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Comprehensive Pharmacology Review – Key Vocabulary

Chapter 50 – Upper GI Pharmacology

Antacids

  • Basic inorganic salts (e.g., aluminum hydroxide, magnesium hydroxide, calcium carbonate, sodium bicarbonate) that chemically neutralise pre-formed gastric hydrochloric acid (HCl), increasing gastric pH. Simethicone, an antiflatulent, is often added to reduce gas and bloating.

  • Combination antacid products often combine aluminum (which tends to cause constipation) or calcium (also constipating) with magnesium (which tends to cause diarrhea) to balance these common side effects and improve patient tolerance.

  • Their primary action is rapid neutralisation of stomach acid. A secondary, less prominent, action involves increasing mucosal defence mechanisms, such as stimulating prostaglandin production and bicarbonate secretion, particularly at lower doses; this helps protect the gastric lining.

  • Indications include symptomatic relief of peptic ulcer disease (PUD), gastritis, gastroesophageal reflux disease (GERD), general hyperacidity, and heartburn, offering quick but temporary relief.

  • Adverse effects (AEs) include: magnesium-containing antacids causing diarrhea; aluminum and calcium-containing antacids causing constipation. Calcium-containing antacids can lead to rebound hyperacidity (acid secretion increases after drug cessation), hypercalcemia, milk-alkali syndrome (hypercalcemia, metabolic alkalosis, renal insufficiency often from excessive intake), and metabolic alkalosis. Sodium-containing antacids are problematic in patients with congestive heart failure (CHF) or hypertension (HTN) due to increased sodium load.

  • Significant drug interactions necessitate avoiding other oral (PO) medications within approximately 2 hours of antacid administration. Interactions occur via: direct adsorption, where antacids bind to other drugs, reducing their bioavailability; chelation, forming insoluble complexes with certain drugs (e.g., tetracyclines, quinolones); increasing gastric pH, which can enhance the absorption of basic drugs (e.g., pseudoephedrine) and decrease the absorption of acidic drugs (e.g., digoxin, phenytoin); and increasing urinary pH, which enhances the excretion of acidic drugs while reducing the excretion of basic drugs.

  • A major clinical risk is significantly decreased absorption of quinolone antibiotics (e.g., ciprofloxacin), leading to up to a 50% loss of antibiotic efficacy due to chelation.

H₂-Receptor Antagonists (H2RAs)

  • H2RAs selectively block histamine-2 ( ext{H}_2 ) receptors on the gastric parietal cells, significantly reducing both basal and stimulated gastric acid secretion (by approximately 90%). This interruption prevents histamine from stimulating the proton pump.

  • Common drugs include cimetidine, famotidine, and nizatidine. Ranitidine was largely removed from the market in 2020 due to potential contaminant issues.

  • Therapeutic uses span gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), erosive oesophagitis, prophylaxis for stress-related mucosal bleeding in critically ill patients, and Zollinger-Ellison (Z-E) syndrome (a hypersecretory condition).

  • Cimetidine is known for its significant inhibition of certain cytochrome P-450 (CYP) isoenzymes, leading to numerous drug interactions with medications like warfarin, phenytoin, and theophylline, increasing their plasma concentrations and risk of toxicity. It is particularly associated with central nervous system (CNS) side effects, such as confusion or delirium, especially in elderly patients due to its ability to cross the blood-brain barrier.

  • Most H2RAs are available over-the-counter (OTC) at lower doses, making them accessible for self-treatment of heartburn.

Proton Pump Inhibitors (PPIs)

  • PPIs are prodrugs that, once activated in the acidic canaliculi of parietal cells, irreversibly bind to and inhibit the ext{H}^+/ ext{K}^+ -ATPase enzyme (the proton pump), which is responsible for the final step of acid secretion. This irreversible binding means that acid secretion is suppressed until new proton pumps are synthesized, leading to prolonged (24-48 hours) and virtually total acid suppression, regardless of the stimulus.

  • Widely used drugs include omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole, and dexlansoprazole. Zegerid is a unique combination product containing omeprazole and sodium bicarbonate, with the bicarbonate enhancing omeprazole absorption and providing immediate antacid effect.

  • PPIs are considered first-line therapy for erosive oesophagitis, refractory GERD (symptoms persist despite H2RA therapy), active duodenal and gastric ulcers, NSAID-induced ulcers, and pathological hypersecretory conditions (e.g., Zollinger-Ellison syndrome). They are also a crucial component of multi-drug regimens (triple or quadruple therapy) for eradicating Helicobacter pylori infection.

  • Key drug interactions include omeprazole's competitive inhibition of the CYP2C19 enzyme, which is necessary for the metabolic activation of the antiplatelet drug clopidogrel (Plavix), potentially reducing its efficacy and increasing cardiovascular risk. PPIs can also increase plasma levels of drugs like diazepam and phenytoin, requiring dosage adjustments, and augment the anticoagulant effect of warfarin, increasing bleeding risk.

  • FDA warnings for long-term or high-dose PPI use include an increased risk of Clostridioides difficile ( ext{C. difficile} )-associated diarrhea due to altered gut microbiota and pH; increased risk of bone fractures (hip, wrist, spine), possibly due to reduced calcium absorption; increased susceptibility to community-acquired pneumonia; and hypomagnesemia ( ext{Mg}^{2+} deficiency), which can lead to cardiac arrhythmias and neurological symptoms.

Miscellaneous Acid Drugs

  • Sucralfate is an aluminum salt of sucrose that, in the acidic environment of the stomach, polymerizes into a viscous paste that selectively binds to ulcer craters and erosions, forming a protective barrier against acid, pepsin, and bile salts. It does not alter stomach pH.

  • Misoprostol is a synthetic prostaglandin ext{E}_1 (PGE₁) analogue that enhances mucosal defense by increasing bicarbonate and mucus secretion and improving mucosal blood flow. Its primary use is to prevent NSAID-induced gastric ulcers, especially in high-risk patients. However, due to its uterine-contracting properties, it is contraindicated in pregnancy and used as an abortifacient.

  • Simethicone is an inert silicone polymer that acts as an antiflatulent by reducing the surface tension of gas bubbles in the GI tract, causing them to coalesce and be more easily expelled as flatus or burping. It is not absorbed and is purely symptomatic.

Nursing Focus – Acid Drugs

  • Perform a thorough assessment of the patient's gastrointestinal status, current medications (including OTCs and herbals), and sodium status (especially for antacids) before administering acid drugs. Due to numerous interactions (adsorption, chelation, pH changes), instruct patients to avoid taking other oral medications within 2 hours of antacid administration.

  • When administering H2RAs intravenously (IV), especially cimetidine, monitor blood pressure closely as rapid IV infusion can cause transient hypotension or bradycardia.

  • For patients on long-term PPI therapy, assess their risk factors for osteoporosis and advise on calcium and vitamin D supplementation, and regular bone density monitoring.

  • Instruct patients to thoroughly chew chewable antacid tablets followed by a full glass ( 240 ext{ mL} ) of water to ensure dissolution and facilitate stomach entry. Liquid antacid suspensions should be shaken well before administration to ensure uniform drug distribution.

  • Monitor patients for signs of gastrointestinal bleeding, which can be masked by symptom relief. Regularly check stools for occult (hidden) blood. Promptly report any visible signs of bleeding, such as black, tarry stools (melena) or vomiting blood (hematemesis), as these indicate active GI hemorrhage possibly from an ulcer.

Chapter 50 – Lower GI Pharmacology

Antidiarrheals

  • Antidiarrheals are categorized into several classes: adsorbents (e.g., bismuth subsalicylate binding toxins and irritants; activated charcoal, a general adsorbent; cholestyramine, a bile acid sequestrant for diarrhea caused by excess bile acids), anticholinergics (e.g., atropine-like drugs that decrease GI motility by blocking acetylcholine), opiates (e.g., loperamide and diphenoxylate, which reduce intestinal peristalsis), and probiotics (e.g., Lactobacillus species, which help restore normal gut flora).

  • Bismuth subsalicylate contains salicylate, similar to aspirin (ASA), posing a risk of Reye's syndrome in children and increasing bleeding risk, especially with concurrent anticoagulants. It commonly causes harmless darkening of the stool and tongue due to bismuth sulfide formation.

