8.2 Major Drug Classes, Actions & Antidotes

8.2 Major Drug Classes, Actions & Antidotes

Pharmacotherapy represents the most frequent therapeutic intervention in modern clinical medicine. To safeguard patient safety, registered nurses practicing under the Department of Health Abu Dhabi (DOH) framework must possess an in-depth understanding of drug mechanisms, therapeutic serum windows, hemodynamic effects, contraindications, and targeted emergency antidotes.

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Antimicrobial & Anti-infective Pharmacology

Antimicrobial stewardship requires vigilance regarding drug spectrum, administration rates, therapeutic drug monitoring (TDM), and organ-specific toxicities.

1. Penicillins & Cephalosporins (Beta-Lactams)

• Mechanism of Action: Inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), causing bacterial lysis.
• Cross-Allergenicity Risk: Cross-reactivity depends mainly on side-chain similarity and the reaction history. Penicillin anaphylaxis does not automatically contraindicate every cephalosporin; a non-cross-reactive agent such as cefazolin may be selected under the approved allergy protocol. Verify the culprit, symptoms and timing, and obtain prescriber/pharmacist review before administering a potentially cross-reactive drug. Severe delayed reactions require specialist advice.
• Nursing Priorities: Confirm allergy history prior to administration. Monitor the patient for at least 30 minutes following the initial parenteral dose. Advise patients that oral cephalosporins and penicillins can cause mild gastrointestinal upset, but acute watery diarrhea containing blood or mucus warrants immediate evaluation for Clostridioides difficile pseudomembranous colitis.

2. Vancomycin (Glycopeptide)

• Mechanism & Spectrum: Binds directly to D-alanyl-D-alanine terminals of cell wall peptidoglycans, preventing polymerization. It is the primary parenteral agent for methicillin-resistant Staphylococcus aureus (MRSA) and severe enterococcal infections. Oral vancomycin acts mainly within the gut and is used for C. difficile infection, including non-severe disease when selected by the treatment protocol.
• Therapeutic Monitoring: For serious invasive MRSA infection, current consensus favors AUC 24/MIC 400–600, assuming MIC 1 mg/L, achieved early in treatment. Obtain precisely timed concentrations using the facility's AUC/pharmacy protocol rather than automatically targeting a 15–20 mcg/mL trough before every fourth dose. Monitoring for other indications follows the prescribed local protocol and renal function.
• Nephrotoxicity & Ototoxicity: Monitor serum creatinine and blood urea nitrogen (BUN) daily. AKI criteria include a creatinine rise ≥0.3 mg/dL within 48 hours, ≥1.5 times baseline within 7 days, or urine output <0.5 mL/kg/hour for 6 hours; promptly escalate a qualifying change. Assess for early ototoxicity manifestations, including high-frequency tinnitus, vertigo, and subjective hearing loss.
• Red Man Syndrome (Histamine Infusion Reaction): A non-immunologic, rate-dependent adverse reaction triggered by the rapid degranulation of mast cells and basophils releasing systemic histamine (not a true IgE allergy). Manifests as profound erythema, pruritus, and maculopapular flushing of the face, neck, chest, and upper extremities, often accompanied by hypotension and tachycardia.
  • Prevention & Intervention: Use the product/facility infusion limit; a common limit is 10 mg/min or at least 60 minutes, whichever requires longer (1 g at 10 mg/min takes 100 minutes). If flushing, pruritus or hypotension develops, stop the infusion, assess ABCs and obtain help. Treat suspected anaphylaxis promptly with IM epinephrine. For an uncomplicated infusion reaction, give ordered treatment and restart only after resolution and clinical review, at a slower prescribed rate.

3. Aminoglycosides (Gentamicin, Tobramycin, Amikacin)

• Mechanism: Irreversibly bind to the bacterial 30S ribosomal subunit, disrupting protein synthesis and causing cell membrane breakdown.
• Black Box Warnings:
  • Nephrotoxicity: Causes direct acute tubular necrosis (ATN); manifests with proteinuria, decreased urine specific gravity, rising serum creatinine, and oliguria. Often reversible if detected early.
  • Irreversible Ototoxicity: Accumulates in inner ear perilymph, destroying vestibular and cochlear sensory hair cells. Symptoms include sensorineural hearing loss, roaring tinnitus, ataxia, and severe vertigo. Ototoxicity is irreversible.
• Therapeutic Drug Monitoring: Follow the specific dosing protocol. Conventional regimens may use a peak about 30 minutes after infusion and a trough immediately before dosing. Extended-interval regimens commonly use a precisely timed post-dose concentration to select the next interval. Record dose/sample times and monitor renal function.
• Concurrent Drug Caution: Avoid additional nephrotoxic or ototoxic exposure when possible. If combination therapy is clinically necessary, confirm the prescriber/pharmacist plan and increase renal, concentration and hearing/balance surveillance; do not substitute an unsupported universal prohibition for risk assessment.

