Autonomics - Adrenergic drugs - Part 2

Question 1

a2 Adrenergic receptor agonists & antagonists: Clinical Uses

Answer 1

• Major physiological response following a2 rec. activation is reduced NE release
• a2 smooth muscle contraction

Question 2

a2 Agonists

Answer 2

Clonidine

Question 3

Clonidine

Answer 3

Used for treatment of hypertension (decreased peripheral sympathetic outflow – CNS effect) and opioid withdrawal.

Side Effects: Bradycardia & hypotension.

Question 4

a2 Antagonists

Answer 4

Yohimbine:

Question 5

Yohimbine

Answer 5

Previously used for male impotence (psychogenic).

Side Effects: increased sympathetic outflow - hypertension

Question 6

Non Selective b Adrenergic Receptor Agonists: Clinical Uses

Answer 6

• Stimulation of β1-adrenergic receptors causes an increase in heart rate and the force of contraction, resulting in increased cardiac output.
• Stimulation of β2-adrenergic receptors causes relaxation of vascular, bronchial, and gastrointestinal smooth muscle.

Question 7

Non selective b receptor agonists

Answer 7

• Isoproterenol:

- Dobutamine:

Question 8

Isoproterenol:

Answer 8

Emergency arrhythmias & bronchospasm. More selective agonists now available.

Side effects: Hypertension, palpitations, tremor

Question 9

Dobutamine:

Answer 9

Has prominent inotropic effects resulting in increased contractility and cardiac output. Short half life due to COMT metabolism. Used in the ACUTE management of heart failure. (note more than just b1 activity)

Inc. contractility but not heart rate – no change in peripheral resistance

Question 10

Selective b2 receptor agonists

Answer 10

Used for treatment of Asthma. Pulmonary drug delivery enhances selectivity of β2-adrenoceptors agonists, avoids cardiac (b1) and skeletal (b2) side effects.

Question 11

Selective b2 receptor agonists (drugs)

Answer 11

Albuterol

Question 12

Albuterol:

Answer 12

Used as „asthma reliever‟. Rapid action (15 min) relative short duration (4-6 hours).

Question 13

β-Adrenergic Antagonists: Clinical Uses

Answer 13

Most significant effect these compounds have to reduce the chronotropic and inotropic actions of endogenous catecholamines at cardiac β1-receptors, resulting in decreased heart rate and myocardial contractility. Blockade of b1 receptors in kidney to reduce renin secretion also clinically relevant in reducing fluid overload and vasomotor tone. Are first line drugs used in treatment of hypertension. Blockade of b2 receptors is clinically undesirable.

Question 13

Non-selctive b adrenoceptor antagonists

Answer 13

Propranolol:

Question 14

Propranolol:

Answer 14

Clinically used for Hypertension, angina. Side effects include sedation (central effect) and dyspnea.

Question 15

Atenolol:

Answer 15

Clinically used in treatment of hypertension and angina, improves life expectancy in patients with HF#.

Side Effects: Similar to Propanolol but much less severe.

Clinical benefit in HF through volume reduction (↓afterload) via ↓ renin production. Contraindicated in severe HF

Question 16

Partial b1 Agonists: Clinical Uses*

Answer 16

As a partial agonist they are effective at reducing the effect of endogenous NE at b1 receptors. This leads to smaller decreases in resting heart rate & blood pressure (compared to b1 receptor antagonists).

Question 17

Partial b1 Agonists

Answer 17

Pindolol

Question 18

Pindolol

Answer 18

Clinically used for treatment of hypertension in patients with bradycardia or low cardiac reserve.

Question 19

Nonselective β- and α1-Antagonists : Clinical Uses

Answer 19

Combine the cardiac effect of b1 receptor blockade with the peripheral vasculature effect of a1 receptor blockade.

Question 20

Nonselective β- and α1-Antagonists :

Answer 20

Carvedilol:

Question 21

Carvedilol:

Answer 21

The α1-receptor blockade results in vasodilation; the β1- blockade prevents a reflex sympathetic increase in heart rate. These effects combine to decrease blood pressure. Also used in treatment of heart failure #

Clinical benefit in HF through volume reduction (↓afterload) via ↓ renin production and vasodilation (↓preload) .

contraindicated in severe HF

Question 22

Inhibitors of Re-Uptake:

Answer 22

Cocaine

Imipramine

Question 23

Inhibitors of storage

Answer 23

Reserpine

Tyramine

Question 24

Cocaine:

Answer 24

Inhibits NET.

Question 25

Tricyclic Antidepressants (TCA‟s) inhibit NET.

Answer 25

Tricyclic Antidepressants (TCA‟s) inhibit NET.

Question 26

Imipramine:

Answer 26

Used for treating mild depression. Side effects Postural hypotension & tachycardia

Question 27

Reserpine

Answer 27

blocks VMAT

Question 28

Tyramine

Answer 28

transported via VMAT & displaces vesicular NE

Question 29

Inhibitors of Metabolism

Answer 29

Phenelzine: MOA inhibitors Selegiline:

Question 30

MOA inhibitors

Answer 30

used for treatment of mild depression

Question 31

Phenelzine:

Answer 31

Non selective MAO Inhibitor. Implicated in elevated tyramine leading to hypertensive crisis

Question 32

Selegiline:

Answer 32

Selective MAO B Inhibitor. Safer with respect to dietary restriction also useful for Parkinson‟s

Question 33

aged cheese and red wine that have high conc. of ___.

Answer 33

tyramine

Question 34

Inhibitors of Re-uptake and Storage

Answer 34

- Amphetamines - Methylphenidate - Ephedrine & Pseudoephedrine

Question 35

Amphetamines

Answer 35

(i) Displaces endogenous catecholamines from storage vesicles (ii) blocks NET (iii) a weak inhibitor of MAO

Question 36

Methylphenidate:

Answer 36

Used for ADHD

Question 37

Ephedrine & Pseudoephedrine

Answer 37

Used for nasal decongestion