  • Opiate antidiarrheals (e.g., loperamide, diphenoxylate) reduce gastrointestinal motility by acting on opioid receptors in the intestinal wall, decreasing propulsive contractions and increasing intestinal transit time, thereby allowing more time for water and electrolyte absorption. They also alleviate abdominal spasm pain.

  • Drug interactions include increased anticholinergic effects when combined with tricyclic antidepressants (TCAs) or monoamine oxidase inhibitors (MAOIs). Antacids can reduce the efficacy of anticholinergic antidiarrheals. Central nervous system (CNS) depressants (e.g., alcohol, sedatives) have additive effects when combined with opiate antidiarrheals, increasing sedation and respiratory depression risk.

Laxatives

  • Bulk-forming laxatives (e.g., psyllium, methylcellulose) are natural or synthetic polysaccharides that absorb water in the intestine, swelling and forming a gel-like mass. This increases fecal bulk, which stimulates peristalsis and facilitates bowel evacuation, mimicking physiological processes. They are generally the safest for long-term use.

  • Emollient laxatives include stool softeners like docusate, which allow water and lipids to penetrate the stool, making it softer and easier to pass, and lubricants like mineral oil, which coats the fecal material, preventing water reabsorption and easing passage.

  • Hyperosmotic laxatives (e.g., polyethylene glycol (PEG), lactulose, glycerin suppositories) work by drawing water into the colon and stool via osmosis, increasing intraluminal pressure and stimulating bowel movement.

  • Saline laxatives (e.g., magnesium citrate, magnesium hydroxide (milk of magnesia)) are poorly absorbed salts that draw water into the colon, producing a watery stool quickly. They are potent and used for bowel preparation or acute constipation.

  • Stimulant laxatives (e.g., senna, bisacodyl) directly irritate the intestinal mucosa or stimulate nerve plexuses in the bowel wall, increasing propulsive peristalsis. They are effective but should not be used long-term due to risk of dependence.

  • Peripheral ext{mu} -opioid receptor antagonists (e.g., naloxegol, methylnaltrexone) specifically block opioid receptors in the GI tract without crossing the blood-brain barrier, thereby counteracting opioid-induced constipation (OIC) without affecting opioid analgesia.

  • Long-term use of most laxative types, especially stimulants and saline laxatives, can lead to cathartic colon (loss of normal bowel function), psychological dependence, and significant fluid and electrolyte imbalances (e.g., hypokalemia, hypocalcemia), which can be dangerous.

  • Laxatives are contraindicated in patients with acute surgical abdomen, suspected intestinal obstruction, fecal impaction, or undiagnosed abdominal pain, as their use could worsen the condition or mask a serious underlying pathology.

IBS Drugs

  • For IBS with diarrhea (IBS-D): alosetron, a selective 5 ext{-} ext{HT}_3 receptor antagonist, reduces visceral pain and slows colonic transit, but carries a Black Box Warning (BBW) for serious ischemic colitis and severe constipation; rifaximin, a non-absorbable antibiotic, targets gut bacteria imbalances; and eluxadoline, a mixed ext{mu} -opioid receptor agonist and ext{delta} -opioid receptor antagonist, reduces abdominal pain and diarrhea without causing significant CNS effects.

  • For IBS with constipation (IBS-C): lubiprostone, a chloride ( ext{Cl}^- ) channel activator, increases fluid secretion into the intestinal lumen, easing stool passage; and linaclotide, a guanylate cyclase-C ( ext{GC-C} ) agonist, also increases intestinal fluid secretion and accelerates transit, while reducing visceral pain.

  • Tegaserod, a 5 ext{-} ext{HT}_4 agonist, enhances peristalsis and secretion. Its use is highly restricted due to an increased risk of serious cardiovascular (CV) events (e.g., heart attack, stroke), primarily in patients with pre-existing CV disease.

Nursing – Bowel Agents

  • Before administering bowel agents, establish a baseline assessment, including auscultating bowel sounds (normal range is 6-32 sounds per minute) to assess gut motility and patency, which is crucial for determining appropriate laxative or antidiarrheal selection.

  • Continuously monitor patients for signs of dehydration and electrolyte imbalances, particularly hypokalemia, as these are common adverse effects of both laxative abuse and severe diarrhea. Elderly patients are at an increased risk due to reduced homeostatic reserves.

  • When administering bulk-forming laxatives, it is critical to mix the powder or granules with at least 240 ext{ mL} (8 ounces) of water or another liquid and to drink it immediately, followed by another glass of fluid, to prevent esophageal or intestinal obstruction from the swelling agent.

  • Educate patients on the proper, short-term use of laxatives and warn them about the potential for laxative abuse, which can lead to dependence, chronic constipation, and serious fluid and electrolyte disturbances.

Chapter 50 – Antiemetics

  • Nausea and vomiting are complex processes mediated by various pathways involving specific neurotransmitters: the vestibular pathway, responsive to acetylcholine (ACh) and histamine ( ext{H}1 ), mediates motion sickness; the chemoreceptor trigger zone (CTZ) in the brainstem, outside the blood-brain barrier, is sensitive to circulating emetics, with receptors for dopamine ( ext{D}2 ), serotonin ( 5 ext{-} ext{HT}3 ), and neurokinin-1 ( ext{NK}1 ); and the gastrointestinal (GI) tract itself, primarily via 5 ext{-} ext{HT}_3 receptors, responds to local irritation.

  • Anticholinergic agents, such as the transdermal scopolamine patch, primarily block muscarinic acetylcholine receptors in the vestibular system, making them effective for motion sickness and postoperative nausea and vomiting (PONV). They are contraindicated in patients with narrow-angle glaucoma due to the risk of increasing intraocular pressure.

  • ext{H}1 antihistamines (e.g., meclizine, dimenhydrinate) block histamine ext{H}1 receptors in the vestibular system and also have anticholinergic properties. They are used for motion sickness and vertigo. Caution is advised in pediatric and geriatric populations due to potential paradoxical excitation (restlessness, insomnia) or increased anticholinergic side effects (e.g., sedation, dry mouth, urinary retention).

  • Dopamine ( ext{D}_2 ) receptor blockers (e.g., prochlorperazine, promethazine, droperidol) primarily act on the CTZ. Promethazine, particularly, should be administered via intramuscular (IM) or oral (PO) routes only; intravenous (IV) administration carries a Black Box Warning due to the severe risk of tissue necrosis and gangrene if extravasation occurs.

  • Amisulpride, an atypical antipsychotic with selective dopamine receptor antagonism, is approved for the prevention and treatment of postoperative nausea and vomiting (PONV), acting primarily in the CTZ.

  • Neurokinin-1 ( ext{NK}1 ) receptor antagonists (e.g., aprepitant, fosaprepitant, rolapitant) block the substance P/ ext{NK}1 pathway in the CTZ, highly effective for preventing chemotherapy-induced nausea and vomiting (CINV), especially the delayed phase. They are significant inhibitors of the CYP3A4 enzyme, leading to drug interactions that can decrease warfarin's International Normalized Ratio (INR, increasing bleeding risk) and reduce the efficacy of oral contraceptives (OCPs).

  • Metoclopramide is a prokinetic agent that primarily blocks dopamine ( ext{D}_2 ) receptors in the CTZ and peripherally, while also enhancing acetylcholine release in the GI tract, which increases gastric emptying and intestinal motility. Its primary risk, especially with long-term or high-dose use, is tardive dyskinesia, a potentially irreversible movement disorder characterized by involuntary, repetitive movements.

  • 5 ext{-} ext{HT}3 receptor blockers (serotonin antagonists, e.g., ondansetron, granisetron), are highly effective antiemetics that selectively block 5 ext{-} ext{HT}3 receptors centrally in the CTZ and peripherally on vagal nerve terminals in the GI tract. They are first-line for preventing chemotherapy-induced nausea and vomiting (CINV) and are also widely used for postoperative nausea and vomiting (PONV).

