Anti-Adrenergics

Question 1

What kind of drugs are drugs ending in -olol

Answer 1

beta blocker

Question 2

Phenoxybenzamine: alpha or beta blocker?

Answer 2

alpha blocker somewhat selective for A1 over A2 irreversible

Question 3

Phentolamine: alpha or beta blocker?

Answer 3

alpha blocker non-selective: so A1 and A2 reversible

Question 4

Atenolol: alpha or beta blocker?

Answer 4

selective B1 blocker

Question 5

Esmolol: alpha or beta blocker?

Answer 5

selective B1 blocker

Question 6

Prazosin: alpha or beta blocker?

Answer 6

selective A1 blocker reversible

Question 7

What are Clonidine and Methyldopa?

Answer 7

A2 agonist acts as anti-adrenergic

Question 8

physiological effect of prazosin

Answer 8

A1 blockade dec BP get reflex tachycardia

Question 9

Why do you get reflex tachycardia with prazosin and phentolamine?

Answer 9

prazosin blocks A1 receptors/phentolamine blocks A1 receptors…get vasodilation…dec BP…baroreceptors activate vasomotor center…inc output signaling from vasomotor center…NE released…already got A1 receptors blocked from prazosin so NE acts only on heart…get tachycardia *remember phentolamine non-selective alpha blocker so also blocks A2 which will give you even greater tachycardia

Question 10

Why is the duration of action longer for phenoxybenzamine?

Answer 10

irreversible alpha blocker duration of action 24 hours B/c must synthesize new receptor to recover A1 effect

Question 11

physiological effect of phentolamine

Answer 11

reversible, non-selective alpha blocker A1 blockade…dec BP…reflex tachycardia A2 blockade…prevents feedback inhibition by released NE…causes more NE to be released onto B1 receptors in heart…even GREATER tachycardia than with selective blocker

Question 12

So difference between selective (prazosin) and non-selective (phentolamine) alpha blocker?

Answer 12

tachycardia is WORSE with a non-selective alpha blocker than with a selective A1 blocker

Question 13

Why even use non-selective alpha blocker (phentolamine) when get worse/double bad tachycardia?

Answer 13

phentolamine and phenoxybenzamine are used in combo with propranolol for pheochromocytoma (which is a tumor that dumps Epi and NE into system) management

Question 14

What is prazosin used for?

Answer 14

HTN

Question 15

What can be used for benign prostatic hypertrophy?

Answer 15

phenoxybenzamine, prazosin, and terazosin relax smooth muscle in bladder, prostate capsule, and prostatic urethra which improves urinary flow

Question 16

Toxicity and side effects of alpha blockers

Answer 16

reflex tachycardia in both selective (prazosin) and non-selective (phentolamine) alpha blockers but worse with non-selective

postural hypotension is caused by A1 blockade

nasal stuffiness

inhibition of ejaculation

Question 17

What is Epi reversal?

Answer 17

as concentration of Epi goes up at first BP is dec due to Epi’s effects on B2 but as inc Epi concentration more BP inc due to Epi’s effects on A1 (bi-phasic effect)

Question 18

What happens when Epi is administered in the presence of an alpha blocker?

Answer 18

no pressor response of BP, don’t get bi-phasic effect, just get depressor response of BP, just get dec in BP due to effects on B2

Question 19

Where are B1 receptors located?

Answer 19

heart

Question 20

Where are B2 receptors located?

Answer 20

lungs

blood vessels

Question 21

Do you ever want to be selective and block only for B2?

Answer 21

NO, causes bronchoconstriction and possible bronchospasm no particular reasons to want to antagonize B2 receptors

Question 22

Since don’t want to be selective for only B2 when say selective for B1 only relatively so

Answer 22

the best selectivity achieved is about 100 fold see picture

Question 23

What is Propranolol?

Answer 23

non-selective beta blocker both B1 and B2

Question 24

cardiac effects of non-selective beta blockers (propranolol)

Answer 24

cardiac effects due to blockage of B1

dec HR

dec cardiac output ( more pronounced during exercise)

dec conduction velocity

dec myocardial oxygen demand

dec spontaneous rate of depolarization

Question 25

vascular and BP effects of non-selective beta blockers (propranolol)

Answer 25

B2 block may inc TPR slightly B1 block dec in plasma renin...so dec BP net effect is dec in BP MECHANISM: dec cardiac output...dec in plasma renin...dec in sympathetic tone via effects in CNS

Question 26

metabolic effects of non-selective beta blockers (propranolol)

Answer 26

no effect on plasma glucose levels in normal person does slow recovery from hypoglycemia in diabetics (less of a problem with B1 selective) inc plasma concentration of triglycerides and VLDL dec plasma concentrations of HDL

Question 27

respiratory tract effects of non-selective beta blockers (propranolol)

Answer 27

blocks B2 so airway resistance increased can be life threatening to asthmatics

Question 28

What is Timolol?

