Mechanisms of Drug Action Flashcards
What is receptor blockade antagonism?
competitive and irreversible
[“Use-dependency” of ion channel blockers
e.g. Local anaesthetics - more AP generated by sensory neurone - more effectivey ]
What is drug tolerance?
Gradual decrease in responsiveness to drug with repeated admin. (days/weeks)
e.g. benzodiazepines for seizures - tolerance develops over time so limited usefulness
What are the factors that affect tolerance?
- Pharmacokinetic factors
- increased rate of metabolism e.g barbiturates; alcohol
2.Loss of receptors
- By membrane endocytosis
Receptor “down-regulation”
-adrenoceptors
- Change in receptors
- Receptor desensitization -> conformational change
e. g nAChR at NMJ - Exhaustion of mediator stores
e. g Amphetamine
5.Physiological adaption
- Homeostatic responses
Tolerance to drug side effects
What are type 1 receptors?
Ion channel-linked receptors
Fast responses (m secs)
e.g nAChR; GABAA
What are type 2 receptors?
G-protein-coupled receptors
Slower responses (secs) e.g B1-adrenoceptors (heart)
What are type 3 receptors?
Kinase-linked type
insulin/growth factors (mins)
What are type 4 receptors?
Intracellular steroid type receptors
steroids/thyroid hormones (hrs)
regulate DNA transcription
What is physiological antagonism?
Different receptors -> opposite effects in same tissue
e.g. NA + histamine on B.P.
What is chemical antagonism?
Interaction in solution
Example : dimercaprol -> heavy metal complexes (chelating agent) - h. metal poisoning treatment - easier excretion and inactivates metal
What is pharmacokinetic antagonism?
Antagonist reduces concn of active drug at site of action - reduces absorption / increases metabolism / increases excretion of co administered drugs
e.g. barbiturates (enzyme inducers)
Clinically important interaction
