Medications and Their Effects on the Human Body: A Comprehensive Review

Posted on Dec 26, 2024 in Biology

Histamine: Mechanisms, Effects, and Therapeutic Uses

Mechanism of Action

Histamine is a biogenic amine acting through H1, H2, H3, and H4 receptors:

1. H1 receptors: Mediate allergic responses, bronchoconstriction, vasodilation, and increased vascular permeability.
2. H2 receptors: Stimulate gastric acid secretion in the stomach.
3. H3 receptors: Regulate neurotransmitter release in the central nervous system.
4. H4 receptors: Modulate immune cell recruitment and inflammation.

Adverse Effects

Histamine release or excessive levels can cause:

• Allergic reactions (rash, anaphylaxis).
• Flushing, itching, and hypotension (vasodilation).
• Gastric discomfort or ulcers (excess acid secretion).
• Bronchospasm and breathing difficulties (in asthma).

Therapeutic Uses

Histamine itself has limited clinical use but indirectly influences treatments:

1. Histamine agonists: Rarely used in diagnostic tests for gastric acid secretion.
2. Antihistamines: H1 antagonists treat allergies, while H2 antagonists manage acid reflux and ulcers.

Histamine’s role in immune responses and neurotransmission also makes it a target in emerging therapies for autoimmune and neurological disorders.

Local Anesthetics: Uses and Administration Techniques

Uses of Local Anesthetics

Local anesthetics are used to block nerve conduction and provide temporary loss of sensation in a specific area. Common applications include:

1. Minor surgical procedures (e.g., suturing wounds).
2. Dental procedures.
3. Diagnostic interventions (e.g., lumbar puncture).
4. Pain relief in childbirth (e.g., epidural).

Technique of Administration

1. Preparation: Clean and disinfect the injection site.
2. Dosage: Select an appropriate local anesthetic (e.g., lidocaine) and determine the dose based on patient factors.
3. Injection: Administer near the nerve supplying the area (nerve block) or in the tissue around the targeted area (infiltration).
4. Aspiration: Aspirate before injecting to avoid intravascular injection.
5. Monitoring: Observe the patient for adverse reactions (e.g., allergies, toxicity).

Examples: Lidocaine, Bupivacaine, and Procaine are commonly used.

Sumatriptan: Treatment for Migraines and Cluster Headaches

Mechanism of Action

Sumatriptan is a 5-HT1B/1D receptor agonist that:

1. Vasoconstriction: Constricts cranial blood vessels, reversing vasodilation linked to migraines.
2. Inhibits Neurotransmitter Release: Reduces the release of inflammatory neuropeptides like CGRP (calcitonin gene-related peptide).
3. Modulates Pain Pathways: Blocks pain signals in the trigeminal nerve.

Adverse Effects

1. Chest tightness or pressure (rarely cardiac ischemia).
2. Dizziness, fatigue, or drowsiness.
3. Nausea or abdominal discomfort.
4. Local irritation (e.g., at injection sites).
5. Rare: Serotonin syndrome when combined with serotonergic drugs.

Therapeutic Uses

1. Acute Migraine Attacks: First-line treatment for moderate to severe migraines.
2. Cluster Headaches: Provides rapid relief.

Sumatriptan is not used for migraine prophylaxis and must be taken early during headache onset for maximum efficacy.

Paracetamol (Acetaminophen): Pain Relief and Fever Reduction

Mechanism of Action

1. Analgesic: Inhibits cyclooxygenase (COX) enzymes in the central nervous system, reducing prostaglandin synthesis, which mediates pain.
2. Antipyretic: Acts on the hypothalamic heat-regulating center to lower body temperature.
3. Minimal Anti-inflammatory Effect: Weak peripheral COX inhibition, so it lacks significant anti-inflammatory activity.

Adverse Effects

1. Hepatotoxicity: Overdose can cause liver damage due to accumulation of the toxic metabolite NAPQI.
2. Allergic Reactions: Skin rash or hypersensitivity.
3. Renal Toxicity: Rare, with chronic use.
4. Gastrointestinal Distress: Minimal compared to NSAIDs.

Therapeutic Uses

1. Pain Relief: Effective for mild to moderate pain (e.g., headaches, dental pain, osteoarthritis).
2. Fever Reduction: Commonly used as an antipyretic.
3. Alternative to NSAIDs: Suitable for patients with gastrointestinal risks or aspirin sensitivity.

Paracetamol is widely used due to its safety profile at therapeutic doses but requires caution to avoid overdose.

