Drugs Affecting the Adrenergic System

Question 1

Oxymetazaline (OTRIVINE) and Phenylephrine (NEO-SYNEPHRINE, SUDAFED PE)

Answer 1

Pharmacodynamics: α1 selective agonist;

Indication for use: treat nasal congestion as well as for eye redness and phenylephrine treats hypotension.

Question 2

Clonidine (CATAPRES, DURACLON)

Answer 2

Pharmacodynamics: α2 selective agonist;

Indication for use: decrease sympathetic tone and lowers blood pressure, used in ADHD and to reduce withdrawal symptoms.

Question 3

Dobutamine (DOBUTREX)

Answer 3

Pharmacodynamics: β1 selective agonist;

Indication for use: increase heart rate and cardiac output so treats acute heart failure.

Question 4

Albuterol (Salbutamol / Ventolin) and Terbutaline

Answer 4

Pharmacodynamics: β2 selective agonist;

Indication for use: causes bronchodilation so used in the treatment of asthma.

Question 5

Mirabegron (MYRBETRIQ)

Answer 5

Pharmacodynamics: β3 selective agonist;
Indication for use: stimulates β3 on surface of detrusor muscle relieving symptoms of over active bladder.
Clinical features: should not be given with metoprolol as Mirabegron enhances effect of other drugs metabolised in the pathway.

Question 6

Ephedrine

Answer 6

Pharmacodynamics: Mixed action agonist;
Indication for use: Vasoconstriction and bronchodilation;
Clinical features: Has a long duration as non - catecholamine, is a poor substrate for COMT and MAO.

Question 7

Pseudoephedrine (SUDAFED)

Answer 7

Pharmacodynamics: Mixed action agonist;
Indication for use: same as ephedrine and activates in nasal passages allowing less fluid to leave and reduces inflammation and mucus production.

Question 8

Phentolamine (REGITINE)

Answer 8

Pharmacodynamics: non selective α receptor antagonist;
Indication for use: treats hypertension caused by pheochromocytoma (rare tumour of the adrenal gland);
Clinical features: α2 is present on presynaptic nerve ending to inhibit NE release; blockage –> more NE which stimulates Beta – 1 receptor on the heart so can cause tachycardia and arrhythmias.

Question 9

Phenoxybenzamine (DIBENZYLINE)

Answer 9

Pharmacodynamics: Irreversible non selective α receptor antagonist;
Indication for use: treats hypertension caused by pheochromocytoma (rare tumour of the adrenal gland);
Clinical features: α2 is present on presynaptic nerve ending to inhibit NE release; blockage –> more NE which stimulates Beta – 1 receptor on the heart so can cause tachycardia and arrhythmias.

Question 10

Prazosin (MINIPRESS), Doxazosin (CARDURA), Terazosin (HYTRIN), Tamsulosin (FLOMAX), Alfuzosin (UROXATRAL) and Silodosin

Answer 10

Pharmacodynamics: Selective α1 blocker;
Indication for use: on vascular smooth muscle which reduces blood pressure and blocks receptors on smooth muscle of bladder neck and prostrate causing smooth muscle to relax leading to relief of urinary issues related to Benign Prostatic Hyperplasia (BPH).

Question 11

Yohimbine (YOCON)

Answer 11

Pharmacodynamics: selective α2 blocker;

Indication for use: Veterinary drug used to reverse sedation.

Question 12

Propranalol (INDERAL LA, INNOPRAN XL), Pindolol (VISKEN), Nadolol (CORGARD), Sotalol, Timolol (BETIMOL, ISTALOL, TIMOPTIC)

Answer 12

Pharmacodynamics: β non-selective (1st generation) competitive inhibitor;
Indication for use: decreases heart rate, delayed conduction through the AV node and reduced contractility –> Decreases cardiac output and decreased oxygen demand; Propranolol also penetrate the CNS and is therefore useful for migraine prophylaxis; Nadalol and Timolol when applied to eye decreases IO pressure and treats Glaucoma.
Clinical features: Blocking of β2 in lungs so can lead to bronchoconstriction.

Question 13

Atenolol (TENORMIN), Acebutalol (SECTRAL), Bisoprolol (ZEBETA), Esmolol (BREVIBLOC), Metoprolol (LOPRESSOR, TOPROL-XL), Betaxalol (BETOPTIC-S, KERLONE)

Answer 13

Pharmacodynamics: β1 selective (second generation) competitive inhibitor;
Indication for use: Similar effects to 1st generation (reduces tachycardia) but more suitable for chronic lung disease such as asthma causing bronchodilation.

Question 14

Carvedilol (COREG, COREG CR), Labetalol (TRANDATE)

Answer 14

Pharmacodynamics: β1 and α1 blocker (3rd generation);

Indication for use: Cause vasodilation - so used for hypertension and heart failure.

Question 15

Nebivolol and Betaxalol

Answer 15

Pharmacodynamics: selective β1 blocker (3rd generation);

Indication for use: Used in treatment of hypertension by blocking calcium channels.

Question 16

What are the common side effects of α1 agonists?

Answer 16

Can cause headache, reflex bradycardia, excitability, and restlessness (cause systemic vasoconstriction); In patients with coronary artery disease can precipitate angina. α1 agonists used as nasal preparation can cause a rebound effect.

Question 17

What are the common side effects of α2 agonists?

Answer 17

Can cause sedation, dry mouth and nasal mucosa (because of increased vagal activity), bradycardia, orthostatic hypotension, and impotence. Constipation, nausea and gastric upset are also associated with the sympatholytic effects of these drugs. Fluid retention and edema is also a problem with chronic therapy; therefore, concurrent therapy with a diuretic is necessary. Sudden discontinuation of clonidine can lead to rebound hypertension, which results from excessive sympathetic activity.

