PHARMACOLOGY ASSIGNMENT #02

SUBMITTED BY: Muhammad Abu Huraira

SUBMITTED TO: Hafiz Bilal
SAP I’D: 70138381 (3B)

TOPIC:-
Drugs effecting on autonomic nervous system
(ANS)
INTRODUCTION TO ANS:
Definition and division of ANS:
The autonomic nervous system is a component of the peripheral nervous system that regulates
involuntary physiologic processes including heart rate, blood pressure, respiration, digestion, and
sexual arousal. It subdivides into three systems:
• Sympathetic nervous system
• Parasympathetic nervous system
• Enteric system

Functions and regulations of ANS:

• The sympathetic nervous system prepares the body for action and stress responses, often
referred to as the "fight or flight" system. It increases heart rate, dilates the airways,
redirects blood flow to muscles, and releases stress hormones like adrenaline.
• The parasympathetic nervous system promotes relaxation and recovery, known as the
"rest and digest" system. It slows heart rate, constricts airways, stimulates digestion, and
conserves energy.
METOPROLOL (AN OVERVIEW):
Definition:
Metoprolol is a medication that belongs to a class of drugs known as beta-blockers. It is
commonly used to treat various cardiovascular conditions.

Metoprolol mainly effects on Sympathetic nervous system:

Metoprolol is a beta-blocker, and its primary mode of action is to affect the sympathetic nervous
system (SNS). By blocking the action of the SNS, metoprolol reduces heart rate and lowers
blood pressure. This makes it a commonly prescribed medication for conditions like high blood
pressure, angina, and certain heart rhythm disorders.

Classification of metoprolol:
• Metoprolol is a beta-adrenergic receptor blocker, specifically a beta-1 receptor blocker. It
selectively blocks the beta-1 adrenergic receptors in the heart and blood vessels.
• Metoprolol is primarily classified as an anti-hypertensive (blood pressure-lowering)
medication. It is used to treat hypertension (high blood pressure) to reduce the workload
on the heart and lower blood pressure.
• Metoprolol is available in different pharmaceutical formulations, including immediate-
release (IR) and extended-release (ER) versions. These formulations determine how
quickly the medication is released into the body and affect the dosing regimen.

Pharmacological properties of metoprolol:

• Selective Beta-1 Blockade
• Negative Chronotropic Effect
• Negative Inotropic Effect
• Antiarrhythmic Effect
• Antihypertensive Effect
• Reduction of Myocardial Oxygen Demand
MECHANISM OF ACTION ON THE ANS:
Role of beta adrenergic receptors in the ANS:
Beta adrenergic receptors are an integral part of the autonomic nervous system (ANS). They play
a crucial role in regulating various physiological processes in the body. There are primarily two
subtypes of beta adrenergic receptors, beta-1 (β1) and beta-2 (β2), each with specific functions:
• Beta-1 Adrenergic Receptors: Predominantly found in the heart (especially in the
sinoatrial node and atrioventricular node), beta-1 receptors are responsible for increasing
heart rate and the force of contraction. Activation of these receptors by the
neurotransmitter norepinephrine from sympathetic nerve fibers or epinephrine from the
adrenal glands leads to increased cardiac output.
• Beta-2 Adrenergic Receptors: Beta-2 receptors are found in various tissues, including
smooth muscles in the bronchi of the lungs, blood vessels, and skeletal muscle.
Activation of these receptors causes bronchodilation, vasodilation, and relaxation of
smooth muscle. This results in increased airflow in the lungs, decreased peripheral
resistance in blood vessels, and increased blood flow to skeletal muscles.

How metoprolol selectively affects beta-1 adrenergic receptors:

Here’s how it achieves this selectivity:
• Receptor Specificity: Metoprolol has a higher affinity for beta-1 adrenergic receptors
compared to beta-2 adrenergic receptors. This means that it is more likely to bind to and
block the activity of beta-1 receptors in a competitive manner.
• Structure-Activity Relationship: The chemical structure of metoprolol is designed in a
way that enhances its selectivity for beta-1 receptors. It contains a side chain that fits well
into the binding site of beta-1 receptors, while it is less effective at binding to the binding
 sites of beta-2 receptors. This structural specificity allows metoprolol to preferentially
block the effects of norepinephrine or epinephrine at beta-1 receptors.
• Therapeutic Dose: In clinical practice, metoprolol is typically prescribed at doses that
primarily affect beta-1 receptors in the heart. At these doses, it helps reduce heart rate and
cardiac contractility, making it useful for conditions like hypertension, angina, and
certain heart rhythm disorders without causing significant bronchoconstriction or other
side effects associated with beta-2 receptor blockade.
• Beta-Blocker Classification: Metoprolol is classified as a "selective" or
"cardioselective" beta-blocker because of its preference for beta-1 receptors. While no
beta-blocker is entirely specific, metoprolol is one of the agents that comes closest to
selective beta-1 blockade.

