Pharmacy 4A: Functional Antagonism in Pharmacology

Autacoids and Histamine

• Autacoids are physiologically active substances with localized and brief effects, including histamine, serotonin, and prostaglandins.
• Histamine is a neurotransmitter crucial for allergic reactions and inflammatory responses, affecting multiple body systems.

Histamine Receptors

• Histamine receptors are G-protein coupled receptors, primarily classified into H1 and H2 subtypes.
• H1 receptors activate phospholipase C (Gq pathway), leading to increased inositol trisphosphate (IP3), diacylglycerol (DAG), and calcium.
• H2 receptors stimulate adenylyl cyclase (Gs pathway), increasing cyclic AMP (cAMP) levels.

Histamine's Role in Allergic Reactions

• Histamine is released from mast cells in response to threats (allergies, stress), causing symptoms like redness, pain, difficulty breathing, and swelling.
• Persistent histamine release can result in hives and other allergic conditions.

Histamine Effects on Various Organs

• Lungs: Bronchoconstriction can lead to asthma symptoms.
• Skin: Causes flushing, swelling, and itchiness due to dilation and increased permeability of capillaries.
• Gastrointestinal: Increases gastric acid secretion impacting digestion.

H1 and H2 Antihistamines

• H1 antihistamines are used in allergic and inflammatory conditions and prevent symptoms like itching and swelling.
• 2nd generation H1 antihistamines are more specific to peripheral receptors, resulting in less sedation and CNS depression.
• H2 antihistamines inhibit gastric acid secretion to manage ulcers and heartburn.

Pharmacokinetics of Antihistamines

• Most H1 antihistamines have an onset of 1-3 hours, with effects lasting up to 24 hours.
• Commonly metabolized by CYP450 enzymes, with differing excretion routes (urine for cetirizine, feces for fexofenadine).

Adverse Effects of H1 Antihistamines

• Possible side effects include drowsiness, dry mouth, urinary retention, tachycardia, and increased appetite.

Anaphylactic Shock

• Excessive histamine release during anaphylaxis leads to vasodilation, low blood pressure, and bronchoconstriction, potentially closing the airway.
• Treatment involves epinephrine administration for vasoconstriction and bronchodilation.

Autonomic Nervous System Overview

• Comprises sympathetic, parasympathetic, and enteric systems, with distinct functions and neurotransmitter pathways.
• Sympathetic system primarily engages in 'fight or flight' responses, while the parasympathetic system governs 'rest and digest' functions.

Chemical Signaling Mechanisms

• Endocrine signaling (hormones), direct contact signaling (local mediators), and synaptic signaling (neurotransmitters) are key communication modes in the body.
• Examples include insulin (endocrine), histamine (local mediator), and acetylcholine (neurotransmitter).

Cholinergic System in Autonomic Control

• Acetylcholine functions in both sympathetic and parasympathetic systems, binding to muscarinic receptors for various physiological effects.
• Organophosphate poisoning antagonizes acetylcholine breakdown, requiring antidotes like pralidoxime for reversal.

Assessment Points for Pharmacology

• Knowledge of various drugs affecting acetylcholine synthesis and storage is essential for understanding cholinergic dynamics and their therapeutic implications.### Neuromuscular Blockers
• Serve as skeletal muscle relaxants, inhibiting muscle contraction.
• Non-depolarizing antagonists prevent acetylcholine (ACh) from binding, blocking muscle contraction.
• Depolarizing agonists mimic ACh, causing transient muscle contraction followed by relaxation.
• Succinylcholine is a key example, useful for rapid intubation during anesthesia.

Adverse Drug Reactions

• Common adverse reactions for succinylcholine include hyperthermia, apnea, and hyperkalemia.

Neurotransmitter Storage and Inhibition

• VMAT (Vesicular Monoamine Transporter) stores norepinephrine (NE) and dopamine.
• Metyrosine, reserpine, bretylium, and guanethidine inhibit the synthesis, storage, and release of NE/dopamine.
• Cocaine and tricyclic antidepressants (e.g., amitriptyline) inhibit the reuptake of NE/dopamine.

Cholinesterase Inhibitors

• AChE inhibitors can reverse non-depolarizing neuromuscular blockers by increasing ACh availability.

Adrenergic Receptors

• All adrenergic receptors are G-coupled proteins.
• Alpha receptors (α1, α2) and beta receptors (β1, β2) initiate various physiological responses via different signaling pathways.

Adrenergic Agonists

• Classified into direct (epinephrine, norepinephrine), indirect (cocaine, amphetamine), and mixed (ephedrine).
• Ephedrine has a longer duration and penetrates the CNS, while phenylephrine and oxymetazoline act as decongestants primarily through α1 receptors.
• Salbutamol is a β2 receptor agonist used as a bronchodilator.

Effects of Adrenergic Receptors

• α1: Causes vasoconstriction, increased blood pressure, and mydriasis.
• α2: Inhibits release of norepinephrine and acetylcholine.
• β1: Increases heart rate and myocardial contractility, stimulating renin release.
• β2: Promotes bronchodilation and vasodilation, lowers peripheral resistance, and relaxes uterine smooth muscle.

Adverse Reactions of Adrenergic Agonists

• Potential side effects include arrhythmias, headaches, hyperactivity, insomnia, nausea, and tremors.

Adrenergic Antagonists

• Alpha blockers (e.g., phenoxybenzamine, prazosin) used for treating conditions like pheochromocytoma and hypertension.
• Beta blockers (e.g., metoprolol, propranolol) manage hypertension, angina, cardiac arrhythmias, and prevent migraines without causing postural hypotension.

Anesthesia

• Anesthesia is the administration of drugs to prevent pain during surgical procedures.
• Benzodiazepines are notable for potential side effects such as oral clefts and altered thermoregulation in newborns.

This quiz focuses on functional antagonism in the context of pharmacology, specifically relating to autacoids and histamine receptors. Students will explore the mechanisms and implications of these physiological substances. Prepare to test your knowledge on crucial concepts in pharmacokinetics and pharmacodynamics.