  • Cannabinoids like dronabinol (synthetic THC) act on cannabinoid receptors in the CNS, reducing nausea and stimulating appetite. They are used for CINV refractory to other agents and for appetite stimulation in AIDS patients. A common adverse effect is orthostatic hypotension, and CNS effects like euphoria and dysphoria can occur.

  • In nursing care, antiemetics for CINV should ideally be administered 30 ext{-}60 ext{ minutes} before chemotherapy to ensure peak effect. Monitor blood pressure, especially with anticholinergics like meclizine, due to potential for hypotension. Watch for extrapyramidal symptoms (EPS) like dystonia and akathisia with dopamine blockers such as metoclopramide. All antiemetics can cause sedation; instruct patients to avoid driving or operating heavy machinery until they know how the medication affects them.

Chapter 28 – Diuretics

CA Inhibitors (acetazolamide)

  • Carbonic Anhydrase (CA) Inhibitors, such as acetazolamide, act primarily in the proximal tubule by inhibiting the enzyme carbonic anhydrase. This inhibition reduces the reabsorption of bicarbonate ( ext{HCO}_3^- ) and sodium ( ext{Na}^+ ) ions, leading to their increased excretion, causing a mild diuresis. The loss of bicarbonate can also result in hyperchloremic metabolic acidosis, a characteristic side effect.

  • Uses include: treating glaucoma by decreasing aqueous humor formation and thus intraocular pressure; preventing and treating acute mountain sickness by inducing metabolic acidosis, which stimulates respiration and aids acclimatization; and occasionally for mild edema.

  • Adverse effects include metabolic acidosis, hypokalemia ( ext{K}^+ loss due to increased ext{Na}^+ reaching the collecting duct), and glycosuria in hyperglycemia (due to inhibited bicarbonate reabsorption in the tubule facilitating glucose excretion). Hypokalemia can sensitize the heart to digoxin, increasing the risk of digoxin toxicity.

Loop (furosemide, bumetanide, torsemide)

  • Loop diuretics (e.g., furosemide, bumetanide, torsemide) are the most potent diuretics, acting on the thick ascending limb of the loop of Henle. They inhibit the ext{Na}^+ ext{-K}^+ ext{-2Cl}^- cotransporter, preventing the reabsorption of sodium, potassium, and chloride ions. This leads to substantial electrolyte and water excretion.

  • They have a rapid onset of action and are highly potent, making them ideal for situations requiring rapid fluid removal. Uniquely, they remain effective even in patients with impaired renal function, specifically when creatinine clearance (CrCl) is below 25 ext{ mL/min} , unlike thiazide diuretics.

  • Adverse effects include significant hypokalemia, hypocalcemia ( ext{Ca}^2+ ) and hypomagnesemia ( ext{Mg}^2+ ) due to increased excretion. Ototoxicity (hearing impairment, tinnitus, or deafness), often transient and dose-related, can occur, especially with rapid IV administration or in combination with other ototoxic drugs. Photosensitivity is also a concern. They carry a Black Box Warning for profound diuresis that can lead to acute fluid and electrolyte depletion.

Osmotic (mannitol)

  • Osmotic diuretics, such as mannitol, are filtered at the glomerulus but poorly reabsorbed. They create an osmotic gradient in the proximal convoluted tubule (PCT) and descending loop of Henle, pulling water from the extracellular fluid into the lumen of the nephron. This action primarily leads to increased water, rather than sodium, excretion. Mannitol is crucial for reducing intracranial pressure (ICP) and intraocular pressure (IOP) by drawing water out of the brain or eye. It's also used to protect renal function in the oliguric phase of acute renal failure (ARF) by maintaining urine flow and preventing tubular casts.

  • Potential adverse effects include: pulmonary edema, especially in patients with pre-existing heart failure, due to rapid fluid shifts into the intravascular space; exacerbation of congestive heart failure (CHF); and, rarely, convulsions due to rapid shifts in brain water content despite reducing ICP.

K-Sparing (spironolactone, amiloride, triamterene)

  • Potassium-sparing diuretics (e.g., spironolactone, amiloride, triamterene) act on the collecting duct. Spironolactone is an aldosterone antagonist, competitively blocking aldosterone receptors, which normally promote sodium reabsorption and potassium excretion. Amiloride and triamterene directly block epithelial sodium channels ( ext{ENaC} ) in the collecting duct, independent of aldosterone.

  • Their primary uses include treating hyperaldosteronism (primary or secondary), managing heart failure (particularly spironolactone for its mortality benefit in selected patients), and counteracting potassium loss induced by loop or thiazide diuretics.

  • The most significant adverse effect is hyperkalemia ( ext{K}^+ ), which can be life-threatening and is exacerbated by concurrent use of ACE inhibitors or ARBs. Spironolactone specifically can cause endocrine side effects like gynecomastia (breast enlargement in males), menstrual irregularities, and sexual dysfunction due to its anti-androgenic effects. Triamterene use is associated with the formation of kidney stones.

Thiazide (HCTZ, chlorthalidone, metolazone)

  • Thiazide diuretics (e.g., hydrochlorothiazide (HCTZ), chlorthalidone, metolazone) primarily act on the distal convoluted tubule, where they inhibit the sodium-chloride cotransporter, leading to increased excretion of sodium, chloride, and water. A key limitation is that most thiazides lose their diuretic efficacy when creatinine clearance (CrCl) falls below 30 ext{ mL/min} , with metolazone being the notable exception, maintaining efficacy in moderate to severe renal impairment.

  • They are considered first-line agents for the treatment of essential hypertension due to their sustained blood pressure-lowering effects. They are also used for edema (e.g., from heart failure, liver cirrhosis), and paradoxically, in nephrolithiasis due to hypercalciuria, as they decrease urinary calcium excretion, thereby reducing stone formation.

  • Common adverse effects include hypokalemia, hypomagnesemia, and hyponatremia. However, they can cause hypercalcemia ( ext{Ca}^2+ ), hyperuricemia (which can precipitate gout attacks), elevations in blood lipids (cholesterol, triglycerides), and hyperglycemia (possibly worsening diabetes due to impaired insulin release). Photosensitivity reactions are also common.

Nursing – Diuretics

  • Before initiating diuretic therapy, obtain a comprehensive baseline assessment, including daily weights (reflecting fluid status), blood pressure (BP) and pulse (for orthostatic changes), serum electrolytes ( ext{Na}^+, ext{K}^+, ext{Cl}^-, ext{Mg}^2+, ext{Ca}^2+ ), and renal function tests (BUN, creatinine, GFR) to guide dosing and monitor for adverse effects.

  • Instruct patients to take diuretics in the morning to prevent nocturia and sleep disturbance. Monitor for orthostatic hypotension (dizziness, lightheadedness upon standing) as a potential side effect, especially at the start of therapy or with dose increases.

  • Carefully assess potassium ( ext{K}^+ ) levels. Patients on loop or thiazide diuretics often require potassium supplementation to prevent hypokalemia. Conversely, avoid potassium supplements and potassium-rich foods, and use extreme caution if combining with potassium-sparing diuretics or ACE inhibitors, due to the high risk of hyperkalemia.

  • Be vigilant for potential ototoxicity when loop diuretics are administered concurrently with other ototoxic drugs (e.g., aminoglycoside antibiotics, vancomycin), as this combination significantly increases the risk of irreversible hearing loss.

Chapter 29 – Fluids & Electrolytes

  • Crystalloids (e.g., Normal Saline (NS, 0.9% NaCl), Lactated Ringer's (LR), and Dextrose 5% in Water (D5W)) are intravenous solutions containing small molecules that can readily pass from the bloodstream into the interstitial fluid. They are primarily used to replace water and sodium and to expand intravascular volume. Risks include peripheral and pulmonary edema, and dilutional hyponatremia. Hypertonic saline (e.g., 3% NaCl) is reserved for severe, symptomatic hyponatremia, and must be administered slowly to prevent Osmotic Demyelination Syndrome (ODS), a potentially irreversible neurological disorder caused by too rapid correction of chronic hyponatremia.

