L8- Adrenergic Blockers

Question 1

In general what are the effects of A1 Block?

A2 Block?

Non-selective block of both?

Answer 1

A1 Block - Vasodilation and lower BP, Relax Iris Radial Muscle, Relax GU muscle, less viscous salivation

A2 Block - Increase NE - Sympathomimetic AND Incrase Insulin secretion from pancreatic beta cells

Non-selective A1/A2 Block - A1 block effects + Beta agonist effects from increase NE from A2 block

Question 2

What is Ergot? How does it work?

Answer 2

Ergot is a Partial Agonist at Alpha-1 receptors and serotonin receptors found in Rye that is infected with fungus [Ergot Alkaloids]

Partial Agonist so when increased Epinephrine/Adrenalin then acts like an Antagonist and blocks Alpha-1 to lower BP in presence of increased epi and cause Beta-2 mediated dilation to be predominant effect

Question 3

What are the 2 Ergot Alkaloid derivatives still used today and what are they used for?

Answer 3

Ergotamine - used for migraines

Ergonovine - used to contract post-partum uterus and prevent hemorrhage

Question 4

Name the Non-selective Alpha Adrenergic Antagonists (blockers) - how are they used?

Answer 4

Phenoxybenzamine - irreversible antagonist, long acting

Phentolamine - competitive antagonist, short acting

Used for surgical resection of pheochromocytoma

*IMPORTANT - alpha block in place before beta block other wise hypertensive crisis!

Question 5

What are the Alpha-1 Antagonists?

What are they used for?

Answer 5

Prazosin, Terazosin -

Used for Primary HTN (although see First Dose effets where postural hypotension); Raynaud’s Disease to cause vasodilation, Benign Prostratic Hypertrophy and Kidney stones to relax urinary tract SM

Tamsulosin - A1A selective

used more for relaxants of urinary tract with less vasodilatory effects on BP

Question 6

What is an Alpha-2 Antagonist?

Answer 6

Yohimbine!!!

Question 7

What happens and how to treat Benign Prostatic Hyperplasia?

Answer 7

BPH causes constriction of upper urethra and so incomplete emptying and incrased urinary frequency

Sympathetic input release of NE onto A1 causes constriction of SM so if use Terazosin or Tamsulosin can act at Alpha1-A receptors at neck of bladder and relax SM and fascilitate voiding

Question 8

What are adverse effects of Alpha-1 block?

Answer 8

Postural Hypotension - get up and faint

Nasal congestion from mucosal vasodilation

Dry mouth - less VISCOUS salivary secretion

*Intraoperative Floppy Iris syndrome bc relaxed radial and vasc smooth muscle so bad for eye surgery

Retrograde Ejaculation and Delayed ejaculation

Priaprism (haha)

Question 9

Why would Alpha Blockers cause erection????

Answer 9

Normally, sympathetic adrenergic input causes contraction (A1) of vascular arteries to penis and of trabecular smooth muscle so more venous outflow

BLOCK symp and relax BV to increase blood flow and relax trabecular SM to compress veins so get engorgement

Question 10

Why use A2 block in Dysautonomia? What is the risk with A2 blcok?

Answer 10

Used to increase NE release to prevent orthostatic hypotension but risk increased HR leading to palpitations

Question 11

In General, what are some systemic effects of Beta-Antagonists?

Answer 11

Decreased HR, CO, O2 Demand, AV Conduction Velocity

Decreased Renin release

Constriction of blood vessels AND bronchioles

Decreased Tremor

Hypoglycemia

Hyperkalemia

Mast cell degranulation incrased

Question 12

What are the Cardiovascular indications for Beta-Blockers?

Answer 12

1) Angina of Effort - used to decrease oxygen consumption in heart and so less demand
2) Post-infarction
3) Cardiac Arrythmia
4) Systolic Heart Failure - First Exacerbation of symptoms bc short-term CO decreae but long term benefits
5) Primary HTN (less effective than other firstline agents)

Question 13

What are the non-cardiovascular indications for Beta-Blockers?

Answer 13

1) Hyperthyroidism to decrease HR, Tremor and Anxiety
2) Migraine - prophylaxis
3) Glaucome - decrease aqueous inflow and IOP bc act on beta-rec in ciliary body
4) Tremor and stagefright

Question 14

What are adverse cardiovascular effects of beta-block / contraindications?

Answer 14

Less exercise capacity, bradycardia, peripheral vasoconstriction

DO nNOT use with AV conduction block - made worse

Can get withdrawal leading to beta-supersensitivity

Question 15

What are the non-cardiovascular adverse effects of beta-block?

Answer 15

Bronchoconstriction - dont use in ASthma or COPD

Mast Cell destabilization - makes anaphylaxis worse and no response to Epi pen

***BLUNTED subjective signs Hypoglycemia and delayed recovery from it - CAREFUL use in insulin dependent diabetics

Exercise induced hyperkalemia - muscle weakness

Question 16

What are First generation Beta-blockers? Name them and action

Answer 16

Non-selective onto beta 1 and beta2

Propanolol *(Lipid Soluble)

Nadolol

Pindolol - Partial Agonist

**timolol **

Question 17

What are the Second Generation Beta-blockers? Name them and action

Answer 17

Beta-1 Selective “Cardioselective”

Atenolol

**Metorpolol ***(Lipid Soluble)

Question 18

What are the third generation beta-blockers. Name them and action

Answer 18

Beta blockers with additional vasodilator actions including NO production, B2 agonist, A1 block, Ca-entry block, K+ opening and antioxidant activity

Non-selective = Carvedilol *(Lipid Soluble) and Labetalol (a1/beta)

B1 selective = **Betaxolol **

Question 19

What are the PArtial Agonist Beta blockers and why are they sometimes advantageous?

Answer 19

Pindolol (First generation) and Lavetalol (Third)

Have intrinsic sympathomimetic Actrivity so good for use in patients with **bradycardia or conduction block **

Question 20

Why is Beta-1 selectivity not gauranteed?

Answer 20

relative advatage of reduced risk of beta-2 adverse effects is diminished with increases doses of beta-1 blocker bc becomes beta-2 blocker at certain levels

Question 21

What are the 2 beta blockers with Biased Signaling and what is that anyways?

Answer 21

Alprenolol and Carvedilol (third)

stimulate Beta-1 mediated transactivation of EGFR

acitvate PKA to decrease contraction via AC to cAMP But also stimulate Beta-Arrestin to cleave EGF to activate EGFR which is anti-apoptotic and prolongs survival of cardiomyocytes!!!!