Pharmacology - chapter 6 - Adrenergic agonists Flashcards
Describe the synthesis of norepinephrine.
Tyrosine is cotransported into the neuron along with sodium. There it is hydroxylated to DOPA - dihydroxypheynylalanine(rate-limiting step).
DOPA is then decarboxylated to form dopamine. Dopamine is transported into vesicles where it is hydroxylated to form norepinephrine.
Note: in the adrenal medulla, norepinephrine is methylated to yield epinephrine by phenyletanolamine N-metyltransferase(PMNT).
Where do you find the adrenergic neuron, and what is its primary neurotransmitter?
In the CNS and the sympathetic nervous system. The primary neurotransmitter of the adrenergic neuron is norepinephrine.
Reserpine?
Blocks amine transporter system than transport dopamine and norepinephrine into the synaptic vesicle.
What are the three ways by which norepinephrine is removed from the synaptic space under normal conditions?
1 Diffuse out of the synaptic space and into the general circulation.
2 Metabolized by Catechol O-methyltransferase on postsynaptic n.
3 Reuptaken and stored in presynaptic neuron.
Increased peripheral resistance, myadrisis, vasoconstriction, increased BP, increased tone of internal spchincter of the bladder… which receptor?
Alpha 1
Increased lipolysis, increased release of renin, increased myocardial contractility and tachycardia.. which receptor?
Beta uno
Inhibition of norepinephrine and ACh release, inhibition of insulin release… which receptor?
Alpha 2
Vasodilation, decreased TPR, bronchodilation, increased muscle and liver glycogenolysis, increased release of glucagon, relaxed uterine smooth muscle.. which receptor?
Beta 2
Alpha receptors: rank order of potency?
- epinephrine
- norepinephrine
- isoproterenol
epinephrine > norepinephrine»_space; isoproterenol
Beta receptors: rank order of potency?
- epinephrine
- norepinephrine
- isoproterenol
isoproterenol > epinephrine»_space; norepinephrine
What G-protein are alpha-1 receptors coupled with?
Gq protein that activate Phospholipase C pathway
Where are alpha-1 receptors primarily found?
on the postsynaptic membrane in effector organ
Where are the alpha-2 receptors primarily found?
On the presynaptic nerveendings, Beta cells of the pancreas and on certain vascular smooth muscle cells. ALpha-2 receptors are also found on the presynapthic parasympathetic membrane.
Tamsulosin?
Selective antagonist that binds to alpha-1a receptors in the urinary tract and the prostate gland.
Tamsulosin are used to treat.. ?
benign prostatic hyperplasia
Three ways of desensitizing receptors?
1 sequestration of the receptors
2 down-regulation(decreased synthesis and increased destruction)
3 inability to to couple with G-protein(phosphorylated receptor)
Effects of epinephrine? 1 Cardiovascular 2 Respiratory 3 Glucose levels 4 Lipid metabolism
1 Cardiovascular - positive ionotrophic and chronotrophic effects by binding beta-1 receptors myocardium, beta-1 receptors in the kidney cause renin release, alpha-1 receptors cause constricion of vessels in the mucos membranes, skin and viscera. Beta-2 receptors cause vasodilation in the liver and skeletal muscle.
2 Respiratory - bronchodilation by binding beta-2 receptors.
3 Glucose - beta-2 activated glycogenolysis in liver and alpha-2 coupled inhibition of insulin release in pancreas = hyperglycemia.
4 Lipids - beta-1 activated lipolysis in adipose tissue. Increased cAMP levels stimulate gormone-sensitive lipase = elevated FFA & glycerol.
Hyperthyroidism and epinephrine?
increased synthesis of adrenergic receptors on the vasculature in the hyperthyroid patient may lead to hypersensitive response. So be careful.
Cocaine and epinephrine?
Cocaine prevents reuptake into presynaptic neuron.
Diabetics and epinephrine?
Since epinephrine increase the release of stored glucose it can exaccerbate the hyperglycemia in diabetics. Therefore insulin levels may have to be increased.
Levarterenol?
Levarterenol = norepinephrine
To what receptor do norepinehrine bind most avidly?
that would be to the alpha-adrenergic receptor. MMMMMYaaaaas.. hub hub hub.
Norepinephrine effects..?
1 cardiovascular
2 baroreceptor reflex
3 atropine treatment
1 cardiovascular - alpha-1 coupled vasoconstriction. NE cause greater vasoconstriction than does epinephrine. This is because it binds less than epinephrine to beta-2 receptors in skeltal muscles etc.
2 baroreceptor reflex - little if any cardiac stimulation is observed. This is due to that increased TPR causes a reflex bradycardia that counteracts the actions of NE on the heart.
3 atropine treatment - atropine blocks cholinergic muscarnic receptors so norepinephrine administration induce tachycardia.
Isoproterenol: receptors and primary effects?
Isoproterenol stimulates both beta-1 and beta-2 receptors. Isoproterenol causes intese stimulation of myocardium by binding beta-1 receptors. Beta-2 mediated vasodilation lowers TPR. Total effect = increased systolic pressure, lowered TPR and diastolic pressure.