Question 18

What are the common side effects of β1 agonists?

Answer 18

Can cause anxiety, hypertension, increased heart rate, and insomnia. Other side effects include headaches and essential tremor. Hypoglycemia was also reported due to increased secretion of insulin.

Question 19

What are the common side effects of β2 agonists?

Answer 19

Acts centrally and blocks NE re-uptake Tachycardia secondary to peripheral vasodilation and cardiac stimulation; tachycardia can be accompanied by palpitations. Tremor, excessive sweating, anxiety, insomnia, and agitation. More severe effects, such as pulmonary edema, myocardial ischemia, and cardiac arrhythmia.

Question 20

What type of receptors is beta 2 and what are its effects?

Answer 20

Gs GPCR - lungs, bronchial smooth muscle lead to bronchodilation. Located on vascular smooth muscle and arteries of skeletal muscle – lead to relaxation of blood vessel. Located on smooth muscle of GIT and uterus lead to relaxation (decreased motility and inhibition of labor), found in pancreas and increase insulin secretion.

Question 21

What are the contraindications for α1 agonists?

Answer 21

Contraindicated in those who suffer from hypertension, bradycardia, prostatic hyperplasia, and anyone using medications, which may also increase blood pressure.

Question 22

What are the contraindications for α2 agonists?

Answer 22

Contraindicated in anyone who has low blood pressure. Geriatric patients may be at increased risk of falls due to the sedating and hypotensive effects.

Question 23

What are the contraindications for β1 agonists?

Answer 23

Contraindicated in patients who have arrhythmias.

Question 24

What are the contraindication for β2 agonists?

Answer 24

Contraindicated in patients who have hypokalemia.

Question 25

What type of receptor is β3 and what are its effects?

Answer 25

Gs GPCR - adipose tissue – lead to lipolysis, found in urinary bladder, relax and prevent urination.

Question 26

What are the contraindications for α (alpha) blockers?

Answer 26

Contraindicated in those with a history of orthostatic hypotension or severe hepatic impairment, dizziness, orthostatic hypotension (due to loss of reflex vasoconstriction upon standing), nasal congestion (due to dilation of nasal mucosal arterioles), headache, and reflex tachycardia (especially with non-selective alpha-blockers). Fluid retention is also a problem that can be rectified by use of a diuretic in conjunction with the alpha-blocker.

Question 27

What are the contraindication of β blockers?

Answer 27

Contraindications include patients with symptomatic bradycardia, AV block, decompensated heart failure, and asthma.

Question 28

Fenoldapam (CORLOPAM)

Answer 28

Pharmacodynamics: Peripheral D1 agonist;

Indications for use: Rapid vasodilator, treats hypertension.

Question 29

What are the side effects associated with D1 agonists?

Answer 29

Headache, flushing, dizziness, nausea, vomiting, and tachycardia (due to vasodilation).

Question 30

Salmetrol (SEREVENT DISKUS) and Formoterol (FORADIL AEROLIZER, PERFOROMIST)

Answer 30

Pharmacodynamics: Long acting β2 selective agonists;
Indications for use: Whenever long terms bronchidilation is required (12 hours).
Clinical features: Salmetrol has a delayed onset. Both should be combined with corticosteroids.

Question 31

Amphetamine (ADDERALL)

Answer 31

Pharmacodynamics: Indirect acting α1 agonist (vasculature), β1-stimulatory effects (heart);
Indication for use: Slightly increases blood pressure.

Question 32

Cocaine (Blow)

Answer 32

Pharmacodynamics: Indirect acting α1 agonist (vasculature), β1-stimulatory effects (heart) (inhibits Na / Cl mediated NE transporter that modulates uptake);
Indication for use: can increase blood pressure but is a drug of abuse.

Question 33

Isoproterenol (ISUPREL)

Answer 33

Pharmacodynamics: direct-acting β1- and β2 agonist;
Indications for use: Increases heart rate, contractility and cardiac output while (β2) decreases peripheral resistance and reduces diastolic blood pressure. Is a bronchodilator and can be used in AV block but has been replaced with other drugs.

Question 34

Reserpine (SERPASIL)

Answer 34

Pharmacodynamics: Inhibits Mg / ATP dependent transport of NE, 5-HT and D from cytoplasm to vesicles reducing sympathetic activity;
Indication for use: Management of hypertension but replaced with newer drugs.

Question 35

Where are α1 receptors found and what is their broad effect?

Answer 35

α1 receptors are found on vascular smooth muscle. They determine both arteriolar resistance and venous capacitance, and thus BP.

Question 36

Where are α2 receptors found and what is their broad effect?

Answer 36

α2 receptors are found both in the brain and in the periphery. In the brain stem, they modulate sympathetic outflow. Their function in the periphery is both to control of sympathetic tone and to local and regional blood flow lowering BP.

Question 37

Where are β1 receptors found and what is their broad effect?

Answer 37

β1 receptors are located in the heart and stimulation leads to increased contractility.

Question 38

Were are β2 receptors found and what is their broad effect?

Answer 38

β2 receptors are located in the bronchioles of the lungs (bronchodilation) and the arteries of the skeletal muscles (vasodilation).

Question 39

Where are β3 receptors found and what is their broad effect?

Answer 39

β3 receptors are located primarily in the small intestine, adipose tissue and vascular endothelium (lypolysis and thermoregulation). Relaxation of bladder.

Question 40

What is the significance of catecholamines?

Answer 40

Catecholamines highly potent but have reduced penetration of the CNS and are rapidly inactivated. Non-catecholamines are poor substrates for MAO and are lipid soluble therefore have longer duration of action and penetrate the CNS.