Ergotamine: Treatment for Migraines and Vascular Headaches

Mechanism of Action (MOA) of Ergotamine

1. Serotonin Receptor Activity: Partial agonist at 5-HT1B and 5-HT1D receptors. Causes vasoconstriction of dilated cranial blood vessels, relieving migraine pain.
2. Neurotransmitter Modulation: Inhibits the release of inflammatory neuropeptides like calcitonin gene-related peptide (CGRP), reducing neurogenic inflammation.
3. Alpha-Adrenergic Receptor Action: Partial agonist/antagonist at alpha-adrenergic receptors. Induces vasoconstriction in peripheral and cranial blood vessels.
4. Central Effects: May act on central serotonin pathways involved in pain modulation and vascular tone.
5. Uterotonic Effect: Stimulates uterine smooth muscle, leading to contractions (used in specific obstetric scenarios).

Adverse Drug Reactions (ADRs)

1. Common ADRs: Nausea and vomiting (due to its effect on the chemoreceptor trigger zone). Dizziness.
2. Serious ADRs: Peripheral vasospasm, which can lead to ischemia or gangrene, especially in patients with peripheral vascular disease. Hypertension. Paresthesia (tingling or numbness in extremities). Chest pain or tightness due to coronary vasoconstriction.
3. Ergotism: Prolonged use or overdose can cause severe vasoconstriction, leading to gangrene and even death.

Uses

1. Primary Use: Acute treatment of migraines, especially those associated with vascular headaches. Effective in cluster headaches.
2. Rare Use in Obstetrics: Used postpartum to control bleeding due to its uterotonic effects (rarely, and only under strict supervision).
3. Caution: Ergotamine is not used for prophylaxis of migraines.

Aspirin: Anti-inflammatory, Antipyretic, Analgesic, and Antiplatelet Agent

Mechanism of Action

1. COX Inhibition: Irreversibly inhibits cyclooxygenase (COX-1 and COX-2) enzymes, reducing prostaglandin and thromboxane synthesis.
2. Anti-inflammatory: Decreases prostaglandins involved in inflammation.
3. Antipyretic: Lowers prostaglandins in the hypothalamus to reduce fever.
4. Analgesic: Reduces pain by decreasing prostaglandin-mediated sensitization of nociceptors.
5. Antiplatelet: Inhibits thromboxane A2, preventing platelet aggregation.

Adverse Effects

1. Gastrointestinal (GI): Dyspepsia, ulcers, and bleeding due to COX-1 inhibition.
2. Bleeding: Increased risk due to impaired platelet function.
3. Reye’s Syndrome: Rare but serious in children with viral infections.
4. Allergic Reactions: Bronchospasm or anaphylaxis, especially in aspirin-sensitive asthma.
5. Renal Toxicity: Reduced renal blood flow with long-term use.

Therapeutic Uses

1. Pain and Fever: Mild to moderate pain and pyrexia.
2. Anti-inflammatory: Used in conditions like rheumatoid arthritis and osteoarthritis.
3. Antiplatelet Therapy:
   • Prevention of myocardial infarction and stroke.
   • Post-cardiovascular interventions (e.g., stenting).
4. Kawasaki Disease: To reduce inflammation and thrombosis.

Aspirin is widely used but requires caution in patients with GI or bleeding risks.

Arthritis Drugs: Managing Pain and Inflammation

Common Drugs for Arthritis

1. NSAIDs (e.g., Ibuprofen, Naproxen)
2. Corticosteroids (e.g., Prednisone)
3. Disease-Modifying Anti-Rheumatic Drugs (DMARDs) (e.g., Methotrexate)
4. Biologic DMARDs (e.g., Adalimumab, Etanercept)
5. Analgesics (e.g., Paracetamol)

Mechanism of Action

1. NSAIDs: Inhibit COX enzymes, reducing prostaglandins to alleviate pain and inflammation.
2. Corticosteroids: Suppress immune responses by inhibiting cytokine production and reducing inflammation.
3. Methotrexate: Interferes with folate metabolism to suppress immune cell proliferation and reduce inflammation.
4. Biologics: Target specific inflammatory mediators like TNF-alpha, IL-1, or IL-6.

Therapeutic Uses

1. NSAIDs: Symptomatic relief of pain and inflammation in osteoarthritis and rheumatoid arthritis.
2. Corticosteroids: Acute flare-ups of arthritis or severe inflammation.
3. DMARDs: Long-term treatment to slow rheumatoid arthritis progression.
4. Biologics: For patients unresponsive to conventional DMARDs in autoimmune arthritis.
5. Paracetamol: For mild arthritis pain when inflammation is not prominent.

