Pharmacodynamics Flashcards
- Membrane potential change opens the channel
- Inactivation occurs after
- Channel returns to closed state
- voltage-gated ion channels
- Binding to receptor
- Transient increase in permeability to a particular ion
- Negative membrane potential
- influx of Na+
- depolarization of cell
- possible AP
- ligand gated ion channel
Nicotinic ACh, GABA type A and glutamate
- ligand gated ion channel examples
- Inhibition of adenylate cyclase (AC)
- decrease of cAMP in cell
- Increase in K+ efflux
- Decrease in Ca+ influx
- Gi/Go protein coupled receptors
Muscarinic ACh (M2), Alpha-2 adrenoceptors, serotonin receptors: 5-HT1
- Gi/Go protein coupled receptors examples
- Activation of phospholipase C
- Increase in InsP3 and Ca2+
- Conversion of PIP2 into DAG
- Increase in protein kinase C
- Gq protein coupled receptors
Muscarinic ACh (M1, M3), Alpha-1 adrenoceptors, serotonin receptors: 5-HT2, Histamine H1
- Gq protein coupled receptors examples
- Activation of adenylate cyclase
2. Increase of cAMP in the cell
- Gs protein coupled receptors
- Ligand binds receptor
- Protein phosphorylation occurs
- Gene transcription
- Protein synthesis
- Cellular effects
- Kinase-linked receptors
Insulin, growth factor and cytokine receptors
- kinase linked receptors
- Ligand enters the nucleus
- Gene transcription
- Protein synthesis
- Cellular effects
- nuclear receptors
Steroids receptors (oestrogen receptor)
- nuclear receptors
Two most important things for drug-receptor interaction
- A close fit between the drug and receptor is essential
2. Strong binding forces
Binding forces
- Covalent > ionic > hydrogen > van der waals > hydrophobic
Excellent receptor fit and elicits a therapeutic response
- agonist
Strength of binding between drug and receptor
- affinity
Weak binding forces means
- short interaction with the receptor
and vice versa with strong binding forces
Measured by the dissociation constant Ko (50% occupancy)
- affinity
Tendency to activate the receptor and the strength of response after binding to the receptor
- efficacy
Drugs with a high ______ usually have a high affinity and occupy a significant proportion of receptors EVEN at LOW concentrations
- potency
Measured for example as EC50 (concentration that leads to 50% of the maximum effect)
- drug potency
- > more to the left on the graph
Agonists
- lead to a response
Antagonists
- lead to no response
Activation is governed by ____
- efficacy
Occupation is governed by ____
- affinity
Antagonist binds with the active site of the enzyme molecule and prevents the binding of a substrate molecule (no product molecules generated)
- competitive antagonist
Antagonist binds with the inhibitor site of enzyme molecule. Molecule may still bind with the enzyme molecule, but the reaction is hindered.
- non-competitive antagonist
When an antagonist is added there is a parallel shift to the right, an increase in the EC50(potency) and no change in maximum effect (efficacy)
- competitive inhibition
- > can overcome antagonist by increasing dose of agonist
When an antagonist is added there is a decreased maximum response (efficacy) and no change in EC50(potency)
- non-competitive inhibition
- > can NOT overcome antagonist by increasing dose of agonist
Acts on receptors that always lead to a response and lowers the constitutive level of receptor activation
- inverse agonists
Prolonged use of an agonist leads to? Prolonged use of an antagonist leads to?
- receptor down-regulation
- receptor up-regulation