4. Fluoroquinolones (Ciprofloxacin, Levofloxacin, Moxifloxacin)

• Mechanism: Inhibit bacterial DNA gyrase (topoisomerase II) and topoisomerase IV, preventing bacterial DNA replication and transcription.
• Black Box Warnings:
  • Tendinitis & Tendon Rupture: Involves the Achilles tendon most frequently; can occur bilaterally within 48 hours of starting or months after completing therapy. Patients must immediately discontinue the drug, avoid physical exertion, and notify the prescriber at the first sign of tendon pain, erythema, or edema.
  • Exacerbation of Myasthenia Gravis: Fluoroquinolones exhibit neuromuscular blocking activity and can precipitate fatal respiratory failure in myasthenic patients.
• Cardiovascular & Interaction Warnings:
  • Causes QT interval prolongation, increasing the risk of Torsades de Pointes dysrhythmias.
  • Chelation Binding: Oral absorption is severely reduced (by up to 90%) when co-administered with divalent/trivalent cations (aluminum/magnesium antacids, calcium supplements, dairy products, iron, sucralfate). Administer fluoroquinolones at least 2 hours before or 4 to 6 hours after cation-containing preparations.

5. Macrolides (Azithromycin, Clarithromycin, Erythromycin)

• Mechanism: Bind reversibly to the 50S ribosomal subunit, inhibiting RNA-dependent protein synthesis.
• Key Adverse Effects: Gastrointestinal hypermotility (cramping, diarrhea due to motilin receptor stimulation), hepatotoxicity (cholestatic jaundice, elevated AST/ALT), and QT interval prolongation.
• CYP450 Enzyme Inhibition: Clarithromycin and erythromycin are potent inhibitors of hepatic CYP3A4, dramatically elevating serum levels of concurrent statins (causing rhabdomyolysis), carbamazepine, theophylline, and warfarin.

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Cardiovascular & Hemodynamic Agents

Cardiovascular drugs require vigilant monitoring of electrical conduction, inotropic performance, fluid balance, and electrolyte equilibrium.

1. Beta-Adrenergic Blockers (-olol)

• Classification:
  • Cardioselective (Beta-1): Metoprolol, Atenolol, Bisoprolol (predominantly affect cardiac myocytes and SA/AV nodal conduction).
  • Non-Selective (Beta-1 and Beta-2): Propranolol, Nadolol, Timolol (block both cardiac receptors and bronchial smooth muscle receptors).
  • Alpha-1 and Beta Blockers: Carvedilol, Labetalol (cause both negative chronotropic/inotropic effects and peripheral vasodilation).
• Pre-Administration Nursing Rules: Auscultate apical pulse for 1 full minute and measure blood pressure prior to every dose. Withhold dose and notify prescriber if apical pulse is < 60 bpm or systolic BP is < 90 to 100 mmHg.
• Critical Safety Alerts:
  • Bronchospasm: Non-selective beta-blockers block beta-2 receptors in the lungs, triggering life-threatening bronchoconstriction in patients with asthma or severe chronic obstructive pulmonary disease (COPD). Non-selective agents are strictly contraindicated in active reactive airway disease.
  • Masking Hypoglycemia: Beta-blockers blunt the sympathetic adrenergic manifestations of acute hypoglycemia (tachycardia, tremulousness, palpitations). Sweating may remain prominent, and neuroglycopenic symptoms such as confusion or dizziness can still occur. Check glucose promptly rather than relying on tachycardia as a warning.
  • Abrupt Discontinuation Rebound: Never abruptly discontinue beta-blocker therapy. Sudden withdrawal triggers up-regulated receptor hyper-responsiveness, causing rebound tachycardia, severe hypertension, acute myocardial infarction, or ventricular dysrhythmias. Taper gradually over 1 to 2 weeks.

2. Renin-Angiotensin-Aldosterone System (RAAS) Inhibitors

• ACE Inhibitors (-pril: Lisinopril, Enalapril, Ramipril, Captopril): Inhibit Angiotensin-Converting Enzyme, blocking the conversion of angiotensin I to angiotensin II (a potent vasoconstrictor) and inhibiting bradykinin degradation.
  • Adverse Effects: Dry, persistent, non-productive hacking cough (caused by accumulation of inflammatory bradykinin and substance P in pulmonary tissues; refractory to cough suppressants; resolves only after drug cessation); Hyperkalemia (suppression of aldosterone prevents renal potassium excretion; avoid salt substitutes containing potassium chloride); First-dose orthostatic hypotension; and Angioedema (life-threatening rapid submucosal extravasation affecting the tongue, glottis, pharynx, and face; requires immediate airway support and lifelong avoidance of all ACE inhibitors).
  • Teratogenic Black Box Warning: Strictly contraindicated during pregnancy (causes fetal cranial hypoplasia, renal tubular dysgenesis, oligohydramnios, and neonatal anuria).
• Angiotensin II Receptor Blockers (ARBs, -sartan: Losartan, Valsartan, Candesartan): Directly block AT1 angiotensin receptors, preventing vasoconstriction and aldosterone release without inhibiting bradykinin breakdown. ARBs do not cause the dry bradykinin cough and carry a significantly lower incidence of angioedema. Same hyperkalemia and pregnancy contraindications apply.