Answer 28

non-selective beta blocker used in glaucoma although non-selective used for B1 actions in the eye

Question 29

Drug of choice to treat glaucoma?

Answer 29

Timolol

Question 30

How does Timolol treat glaucoma?

Answer 30

dec aqueous humor produciton b/c B1 is responsible for production of aqueous humor in the eye

Question 31

Atenolol and Esmolol are both selective B1 blockers. When do you use Esmolol over Atenolol?

Answer 31

in emergency procedures because Esmolol has 8 min half-life

Question 32

cardiac effects of selective B1 blockers (Atenolol)

Answer 32

same as non-selective beta blockers: cardiac effects due to blockage of B1 dec HR dec cardiac output ( more pronounced during exercise) dec conduction velocity dec myocardial oxygen demand dec spontaneous rate of depolarization

Question 33

Is there more or less danger of respirator side effects with selective B1 or non-selective beta blockers?

Answer 33

less danger with selective B1 blockers

Question 34

Are beta blockers really "selective" at high doses?

Answer 34

NO Remember card with picture where when 100% B1 blockage saw 50% B2 blockage

Question 35

what do mixed alpha and beta blockers end with?

Answer 35

-alol or -ilol just not -olol (that's beta blockers)

Question 36

What are therapeutic uses of beta blockers?

Answer 36

\*recent reports suggest B blockers may inhibit cancer progression\* HTN (usually with diuretics and vasodilators) Cardiac arrhythmias Angina Prophylaxis of migraine Early in MI reduces high sympathetic tone Prophylaxis to dec mortality after MI Glaucoma Performance anxiety Pheochromocytoma (with alpha blocker) Heart failure (carvedilol)

Question 37

Side effects and toxicity of beta blockers

Answer 37

B1 block= dec cardiac output, heart block, bradycardia B2 block= bronchoconstriction CNS: depression and lethargy

Question 38

Give example of a drug that works at presynapse

Answer 38

Guanethidine and Reserpine

Question 39

How does Guanethidine work?

Answer 39

enters via the NET (revolving hotel door) and concentrates in vesicles and depletes NE over time

Question 40

Therapeutic uses of Guanethidine

Answer 40

historically but not any more as antihypertensive used therapeutically as a BOARD QUESTION

Question 41

side effects of Guanethidine

Answer 41

postural hypotension diarrhea impaired sexual function (all related to peripheral antiadrenergic actions)

Question 42

How does Reserpine work?

Answer 42

enters terminal, blocks VMAT, causing depletion of NE over time

Question 43

Therapeutic uses of Reserpine

Answer 43

historically used for hypertension

Question 44

Side effects of Reserpine

Answer 44

CNS: depression Peripheral: orthostatic hypotension

Question 45

Mechanism of action of A2 agonists

Answer 45

A2 receptors at pre and post synaptic sites in the brain and block sympathetic outflow (A2 agonists acting on the presynaptic A2 receptors to inhibit NE release) increases neg feedback = less NE released functionally working as anti-adrenergic

Question 46

Give two examples of A2 agonists

Answer 46

Clonidine and alpa-methyl-dopa and dexmedetomide

Question 47

EXAM QUESTION: What is the difference between the two A2 agonists Clonidine and alpha-methyl-dopa?

Answer 47

Cloninine works directly at A2 receptors alpha-methyl-dopa must be metabolized to alpha-methly-NE

Question 48

Therapeutic uses of Clonidine

Answer 48

essential HTN reduction of unpleasant side effects associated with opioid withdrawal ADHD open angle glaucoma (apraclonidine: also dec production of aqueous humor)

Question 49

Therapeutic uses of alpha-methyl-dopa

Answer 49

essential HTN safe in pregnancy

Question 50

toxicities and side effects of A2 agonists (Clonidine and alpa-methly-dopa)

Answer 50

dry mouth sedation hypertensive crisis may occur upon abrupt withdrawal from Clonidine high incidence of autoimmune response with alpha-methly-dopa (positive Coombs test/antiglobulin test)