Adrenergic antagonists

Question 1

What is a reversible alpha antagonist?

Answer 1

Competitively inhibits the binding of physiological agonist; example: phentolamine
Graph –causes more NE needs to be added to get the same effect

Question 2

What is an irreversible alpa antagonist

Answer 2

Covalently binds to the receptor; example: phenoxybenzamine
Inactivates the R and only way to get more R is to make new
Graph- causes a reduced max response– no matter how much NE added

Question 3

What are the cardiovascular effects of alpha antagonists?

Answer 3

Hypotension; can cause orthostatic hypotension and reflex tachycardia. Nonspecific agents (alpha 1 and 2) are more likely to cause tachycardia

Question 4

What happens with a high dose of epi

Answer 4

Alpha response predominates; resulting in increased blood pressure.

Question 5

If you give an alpha antagonist prior to epinepherine

Answer 5

The effect of epinephrine at beta receptors will prevail and blood pressure will fall.

Question 6

Why do we get rebound hypertension due to abrupt withdrawal on alpha antagonists

Answer 6

Due to upregulation of receptors, during continued administration of drug

Question 7

What is the action of alpha-1 receptor antagonists at urethral sphincters and prostate?

Answer 7

These receptors cause contraction, so blockade can facilitate flow in patients with urinary retention.

Question 8

Additional effects of alpha antagonists; eye

Answer 8

particularly alpha-1 (allowing parasympathetic to predominate) effects the radial muscle produces miosis

Question 9

Additional effect of alpha antagonists; GI

Answer 9

Blockade of these receptors removes the relaxing influence of alpha receptors; causing hypermotility

Question 10

Phenoxybenzamine

Answer 10

Non-selective, irreversible alpha blocker

• used for hypertension resulting from Pheochromocytoma -Raynaud’s
• adverse - tachy

Question 11

Phentolamine

Answer 11

Non-selective alpha blocker used in hypertensive emergencies, has a short half-life
-adverse- tachy

Question 12

Prazosin

Answer 12

Selective alpha 1 blocker

• used in mild hypertension
• less likely to cause tachy than phentolamine

Question 13

Doxazosin

Answer 13

Alternatives to prazosin (alpha 1 antag) with longer half-lives
- used in BPH and mild hypertension

Question 14

Tamsulosin

Answer 14

Selective alpha-1 blocker in prostate

-used in BPH

Question 15

Yohimbine

Answer 15

Selective alpha-2 blocker

-used for postural hypotension and occasionally impotence

Question 16

Pharmacokinetics of B blockers

Answer 16

Low bioavailability due to significant first pass metabolism; requiring dose titration per patient.

• Possible high clearance due to extensive metabolism in the liver
• polymorphisms cause some patients to be poor metabolizers leading to elevated concentrations.

Question 17

What are the cardiovascular effects of B blockers? What happens with abrupt withdrawal

Answer 17

Bradycardia

• decreased contractility and excitability
• Abrupt withdrawal can cause rebound hypertension or myocardial infarction (possibly due to upregulation of receptors).

Question 18

Renin release

Answer 18

Beta-1 stimulation causes this, therefore beta-1 blockers will suppress leading to a decrease in angiotensin; this may lower blood pressure in patients with hypertension

Question 19

What are the cardiovascular effects of blocking B-2

Answer 19

Early rise in blood pressure (due to unopposed alpha-1 mediated vasoconstriction); can cause cold extremities (not good for Raynaud’s)

Question 20

Contraindications: B2 and bronchoconstriction

Answer 20

Particularly in patients with asthma, contraindicated

• beta-1 antagonist should be chosen, however receptor specificity is not complete
• class of drugs should be avoided

Question 21

Which class of drugs should we use for glaucoma?

Answer 21

Beta blockers are among the most widely used; decrease production of aqueous humor

Question 22

What happens when we block B2 receptors?

Answer 22

Inhibits epinephrine mediated stimulation of glycogenolysis; may cause bronchospasm, blocks tremor

Question 23

What masks the symptoms of hypoglycemia in diabetes?

Answer 23

Beta blockade may block tachycardia and inhibit tremors; the primary reason these drugs are problematic in diabetic patients

Question 24

What do unopposed alpha-2 stimulation with non-specific beta blockers do on lipids?