Adverse Effects

1. NSAIDs: GI irritation, ulcers, bleeding, renal toxicity.
2. Corticosteroids: Weight gain, osteoporosis, hypertension, hyperglycemia.
3. Methotrexate: Hepatotoxicity, bone marrow suppression, GI upset.
4. Biologics: Increased risk of infections, injection site reactions, malignancies.
5. Paracetamol: Hepatotoxicity at high doses.

Combination therapy is often used for better symptom control and disease management.

Drugs for Gout: Acute and Chronic Management

Drugs to Treat Acute Gout

• NSAIDs: Indomethacin, Naproxen, Diclofenac. Inhibit prostaglandin synthesis, reducing inflammation.
• Colchicine: Disrupts microtubule formation, inhibiting leukocyte migration and phagocytosis in joints.
• Corticosteroids: Prednisolone. Suppress inflammation when NSAIDs/colchicine are contraindicated.

Drugs to Prevent Gout (Chronic Gout)

• Xanthine Oxidase Inhibitors: Allopurinol, Febuxostat. Decrease uric acid synthesis by inhibiting xanthine oxidase.
• Uricosuric Agents: Probenecid, Sulfinpyrazone. Increase renal excretion of uric acid by inhibiting its reabsorption in renal tubules.
• Uricase Enzymes: Pegloticase, Rasburicase. Convert uric acid to allantoin, a more soluble and easily excreted form.

Mechanism of Action (MOA)

1. NSAIDs: Inhibit cyclooxygenase (COX) enzymes to reduce inflammation and pain.
2. Colchicine: Prevents neutrophil activation and migration to the site of inflammation.
3. Xanthine Oxidase Inhibitors: Block conversion of xanthine to uric acid, lowering serum uric acid levels.
4. Uricosuric Agents: Promote uric acid excretion by decreasing its tubular reabsorption.
5. Uricase Enzymes: Oxidize uric acid to a soluble form (allantoin) for excretion.

Adverse Drug Reactions (ADRs)

• NSAIDs: Gastric irritation, bleeding, renal impairment.
• Colchicine: Diarrhea, abdominal pain, bone marrow suppression.
• Allopurinol/Febuxostat: Skin rash, hypersensitivity, hepatotoxicity.
• Probenecid: Renal stones, GI upset.
• Pegloticase/Rasburicase: Allergic reactions, hemolysis in G6PD deficiency.

Uses

1. Acute gout attack: NSAIDs, Colchicine, or Corticosteroids.
2. Chronic gout: Allopurinol, Febuxostat, Probenecid.
3. Severe refractory gout: Pegloticase or Rasburicase.

Ipratropium: An Anticholinergic for Respiratory Conditions

Classification

• Drug Class: Anticholinergic (Muscarinic receptor antagonist).
• Type: Short-acting muscarinic antagonist (SAMA).

Mechanism of Action (MOA)

1. Muscarinic Receptor Blockade:
   • Blocks M3 receptors on airway smooth muscles.
   • Inhibits acetylcholine-mediated bronchoconstriction, leading to bronchodilation.
2. Reduced Mucus Secretion: Decreases mucus secretion in the respiratory tract by blocking parasympathetic stimulation.
3. Onset and Duration:
   • Onset: 15–30 minutes.
   • Duration: 4–6 hours.

Adverse Drug Reactions (ADRs)

1. Dry mouth.
2. Cough and throat irritation.
3. Nausea.
4. Rare: Blurred vision (if sprayed in eyes), urinary retention.
5. Allergic reactions (e.g., rash, itching).

Uses

1. Chronic Obstructive Pulmonary Disease (COPD): First-line therapy for bronchodilation.
2. Asthma: Used as an add-on therapy for acute exacerbations or in patients intolerant to beta-agonists.
3. Rhinorrhea (runny nose): Used intranasally for symptomatic relief.

Important Notes

• Often combined with beta-agonists like albuterol (e.g., in Duoneb) for synergistic effects.
• Avoid in patients with a history of hypersensitivity to atropine or similar drugs.