  • Colloids (e.g., 5% albumin, dextran, hetastarch) are intravenous solutions containing large molecules that remain primarily in the intravascular space, exerting high oncotic pressure to draw fluid from the interstitial compartment into the plasma and expand blood volume. While effective for volume resuscitation, they can dilute coagulation factors and plasma proteins, potentially increasing bleeding risk, and some (e.g., hetastarch) have fallen out of favor due to renal toxicity concerns.

  • Blood products (e.g., packed red blood cells, plasma, platelets) provide oxygen-carrying capacity, coagulation factors, or platelets, in addition to volume expansion. They must only be infused with normal saline (0.9% NaCl) to prevent cell lysis or clotting, and patients must be closely monitored for signs of acute or delayed transfusion reactions (e.g., fever, chills, urticaria, dyspnea, hypotension).

  • Potassium ( ext{K}^+ ) is a crucial intracellular cation with a narrow normal serum range of 3.5 ext{-}5.0 ext{ mEq/L} . Intravenous (IV) potassium replacement should not exceed 10 ext{ mEq/hour} in unmonitored settings due to the risk of cardiac arrhythmias. Early signs of hypokalemia ( < 3.5 ext{ mEq/L} ) include muscle weakness, fatigue, hypotension, and lethargy. Hyperkalemia ( > 5.5 ext{ mEq/L} ) is a medical emergency, primarily affecting cardiac conduction and prone to causing life-threatening arrhythmias (e.g., peaked T waves, wide QRS, ventricular fibrillation).

  • Sodium ( ext{Na}^+ ) is the primary extracellular cation, with a normal serum range of 135 ext{-}145 ext{ mEq/L} . Hyponatremia ( < 135 ext{ mEq/L} ) can be severe. Rapid correction of chronic hyponatremia (developed over > 48 ext{ hours} ) is highly dangerous and can lead to Osmotic Demyelination Syndrome (ODS), causing severe and permanent neurological damage due to rapid osmotic shifts in brain cells. Correction rates should generally not exceed 8 ext{-}12 ext{ mEq/L} over 24 hours.

  • Vaptans (e.g., conivaptan, tolvaptan) are vasopressin receptor antagonists that promote free water excretion without affecting sodium excretion. They are specifically used to treat euvolemic and hypervolemic hyponatremia (e.g., Syndrome of Inappropriate Antidiuretic Hormone (SIADH)). Tolvaptan carries a Black Box Warning due to the risk of too-rapid correction of hyponatremia and potential liver injury, thus requiring initiation and re-initiation in an inpatient setting under close monitoring.

  • For chronic hyperkalemia, newer potassium-binding agents like patiromer and sodium zirconium cyclosilicate (Lokelma) are used. These oral agents bind potassium in the GI tract, facilitating its excretion and preventing absorption, thus lowering serum potassium levels without causing significant changes in fluid volume.

Chapter 24 – Heart Failure Drugs (Key Points)

  • Positive inotropes are a class of drugs that increase the force of myocardial contraction (contractility) of the heart, thereby improving cardiac output. Examples include cardiac glycosides like digoxin, and sympathomimetics (dobutamine) or phosphodiesterase inhibitors (milrinone) used in acute heart failure settings.

  • First-line therapy for chronic heart failure with reduced ejection fraction (HFrEF) typically involves a combination of: an ACE inhibitor (ACEI) or Angiotensin Receptor Blocker (ARB) to block the renin-angiotensin-aldosterone system (RAAS), beta-blockers (e.g., metoprolol succinate, carvedilol) to reduce sympathetic overactivity and improve cardiac remodeling, and a loop diuretic to manage fluid overload and symptoms. Aldosterone antagonists (e.g., spironolactone, eplerenone) are added next, particularly for patients with persistent symptoms, to further block deleterious RAAS effects and improve outcomes. Digoxin is generally reserved for patients with persistent symptoms despite optimal guideline-directed medical therapy, especially if atrial fibrillation is present.

  • Angiotensin Receptor-Neprilysin Inhibitors (ARNIs), such as sacubitril/valsartan, combine an ARB (valsartan) with a neprilysin inhibitor (sacubitril), which enhances natriuretic peptides. They are a Class I recommendation for symptomatic heart failure with reduced ejection fraction (HFrEF) to further reduce morbidity and mortality. Important side effects to monitor include hypotension, hyperkalemia, and increased serum creatinine due to their mechanism of action.

  • Ivabradine is a novel agent that selectively inhibits the ext{I_f} ('funny') current in the sinoatrial (SA) node, reducing heart rate without affecting contractility or blood pressure significantly. It is indicated for patients with symptomatic stable chronic HFrEF who are in sinus rhythm with a heart rate ext{\ge} 70 ext{ beats/min} and are already on maximally tolerated beta-blocker therapy, or for whom beta-blockers are contraindicated.

  • Nesiritide, a recombinant human B-type natriuretic peptide (BNP), and milrinone, a phosphodiesterase-3 inhibitor (PDE-3), are intravenous agents reserved for hospitalized patients with acutely decompensated heart failure, particularly those with persistent symptoms despite diuretics and vasodilators, and managed in an intensive care unit (ICU) setting due to their potent hemodynamic effects and potential for adverse reactions.

  • Digoxin has a very narrow therapeutic index (target serum concentration typically 0.5 ext{-}2.0 ext{ ng/mL} for heart failure). Toxicity risk significantly increases with hypokalemia and hypomagnesemia (as these electrolyte imbalances potentiate its effects) and in patients with renal failure (as it is primarily excreted renally). Classic signs of digoxin toxicity include bradycardia, anorexia, nausea, fatigue, and visual disturbances like yellow or green halos around lights. The specific antidote for severe digoxin toxicity is digoxin immune Fab (Digibind).

  • Before administering digoxin, a crucial nursing intervention is to measure the patient's apical pulse for a full minute. The dose should be withheld if the apical pulse is less than 60 ext{ beats/min} (or as per physician's order) and the healthcare provider notified, as bradycardia can be a sign of toxicity or potential adverse effect.

Chapter 25 – Antidysrhythmics (Vaughan-Williams)

  • The Vaughan-Williams classification categorizes antidysrhythmic drugs based on their primary mechanism of action. Class I agents are sodium ( ext{Na}^+ ) channel blockers, decreasing the rate of depolarization and impulse conduction. Subclass Ia (e.g., quinidine, procainamide) moderately block ext{Na}^+ channels and prolong repolarization. Subclass Ib (e.g., lidocaine) weakly block ext{Na}^+ channels, accelerate repolarization, and primarily affect ischemic tissue. Subclass Ic (e.g., flecainide) potentiate block ext{Na}^+ channels with minimal effect on repolarization, and are contraindicated post-MI due to proarrhythmic risk.

  • Class II agents are beta-blockers (e.g., metoprolol, propranolol), which reduce sympathetic activity, slowing heart rate and conduction. Class III agents (e.g., amiodarone, dofetilide, sotalol) are potassium ( ext{K}^+ ) channel blockers, which prolong repolarization and the refractory period. Class IV agents (e.g., verapamil, diltiazem) are calcium ( ext{Ca}^2+ ) channel blockers, specifically non-dihydropyridines, which primarily slow conduction through the AV node and reduce myocardial contractility.

  • Amiodarone, a Class III agent, is highly effective but associated with significant toxicities given its very long half-life. It carries Black Box Warnings for severe pulmonary toxicity (e.g., pulmonary fibrosis), hepatotoxicity, and proarrhythmia (ability to induce new or worsen existing arrhythmias). It has numerous drug interactions due to CYP inhibition, significantly increasing the levels of warfarin (requiring INR monitoring and dose reduction) and digoxin.

  • Dronedarone, a structural analog of amiodarone lacking iodine, also carries a Black Box Warning for increased risk of death, stroke, and heart failure exacerbation in patients with permanent atrial fibrillation (AF) and in patients with NYHA Class IV heart failure or recent decompensation.

  • Dofetilide, a pure Class III ext{K}^+ channel blocker, requires mandatory inpatient initiation and dose titration with continuous ECG monitoring for at least 3 days. This is crucial due to the significant risk of dose-dependent QT interval prolongation, which can lead to the life-threatening ventricular arrhythmia Torsades de Pointes.