Answer 24

Inhibit the hormone sensitive lipase; increase VLDL and decrease HDL; altering HDL/LDL ratio

Question 25

Beta blockers and membrane stabilization

Answer 25

May significantly contribute to toxicity by prolonging QRS duration and impair cardiac conduction; blocks myocyte sodium channels

Question 26

Pindolol & Acebutelol

Answer 26

Have beta agonist properties (partial agonist); weaker than catecholamines, demonstrate less bradycardia, slight vasodiation and minimal change in lipids: intrinsic sympathomimetic activity -treats hypertension

Question 27

What are the CNS effects of B blockers?

Answer 27

Cause dizziness, fatigue, depression and sexual dysfunction; more hydrophilic drugs such as atenolol have fewer effects

Question 28

Nadolol

Answer 28

Non-selective, long lasting (24 hr) beta blocker used in hypertension and angina

Question 29

Metoprolol

Answer 29

Beta-1 selective blocker with high lipid solubility; membrane stabilizer, used widely for hypertension, angina and MI

Question 30

Esmolol

Answer 30

Very short acting beta blocker (beta-1) used for intraoperative and postoperative hypertension, arrythmias -good for critically ill

Question 31

Labetolol

Answer 31

Non-selective for beta - also blocks alpha-1 - used in severe hypertension

Question 32

Carvedilol

Answer 32

Non-selective for beta blockade; mild alpha-1 block, used in CHF and hypertension

Question 33

Guanethidine

Answer 33

Rarely used now, was used for hypertension | - acute effect is to release NE, chronic effect is to deplete NE from nerve terminals

Question 34

Resperine

Answer 34

Inhibits vesicular transport (indirect acting adrenergic antagonist) so NE cannot be taken up into vesicles - also rarely used, causes depletion of dopamine and seratonin in the CNS leading to depression

Question 35

What are the clinical uses of B antagonists

Answer 35

Ischemic heart disease, arrhythmias, heart failure, glaucoma, hyperthyroidism, migraine, tremors; performance anxiety

Question 36

What does the B-1 blockade cause?

Answer 36

Causes decreased heart rate, stroke volume and cardiac output - decreased renin release - decreased aqueous humor production

Question 37

A BEAM

Answer 37

Beta-1 blockers: Acebutalol, Betaxolol, Esmolol, Atenolol, Metoprolol

Question 38

Please Try Not being Picky (non-selective beta blockers)

Answer 38

Propranolol, Timolol, Nadolol, Pindolol

Question 39

PAPA

Answer 39

Partial Agonist Pindolol Acebutolol

Question 40

Clinical uses for alpha blockers for urinary obstruction

Answer 40

-BPH treated with alpha 1 antag (opens up the urethra)

Question 41

alpha blockers treatment for peripheral vascular disease

Answer 41

- Sometimes prazosin or phenoxybenzamine used to treat vasospasm in peripheral circulation (Raynauds) - Ca channel blockers preferred - Behavioral modifications preferred. Like wearing gloves outside

Question 42

Which alpha blockers would you use for chronic hypertension and what are the adverse effects?

Answer 42

- use alpha 1 blocker (like prazosin) but usually not used alone - major adverse effect: orthostatic hypotension and palpitations

Question 43

What alpha blockers would you give for pheochromocytoma?

Answer 43

- phenoxybenzamine mostly used-- for several weeks before surgery to reverse chronic changes (from having incr NE circulating) - May need to give B blocker also-- but should ONLY be given AFTER alpha block to avoid alpha-1 vasoconstriction

Question 44

What happens when you stim alpha-2 presynaptically?

Answer 44

Inh NE release

Question 45

NE effect with alpha B blocker pretreats (bp)

Answer 45

NE doesn't stim B-2 so no vasodilation | alpha block- lowers bp

Question 46

Epi response with alpha and beta block pretreats (bp)

Answer 46

alpha- decr bp | beta- incr bp

Question 47

Isoproterenol effect with alpha and beta block pretreats (bp)

Answer 47

- isoproterenol is beta agonist - alpha- no effect - beta- less of a decr in bp

Question 48

Terazosin

Answer 48

Alternatives to prazosin (alpha 1 antag) with longer half-lives - used in BPH and mild hypertension