PNS Pharmacology: Adrenergic Drugs

Question 1

Name the three sites named under symatptheic predominate tone.

Answer 1

arterioles- adrenergic (vasoconstriction important for perfusion)
veins- adrenergic (vasoconstriction important to reduce peripheral pooling)
sweat glands-cholinergic (allows for normal sweating)

Question 2

Mecamylamine

Answer 2

competitive antagonist at nicotinic Nn receptors

used to treat moderate to severe hypertension

can have central effects related to low ACh receptor availability, caution in those particularly vulnerable to lower- than normal perfusion

lowering BP can cause HR baroreceptor reflex, although a blunted response

Question 3

1. List the types and subtypes of adrenergic receptors and their selectivity for Epi, NE an DA.

Answer 3

a1A,B,D: Epi, NE and DA
a2 A,B, C: Epi and NE
B1: Epi, NE and DA
B2 : Epi
(and B3)
D1, D2, D3, D4, D5: DA

Question 4

What signaling cascade does a1 receptor’s use

Answer 4

Gq that activates PLC pathway

Question 5

What signaling cascade do B and a2 receptors use?

Answer 5

B Gs, activating cAMP pathway

a2 Gi, inhibiting cAMP pathway

Question 6

3. List the major endogenous adrenergic agonist, its mechanism and indications.

Answer 6

epinephrine, one of the most potent vasopressors

acts by activation of both a and B receptors

used as tx. for anaphylaxis, local anesthetics to prolong anesthetic and keep drug local; action lasts 1-4 hrs. regardless of route

precaution use for non anaphylactic shock, during labor (fetal anoxia) and any other situation when sympathetic activation is undesirable

Question 7

Phenylephrine (NeoSynephrine or SudafedPE)

Answer 7

selective a1 agonist, main effect of vasoconstriction (pressor) without substantial effect on B1 or B2 receptors

used to treat nasal congestion or for mydriasis, metabolized by MAO in the liver

caution with CV disease, labor, narrow angle glaucoma and extravasation

Question 8

Clonidine (Catapres, Duraclon)

Answer 8

agonist at presynaptic a2 receptors (auto receptors) resulting in inhibition of sympathetic outflow tone (actions on the brainstem)

used mainly as a Tx of hypertension (100% lipid soluble), epidural clonidine, also has a sedating effect due to effect on CNS

precaution that patients must be weaned off drug due to rebound increase in catecholamines and drop in BP may lead to decrease in perfusion to brain or heart

Question 9

Describe how a presynaptic a2 receptor can result in inhibition of outflow?

Answer 9

by acting on auto receptors, drug works to cause increased feedback message to decrease output

Question 10

Isoproterenol

Answer 10

agonist at B1 and B2 adrenergic receptors with little or no effect on a receptors, whose effect is to increase CO with a decrease in vascular resistance

used to improve AV conduction during heart block and as a stimulant in cardiac arrest (B2); also used to treat acute bronchospasm

COMT metabolism, adverse effects; caution with heart arrhythmias, palpitations or angina

Question 11

2. Describe the major differences in mechanism between direct and indirect acting sympathomimetic drugs

Answer 11

direct: acts as a pseudo neurotransmitter (ie. like Epi or NE)
indirect: alters sympathetic function by altering synthesis, release, reuptake etc.

Question 12

Why would you use precaution when giving a B2 agonist to a diabetic? What about a patient with hyperthyroidism?

Answer 12

in diabetics, B2 activation can lead to glycongenolysis in the liver
patients with hyperthyroidism can be sensitive to catecholamines

Question 13

What is the effect of NE on pulse rate, blood pressure and peripheral resistance.

Answer 13

a1 and B1 action

increases peripheral resistance- primary response and causes the following responses through reflex:
decreases pulse rate
increases systolic and diastolic

Question 14

What is the effect of Epi on pulse rate, blood pressure and peripheral resistance.

Answer 14

a1, B1 and B2
acts mainly to open up blood vessels while increasing output:
increase pulse rate
increase systolic, decrease diastolic 
minor decrease in peripheral resistance

Question 15

What is the effect of isoproterenol on pulse rate, blood pressure and peripheral resistance.

Answer 15

basically exaggerate effects of Epi

increased plus rate (B1 action on heart)
increased systolic and decreased diastolic
significant decrease in peripheral resistance

Question 16

Dobutamine (Dobutrex)

Answer 16

primarily a agonist at B1 adrenergic receptors, with minor B2 and a1 effects, increasing myocardial contractility and stroke volume, increasing CO

used as tx. in acute heart failure

metabolized by COMT/glucoronidation; caution with hypertorphic sub aortic stenosis. arrythmias and hypovolemia, can cause PVCs, tachy and agina

Question 17

Albuterol (Proventil, Ventolin)

Answer 17

modernly selective B2 adrenergic receptor agonist, acting to bronchodilate and inhibit degranulation of inflammatory substances

used as a short acting bronchodilator (manage acute asthmatic episode or COPD)

adverse rxns are extension of the pharmacology, with some systematic effects; increasing use should be addressed with inhaled corticosteroid, some risk for angioedema

Question 18

Salmeterol

Answer 18

highly selective B2 adrenergic receptor agonist with slower onset but longer effects

for long-term prophylactic treatment of asthma and adults with reversible COPD

not for use as a rescue inhaler, should only be added to tx. regimen if other drugs do not control asthma; black box warning that there is an increased incidence of asthma-related death with long-acting B2 agonists