RCS 10 - Adrenergic Agonists & Antagonists 2

Question 1

List the different classes of adrenergic antagonists we need to know and the drugs in each class that we need to know.

Answer 1

• α-antagonists
  
  • Nonselective - phenoxybenzamine & phentolamine
  • α1 selective - prazosin, terazosin, doxazosin, tamsulosin
• β-antagonists
  
  • Nonselective - propranolol, nadolol, timolol
  • β1 selective - atenolol, metoprolol, esmolol,
• α1 and β antagonists - labetalol, carvedilol
• Partial agonists - pindolol
• Presynaptic acting drugs
  
  • Inhibitors of NE synthesis - α-methyltyrosine (aka - metyrosine)
  • Inhibitors of NE storage - reserpine, tetrabenazine

Question 2

What is the primary effect of α adrenergic blockers and why?

Answer 2

To cause vasodilation, thereby decreasing PVR.

The main receptor causing vasoconstriction and maintaining vascular tone is the α1 receptor

Question 3

Give the MOA, effects, and uses of phenoxybenzamine.

Answer 3

• Nonselective Irreversible antagonist of α receptors
• Used for chronic management of inoperable pheochromocytomas and is given to patients prior to surgical removal of operable pheochromocytomas.
• Not successful for HTN

Question 4

Give the MOA, effects, and uses of phentolamine.

Answer 4

• Reversibly blocks α1 and α2 receptors
• Causes vasodilation and a drop in BP
• Uses
  
  • Diagnosis of pheochromocytoma - phentolamine blocking test
  • Control of HTN during preoperative preparation and surgical excision of a pheochromocytoma
  • Sometimes NE is given to patients in shock, resulting in potent vasoconstriction which possibly leads to dermal necrosis. Phentolamine can be given to prevent this
  • HTN crisis caused by stimulant drug OD

Question 5

Describe the concept of epinephrine reversal

Answer 5

Normally, E causes vasoconstriction via the α1 receptors. However, if an α blocker is given beforehand, E will actually cause vasodilation because it also activates the β2 receptors.

Question 6

What is the prototye selective α1 blocker? What are these types of drugs usually used for?

Answer 6

Prazosin

• DOC for benign prostatic hyperplasia (BPH) symptom relief (it relaxes the smooth muscle in the prostatic urethra to make urination easier)
• Treating HTN, but they are not usually the DOC for HTN

Question 7

Important note about α1 blocker administration

Answer 7

The first dose often produces an exaggerated hypotensive response that can result in syncope. Therefore, the first dose must be 1/3 or 1/4 the normal dose

Question 8

List the MOA, effects, and uses for terazosin & doxazosin.

Answer 8

These are just analogs of prazosin with a longer half-life and have the same MOA, effects, and uses

Question 9

Give the MOA, effects, and uses of tamsulosin

Answer 9

• There are three subtypes of the α1 receptor, Tamsulosin is selective for the α_1a receptor which predominate in the genitourinary smooth muscle
• Has a very small effect on BP and is less likely to cause orthostatic hypotension than other α blockers
• Used to treat symptoms of BPH

Question 10

List the non-selective β blockers and their general effects on the CVS, respiratory systems, and metabolism.

Answer 10

Propranolol, Nadolol, Timolol

• CVS - slow HR and decrease contractility
• Respiratory - bronchoconstriction
• Metabolism - decreases glycogenolysis and glucagon secretion

Question 11

What’s the primary contraindication for nonselective β blockers?

Answer 11

Patients with COPD or asthma because they can precipitate a respiratory crisis.

Question 12

Describe the MOA, effects, and uses of atenolol & metoprolol

Answer 12

• β1 selective antagonists
• Uses
  
  • Treat HTN in patients with impaired pulmonary function
  • Treat HTN in patients who are receiving insulin or oral hypoglycemic agents (a nonselective blocker would worsen the hypoglycemia)

Question 13

Describe the MOA, effects, and uses of esmolol.

Answer 13

• β1 selective antagonist
• Same effects as other β1 antagonists
• Used for rapid control of ventricular rate in patients with atrial fibrillation or atrial flutter because esmolol is ultra short acting (half life is 10 minutes)

Question 14

Describe the MOA, effects, and uses of labetalol.