  • A critical consideration for all antidysrhythmic drugs is their inherent proarrhythmic potential, meaning they can paradoxically cause or worsen arrhythmias. Therefore, close monitoring of the electrocardiogram (ECG) for rhythm changes and QT prolongation, along with regular assessment of serum electrolytes (especially potassium and magnesium), is essential during therapy.

Chapter 22 – Antihypertensives

  • Antihypertensive agents are diverse, targeting various mechanisms of blood pressure regulation. Categories include: diuretics (e.g., thiazides, which are often first-line); adrenergic inhibitors, acting on the sympathetic nervous system, such as ext{alpha}2 agonists (clonidine, reducing central sympathetic outflow), ext{alpha}1 blockers (doxazosin, causing vasodilation), ext{beta} -blockers (metoprolol, reducing heart rate and contractility), and mixed ext{alpha-beta} blockers (carvedilol); Angiotensin-Converting Enzyme Inhibitors (ACEIs); Angiotensin Receptor Blockers (ARBs); Calcium Channel Blockers (CCBs); direct vasodilators (hydralazine, minoxidil, direct arterial vasodilators; nitroprusside, a balanced arterial and venous dilator); and direct renin inhibitors (aliskiren, blocking the first step of the RAAS cascade).

  • ACE inhibitors (e.g., lisinopril, enalapril) prevent the conversion of angiotensin I to angiotensin II, leading to vasodilation and reduced aldosterone. Common side effects include a persistent dry cough (due to bradykinin accumulation), and hyperkalemia. A rare but serious adverse effect is angioedema (swelling of face, lips, tongue), which can be life-threatening. They carry a Black Box Warning for fetal toxicity, making them contraindicated in pregnancy.

  • Angiotensin Receptor Blockers (ARBs, e.g., valsartan, losartan) selectively block the angiotensin II type 1 ( ext{AT}_1 ) receptor, achieving similar hemodynamic effects to ACEIs without affecting bradykinin metabolism, thus significantly reducing the incidence of cough and angioedema compared to ACEIs. Like ACEIs, they are contraindicated in pregnancy due to fetal harm.

  • ext{Alpha}1 selective blockers (e.g., doxazosin) are associated with 'first-dose syncope' (a sudden and severe drop in blood pressure upon initial dosing), requiring the first dose to be given at bedtime. Clonidine, an ext{alpha}2 agonist, can cause severe rebound hypertension if abruptly discontinued, thus requiring gradual tapering of the dose.

  • Sodium nitroprusside is a potent and rapid-acting intravenous vasodilator used in hypertensive emergencies or crises. It non-selectively relaxes both arterial and venous smooth muscle. Its metabolism releases nitric oxide, but also cyanide ions, posing a risk of cyanide toxicity, especially with prolonged use or high doses, necessitating careful monitoring, particularly of thiocyanate levels.

  • African-American patients tend to respond less effectively to ACE inhibitor or ARB monotherapy for hypertension compared to other ethnic groups, likely due to a lower prevalence of renin-dependent hypertension. They often respond better to diuretics or calcium channel blockers as initial therapy, or a combination regimen.

Chapter 23 – Antianginals

Nitrates

  • Nitrates (e.g., nitroglycerin, isosorbide dinitrate, isosorbide mononitrate) are vasodilators that relax vascular smooth muscle. Their primary effect is venodilation, which significantly reduces venous return to the heart (preload), diminishing cardiac workload and myocardial oxygen demand. At higher doses, they also dilate arteries, reducing afterload. Rapid-acting formulations (e.g., sublingual nitroglycerin) are used for acute angina attacks, while long-acting forms (oral, transdermal) are for prophylaxis of chronic stable angina.

  • Common adverse effects include severe headache (due to cerebral vasodilation), reflex tachycardia (as a compensatory response to vasodilation and reduced BP), and significant hypotension, which can lead to dizziness or syncope. To prevent nitrate tolerance (tachyphylaxis), a daily nitrate-free interval of 8-12 hours is recommended, typically achieved by removing transdermal patches or omitting a dose during sleep.

  • Nitrates are absolutely contraindicated with phosphodiesterase-5 (PDE-5) inhibitors (e.g., sildenafil, tadalafil, vardenafil, avanafil), used for erectile dysfunction or pulmonary hypertension. Concurrent use can lead to a synergistic and profound drop in blood pressure, resulting in severe hypotension and potentially life-threatening cardiovascular collapse due to extreme vasodilation.

ext{beta} -Blockers (atenolol, metoprolol, propranolol)

  • Beta-blockers (e.g., atenolol, metoprolol, propranolol) reduce myocardial oxygen demand by decreasing heart rate, myocardial contractility, and blood pressure. They also reduce renin release from the kidneys, further contributing to blood pressure control. They are cornerstone therapy for stable angina, improving exercise tolerance and reducing anginal episodes.

CCB (diltiazem, verapamil, amlodipine)

  • Calcium Channel Blockers (CCBs, e.g., diltiazem, verapamil, amlodipine) cause both coronary and peripheral vasodilation by blocking calcium influx into vascular smooth muscle cells and myocardial cells. They improve oxygen supply to the myocardium and reduce cardiac workload. Non-dihydropyridine CCBs (diltiazem, verapamil) also reduce heart rate and conduction. They are particularly effective for Prinzmetal's (variant) angina, which is caused by coronary artery spasm, as they directly relax coronary arteries.

Ranolazine – late ext{Na}^+ current inhibitor (QT prolong).

  • Ranolazine is a relatively new antianginal agent that selectively inhibits the late sodium ( ext{Na}^+ ) current in cardiac myocytes, which reduces intracellular sodium and calcium overload, improving myocardial relaxation and efficiency without significantly affecting heart rate or blood pressure. Its use is associated with dose-dependent QT interval prolongation, requiring caution in patients with pre-existing QT abnormalities.

Chapter 27 – Antilipemics

  • Statins, also known as HMG-CoA reductase inhibitors (e.g., atorvastatin, simvastatin, rosuvastatin), are considered first-line therapy for hypercholesterolemia. They potently lower LDL-C (low-density lipoprotein cholesterol) by 30-50% by inhibiting cholesterol synthesis in the liver and increasing LDL receptor expression. Key adverse effects include myopathy (muscle pain/weakness), which can progress to rhabdomyolysis (severe muscle breakdown) requiring immediate medical attention, and elevated liver function tests (LFTs). Most statins should be taken in the evening as cholesterol synthesis is highest at night. Patients should avoid grapefruit juice, which can inhibit CYP3A4-mediated statin metabolism, leading to increased statin levels and toxicity risk.

  • Bile-acid sequestrants (e.g., cholestyramine, colestipol) are non-systemic agents that bind bile acids in the intestine, preventing their reabsorption and increasing their fecal excretion. This prompts the liver to synthesize more bile acids from cholesterol, thereby lowering LDL-C. Common gastrointestinal (GI) adverse effects include constipation, bloating, and nausea. They can interfere with the absorption of fat-soluble vitamins (A, D, E, K) and many other oral medications (e.g., digoxin, warfarin, thyroid hormones), necessitating administration of other oral medications at least 1 hour before or 4-6 hours after the sequestrant.

  • Niacin (nicotinic acid) is a B vitamin that, at pharmacologic doses, significantly increases HDL-C (high-density lipoprotein cholesterol) and lowers triglycerides (TG) and LDL-C. Its main adverse effect is intense cutaneous flushing and itching, which can be mitigated by taking aspirin ( 325 ext{ mg} ) 30 minutes before the niacin dose. Other AEs include hyperuricemia (gout risk), hyperglycemia (worsening glycemic control in diabetics), and hepatotoxicity at high doses.

  • Fibrates (e.g., gemfibrozil, fenofibrate) primarily activate PPAR- ext{alpha} (peroxisome proliferator-activated receptor alpha), leading to significant reductions in triglycerides and modest increases in HDL-C. Common adverse effects include gastrointestinal upset and an increased risk of gallstones (cholelithiasis). When combined with statins, there is an increased risk of myopathy, and they can potentiate the anticoagulant effect of warfarin, increasing bleeding risk.

