Analyze Pathopharmacological Concepts to Guide Clinical Decisions

Pathology and Disease Manifestation in the Neuromuscular System

(Lehn’s Ch. 12-20 & 55-59)
Chapters 12–15: Peripheral Nervous System (PNS) Drugs

Cholinergic (Muscarinic) Agonists

 Mechanism: Mimic acetylcholine at muscarinic receptors → increased glandular secretion, smooth

muscle contraction, slowed heart rate

 Treats: Postoperative urinary retention, glaucoma (topical), gastrointestinal (GI) motility disorders

 Examples: Bethanechol; Pilocarpine; Carbachol

 Side Effects: Diarrhea, abdominal cramps, urinary urgency, bradycardia (slow heart rate)

 Contraindications/Cautions: Asthma (bronchoconstriction risk), bradycardia, peptic ulcer disease

 Other: Pilocarpine used in Sjögren’s syndrome (dry mouth) off-label

Muscarinic (Cholinergic) Antagonists

 Mechanism: Block muscarinic receptors → decreased secretions, relaxation of smooth muscle,

increased heart rate

 Treats: Overactive bladder, motion sickness, COPD bronchodilation, bradycardia (atropine)

 Examples: Atropine; Oxybutynin; Tolterodine; Ipratropium; Tiotropium; Scopolamine

 Side Effects: Dry mouth, blurred vision, constipation, urinary retention, tachycardia

 Contraindications/Cautions: Narrow-angle glaucoma, BPH, elderly (confusion)

 Other: Inhaled ipratropium/tiotropium preferred in COPD to minimize systemic effects

Adrenergic (Sympathomimetic) Agonists

 Mechanism: Stimulate α- and/or β-adrenergic receptors → vasoconstriction (α₁), bronchodilation (β₂),

increased heart rate/contractility (β₁)

 Treats: Hypotension/shock (vasopressors), asthma/COPD (bronchodilators), nasal decongestion, cardiac

arrest (β₁)

 Examples: Epinephrine; Norepinephrine; Phenylephrine (α₁); Albuterol (β₂); Dobutamine (β₁)

 Side Effects: Hypertension, tachycardia, anxiety, arrhythmias

 Contraindications/Cautions: Pheochromocytoma, uncontrolled hypertension; use caution in CAD

 Other: Epinephrine autoinjector for anaphylaxis

Adrenergic Antagonists
α-Adrenergic Blockers

 Mechanism: Block α₁ receptors → vasodilation

 Treats: Hypertension, pheochromocytoma, BPH symptoms

 Examples: Prazosin; Terazosin; Doxazosin

 Side Effects: Orthostatic hypotension (postural drop in BP), reflex tachycardia, nasal congestion

 Contraindications/Cautions: Hypotension; first-dose syncope risk

 Other: Use low initial dose at bedtime

β-Adrenergic Blockers

 Mechanism: Block β₁ and/or β₂ receptors → decreased heart rate, contractility, renin release

 Treats: Hypertension, angina, arrhythmias, heart failure, migraine prophylaxis

 Examples: Metoprolol (β₁-selective); Atenolol; Propranolol (β₁+β₂); Carvedilol (α+β)

 Side Effects: Bradycardia, fatigue, bronchospasm (β₂ block), sexual dysfunction

 Contraindications/Cautions: Asthma/COPD (nonselective agents); AV block; decompensated CHF

 Other: Titrate slowly; monitor blood glucose masking in diabetics

Neuromuscular Blockers

 Mechanism: Compete with acetylcholine at nicotinic receptors (nondepolarizing) or depolarize then

block (succinylcholine)

 Treats: Surgical muscle relaxation, intubation

 Examples: Succinylcholine (depolarizing); Rocuronium; Vecuronium

 Side Effects: Malignant hyperthermia (succinylcholine); prolonged paralysis; histamine release

 Contraindications/Cautions: Hyperkalemia; neuromuscular diseases

 Other: Always use with sedation and analgesia; monitor neuromuscular function

Chapters 17–20: Central Nervous System (CNS) Drugs

Antiseizure (Antiepileptic) Drugs

Drugs by Seizure Type

 Generalized Tonic-Clonic & Partial Seizures: Sodium channel blockers (phenytoin, carbamazepine,
lamotrigine), broad-spectrum (valproic acid, levetiracetam)

 Absence Seizures: Ethosuximide; Valproic acid

 Myoclonic & Atonic Seizures: Valproic acid; Clonazepam

 Status Epilepticus: IV Lorazepam/Diazepam → IV Phenytoin or Fosphenytoin

Common Antiseizure Classes

 Sodium Channel Blockers

o Examples: Phenytoin; Carbamazepine; Lamotrigine; Oxcarbazepine

o Mechanism: Prolong inactivated state of Na⁺ channels → reduce neuronal firing

o Side Effects: CNS sedation, ataxia, GI upset; phenytoin → gingival hyperplasia, hirsutism

o Contraindications/Cautions: Pregnancy (neural tube defects); bone marrow suppression