Answer 14

• Competitive antagonist of α1 and β receptors but more potently antagonizes β receptors
• Used to treat HTN

Question 15

Describe the MOA, effects, and uses of carvedilol

Answer 15

Very similar to labetalol but also has antioxidant properties

Used to treat HTN and CHF

Question 16

Describe the MOA and uses of pindolol.

Answer 16

• Partial β agonist.
• May be used in individuals with diminished cardiac reserve or a propensity to bradycardia

Question 17

List the most common uses of β blockers and briefly explain how they work for these purposes.

Answer 17

• Lower BP by decreasing CO.
• Decreasing IOP by reducing aqueous humore secretions
• Prevention of migraines (not treatment of migraines)
• Blunt sympathetic stimulation of the heart in hyperthyroidic patients
• Chronic management (not acute) of angina pectoris by reducing O2 requirements of the heart
• Control atrial fibrillations
• Given to patients who’ve had an MI to reduce further stress on heart
• Control performance anxiety
• Treatment of essential tremor

Question 18

Describe the adverse effects and contrainidcations of non-selective and selective β blockers on the respiratory system.

Answer 18

• Nonselective β blockers cause a relatively strong bronchoconstriction
• β1-selective blockers are less likely to evoke bronchoconstriction

The use of these drugs should be avoided in COPD and asthma patients whenever possible. β1 selective drugs are preferred if they have to be used

Question 19

Describe the adverse effects and contrainidcations of non-selective and selective β blockers on sugar metabolism.

Answer 19

• Nonselective β blockers will antagonize the β2 receptors in the liver, decreasing glycogenolysis and gluconeogenesis. This can make recovery from hypoglycemia (particularly with insulin dependent diabetics) difficult.
• A major warning sign for patients prone to hypoglycemia is tachycardia. A nonselective β blocker will suppress this increasing the chances of a person becoming dangerous hypoglycemic
• For patients prone to hypocglycemia, a β1 selective blocker is preferred

Question 20

Describe the adverse effects and contrainidcations of non-selective and selective β blockers on lipid metabolism. Which β blockers don’t seem to have this effect?

Answer 20

• Even though a β receptor blockade inhibits the release of FFAs from adipose tissue, both nonselective and selective β blockers increase plasma TG and decrease HDL
• The α1 and β blocker, labetalol, along with the partial β agonist, pindolol, do not seem to have these effects

Question 21

Describe the adverse effects and contrainidcations of non-selective and selective β blockers on the CNS.

Answer 21

• Sedation
• Dizziness
• Lethargy
• Fatigue

Question 22

Impotant notes about how to administer β blockers

Answer 22

When β recetors are blocked, the body will upregulate the amount of receptors. This effect typically isn’t seen, because they are also being blocked. Because of this, it is very important to gradually taper a patient off of β blockers to avoid acute tachycardia, HTN, and/or ischemia.

Question 23

Describe the MOA and uses for α-methyltyrosine

Answer 23

• Inhibits synthesis of NE in the presynaptic terminal by competitively inhibiting tyrosine hydroxylase
• Use for management of malignant pheochromocytoma and for preoperative preparation of patients for resection of an operable pheochromocytoma

Question 24

Describe the MOA, effects, and uses of reserpine.

Answer 24

• Inhibits NE storage in the presynaptic terminal by irreversibly blocking VMAT
• This causes depletion of NE, since MAO degrades it in the cytoplasm. This is seen as a gradual decrease in BP and HR
• Used in the past to treat HTN (but still tested on the STEP)

Question 25

Describe the MOA, effects, and uses of tetrabenazine.

Answer 25

• Inhibits storage of NE in the presynaptic terminal by reversibly inhibiting VMAT
• Causes presynaptic depletion of NE
• Indicated for the treatment of chorea (jerky involuntary movements) associated with Huntington’s Disease

Question 26

List the tissues in the eye controlled by the ANS that we need to know. Include their receptors and response to receptor stimulation

Answer 26

• Dilator pupillae - α1 - mydriasis
• Constrictor pupilae - M3 - miosis
• Ciliary muscle - M3 - lens accommodation for near vision and facilitation fo aqueous humor outflow
• Ciliary epithelium - ß2 - secretion of aqueous humor