3. Calcium Channel Blockers (CCBs)

• Dihydropyridines (-dipine: Amlodipine, Nifedipine, Nicardipine): Selectively block L-type calcium channels in vascular smooth muscle, promoting profound systemic arterial vasodilation with minimal direct cardiac conduction suppression.
  • Adverse Effects: Peripheral dependent pitting ankle/pedal edema (due to precapillary arteriolar dilation and hydrostatic fluid transudation), reflex tachycardia (baroreceptor response to rapid peripheral vasodilation), dizziness, and facial flushing.
• Non-Dihydropyridines (Diltiazem, Verapamil): Exert potent inhibitory effects on cardiac conduction tissue (SA and AV nodes) and myocardial contractility (negative chronotropic, dromotropic, and inotropic actions). Used for rate control in atrial fibrillation, flutter, and supraventricular tachycardia.
  • Adverse Effects: Bradycardia, first-, second-, or third-degree heart block, worsening congestive heart failure, and severe constipation (verapamil relaxes gastrointestinal smooth muscle and halts colonic peristalsis). Co-administration with beta-blockers requires continuous telemetry due to severe risk of profound bradycardia and complete AV nodal arrest.

4. Diuretics

• Loop Diuretics (Furosemide, Bumetanide, Torsemide): Inhibit the Na+/K+/2Cl- cotransporter in the thick ascending limb of the loop of Henle, producing potent natriuresis and diuresis even in impaired renal function.
  • Toxicities: Severe hypokalemia, hyponatremia, hypomagnesemia, prerenal dehydration, and hyperuricemia.
  • Ototoxicity Warning: Rapid intravenous push causes transient or permanent sensorineural hearing loss and tinnitus. Administer furosemide IV push at a rate not exceeding 20 mg/min (or <= 4 mg/min for continuous infusions).
• Thiazide Diuretics (Hydrochlorothiazide, Chlorthalidone): Inhibit Na+/Cl- reabsorption in the early distal convoluted tubule. Diuretic efficacy generally decreases as GFR falls, but agents such as chlorthalidone, metolazone and indapamide can remain effective below 30 mL/min/1.73 m²; selection and monitoring follow the prescribed renal/BP plan. Cause hypokalemia, hyponatremia, hyperuricemia (triggering acute gouty arthritis), and hypercalcemia (unlike loop diuretics, which promote calciuria).
• Potassium-Sparing Diuretics / Aldosterone Antagonists (Spironolactone, Eplerenone): Competitively antagonize aldosterone receptors in late distal tubules and collecting ducts, excreting sodium while conserving potassium.
  • Adverse Effects: Severe hyperkalemia (especially when combined with ACE inhibitors, ARBs, or potassium supplements); spironolactone exhibits anti-androgenic effects including painful gynecomastia, erectile dysfunction, and menstrual irregularities.

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Autonomic & CNS Drugs: Anticholinergics (Atropine)

Atropine is a competitive muscarinic receptor antagonist that blocks parasympathetic (vagal) stimulation at postganglionic cholinergic neuroeffector sites.

• Clinical Indications: First-line emergency drug for symptomatic sinus bradycardia (ACLS adult dose: 1 mg IV push every 3 to 5 minutes, up to a maximum cumulative dose of 3 mg); pre-operative reduction of oral and respiratory secretions; and antidote for cholinergic toxidromes (organophosphate poisoning).
• Adverse Effects & The Anticholinergic Toxidrome:
  • Xerostomia (dry mouth) and absent sweating (anhidrosis)
  • Mydriasis (dilated pupils), cycloplegia, blurred near vision, and photophobia
  • Urinary retention (due to detrusor relaxation and urinary sphincter contraction)
  • Constipation and paralytic ileus
  • Hyperthermia (impaired thermoregulation secondary to absent sweat production)
  • Central Anticholinergic Syndrome: Agitation, confusion, hallucinations, delirium ("dry as a bone, red as a beet, hot as a hare, blind as a bat, mad as a hatter, full as a flask").
• Strict Contraindications: Acute narrow-angle glaucoma (mydriasis blocks the canal of Schlemm, precipitating blindness from acute intraocular pressure spikes), obstructive uropathy (benign prostatic hyperplasia), and intestinal obstruction.

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Comprehensive Antidote Master Reference Table