Metoprolol’s influence on heart rate, cardiac output, and blood

pressure:
Here's how metoprolol affects these parameters:
• Heart Rate: Metoprolol primarily acts on beta-1 adrenergic receptors in the heart. By
blocking the effects of norepinephrine and epinephrine on these receptors, it reduces the
heart rate. This effect is particularly useful in conditions such as tachycardia (high heart
rate) and certain types of arrhythmias, where slowing down the heart rate can be
therapeutic.
 • Cardiac Output: Cardiac output is the amount of blood the heart pumps in one minute
and is determined by heart rate and stroke volume (the amount of blood ejected with each
heartbeat). Metoprolol, by reducing heart rate and myocardial contractility (the strength
of heart muscle contractions), decreases cardiac output. This can be advantageous in
conditions where a lower cardiac output is desired, such as in the management of heart
failure or angina, to reduce the heart’s workload and oxygen demand.
• Blood Pressure: Metoprolol lowers blood pressure by several mechanisms:
Reduced Heart Rate: Slowing the heart rate decreases the force with which the heart
pumps blood, resulting in decreased systolic blood pressure.
Reduced Contractility: Metoprolol reduces the strength of each heartbeat, which
decreases the pressure within the arteries.
Vasodilation: Metoprolol may also cause mild vasodilation (relaxation of blood vessels),
further lowering blood pressure.

CLINICAL APPLICATIONS OF METOPROLOL:

Here are the expected outcomes for some of the conditions for which metoprolol is commonly
prescribed:
• Hypertension: Metoprolol is often prescribed to lower blood pressure in individuals with
hypertension. It reduces the workload on the heart and helps the heart to beat more
regularly.
• Angina (Chest Pain): Metoprolol aims to relieve angina symptoms, reduce the
frequency and severity of chest pain, and improve the patient's quality of life.
• Arrhythmias (Irregular Heart Rhythms): Metoprolol is employed to control certain
irregular heart rhythms (arrhythmias) by regulating the electrical impulses in the heart.
• Heart Failure: Metoprolol, when used in heart failure, can improve the heart's pumping
ability, reduce symptoms such as shortness of breath and fatigue, and enhance overall
heart function.
• Post-Myocardial Infarction (Post-Heart Attack) Care: It is often used in the
management of patients who have had a heart attack to reduce the risk of future heart-
related events.
• Migraine Prevention: Metoprolol is expected to reduce the frequency, severity, and
duration of migraines in individuals who suffer from recurrent migraines.
• Essential Tremor: The expected outcome is a reduction in the severity of essential
tremor, leading to improved control and reduced impact on daily activities.
• Anxiety Disorders: In cases of anxiety, metoprolol may help control physical symptoms
such as a rapid heartbeat, contributing to a sense of calm and reduced physical anxiety
symptoms.
• Thyrotoxicosis: Metoprolol can help alleviate some of the symptoms associated with
hyperthyroidism, such as a rapid heart rate and palpitations.
 • Atrial Fibrillation and Atrial Flutter: The therapeutic outcome is the control of heart
rate and, in some cases, prevention of symptoms associated with irregular heart rhythms.
• Hypertrophic Cardiomyopathy: Metoprolol can reduce symptoms and improve
exercise tolerance in individuals with this condition, as well as decrease the risk of
arrhythmias.
• Preoperative Preparation: Metoprolol may be used to stabilize heart rate and blood
pressure before surgery to reduce the risk of perioperative cardiac events.

SIDE EFFECTS AND ADVERSE REACTIONS OF

METOPROLOL:
Common Side effects:
• Fatigue: Many people experience mild to moderate tiredness when taking metoprolol,
especially when they first start the medication. This can improve over time as the body
adjusts.
• Dizziness or Lightheadedness: Some individuals may feel dizzy or lightheaded when
standing up quickly, especially at the beginning of treatment.
• Slow Heart Rate (Bradycardia): Metoprolol can slow the heart rate. While this is the
desired effect in some cases, an excessively slow heart rate can cause symptoms like
fatigue and dizziness.
• Cold Extremities: Some people may notice that their hands and feet feel cold or numb
while taking metoprolol.
• Gastrointestinal Distress: Side effects like nausea, diarrhea, or abdominal discomfort
can occur.
• Sleep Disturbances: Metoprolol might affect sleep patterns in some individuals, leading
to difficulty falling asleep or staying asleep.

Adverse Reactions (Less Common, but Potentially Serious):

• Allergic Reactions: In rare cases, metoprolol can cause allergic reactions, such as skin
rash, itching, swelling, severe dizziness, or difficulty breathing. Seek immediate medical
attention if you experience these symptoms.
• Worsening of Heart Conditions: While metoprolol is often used to treat heart
conditions, it can, in rare cases, worsen certain conditions, leading to heart block or heart
failure.
• Bronchospasm: Metoprolol can cause bronchospasm in individuals with underlying
respiratory conditions, leading to wheezing and difficulty breathing.
• Mental/Mood Changes: Some people may experience changes in mood, such as
depression or vivid dreams, while taking metoprolol.
• Changes in Blood Sugar: Metoprolol can mask the symptoms of low blood sugar,
making it harder to recognize in people with diabetes.
 • Peripheral Vascular Disorders: Rarely, metoprolol can cause peripheral vascular
disorders leading to symptoms such as leg pain or changes in skin color.
• Interactions: Metoprolol can interact with other medications, potentially causing adverse
effects or reducing the effectiveness of other drugs.

CONCLUSION:
Metoprolol’s action on the ANS makes it a valuable medication for conditions such as
hypertension, angina, arrhythmias, and heart failure by modulating heart rate, blood pressure,
and cardiac function.

REFERENCES:
• “Autonomic Nervous System in Physiology and Pharmacology” by Clinton B. Wright
–
• “Basic and Clinical Pharmacology” by Bertram G. Katzung and Susan B. Masters –
• “Clinical Pharmacology Made Ridiculously Simple” by James Olson –