Pharmacology of Adrenergic Receptors

Adrenergic Pharmacology (colo-05)

• Course code: PHR2001M
• Instructor: Professor Terence Herbert
• Email: [email protected]

Resources

• YouTube video: https://www.youtube.com/watch?v=KtmV-yMDYPI
• YouTube video: https://www.youtube.com/watch?v=41Xloc_vvX8
• Pharmacology textbook resource: https://www.youtube.com/watch?v=FCOJq_G-1TE
• Additional resource: http://www.uky.edu/~mtp/pha824ar/PHA824ar.html

Intended Learning Outcomes

• Name the autonomic nervous system divisions.
• Describe the role of the sympathetic nervous system and its communication pathways.
• Describe the synthesis location of noradrenaline (norepinephrine).
• Describe the classification, structure, signalling, and function of adrenergic receptors.
• Provide examples of drugs targeting adrenergic receptors.
• Understand sympatholytics and sympathomimetics, along with examples.

The Nervous System

• Composed of central nervous system (CNS) and peripheral nervous system (PNS).
• The PNS is subdivided into efferent and afferent pathways.
• Efferent system comprises:
  • Autonomic nervous system (ANS): Controls involuntary bodily functions, regulates specific functions (e.g., breathing, circulation), and innervates smooth muscle, cardiac muscle, glands, and GI tract neurons.
    • Subdivided into:
      • Parasympathetic nervous system
      • Sympathetic nervous system
      • Enteric nervous system
  • Somatic nervous system (SNS): Controls skeletal muscle movement

Parasympathetic and Sympathetic Systems

• Parasympathetic system: "Feed and breed" / "rest and digest" function.
• Sympathetic system: "Fight or flight" response.

PNS: Comparison of Somatic and Autonomic Nervous Systems

• Somatic nervous system: Uses acetylcholine (ACh) as a neurotransmitter, directly innervates skeletal muscles.
• Autonomic nervous system: Uses both acetylcholine and norepinephrine as neurotransmitters.

Sympathetic Neuronal Signalling

• Norepinephrine released from adrenergic neurons.
• Adrenaline (epinephrine) and noradrenaline (15%) released from adrenal glands into the bloodstream.
• Norepinephrine and epinephrine bind to adrenergic receptors on target organs/tissues to control/mediate sympathetic nervous system effects.

Adrenergic Pharmacology

• Study of drugs affecting adrenaline or noradrenaline actions.
• Many such drugs target adrenergic receptors/adrenoceptors, which are G protein-coupled receptors.

Noradrenaline and Adrenaline

• Catecholamines: Include noradrenaline and adrenaline.
• Catecholamines contain a catechol moiety (a benzene ring with two adjacent hydroxyl groups) and an amine side chain.
• Synthesized from tyrosine.
• Noradrenaline synthesized and released from noradrenergic neurons and adrenal medulla.
• Adrenaline is the primary hormone synthesized and released from the adrenal medulla.

Adrenergic Receptors

• Subdivided into alpha and beta by Raymond P. Ahlquist.
• Distinction based on organ sensitivities to catecholamines (e.g., adrenalin, noradrenalin, and isoprenaline).

Adrenaline/Noradrenaline/Isoprenaline Effects

• Differentiate effects on alpha and beta receptors.
• Different potency in regard to receptors.

Beta1/Beta2 Receptors

• Specific effects on heart muscle cells and airway smooth muscle cells are regulated by their respective receptors.
• Ability to activate the receptors depends on their structure and concentration.

Beta Receptor Subtypes

• Different subtypes exist for beta receptors.
• Their effects vary in heart, airway smooth muscle, and other tissues.
• Corresponding agonist/antagonist drugs for these subtypes exist.

Adverse Effects

• Stimulation of beta-2 receptors elsewhere in the body produces adverse effects, such as muscle tremors, tachycardia, palpitations, etc. Related to their systemic nature of action.

Beta Blockers

• Antagonists to beta 1, blocking receptor activation.
• Used to treat various cardiac conditions.

Alpha 2 Agonists

• Act on presynaptic alpha-2 receptors, reducing noradrenaline release.
• Used in hypertension treatment.

Alpha 1 Blockers

• Antagonists to alpha-1 receptors.
• Used to treat hypertension and other conditions.

Drugs Acting on Adrenergic Nervous System

• Sympathomimetics: Mimic sympathetic nervous system effects.
• Sympatholytics: Inhibit sympathetic nervous system effects.
• Direct acting drugs: Affect adrenergic receptors directly.
• Indirect acting drugs: Influence adrenergic receptors by altering neurotransmitter levels.
• Mixed acting drugs: Have both direct and indirect effects.

Pharmacological Manipulation of Adrenergic Transmission

• Mechanism of action from indirect acting drugs focusing on neurotransmitter synthesis, storage, release, and receptor binding.

Common Prescribed Direct Acting Sympathomimetics

• Drugs used for treating asthma, cardiac arrest, and low blood pressure, etc. (e.g., pseudoephedrine, salbutamol).
• Differentiating drug actions by their receptor selectivity (e.g., selective beta2 agonists).

Direct Acting Sympatholytics for Hypertension

• Drugs (e.g., doxazosin, prazosin, terazosin) used for treating hypertension, as alpha-1 blockers.

Sympathomimetics and Sympatholytics

• Detailed classification and examples of different types of drugs influencing the adrenergic system.

Adrenergic Receptor Signalling

• Specific mechanisms describing receptor types, G-protein subtypes, and intracellular signaling pathways activated by adrenergic receptors.
• Includes information on the various signalling pathways from different receptor types (alpha 1, alpha 2, beta 1, beta 2, beta 3).

SABAs and LABAs – Beta2 Adrenoreceptor Activation

• Explain the mechanism of short-acting (SABAs) and long-acting beta2-agonists (LABAs).

Important Note

• This is a summary of the provided information and may not cover every detail.

This quiz explores the functions and effects of adrenergic receptors in the cardiovascular and smooth muscle systems. Test your knowledge on beta and alpha receptor actions, drug classifications, and mechanisms like cAMP in smooth muscle cells.