Anti-Emetic Drugs: Managing Nausea and Vomiting

Classification

1. 5-HT3 Receptor Antagonists
   • Examples: Ondansetron, Granisetron.
   • MOA: Block 5-HT3 receptors in the CTZ and GI tract.
2. D2 Receptor Antagonists
   • Examples: Metoclopramide, Domperidone.
   • MOA: Block D2 receptors in the CTZ.
3. H1 Receptor Antagonists
   • Examples: Meclizine, Promethazine.
   • MOA: Block H1 receptors, effective in motion sickness.
4. Anticholinergics
   • Example: Scopolamine.
   • MOA: Block M1 receptors, reduce vestibular-related nausea.
5. NK1 Receptor Antagonists
   • Example: Aprepitant.
   • MOA: Block NK1 receptors, useful in CINV.
6. Benzodiazepines
   • Examples: Lorazepam.
   • MOA: Sedative effects reduce anticipatory nausea.
7. Cannabinoids
   • Examples: Dronabinol.
   • MOA: Act on CB1 receptors to reduce nausea.

Adverse Drug Reactions (ADRs)

1. 5-HT3: Headache, QT prolongation.
2. D2: EPS, sedation.
3. H1: Sedation, dry mouth.
4. Anticholinergics: Dry mouth, blurred vision.
5. NK1: Fatigue, dizziness.

Uses

1. PONV: Ondansetron, Dexamethasone.
2. CINV: Aprepitant, Ondansetron.
3. Motion Sickness: Scopolamine, Meclizine.
4. Pregnancy Nausea: Pyridoxine + Doxylamine.

Drugs for Peptic Ulcer Disease (PUD)

Common Drug Classes

1. Proton Pump Inhibitors (PPIs) (e.g., Omeprazole, Pantoprazole)
2. H2 Receptor Antagonists (e.g., Ranitidine, Famotidine)
3. Antacids (e.g., Magnesium hydroxide, Aluminum hydroxide)
4. Cytoprotective Agents (e.g., Sucralfate, Misoprostol)
5. Antibiotics (e.g., Clarithromycin, Amoxicillin for H. pylori eradication).

Mechanism of Action

1. PPIs: Irreversibly inhibit the H+/K+ ATPase enzyme in gastric parietal cells, suppressing gastric acid secretion.
2. H2 Receptor Antagonists: Block H2 receptors on parietal cells, reducing histamine-stimulated acid production.
3. Antacids: Neutralize stomach acid to provide symptomatic relief.
4. Sucralfate: Forms a protective barrier over the ulcer, shielding it from acid and pepsin.
5. Misoprostol: Prostaglandin analog that enhances mucus and bicarbonate secretion while reducing acid secretion.
6. Antibiotics: Eradicate H. pylori, the bacterial cause of many ulcers.

Adverse Effects

1. PPIs: Headache, nausea, diarrhea, long-term use may cause hypomagnesemia, osteoporosis, and increased infection risk.
2. H2 Receptor Antagonists: Dizziness, diarrhea, rare gynecomastia (cimetidine).
3. Antacids:
   • Magnesium-based: Diarrhea.
   • Aluminum-based: Constipation.
4. Sucralfate: Constipation, reduced absorption of other drugs.
5. Misoprostol: Diarrhea, abdominal cramping, contraindicated in pregnancy (causes uterine contractions).
6. Antibiotics: Diarrhea, nausea, antibiotic resistance, or allergic reactions.

Therapeutic Approach

Combination therapy (e.g., PPI + antibiotics) is common for H. pylori eradication, while PPIs or H2 blockers manage acid-related symptoms.

Prokinetic Drugs: Enhancing Gastrointestinal Motility

Definition

Enhance gastrointestinal motility by acting on smooth muscles or the enteric nervous system.

Classification

1. Dopamine (D2) Receptor Antagonists
   • Examples: Metoclopramide, Domperidone.
   • MOA: Block D2 receptors, increase acetylcholine release.
2. Serotonin (5-HT4) Receptor Agonists
   • Examples: Cisapride, Prucalopride.
   • MOA: Stimulate 5-HT4 receptors, enhance motility.
3. Motilin Receptor Agonists
   • Examples: Erythromycin.
   • MOA: Mimic motilin, improve gastric emptying.
4. Cholinergic Agents
   • Examples: Bethanechol, Neostigmine.
   • MOA: Stimulate muscarinic receptors or inhibit acetylcholinesterase.

Adverse Drug Reactions

1. Metoclopramide: EPS, drowsiness.
2. Domperidone: QT prolongation.
3. Cisapride: Arrhythmias.
4. Erythromycin: Cramps, resistance.
5. Bethanechol/Neostigmine: Bradycardia.

Uses

1. GERD: Metoclopramide, Domperidone.
2. Gastroparesis: Metoclopramide, Erythromycin.
3. IBS (constipation): Prucalopride.
4. Postoperative Ileus: Bethanechol, Neostigmine.
5. Nausea/Vomiting: Metoclopramide, Domperidone.

