Adrenergic Pharmacology 1 Flashcards
What are the important control points in adrenergic nerve function?
- Synthesis of Norepinephrine
- Uptake into storage vesicles
- Release of Neurotransmitter
- Receptors
- Feedback
- Metabolism
What are the important control points in adrenergic nerve function: 1. Synthesis of Norepinephrine
Hydroxylation of tyrosine is the rate-limiting step
What are the important control points in adrenergic nerve function: 2. Uptake into storage vesicles
- Dopamine enters a vesicle and is converted to norepinephrine
- Norepinephrine is protected from degradation in the vesicle
- Transport into the vesicle is inhibited by reserpine
What are the important control points in adrenergic nerve function: 3. Release of Neurotransmitter
- Influx of Ca2+ causes fusion of the vesicle with the cell membrane via exocytosis
- Release is blocked by guanethidine and bretylium
What are the important control points in adrenergic nerve function: 4. Receptors
- Postsynaptic receptor is activated by the binding of neurotransmitter
What are the important control points in adrenergic nerve function: 5. Feedback
- Released norepinephrine is rapidly taken into the neuron
- Reuptake is inhibited by cocaine and imipramine
What are the important control points in adrenergic nerve function: 6. Metabolism
- Norepinephrine is methylated by COMT and oxidised by MAO
What indirect-acting sympathomimetic amines and what are their roles?
- Drugs that increase levels of catecholamines without directly acting on adrenergic receptors
- Affect level of neurotransmitter itself rather than affecting receptor
What is the overall effect of cocaine and amphetamines?
- Increased levels of noradrenaline, serotonin and dopamine at the synapse causing increased stimulation of corresponding adrenergic receptors
What is the role of monoamine oxidase (MAO)?
- Involved in the degradation process of DA, serotonin and NE
What is the role of catechol-O-methyltransferase (COMT)?
- Important for degradation of circulating adrenaline taken up by uptake 2
What does MAO and COMT do to NA?
Remove and metabolise
What are the roles of MAO and COMT inhibitors?
- Increase levels of endogenous catecholamines or adrenergic drugs
Describe Uptake 1: Neuronal
- Selective for NA (uses NET)
- Acts between nerves at the synapse
- Presynaptic nerve involved
- OBJECTIVE: to have quick effect by removing NA from synapse
- High affinity: low maximum rate
Describe Uptake 2: Extraneuronal (systems that take up neurotransmitters from the blood)
- Non-neuronal tissue: smooth muscle, cardiac muscle, endothelium
- Collect NA from blood
- NA and Adrenaline then metabolised by MAO & COMT
- Low affinity: high maximum rate
What are the classes of MAO inhibitors?
- Selective MAO-A inhibitors
- Selective MAO-B inhibitors
- Non-selective
What do α-adrenergic receptors respond to?
Mainly to noradrenaline
Where are α1 receptors found and what are their effects?
- Found in smooth muscle, heart and liver
- Effects: vasoconstriction, intestinal relaxation, uterine contraction and pupillary dilation
Where are α2 receptors found and what are their effects?
- Found in: platelets, vascular smooth muscle, nerve termini, pancreatic islets
- Effects: vasoconstriction, inhibition of NA release and of insulin secretion
What do β-adrenergic receptors respond to?
Mainly adrenaline
Where are β1 adrenergic receptors location and what do they target?
- Located: mainly in heart
- Target: many drugs prescribed for heart conditions
Where are β2 adrenergic receptors location and what do they target?
- Located: mainly in lungs, GI, liver, uterus, vascular smooth muscle and skeletal muscle
- Target: Many drugs
Where are β3 adrenergic receptors location and what do they target?
- Located: fat cells
- Target: not targets for drugs
What are the physiological consequences of adrenergic receptor activation?
- Activation of a receptors: smooth muscle contraction
- Activation of β1 receptors (heart): smooth and cardiac muscle contraction
- Activation of β2 receptors (airways): smooth muscle relaxation