  • Ezetimibe selectively inhibits cholesterol absorption at the brush border of the small intestine, leading to reduced delivery of cholesterol to the liver and increased cholesterol clearance from the blood. It minimally affects triglycerides or HDL. It is often combined with a statin to achieve additive LDL-C lowering, particularly when statin monotherapy is insufficient.

  • PCSK-9 (Proprotein Convertase Subtilisin/Kexin type 9) inhibitors (e.g., alirocumab, evolocumab) are monoclonal antibodies administered via subcutaneous (SQ) injection every 2 to 4 weeks. They block PCSK9 protein, which normally degrades LDL receptors on liver cells. By inhibiting PCSK9, more LDL receptors remain on the liver surface, leading to a dramatic reduction in circulating LDL-C by approximately 60%, making them highly effective for patients with familial hypercholesterolemia or established cardiovascular disease unable to achieve LDL goals with other therapies.

Chapter 30 – Pituitary Drugs

  • Cosyntropin is a synthetic analog of adrenocorticotropic hormone (ACTH). It is primarily used diagnostically in the cosyntropin stimulation test to assess adrenal cortical function. In healthy individuals, it stimulates the adrenal glands to produce and release cortisol; a blunted or absent rise in cortisol after administration indicates primary or secondary adrenal insufficiency.

  • Somatropin is a recombinant human growth hormone (rhGH). Its main therapeutic indications are for children with growth hormone deficiency (pituitary dwarfism) and for adults with GH deficiency or cachexia/wasting associated with HIV. Potential adverse effects include hyperglycemia (due to its anti-insulin effects), intracranial hypertension, and in children, slipped capital femoral epiphysis.

  • Octreotide is a synthetic analog of somatostatin, an inhibitory hormone. It acts as a growth hormone (GH) antagonist, suppressing the release of GH, as well as several other hormones including insulin, glucagon, and gastrointestinal peptides. It is primarily used to treat acromegaly (excess GH production) and to manage symptoms (e.g., severe diarrhea, flushing) associated with carcinoid syndrome and vasoactive intestinal peptide (VIP)–secreting tumors (VIPomas). Nursing considerations include monitoring blood glucose (BG) due to its effects on insulin/glucagon, and ECG for QT prolongation.

  • Vasopressin (antidiuretic hormone, ADH) and its synthetic analogue desmopressin are used for various conditions. Desmopressin is primarily used to treat central diabetes insipidus (DI) by replacing deficient ADH, and for nocturnal enuresis. Vasopressin (at higher, non-physiological doses) is a potent vasoconstrictor and is used in certain types of vasodilatory shock (e.g., septic shock) to increase systemic vascular resistance and blood pressure that are refractory to other vasopressors. When administering, closely monitor for hyponatremia due to increased water reabsorption and for blood pressure changes due to vasoconstrictive effects.

  • General nursing considerations for pituitary drugs include closely monitoring for therapeutic response (e.g., height and weight in children on somatropin), fluid balance and urine osmolality (for ADH analogs), and regularly checking liver and renal function tests due to potential drug metabolism and excretion alterations.

Chapter 31 – Thyroid

Hypothyroid Replacement

  • Levothyroxine sodium is the synthetic form of thyroxine ( ext{T}_4 ) and is the preferred drug for chronic replacement therapy in hypothyroidism due to its consistent potency, long half-life (allowing once-daily dosing), and low cost. It has a narrow therapeutic index, meaning small changes in dose can have significant clinical effects, so dosing involves starting low (especially in elderly or cardiac patients) and gradually increasing ('go slow') based on TSH levels. It must be taken in the morning on an empty stomach (at least 30-60 minutes before food or other medications) to ensure consistent absorption. It has numerous drug interactions, notably increasing the anticoagulant effect of warfarin (due to increased catabolism of vitamin K-dependent clotting factors), requiring careful INR monitoring.

  • Adverse effects of levothyroxine are typically signs of overdose or hyperthyroidism (thyrotoxicosis) and include tachycardia, palpitations, angina, dysrhythmias, insomnia, nervousness, tremors, heat intolerance, weight loss, and diarrhea.

Antithyroid

  • Thioamides, specifically propylthiouracil (PTU) and methimazole, are the primary drugs for treating hyperthyroidism (e.g., Graves' disease). They inhibit thyroid hormone synthesis by blocking the peroxidase enzyme, which is crucial for the organification of iodine (incorporation of iodine into tyrosine residues) and the coupling of iodotyrosines to form ext{T}3 and ext{T}4 hormones. PTU also inhibits the peripheral conversion of ext{T}4 to the more active ext{T}3 , making it useful in thyroid storm.

  • Radioactive iodine ( ext{I}^{131} ) therapy involves oral administration of a radioactive isotope of iodine that is selectively concentrated by the thyroid gland, leading to the gradual destruction of overactive thyroid tissue without significantly affecting other body tissues. It is a common and effective treatment for Graves' disease and toxic nodular goiter, often resulting in permanent hypothyroidism.

  • Adverse effects of thioamides include hepatotoxicity (PTU carries a Black Box Warning for severe liver injury and acute liver failure, warranting it as a second-line option except in specific circumstances like thyroid storm or first trimester of pregnancy), and the very serious but rare agranulocytosis (a severe reduction in white blood cell count, increasing infection risk). Patients should be advised to avoid iodine-rich foods (e.g., iodized salt, seafood) and iodine-containing medications like amiodarone, as iodine can exacerbate hyperthyroidism.

  • Therapy for thyroid disorders requires close monitoring. Thyroid-stimulating hormone (TSH) and free ext{T}_4 levels should be checked every 4 to 6 weeks until stable, and then periodically (e.g., every 6-12 months) to ensure optimal dosing and therapeutic efficacy.

Chapter 32 – Antidiabetics (Key Highlights)

  • Insulin therapy involves various types categorized by their onset, peak, and duration of action: rapid-acting (e.g., lispro, aspart, glulisine; inhaled Afrezza) for mealtime coverage; short-acting (regular) for mealtime or IV use; intermediate-acting (NPH) with cloudy appearance; and long-acting (e.g., glargine, detemir, degludec; concentrated U-500 regular insulin) for basal coverage. Mixed insulins combine rapid/short and intermediate insulins.

  • The basal-bolus regimen, mimicking physiological insulin secretion, is generally preferred for optimal glycemic control, involving a long-acting (basal) insulin for continuous coverage and rapid-acting (bolus) insulin before meals. Only regular insulin can be administered intravenously (IV), making it the insulin of choice for emergency situations like diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS).

  • Hypoglycemia (blood glucose < 70 ext{ mg/dL} ) is a common and serious side effect of insulin and some oral agents. Mild to moderate hypoglycemia should be treated with 15 ext{ grams} of a fast-acting carbohydrate (e.g., glucose tablets, juice). For unconscious patients or those unable to swallow, glucagon (a hormone that raises blood glucose) can be administered subcutaneously (SQ) or intramuscularly (IM) and is typically supplied as an emergency kit.

  • Oral antidiabetic agents are used for type 2 diabetes. Metformin, a biguanide, is the first-line oral therapy. It works by decreasing hepatic glucose production and increasing insulin sensitivity. It carries a Black Box Warning for lactic acidosis, a rare but potentially fatal metabolic complication, particularly in patients with renal impairment. It must be discontinued if estimated glomerular filtration rate (eGFR) falls below 30 ext{ mL/min/1.73 m}^2 or before contrast dye administration.

  • Sulfonylureas (e.g., glipizide, glyburide) stimulate insulin release from pancreatic beta cells by blocking ATP-sensitive potassium channels. They are effective at lowering glucose but carry a significant risk of hypoglycemia and weight gain.

  • Glinides (e.g., repaglinide, nateglinide) are meglitinide analogues that also stimulate insulin secretion from beta cells but have a rapid onset and short duration of action, making them ideal for administration just before meals to control postprandial glucose excursions, with a lower risk of hypoglycemia than sulfonylureas if a meal is skipped.

  • Thiazolidinediones (TZDs, e.g., pioglitazone, rosiglitazone) improve insulin sensitivity in peripheral tissues (muscle, adipose) and reduce hepatic glucose output. They carry a Black Box Warning for exacerbation of existing congestive heart failure and are contraindicated in patients with symptomatic heart failure (NYHA Class III or IV) due to fluid retention and increased risk of cardiovascular events.