Drugs for GERD (Gastroesophageal Reflux Disease)

Common Drug Classes

1. Proton Pump Inhibitors (PPIs) (e.g., Omeprazole, Esomeprazole)
2. H2 Receptor Antagonists (e.g., Ranitidine, Famotidine)
3. Antacids (e.g., Magnesium hydroxide, Aluminum hydroxide)
4. Prokinetics (e.g., Metoclopramide, Domperidone).

Mechanism of Action

1. PPIs: Irreversibly inhibit the H+/K+ ATPase pump in gastric parietal cells, reducing gastric acid secretion.
2. H2 Receptor Antagonists: Block histamine H2 receptors on parietal cells, decreasing acid production.
3. Antacids: Neutralize stomach acid, providing rapid symptom relief.
4. Prokinetics: Increase gastrointestinal motility and lower esophageal sphincter tone to prevent acid reflux.

Therapeutic Uses

1. PPIs:
   • First-line therapy for GERD, especially for severe or erosive esophagitis.
   • Long-term management of chronic GERD.
2. H2 Receptor Antagonists: Used for mild GERD or as adjunct therapy to PPIs.
3. Antacids: Symptomatic relief of heartburn or mild GERD.
4. Prokinetics: Adjunctive treatment in GERD with motility disorders.

Adverse Effects

1. PPIs:
   • Headache, nausea, diarrhea.
   • Long-term use: Hypomagnesemia, osteoporosis, and increased risk of infections (e.g., C. difficile).
2. H2 Receptor Antagonists:
   • Dizziness, diarrhea.
   • Rare: Gynecomastia (with cimetidine).
3. Antacids:
   • Magnesium-based: Diarrhea.
   • Aluminum-based: Constipation.
4. Prokinetics:
   • Metoclopramide: Drowsiness, fatigue, extrapyramidal symptoms (e.g., tardive dyskinesia).
   • Domperidone: Rare arrhythmias.

Management Approach

• Mild GERD: Lifestyle modifications + antacids or H2 blockers.
• Severe or Chronic GERD: PPIs as the mainstay therapy, with possible prokinetic adjuncts for refractory cases.

Anticholinergic Poisoning: Treatment, Mechanism, and Adverse Effects

Treatment

1. Activated Charcoal: Used for decontamination if ingestion is recent.
2. Physostigmine (Antidote): A reversible acetylcholinesterase inhibitor.
3. Symptomatic Support:
   • Benzodiazepines for agitation or seizures.
   • Cooling measures for hyperthermia.
   • IV fluids for dehydration.

Mechanism of Action (Physostigmine)

• Inhibits acetylcholinesterase, the enzyme that breaks down acetylcholine.
• Increases acetylcholine levels at synapses, counteracting the effects of anticholinergic agents by restoring cholinergic signaling in both the central and peripheral nervous systems.

Adverse Effects (Physostigmine and Supportive Care)

1. Physostigmine:
   • Bradycardia.
   • Hypotension.
   • Seizures (rare, with rapid administration).
   • Bronchospasm or respiratory distress.
2. General Supportive Measures:
   • Benzodiazepines may cause respiratory depression if overdosed.
   • Aggressive cooling can lead to hypothermia if not monitored.

Key Points

Anticholinergic poisoning presents with symptoms like dry mouth, blurred vision, urinary retention, tachycardia, hyperthermia, and confusion. Physostigmine is highly effective but must be used cautiously under monitoring to avoid complications like bradycardia or seizures.

Adrenaline in Anaphylactic Shock

Mechanism of Action (MOA)

• Adrenergic Receptor Activation: Adrenaline stimulates alpha-1, beta-1, and beta-2 adrenergic receptors.
• Alpha-1: Vasoconstriction, increases blood pressure.
• Beta-1: Increases heart rate and cardiac output.
• Beta-2: Bronchodilation, improves airflow.

Indications

First-line treatment for anaphylaxis: Rapid reversal of life-threatening symptoms like airway constriction, hypotension, and shock.

Administration

• Route: Intramuscular (IM) injection into the thigh.
• Dosage: 0.3–0.5 mg (for adults), 0.01 mg/kg (for children).

Adverse Drug Reactions (ADRs)

1. Tachycardia: Increased heart rate.
2. Hypertension: Elevated blood pressure.
3. Anxiety: Nervousness or restlessness.
4. Tremors: Muscle shaking due to beta-2 stimulation.

Uses

• Anaphylactic shock: Rapid treatment to reverse airway constriction, hypotension, and prevent cardiovascular collapse.
• Allergic reactions: Used for severe allergic reactions with systemic symptoms.