PHC513: Tutorial 1

FACULTY OF PHARMACY
UNIVERSITI TEKNOLOGI MARA (UiTM)

PHC513: Pharmacology of Drugs Affecting the Peripheral Nervous System

Learning Outcome: Nonselective Adrenergic Agonists, α-Adrenergic Receptor Agonists, β-Adrenergic

Agonists, Indirect Acting Sympathomimetics, α-Adrenergic Receptor Antagonists, β-Adrenergic
Receptor Antagonists

ANSWER ALL QUESTIONS

1. Discuss the advantages of cardioselective β-Blockers (i.e. metoprolol) over nonselective

blockers (i.e. propranolol).
(5 Marks)

2. Compare the mechanism underlying the antihypertensive effect of clonidine and propranolol.

(6 Marks)

3. Explain the pharmacological effects of isoproterenol.

(5 Marks)

4. List FIVE (5) therapeutic uses of direct acting β-agonists. For each use, state ONE drug example
and explain the pharmacological rationale underlying the effectiveness of each drug in each
therapeutic use indicated.
(15 Marks)

5. Phenylephrine is given to a patient for the management of hypotension. List FOUR (4)
potential adverse effects of phenylephrine and explain how it can occur.
(8 Marks)

6. Mr. Kim is a 50-year-old male who came to the outpatient clinic with complain of cold,
presenting nasal congestion. The doctor in charge prescribed phenylephrine 1% nasal spray
to relieve the nasal stuffiness. While checking the prescription, you noticed that Mr. Kim had
a history of heart bypass surgery due to coronary artery disease.
(6 Marks)

i. Predict ONE (1) potential side effect of phenylephrine in a patient with existing coronary
artery disease.

ii. Explain the underlying reason for your answer in (i).

 PHC513: Tutorial 1

7. A 16-year-old patient arrives in the emergency department suffering from an anaphylactic

reaction to peanuts. The patient is having difficulty breathing, has severe urticaria, and is
hypotensive.
(6 Marks)

i. Suggest ONE (1) adrenergic agonist that should be used in treating the patient's potentially
life-threating condition?

ii. Provide the pharmacological rationale for your suggestion in (i). dilate
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¥ If use non-selective beta blockers, they can cause blocking of β2 receptors in the airways.
The blocking will cause bronchoconstriction lead to asthma or COPD.
Heart will pump the blood vigorously and constriction of blood vessels occur during exercise.
Dilation of blood vessels and heart pumping activity will return to normal after exercise. If use Non-
selective β-blockers, they can affect the beta 2 receptors on blood vessel thus interfere with the
vasodilation effect lead to increase in blood pressure.

Use of non-selective blocker causes vasoconstriction of beta 2 receptor blocker

They do not interact with beta 2 and beta 3 receptor in adipose tissue

Metoprolol is most widely used β blockers in the treatment of hypertension. Metoprolol is approximately
equipotent to propranolol in inhibiting stimulation of β1 adrenoceptors such as those in the heart but 50-
to 100-fold less potent than propranolol in blocking β2 receptors. Relative cardioselectivity is
advantageous in treating hypertensive patients who also suffer from asthma, diabetes, or peripheral
vascular disease. Although cardioselectivity is not complete, metoprolol causes less bronchial
constriction than propranolol at doses that produce equal inhibition of β1-adrenoceptor responses.
Metoprolol is extensively metabolized by CYP2D6 with high first-pass metabolism. The drug has a
relatively short half-life of 4–6 hours, but the extended-release preparation can be dosed once daily.
Sustained-release metoprolol is effective in reducing mortality from heart failure and is particularly useful
in patients with hypertension and heart failure.

Action of clonidine: Selectivity only towards alpha 2 receptor

Action of propranolol: Blocks both beta 1 and beta 2 with equal affinity
Antihypertensive effect of clonidine: Stimulation of alpha 2 receptors cause sympathetic nervous system
activity decreases. It leads to:
-decrease total peripheral resistance. Vasodilation occurs to prevent muscles walls of arteries and veins
from becoming narrowed and tightened. Hence, there will be more blood flow through vessels affecting
heart to pump at normal rate.
-decrease heart rate and blood volume
-renal vascular resistance binds to the β1 adrenergic receptor on the heart.
-lower blood pressure
● decreasing the contractility of heart rate which
Antihypertensive effect of propanolol:
leads to reduce of cardiac output.
Decrease cardiac output through negative effects of ● When cardiac output is low, blood pressure also is
inotropic and chronotropic, which results in slower reduce.
heart rate (bradycardia). ● Next, propranolol also helps in inhibiting the release
Low TPR after being used for a long time. of renin that responsible for
- The reduction in cardiac output by beta blocker the conversion of angiotensinogen protein into
leads to decrease in blood pressure angiotensin I, which will further inhibits this product
Inhibit the renin release by the kidney. being converted into angiotensin II by angiotensin
- Reduced circulating plasma renin explains the converting enzyme (ACE).
decreased angiotensin II and aldosterone. ● When angiotensin II is reduced, reabsorption of
- This promotes the renal loss of sodium and water water and sodium increase resulting in decrease of
- Then, diminish arterial pressure blood pressure.
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Isoproterenol is an adrenergic agonist which acts on beta-1 and beta-2 receptors.