  • Alpha-glucosidase inhibitors (e.g., acarbose, miglitol) delay the digestion and absorption of carbohydrates in the small intestine, primarily lowering postprandial glucose levels. Because their mechanism does not involve insulin secretion, they do not cause hypoglycemia directly. If hypoglycemia occurs from concomitant insulin or sulfonylurea use, it must be treated with pure glucose (dextrose) tablets, not sucrose (table sugar), as sucrose breakdown is inhibited.

  • Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g., sitagliptin, saxagliptin) enhance the body's natural incretin system. They inhibit DPP-4 enzyme, which prolongs the activity of GLP-1 and GIP hormones, leading to glucose-dependent insulin release and suppression of glucagon secretion, thus lowering glucose levels with a low risk of hypoglycemia.

  • Glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., exenatide, liraglutide, dulaglutide, semaglutide) are injectable (SQ) agents that mimic the action of natural incretins, promoting glucose-dependent insulin secretion, suppressing glucagon, slowing gastric emptying, and promoting satiety. They are effective for weight loss. Most agents in this class carry a Black Box Warning for risk of thyroid C-cell tumors (including medullary thyroid carcinoma) observed in rodent studies, and are contraindicated in patients with a personal or family history of such cancers or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

  • Sodium-glucose cotransporter 2 (SGLT2) inhibitors (e.g., canagliflozin, empagliflozin, dapagliflozin) lower blood glucose by blocking SGLT2 in the renal proximal tubule, reducing glucose reabsorption and increasing urinary glucose excretion (glycosuria). While effective for glycemic control, they carry risks including increased incidence of genitourinary infections, diabetic ketoacidosis (DKA) even with near-normal glucose levels (eu-DKA), and a rare but serious genital infection called Fournier's gangrene, a necrotizing fasciitis of the perineum.

Chapter 14 – Antiepileptics

  • The primary goal of antiepileptic drug (AED) therapy is to achieve seizure freedom with minimal adverse effects (AEs). Treatment typically begins with monotherapy (a single agent) to minimize side effects and drug interactions. Therapeutic drug monitoring (measuring plasma drug levels) is often employed for many AEDs with narrow therapeutic ranges or variable pharmacokinetics to optimize dosing and ensure efficacy while avoiding toxicity.

  • Classic AEDs frequently used include: phenytoin, a sodium channel blocker, known for non-linear pharmacokinetics and significant drug interactions; carbamazepine, a sodium channel blocker, carries a Black Box Warning for serious dermatologic reactions (e.g., SJS/TEN) and aplastic anemia/agranulocytosis; valproate, which enhances GABA, inhibits sodium channels, and modulates calcium channels, carries Black Box Warnings for hepatotoxicity (especially in young children) and pancreatitis, and fetal neural tube defects; and phenobarbital, a barbiturate that enhances GABA action, known for its sedative effects and enzyme induction.

  • Newer generation AEDs generally have more favorable side effect profiles and fewer drug interactions: levetiracetam, with a unique mechanism of action (SV2A protein binding), is well-tolerated; lamotrigine, a sodium channel blocker, carries a Black Box Warning for severe, potentially life-threatening skin rashes including Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN), necessitating slow dose titration; and topiramate, with multiple mechanisms including sodium channel blockade, GABA potentiation, and AMPA/kainate receptor antagonism, is associated with cognitive effects and kidney stones.

  • Many classic AEDs (e.g., phenytoin, carbamazepine, phenobarbital) are potent inducers of hepatic cytochrome P450 (CYP) enzymes. This enzyme induction can accelerate the metabolism of other drugs, notably leading to reduced efficacy or failure of oral contraceptives, requiring alternative birth control methods for women of childbearing potential on these AEDs.

  • A class-wide Black Box Warning for all antiepileptic drugs indicates an increased risk of suicidal thoughts or behavior (suicidal ideation) in patients taking these medications, regardless of the indication. Patients and caregivers should be monitored for new or worsening depression, suicidal thoughts, or unusual changes in mood or behavior.

  • Intravenous (IV) phenytoin administration requires careful attention: it must be infused slowly, at a rate no faster than 50 ext{ mg/min} in adults, to avoid severe hypotension, cardiac arrhythmias (especially bradycardia), and CNS depression, often referred to as 'purple glove syndrome' (extravasation leading to tissue necrosis). A filter should be used during administration, and it should only be diluted and infused in normal saline (0.9% NaCl) due to its instability in other solutions.

Chapter 15 – Parkinson’s

  • Levodopa combined with carbidopa (Sinemet) is the most effective pharmacologic treatment and the cornerstone therapy for Parkinson's disease (PD). Levodopa is a dopamine precursor that crosses the blood-brain barrier and is converted to dopamine in the brain, while carbidopa inhibits the peripheral breakdown of levodopa, allowing more to reach the brain and reducing peripheral side effects. However, long-term use (typically after 5-10 years) is associated with motor complications such as 'wearing-off' phenomena and dyskinesias. Absorption of levodopa can be affected by high-protein meals, so it is recommended to administer it 30 minutes before a protein-rich meal.

  • Catechol-O-methyltransferase (COMT) inhibitors (e.g., entacapone, tolcapone) are used as adjuncts to levodopa/carbidopa. They prolong the duration of action of levodopa by inhibiting its peripheral breakdown by the COMT enzyme, thus allowing more levodopa to enter the brain and reducing 'wearing-off' symptoms. A common but harmless side effect is orange-brown discoloration of the urine. Tolcapone carries a Black Box Warning for potentially fatal hepatotoxicity and requires liver function monitoring, making it less commonly used than entacapone.

  • Monoamine oxidase-B (MAO-B) inhibitors (e.g., selegiline, rasagiline) selectively inhibit the MAO-B enzyme, which metabolizes dopamine in the brain, thereby increasing dopamine levels in the synaptic cleft. While MAO-B inhibitors generally do not require strict dietary tyramine restriction at recommended doses, large amounts of tyramine-rich foods (e.g., aged cheeses, cured meats) should be avoided due to the theoretical risk of hypertensive crisis, especially with older non-selective MAOIs. Meperidine (pethidine) is contraindicated with MAOIs due to potential for severe serotonin syndrome.

  • Dopamine agonists (e.g., pramipexole, ropinirole, rotigotine) directly stimulate dopamine receptors in the brain. They are often used as initial therapy in early Parkinson's disease to delay the need for levodopa or as adjuncts in advanced disease. A notable class effect is the potential for impulse control disorders (e.g., pathological gambling, hypersexuality, compulsive shopping) and sudden sleep attacks.

  • Anticholinergic agents (e.g., benztropine, trihexyphenidyl) block muscarinic acetylcholine receptors, primarily used to reduce tremor and rigidity in Parkinson's disease, particularly in younger patients. Their use is limited by classic anticholinergic side effects such as dry mouth, blurred vision (due to cycloplegia), urinary retention, constipation, and cognitive impairment (especially in the elderly).

Chapter 12 – CNS Depressants & Muscle Relaxants

  • Benzodiazepines (e.g., diazepam, lorazepam, alprazolam) are a class of CNS depressants that enhance the inhibitory effects of gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain, by increasing the frequency of chloride channel opening. They are widely prescribed for anxiety disorders, acute seizures, and short-term management of insomnia. In 2020, the FDA issued a Black Box Warning regarding the risks of abuse, misuse, addiction, and physical dependence, especially when co-administered with opioids. The specific antidote for benzodiazepine overdose is flumazenil, a competitive GABA receptor antagonist.

  • Non-benzodiazepine hypnotics, often called 'Z-drugs' (e.g., zolpidem, zaleplon, eszopiclone), selectively bind to specific GABA-A receptor subunits, promoting sleep with less anxiolytic or anticonvulsant activity than benzodiazepines, but still carrying similar risks for dependence and complex sleep behaviors. Suvorexant is an orexin receptor antagonist, which blocks the wake-promoting neurotransmitter orexin, promoting sleep through a different mechanism.

