Pharmacology Essentials: Psychoactive Drugs & Hypertension Management

Posted on Aug 25, 2025 in Medicine & Health

Psychoactive Substances Pharmacology

1. Lysergic Acid Diethylamide (LSD)

Pharmacological Effects

• Altered Consciousness: Produces significant changes in perception and awareness.
• Euphoria: Induces feelings of intense happiness.
• Increased Sensory Awareness: Heightens sensory perception (sight, sound, touch).
• Sympathomimetic Activity:
  • Pupillary Dilation
  • Increased Blood Pressure
  • Tachycardia (increased heart rate)

Adverse Effects

• “Bad Trips”: Severe anxiety, visual disturbances, intense depression.
• Tolerance: Develops rapidly with repeated use, but dissipates quickly; no significant withdrawal syndrome.
• Flashbacks: Hallucinogenic Persisting Perception Disorder (HPPD).

Effects on Consciousness

• LSD affects the 5-Dimensional Altered States of Consciousness Rating Scale, which quantifies subjective experiences of psychedelics.

2. Methylenedioxymethamphetamine (MDMA, “Ecstasy”)

Pharmacological Effects

• Synthetic Stimulant: Related to amphetamines with psychedelic effects.
• Low Dose Effects: Tachycardia, dry mouth, jaw clenching, muscle aches.
• High Dose Effects: Visual hallucinations, agitation, hyperthermia, panic attacks.
• Psychological Effects: Euphoria, increased sociability, relaxation.

Abuse Potential

• Low Abuse Potential: Pleasurable effects diminish with repeated use, while adverse effects increase.

3. Cannabinoids

Key Components

• THC (Δ9-Tetrahydrocannabinol): Active psychoactive component in cannabis.
• CBD (Cannabidiol): Non-psychoactive; used for medicinal purposes.

Cannabis Forms

• Marijuana: Dried leaf material (THC content has increased from ~3% in the 1980s to ~15% today).
• Hashish: Extracted resin from cannabis (up to 60% THC).
• Cannabis Oil: Extract dissolved in oil.
• Edibles: Foods/drinks containing cannabis extracts.
• Tinctures/Sprays: Cannabis extract in a solvent, often alcohol.
• Creams/Salves: Topical applications containing cannabis extracts.

Mechanism of Action

• Endocannabinoid System (ECS): Comprises CB1 and CB2 receptors.
  • CB1: Predominantly in the brain; involved in central nervous system (CNS) functions.
  • CB2: Predominantly in the periphery; involved in immune functions.
• Endocannabinoids: Naturally occurring in the body (e.g., AEA, 2-AG).

Physiological Roles

• Mood and Emotion: Dysfunction in ECS linked to mood disorders.
• Pain Regulation: Endocannabinoids lower sensory neuron excitability.
• Appetite: Agonists increase food intake.

Pharmacodynamics of THC

• CB1 Partial Agonist: Inhibits neurotransmitter release.
• Bimodal Effects: CNS depression and stimulation.
• Psychotropic Effects: Impaired cognitive functions, perception, and increased hunger.

Medicinal Uses of THC

• Antiemetic: Suppresses nausea/vomiting.
• Muscle Relaxation: Reduces spasticity (e.g., in multiple sclerosis).
• Intraocular Pressure: Treatment for glaucoma.
• Sativex: Combination of THC and CBD for pain relief.

4. Nicotine

Overview

• Naturally Occurring Substance: Found in tobacco; one of the most used psychoactive drugs.
• Absorption: Rapidly absorbed in the body; approximately 20% absorbed from cigarette smoke.

Mechanism of Action

• CNS Stimulation: Enhances cognitive function, attention, and memory.
• Peripheral Nervous System: Facilitates impulse transmission.

Pharmacological Effects

• Short-Term Use: Mild euphoria, increased concentration, relaxation.
• Long-Term Use: Linked to cardiovascular disease, lung disease, and various cancers.

Dependence and Withdrawal

• Withdrawal Symptoms: Irritability, anxiety, impatience, difficulty concentrating, increased appetite.
• Nicotine Replacement Therapies: Used to alleviate withdrawal symptoms.
• High Abuse Potential: Strong reinforcing properties.

