What are the major drugs used for these conditions?
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?
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)
What are the alpha-1 agonists you should know?
What is the alpha-2 agonist you should know?
Clonidine. Lowers blood pressure by activating alpha-2 receptor which in turn inhibits NE release.
A patient comes to see you with supra ventricular tachycardia (HR = 132 bpm). How would an alpha-1 agonist help treat this patient?
Administration of an alpha-1 agonist like phenlyephrine increases blood pressure, which causes vagal discharge which will in turn slow the heart rate.
What drug is used to dilate bronchioles and what receptor does it act on?
Albuterol, it acts on beta-2 receptors very specifically.
On rotations your attending physician administers a drug to a patient in the ICU to lower his severely high blood pressure and increase blood flow to the kidneys. What drug is this and what receptors does it act on?
Fenoldopam. It is a D1 dopamine receptor agonist.