When the beta-1 receptor is stimulated by isoproterenol, cardiac contractility
increases, heart rate increases, thus cardiac output increases. When the beta-2
receptor is stimulated, it will cause vasodilation thus decreasing the diastolic and
mean arterial pressure. So isoproterenol acts as a cardiac stimulant for heart block
or severe bradycardia.

- Direct-acting synthetic catecholamine — bind n react -

- Stimulate heart (β1) : increase heart rate, contractility, and cardiac
output
- Dilates the arterioles of skeletal muscle (β2): reduction in
peripheral resistance
- Increase systolic bp slightly, significantly reduces mean arterial and
diastolic bp
- Potent bronchodilator (β2)
- Useful in atrioventricular (AV) block

netwon

selective
1- nonselective

5 uses
,
5 drug example , pharmacological explanation
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Therapeutic uses

① Cardiac stimulant for heart block or severe bradycardia

✗
Terbutaline
Drug example

Isoproterenol ( nonselective )

Pharmacolo i cat rationale .

- It is a beta-1 and beta-2 adrenergic receptor agonist

- Beta-1 adrenergic receptors are primarily abundant in the heart.
- Upon activation, an influx of calcium ions will occur causing the
increase of the action potential at the pacemaker cells.
- The membrane potential will reach the threshold more rapidly thus contributing to the increase of the heart rate.
- The influx of calcium ions in the myocytes will increase its contractility.
 Therapeutic uses

/ Heart failure and Cardiogenic shock

-
Drug example

(
Dobutamine C.selective )
Activates beta1 receptors
i. Stimulation of beta1 receptors leads to increased cardiac
pharmacological rationale .
contractility. It increases the Cardiac output
ii. Blood supply to the body
β1 = ↑ Cardiac contractility, ↑ SV , ↑ HR→↑ CO
Very minimal effect on vascular resistance→slight decrease in
systemic vascular resistance

Therapeutic uses

/ Management of Asthma and COPD

Drug example
-

Albuterol

( Pharma colo i cat rationale .

- Albuterol is a type of short-acting beta-agonist (SABA)

bronchodilator.
- a β2 receptor activated by agonist binding will lead to conversion of ATP to cAMP by adenylyl cyclase
- downstream inhibition of intracellular calcium
- release subsequent bronchial smooth muscle relaxation
- It provides relief from an asthma attack by relaxing the smooth
muscles in your airways.

Therapeutic uses

Management of preterm labour

Drug example

(
Salbutamol

Pharma.co/oc:gical rationale .

relaxes the muscles in the uterus and stops contractions due to labour during this stage of pregnancy. '

- Acts on the beta-2 adrenergic receptors (predominant in myometrium, 80%)

- Activates adenylyl cyclase, increases cAMP which activates the protein kinase A.
- Inactivates MLCK and decrease intracellular calcium, preventing myometrium contraction
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 Therapeutic uses

/ Management of asthma and chronic obstructive pulmonary

disease (COPD)

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9 example

Formoterol

Pharmacolo ICGI rationale .

Formoterol is a type of long-acting beta-agonist (LABA)

bronchodilator
- works like other β2 agonists, causing bronchodilation by relaxing
the smooth muscle in the airway so as to treat the exacerbation of asthma

Reflex bradycardia
When phenylephrine binds to alpha-1 receptors, vasoconstriction will occur and increase in systemic vascular
resistance. The condition will lead to increase in blood pressure that can cause reflex bradycardia due to an
increase in baroreceptor firing rate. Phenylephrine does not have any beta agonist properties to support
cardiac output.
Hypertension
Binding of phenylephrine to alpha-1 receptors can cause vasoconstriction of blood vessels leading to an
increase in arterial blood pressure, and a decrease in heart rate. Thus, hypertension occur.
Restlessness
Phenylephrine is a non-catecholamines adrenergic agonist so it can cross the central nervous system and
causes restlessness, sleeplessness, and anxiety due to its non-polar nature.
Headache
When phenylephrine binds and activates the alpha-1 receptor, vasoconstriction occur that lead to an increase
in systemic vascular resistance and an increase in systolic blood pressure.
i. Myocardial Infarction.

ii. Phenylephrine is a selective α1 adrenoceptor agonist. When phenylephrine binds to the αlpha 1
receptor, vasoconstriction occur. It will affect systemic vascular resistance and systemic blood
pressure to increase while cardiac output is decrease.

i. Epinephrine

ii. Epinephrine act as non-selective adrenergic agonist that function on alpha and beta receptors.
From the case study, the patient had anaphylactic shock that leads to difficulty breathing because
of bronchi constriction and hypotensive. So, alpha 1 adrenergic actions of epinephrine work to
increase peripheral vascular resistance and reverse peripheral vasodilation while also decreasing
angioedema and urticaria. Vasoconstriction occur cause increasing in blood pressure as the patient
had hypotension thus it can counteract. Epinephrine also activate beta 1 and beta 2 receptors. For
beta 1 receptor, the adrenergic effects have positive chronotropic and inotropic effects on the heart,
while the beta 2 adrenergic effects cause bronchodilation and reduction of inflammatory mediator
release from mast cells and basophils. Binding of epinephrine to beta 2 receptors on smooth
muscles of lungs will cause muscle relaxation thus help breathing in normal state. Epinephrine also
gives rapid onset by intravenous injection as anaphylaxis is a severe, potentially life-threatening
allergic reaction which needs fast treatment. The combination of these adrenergic effects help to
reverse the anaphylactic process and make the patient feels better especially breathing.