(carbamazepine)

o Other: Monitor levels; many drug interactions via CYP

 GABA Enhancers

o Examples: Phenobarbital; Benzodiazepines (diazepam, lorazepam)

o Mechanism: Enhance GABA_A receptor activity → increased inhibitory tone

o Side Effects: Sedation; dependence; respiratory depression

o Contraindications/Cautions: History of substance abuse; severe respiratory insufficiency

o Other: Phenobarbital enzyme inducer; narrow therapeutic index

 Calcium Channel (T-Type) Blockers

o Examples: Ethosuximide

o Mechanism: Inhibit T-type Ca²⁺ currents in thalamic neurons → prevent absence seizures

o Side Effects: GI upset; fatigue; headache

o Contraindications/Cautions: Severe hepatic impairment

o Other: First-line for absence seizures

 Broad-Spectrum Agents

o Examples: Valproic acid; Levetiracetam

o Mechanism: Multiple actions (Na⁺ channel, GABA metabolism, Ca²⁺ channels)

o Side Effects: Weight gain, tremor, hair loss (valproate); behavioral changes (levetiracetam)

o Contraindications/Cautions: Hepatic disease (valproate); mood disorders (levetiracetam)

o Other: Lamotrigine also broad-spectrum; risk of rash (Stevens-Johnson syndrome)

Anxiolytics & Hypnotics

 Benzodiazepines

o Examples: Diazepam; Lorazepam; Alprazolam

 o Mechanism: Enhance GABA_A receptor → ↑ Cl⁻ influx

o Treats: Anxiety disorders; insomnia; seizure adjunct; alcohol withdrawal

o Side Effects: Sedation; dependence; respiratory depression

o Contraindications/Cautions: COPD; sleep apnea; substance use history

o Other: Flumazenil reverses overdose

 Nonbenzodiazepine Hypnotics (Z-drugs)

o Examples: Zolpidem; Zaleplon; Eszopiclone

o Mechanism: GABA_A receptor α1 subunit agonist → sedation

o Treats: Insomnia

o Side Effects: Sleepwalking; next-day drowsiness

o Contraindications/Cautions: Same as benzodiazepines; elderly at fracture risk

 Buspirone

o Mechanism: 5-HT1A partial agonist → anxiolytic without sedation

o Treats: Generalized anxiety disorder (GAD)

o Side Effects: Dizziness; nausea; headache

o Contraindications/Cautions: MAO inhibitors (serotonin syndrome risk)

o Other: Non-sedating; no dependence

Antidepressants & Antipsychotics (Overview)

(Focus on most common classes; see separate guide for full detail)

Chapters 55–56: Cyclooxygenase Inhibitors & Glucocorticoids

NSAIDs (Nonsteroidal Anti-Inflammatory Drugs)

 Mechanism: Inhibit COX-1/COX-2 enzymes → ↓ prostaglandin synthesis (mediators of inflammation,

pain)

 Treats: Pain; inflammation; fever; dysmenorrhea; osteoarthritis; rheumatoid arthritis

 Examples: Ibuprofen; Naproxen; Diclofenac; Celecoxib (COX-2 selective)

 Side Effects: GI ulceration; bleeding; renal impairment; cardiovascular risk (COX-2 inhibitors)

 Contraindications/Cautions: Peptic ulcer disease; kidney disease; heart failure; aspirin allergy

 Other: COX-2 inhibitors spare gastric mucosa but ↑ CV risk; use lowest effective dose

Glucocorticoids
  Mechanism: Bind glucocorticoid receptor → alter gene transcription → potent anti-inflammatory and
immunosuppressive effects

 Treats: Autoimmune diseases (RA, asthma exacerbations, dermatitis), adrenal insufficiency,

chemotherapy adjunct

 Examples: Prednisone; Methylprednisolone; Dexamethasone; Hydrocortisone

 Side Effects: Cushingoid features (moon face, truncal obesity), osteoporosis, hyperglycemia,
immunosuppression

 Contraindications/Cautions: Active infections; diabetes; osteoporosis; monitor for adrenal suppression

 Other: Taper slowly to avoid adrenal crisis; use local (inhaled, topical) to minimize systemic effects

