Essential Pharmacology & Autonomic and Neuromuscular Pharmacology Flashcards
Describe the basic functions of receptors.
Enable specificity, evoke an appropriate response.
What is the function of the G-protein receptor?
Regulate protein function
What is the largest class of receptor?
G-protein receptors
What is the secondary messenger commonly associated with the G-protein receptor?
cAMP - by the adenyl cyclase associated with the receptor or phospholipase C.
What is the function of G-protein receptors that are coupled to ion channels?
Evoke slow EPSPs or IPSPs.
What are the two main locations of receptors?
Transmembrane and intracellular.
Define agonist.
Mimic normal effect of the receptor.
Define antagonist.
Block normal action of receptor.
Describe the affinity and efficacy of agonists.
Full agonist = high affinity and high efficacy.
Partial agonist = high affinity and low efficacy.
Describe the affinity of antagonists.
High affinity and no efficacy.
Describe the relationship between the concentration of the agonist and the effect.
Increasing agonist con concentration, increases the response until drug binds and activates all receptors. The number of receptors are limited so the maximum saturated response will be reached.
Define affinity.
Does it bind receptor?
- Strength of chemical attraction between drug and receptor (lower EC50 = higher affinity)
How much of a drug would be required if it has higher affinity?
Less of the drug.
Where on the dose response curve would you find a curved for a drug with low affinity?
Shifted to the right (higher EC50).
Define efficacy.
Does it activate the receptor?
- how good the drug is at activating the receptor.
Where on the dose response curve would you find a curve for a drug with low efficacy?
Below the curve.
Compare efficacy in full and partial agonists.
Full agonist = High efficacy
Partial agonist = Low efficacy
Describe the process of transmembrane signalling (G-protein coupled receptors), giving two examples.
- Adenyl cyclase - produces cAMP and regulates PKA.
2. Phospholipase C - produces DAG and regulates PKC and IP3 that regulate calcium (secondary messenger)
List 5 transmembrane receptors.
- Enzyme-linked
- Ligand-gated ion channel
- G-protein coupled
- Voltage-gated
- Cytokine receptor
List three sources of intracellular calcium.
- Internal stores (via IP3 or Ca2+ stimulated release form endoplasmic reticulum)
- Outside cell (via voltage-gated or ligand-gated calcium channels)
- Via inhibition of calcium transport out of cell.
What are the effects of calcium?
- Directly effect target protein (e.g PKC)
- Bind to calmodulin which activated target.
- Via some other binding protein e.g troponin.
Where would you find the dose response curve for an agonist in presence of competitive antagonist.
Shifted to right (agonist less likely to bump into free receptors)
What are the potential sites of action for drugs to modulate synaptic transmission in ANS?
- Inhibit acetylcholine transport
- block voltage-gated Ca2+ ion channels
- block vessel fusion
- block ACh activated channel
- block non-depolarising nicotinic receptors
- block depolarising nicotinic receptors
How can postganglionic parasympathetic transmission be targeted?
Mimic (agonist) or block (antagonist) muscarinic receptors.
How can postganglionic sympathetic transmission be targeted?
- Block enzymes that produce NA
- Block transporter or transmitter
- Introduce false transmitter
- Block alpha or beta receptors
- Sympathiometics (potentiate synapse)
What is the function of indirect sympathomimetics?
Triggers release of noradrenaline.
Give an example of an indirect sympathomimetic.
Amphetamine.
Give an example of a sympathomimetic
Cocaine.
What is the function of a sympathomimetic?
Act directly at the post-synaptic adrenergic receptor.
Describe a clinical application of an a1 agonist.
Decongestant and dilate pupils.
Describe a clinical application for an a2 agonist.
Hypertension
Describe a clinical application for a B2 agonist.
Asthma.
Give an example of a B2 agonist.
Salbutamol
Describe a clinical application for a B1 antagonist.
Hypotension and angina.
Give an example of a B1 antagonist.
Atenolol.
Describe the mechanisms by which drugs modulate transmission at the NMJ.
- Inhibit choline transport
- Block voltage-gated calcium channels
- Block vessel fusion
- Use depolarising or non-depolarising nicotinic receptor blockers (e.g for paralysis during surgery)
How can you make synapses function better at the NMJ?
- Prolong the AP (more calcium release)
2. Block acetylcholinesterase (stop breakdown of ACh)
What are the consequences of modulating synaptic transmission in the ANS and NMJ?
Too many side-effects so next to no clinical applications. Drugs modulate both sympathetic, parasympathetic and NMJ transmission.
What type of receptors does Acetylcholine bond to?
Cholinergic receptors.
Give two examples of cholinergic receptors.
- Nicotinic
2. Muscarinic
What cholinergic receptor is a g-protein receptor?
Muscarinic
What cholinergic receptor is ionotropic?
Nicotinic
How many sub-types does the muscarinic receptor have?
3 (M1, M2, M3)
How many sub-types does the nicotinic receptor have?
2 (N1, N2)
What type of receptors does Noradrenaline and adrenaline bind to?
Adrenergic
What type of receptors are the adrenergic receptors?
G-protein receptors
How many sub-types does the adrenergic receptor have?
5 (a1, a2, b1, b2, b3)
What does the sympathetic and parasympathetic systems act on?
Smooth muscle, cardiac muscle, GI neutrons and glands.