Blood Pressure Regulation & Antihypertensive Agents

Blood Pressure Regulation Mechanisms

Renal Blood Volume-Pressure Control

Renin-Angiotensin-Aldosterone System (RAAS)

• Kidneys secrete renin, which converts α2-globulin to angiotensin I. Angiotensin-converting enzyme (ACE) then converts angiotensin I to angiotensin II.
• Angiotensin II increases blood pressure via:
  • Vasoconstriction: Increases peripheral vascular resistance (PVR).
  • Aldosterone Secretion: Increases sodium (Na+) and water retention, increasing blood volume.

Baroreceptor Reflexes

• Detect changes in blood pressure.
• Decreased blood pressure leads to decreased renal blood flow, which in turn increases renin secretion.

Hypertension

Definition

• A pathological condition characterized by abnormally high arterial blood pressure.

Classification

• Normotensive: < 130/85 mmHg
• High normal: 130-139/85-89 mmHg
• Hypertension Stage I: 140-159/90-99 mmHg
• Stage II: 160-179/100-109 mmHg
• Stage III: 180-209/110-119 mmHg
• Stage IV: > 210/120 mmHg

Etiology

• Approximately 90% is essential hypertension (of unknown cause).
• Approximately 10% is secondary hypertension (due to a known cause).

Antihypertensive Agents

Mechanisms of Action

• Decrease blood volume.
• Decrease sympathetic tone.
• Decrease vascular smooth muscle tone.
• Decrease angiotensin concentration.

Major Categories of Antihypertensive Agents

Diuretics

• Mechanism: Decrease sodium (Na+) reabsorption, leading to decreased blood volume.
• Types:
  • Thiazides (e.g., hydrochlorothiazide).
  • Loop Diuretics (e.g., furosemide) for severe hypertension.
• Adverse Effects: Dehydration, electrolyte imbalances, gout, hyperglycemia.

Sympathetic Blocking Agents

Centrally Acting

• Methyldopa, Clonidine: Decrease norepinephrine (NE) release, leading to decreased sympathetic outflow and reduced peripheral vascular resistance (PVR).
• Adverse Effects: Sedation, impaired concentration.

Peripherally Acting

• Reserpine: Decreases norepinephrine (NE) release, resulting in decreased cardiac output (CO) and PVR.
• Propranolol (non-selective β-blocker): Decreases heart rate and myocardial contractility.
• Prazosin (α1 blocker): Induces vasodilation, leading to decreased blood pressure (BP).
• Adverse Effects: Sedation, depression, worsening asthma.

Vasodilators

• Mechanism: Directly relax vascular smooth muscle, leading to decreased PVR.
• Types:
  • Hydralazine (oral): Arterial dilation.
  • Sodium Nitroprusside (IV): Arterial and venous dilation for emergencies.
  • Calcium Channel Blockers (e.g., Verapamil): Inhibit calcium (Ca++) influx, causing peripheral vasodilation.
• Adverse Effects: Reflex tachycardia, excessive hypotension, cardiac depression.

ACE Inhibitors

• Mechanism: Inhibit the conversion of angiotensin I to angiotensin II, thereby decreasing vasoconstriction and aldosterone secretion.
• Examples: Captopril, Enalapril.
• Adverse Effects: Persistent dry cough, angioedema, hyperkalemia.

Clinical Management of Hypertension

Essential Hypertension

• A chronic disease requiring lifelong management.

Step Therapy

• Lifestyle Changes: Low-salt diet, weight reduction.
• Monotherapy: Start with a single agent (e.g., β-blocker or thiazide).
• Combined Therapy: Use multiple agents to reduce side effects and enhance efficacy.

Important Notes

• Blood Pressure Equation: BP = Cardiac Output (CO) x Peripheral Vascular Resistance (PVR).
• Compensatory Mechanisms: Baroreceptor reflexes and RAAS may counteract antihypertensive effects.
• Monitor for Adverse Effects: Be aware of potential side effects associated with each class of antihypertensive agents.

Quick Reference Table of Antihypertensive Agents