-linked) receptor
Subunits and TM segments
Give 2 examples of type 1 receptors
nicotininc ACh receptors
GABA
Give 2 examples of type 2 receptors
muscarinic ACh receptors
Adrenoceptors
Give 3 examples of type 3 receptors
Insulin receptors
Growth Factors
Cytokine receptors
Give 2 examples of type 4 receptors
Steroid receptors
Thyroid receptors
Define “drug tolerance”
Gradual reduction in response to the drug over a period of days or weeks
Give an example of a drug which patients commonly show tolerance to
Benzodiazapenes eg diazepam
Recall 5 cellular mechanisms which may account for the phenomenon of drug tolerance
- Increased rate of metabolism (eg with alcohol)
- Loss of receptors (endocytosis)
- Change in receptors (desensitised by conformational change)
- Exhaustion of mediator stores
- Physiological adaption (tolerance to side effects whilst efficacy of drug maintained)
