Pharmacology-Adrenergics Flashcards
What are the major drugs used for these conditions?
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What adrenergic receptors are in the heart, blood vessels. What receptor is on the adrenal gland?
Heart = B1. Blood vessels = a1. Adrenal gland = nicotinic (ACh binding stimulates EPI release, which binds to B2 on smooth muscle vascular beds).
Which adrenergic receptor is inhibitory and makes sure NE doesn’t have too strong of an effect? How does it work?
alpha-2 receptors. They down regulate adenylyl cyclase, open K+ channels (hyperpolarizes) and closes Ca2+ channels via G-protein signal transduction.
What is the difference in receptor activation between NE and EPI?
NE only activates alpha-1, alpha-2 and beta-1. EPI activates all beta and alpha receptors (including beta-2).
Why, in a fight or flight response, do most blood vessels constrict but liver and skeletal blood vessels dilate?
Most blood vessels have alpha-1 receptors, which stimulate vasoconstriction when NE binds. Skeletal muscle vasculature and liver vasculature have beta-2 receptors, which stimulate vasodilation when bound by EPI.
Binding to what receptor causes bronchiole dilation?
EPI binding to Beta-2 receptors
Binding of NE to what receptor causes mydriasis?
Alpha-1 (pupil dilation)
If a woman is going into labor early, what could you give her to relax the uterus?
Epinephrine. It stimulates beta-2 receptors that will cause the uterus to relax.
Activation of what receptors will result in increased glucose production by the liver? Increased fatty acid release by fat? Decreased insulin secretion? Renin secretion?
Liver = alpha-1 and beta-2. Fat = beta-1 and beta-3. Pancreas = alpha-2. Kidney = beta-1.
Where are the general locations of these receptors?
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Why would phentolamine be a poor choice for controlling hypertension?
It is a nonselective alpha-blocker, which will block the alpha-2 receptor, result in increased accumulation of NE and the heart will pump harder.
How does binding of NE to alpha-1 receptors cause vasoconstriction?
It stimulates G-protein signal transduction that increases Ca2+ and thus muscle contraction.
How does binding of NE to beta-1 receptors cause increased heart rate?
Gs protein signal transduction results in adenylyl cyclase activity, increases Ca2+ levels and thus increased muscle contraction.
How does binding of EPI to beta-2 receptors cause vasodilation in skeletal muscle and the liver?
G protein signal transduction results in increased cAMP which relaxes smooth muscle.
How does administration of epinephrine affect the nodal action potential in the heart? How does this affect the heart.
It decreases phase 4 so you get action potentials more often because it increases Ca++ entry into cardiac myocytes when it binds to beta-1 receptors.
How does the level of epinephrine in the blood affect vasculature in smooth muscle?
At low levels, beta-2 receptors are stimulated and vessels vasodilate. At high levels, alpha-1 receptors are stimulated and vessels vasoconstrict.
When you administer epinephrine to a patient, the heart begins to pump harder due to beta-1 stimulation and systolic blood pressure increases. What would cause the diastolic blood pressure to decrease at the same time?
Low doses of epinephrine stimulates mostly beta-2 receptors that vasodilate. This will lower the diastolic pressure. As epinephrine does increases, alpha-1 receptors are stimulated, vasoconstriction occurs and the diastolic pressure will increase.
How would this “cat test” look if you administered norepinephrine instead of epinephrine?
NE does not stimulate beta-2 receptors so you do not get any vasodilation. The blood pressure will increase significantly and cause vagal reflex to try and bring pressure back down.
How would this “cat test” look if you administered isoproterenol instead of NE?
Isoproterenol only stimulates beta-1 and beta-2 receptors. Consequently you would see an increase in heart rate from beta-1 stimulation and a decrease in diastolic pressure due to beta-2 stimulation.
Why does isoproterenol have lower hyperglycemic effects than epinephrine?
It does not act on alpha-1 and thus only beta-2 is stimulated.
Why is it important that dopamine is administered at low doses?
At low doses, D1,D2 and beta-1 receptors are stimulated, promoting increased cardiac function and vasodilation. At higher doses alpha-1 and alpha-2 receptors are stimulated which vasoconstrict and will raise the blood pressure significantly.
What would you expect to see in the “cat experiment” if you gave low dose dopamine instead of epinephrine?
Similar results because D1 vasodilates kidney blood vessels and effectively lowers diastolic pressure.
What beta-1 agonist is thought to be slightly safer than others when prescribing it to a patient in heart failure?
Dobutamine. It increases myocardial contractility more than HR and automaticity.
Which of these molecules has an easier time getting into the brain?
Amphetamine. It lost its OH group and is less hydrophobic.
Why do these molecules have long half lives?
Alpha carbon methylation blocks metabolism by MAO (monoamine oxidase)
You have a patient that is taking phenelzine, a MAOI (monamine oxidase inhibitor) for depression. After a late night eating cheese and drinking beer, what is she at risk for?
Widespread vasoconstriction. Tyramine is in fermented foods and can displace NE when MAO is inhibited.
What are 5 therapeutic uses for alpha-1 agonists?
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What drug is preferred to phentolamine?
Prazosin. Phentolamine competitively blocks alpha-1 and alpha-2 receptors where prazosin only competitively blocks alpha-1 receptors.
What drug is preferred to propranolol?
Metoprolol. Propranolol blocks beta-1 and beta-2 where metoprolol only blocks beta-1 receptors.
Which alpha antagonist is noncompetitive?
Phenoxybenzamine covalently binds alpha-1 and alpha-2 receptors.
How does the cat react to phentolamine when epinephrine is acting on receptors? What about when NE is acting on receptors?
When EPI is acting, HR increases because phentolamine causes a large drop in blood pressure due to alpha-1 blockage. When NE is acting, BP drops because alpha-1 is blocked and peripheral resistance decreases.
What are 5 therapeutic uses for alpha antagonists?
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An old man has trouble peeing. What drug can you prescribe to help him get better flow? Why this drug and not phentolamine?
Tamsulosin. It is an alpha-1a selective antagonist that relaxes smooth muscle in the urethra to improve urine flow. Phentolamine also blocks alpha-1b, which will lower BP. If your patient already has low BP you want to leave those receptors alone.
What adverse effects do you need to be aware of with alpha-1 blockers?
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What are the beta receptor antagonists?
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A patient comes to see you with a failing heart and no asthmatic issues. What is your drug of choice and why do you need to consider asthmatic issues?
Propranolol. You need to consider asthma because the drug also blocks beta-2 receptors which could cause further bronchial constriction.
After prescribing propranolol to a hypertensive patient, you see a delayed decrease in blood pressure. Why is this?
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You see a patient with high blood pressure and asthmatic problems. What drug do you prescribe and how does this drug utilize the kidneys to decrease blood pressure?
Metoprolol. It is a selective beta-1 blocker, leaving beta-2 untouched so bronchioles can remain dilated. It utilizes the kidneys by decreasing beta-1 stimulation of renin secretion.
What are 8 therapeutic uses of beta blockers?
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What are 8 adverse effects of beta blockers?
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What drug is used to control blood pressure and is a neuron blocking agent?
Guanethidine. It blocks action potential-induced release of NE, displaces NE from vesicles and sends it for metabolism by MAO, lowering NE levels.