Chapters 57–59: Rheumatoid Arthritis, Gout, and Bone Mineralization

Rheumatoid Arthritis (RA) Therapy

 NSAIDs & Glucocorticoids: Symptomatic relief; bridge until DMARD onset

 Conventional DMARDs (disease-modifying antirheumatic drugs)

o Examples: Methotrexate; Sulfasalazine; Hydroxychloroquine

o Mechanism: Various immunomodulatory effects → slow joint damage

o Side Effects: Hepatotoxicity; bone marrow suppression; GI upset

o Contraindications/Cautions: Pregnancy (methotrexate); liver/renal disease

o Other: Methotrexate first-line; monitor CBC/LFTs; folate supplementation

 Biologic DMARDs

o Examples: Etanercept; Infliximab; Adalimumab; Tocilizumab (IL-6 inhibitor); Abatacept (T-cell

modulator)

o Mechanism: Target TNFα, IL-6, or costimulatory signals → reduce inflammation

o Side Effects: Infection risk (TB reactivation); injection site reactions

o Contraindications/Cautions: Active infection; latent TB; heart failure (TNF inhibitors)

o Other: Screen for TB before initiation

Osteoarthritis (OA) Therapy

 First-line: Acetaminophen (analgesic without anti-inflammatory) for mild pain

 NSAIDs: Ibuprofen; Naproxen for inflammation and pain

 Topical agents: Diclofenac gel

 Intra-articular steroids: Triamcinolone injections

  Other: Weight reduction; physical therapy; no DMARDs—OA is degenerative not autoimmune

Gout Treatment

 Acute flare

o NSAIDs: Indomethacin; Naproxen

o Colchicine: Inhibits microtubule polymerization → ↓ neutrophil chemotaxis

o Glucocorticoids: Oral prednisone or intra-articular injection

 Chronic management (urate-lowering)

o Xanthine oxidase inhibitors: Allopurinol; Febuxostat → inhibit uric acid synthesis

o Uricosurics: Probenecid → increase renal excretion of uric acid

o Recombinant uricase: Pegloticase → degrade uric acid to allantoin

o Other: Start prophylaxis with low‐dose colchicine or NSAID when initiating urate‐lowering
therapy

Bone Mineralization & Osteoporosis

 When to treat: T-score ≤ –2.5 (DEXA scan), hip/vertebral fracture, high FRAX risk (fracture risk
assessment tool)

 Bisphosphonates

o Examples: Alendronate; Risedronate; Ibandronate; Zoledronic acid

o Mechanism: Inhibit osteoclast-mediated bone resorption → increase bone density

o Side Effects: Esophagitis; osteonecrosis of jaw; atypical femur fractures

o Contraindications/Cautions: Esophageal disorders; hypocalcemia; renal impairment

o Other: Take on empty stomach with water; remain upright 30–60 minutes

 Selective Estrogen Receptor Modulators (SERMs)

o Examples: Raloxifene

o Mechanism: Estrogen agonist in bone→ decrease resorption; antagonist in breast/uterus

o Side Effects: Hot flashes; thromboembolism

o Contraindications/Cautions: History of DVT/PE

 RANKL Inhibitor

o Example: Denosumab

o Mechanism: Monoclonal antibody binds RANKL → prevents osteoclast formation

o Side Effects: Hypocalcemia; infection risk; osteonecrosis of jaw

 o Contraindications/Cautions: Hypocalcemia; monitor calcium

 PTH Analog

o Example: Teriparatide

o Mechanism: Recombinant PTH fragment → stimulates osteoblasts → bone formation

o Side Effects: Hypercalcemia; leg cramps

o Contraindications/Cautions: Paget disease; bone metastases

o Other: Limited to 2 years of therapy

Additional Questions

1. What type of drugs are used for different types of seizures?

o Generalized tonic-clonic & partial seizures: Sodium channel blockers (phenytoin,

carbamazepine), broad-spectrum (valproic acid, levetiracetam)

o Absence seizures: Ethosuximide; valproic acid

o Myoclonic & atonic seizures: Valproic acid; clonazepam

o Status epilepticus: IV benzodiazepines (lorazepam, diazepam) → IV phenytoin/fosphenytoin

2. What is the difference between treatment in rheumatoid arthritis (RA) and osteoarthritis (OA)?

o RA: Autoimmune—use DMARDs (methotrexate) and biologics to slow disease progression plus
NSAIDs/glucocorticoids for symptoms

o OA: Degenerative—focus on pain relief with acetaminophen, NSAIDs, physical therapy; no

disease-modifying agents

3. When do you treat osteoporosis?

o T-score ≤ –2.5 on DEXA

o History of hip or vertebral fracture

o High fracture risk by FRAX tool

4. What is the best treatment for gout?

o Acute flare: NSAIDs (indomethacin), colchicine, or glucocorticoids

o Chronic management: Xanthine oxidase inhibitors (allopurinol) to lower uric acid; add
prophylaxis (colchicine) when initiating therapy