  • Barbiturates (e.g., phenobarbital) are older CNS depressants that enhance GABA action by increasing the duration of chloride channel opening. They have a very low therapeutic index, meaning the difference between therapeutic and toxic doses is small, making overdose highly dangerous. They induce numerous hepatic cytochrome P450 (CYP) enzymes, leading to significant drug interactions and accelerating the metabolism of many concurrent medications.

  • Muscle relaxants are used to alleviate muscle spasms and spasticity. Baclofen and cyclobenzaprine (a tricyclic antidepressant derivative) act centrally on the CNS to reduce muscle tone, both cause significant sedation. Dantrolene is unique as it acts directly on skeletal muscle by inhibiting calcium release from the sarcoplasmic reticulum, making it effective for malignant hyperthermia and severe spasticity. Nursing care for all muscle relaxants involves close monitoring for sedation and falls risk due to CNS depression.

Chapter 13 – CNS Stimulants

  • CNS stimulants (e.g., amphetamine, methylphenidate, lisdexamfetamine) are primarily used to treat Attention-Deficit/Hyperactivity Disorder (ADHD) and narcolepsy. They increase levels of norepinephrine and dopamine in the brain. Common adverse effects include increased blood pressure and heart rate, insomnia (if taken late in the day), decreased appetite and weight loss, and potential growth suppression in children. All are Schedule II controlled substances due to their high potential for abuse and dependence.

  • Anorexiants are medications used to suppress appetite and aid in weight loss. Phentermine is a sympathomimetic amine that stimulates the release of norepinephrine from nerve terminals in the brain's appetite control center. Orlistat is a peripheral lipase inhibitor that reduces the absorption of dietary fats by inhibiting gastric and pancreatic lipases, leading to common gastrointestinal side effects such as oily stools (steatorrhea), flatulence with discharge, and fecal urgency.

  • For migraine headaches, triptans (e.g., sumatriptan) are first-line acute treatment for moderate to severe attacks. They are selective serotonin ( 5 ext{-} ext{HT}_{1B/1D} ) receptor agonists that cause vasoconstriction of intracranial blood vessels (which are dilated during migraines) and inhibit the release of pro-inflammatory neuropeptides. They are contraindicated in patients with coronary artery disease (CAD), uncontrolled hypertension, or a history of stroke due to their vasoconstrictive effects. Newer agents include CGRP (calcitonin gene-related peptide) inhibitors (e.g., erenumab), which are monoclonal antibodies that block the CGRP receptor, preventing migraine attacks by targeting a key neurotransmitter involved in migraine pathophysiology.

  • Analeptics are CNS stimulants that primarily stimulate the respiratory center in the medulla, increasing the depth and rate of respiration. Examples include caffeine and doxapram. They are used to treat respiratory depression, such as from drug overdose or apnea of prematurity. However, their use requires careful monitoring due to the risk of significant CNS excitation, including seizures, especially at higher doses.

Chapter 45 – Cancer Basics

  • Chemotherapeutic agents are broadly classified based on their mechanism of action. Cell-cycle specific (CCS) drugs are active only during specific phases of the cell cycle. This includes: antimetabolites (e.g., methotrexate, 5-fluorouracil (5-FU)), which interfere with DNA and RNA synthesis; mitotic inhibitors (e.g., vincristine, paclitaxel), which disrupt microtubule formation or function, halting cell division; topoisomerase I inhibitors (e.g., irinotecan), which block DNA unwinding; topoisomerase II inhibitors (e.g., etoposide), which interfere with DNA strand breaking and re-ligation; and asparaginase, which deprives cancer cells of essential asparagine.

  • Cell-cycle non-specific (CCNS) drugs act at any phase of the cell cycle, including the resting phase. Key examples include: alkylating agents (e.g., cyclophosphamide, cisplatin), which form covalent bonds with DNA, causing cross-linking and inhibiting replication; and anthracyclines (e.g., doxorubicin, daunorubicin), which intercalate into DNA, inhibit topoisomerase II, and generate free radicals, leading to DNA damage.

  • Chemotherapy agents often have dose-limiting toxicities, which are severe side effects that necessitate reducing the drug dose or delaying treatment. Common examples include myelosuppression (bone marrow suppression, leading to neutropenia, anemia, thrombocytopenia), mucositis (inflammation and ulceration of mucous membranes throughout the GI tract), alopecia (hair loss), and severe nausea and vomiting (N/V).

  • During chemotherapy, close monitoring of the absolute neutrophil count (ANC) is crucial to assess myelosuppression. Chemotherapy is typically held or delayed if the ANC falls below 500 ext{ cells/mm}^3 (severe neutropenia) to prevent life-threatening infections, as the patient's immune system is severely compromised.

  • Cytoprotectant agents are used to reduce the toxicity of chemotherapy without compromising its efficacy. Examples include: allopurinol, used to prevent hyperuricemia and tumor lysis syndrome (TLS) by inhibiting uric acid formation; dexrazoxane, which protects the heart from anthracycline-induced cardiotoxicity by chelating iron; and mesna, which protects the bladder from hemorrhagic cystitis caused by ifosfamide (and cyclophosphamide) by binding to toxic metabolites.

  • Extravasation, the leakage of chemotherapy from a vein into surrounding tissue, can cause severe local tissue damage including necrosis. Vinca alkaloids (e.g., vincristine, vinblastine) are potent vesicants and especially problematic; intrathecal (spinal) administration of vinca alkaloids is absolutely contraindicated and can be fatal, making careful route verification paramount.

  • Targeted therapies are newer cancer treatments that specifically target molecular pathways or proteins involved in cancer cell growth, progression, and survival, generally having fewer systemic side effects than traditional chemotherapy. Examples include: monoclonal antibodies (e.g., trastuzumab, rituximab), which bind to specific receptors on cancer cells; tyrosine kinase inhibitors (TKIs, e.g., imatinib), which block signaling pathways essential for cancer growth; and immune checkpoint inhibitors (e.g., pembrolizumab, nivolumab), which block proteins that prevent the immune system from attacking cancer cells, thereby enhancing the anti-tumor immune response.

Chapter 35 – Men’s Health

  • Testosterone replacement therapy (TRT) is used to treat male hypogonadism. Available formulations include intramuscular (IM) injections, transdermal patches or gels, and oral forms. Adverse effects include an increased risk of thromboembolism (blood clots), including a Black Box Warning for increased risk of venous thromboembolic events (VTE) such as DVT and pulmonary embolism; gynecomastia (breast tissue enlargement), fluid retention (leading to weight gain and edema), and potential prostate enlargement or exacerbation of prostate cancer (contraindicated if known prostate cancer).

  • 5 ext{-} ext{alpha} -reductase inhibitors (e.g., finasteride, dutasteride) block the enzyme that converts testosterone to dihydrotestosterone (DHT), a potent androgen responsible for prostate growth. They are used to shrink the prostate in benign prostatic hyperplasia (BPH) and to treat androgenetic alopecia (male pattern baldness). Pregnant women must avoid handling these drugs (especially crushed or broken tablets) due to their teratogenic effects on a male fetus (risk of genital abnormalities). They also reduce prostate-specific antigen (PSA) levels by approximately 50%, which needs to be considered when interpreting PSA screening results for prostate cancer.

  • ext{alpha-1} adrenergic blockers (e.g., tamsulosin, alfuzosin, silodosin, doxazosin) relax the smooth muscle in the prostate and bladder neck by blocking ext{alpha-1} adrenergic receptors. This rapidly improves urine flow and reduces BPH symptoms without shrinking the prostate. Tamsulosin is uroselective, causing less impact on blood pressure compared to non-selective agents.

  • Phosphodiesterase-5 (PDE-5) inhibitors (e.g., sildenafil, tadalafil, vardenafil, avanafil) treat erectile dysfunction (ED) by increasing cyclic guanosine monophosphate (cGMP) in the corpus cavernosum, leading to smooth muscle relaxation and enhanced blood flow during sexual arousal. They are absolutely contraindicated with nitrates due to the synergistic increase in cGMP and profound, potentially fatal hypotension. Common adverse effects include headache, flushing, dyspepsia, and nasal congestion. Rare but serious AEs are sudden vision loss (non-arteritic anterior ischemic optic neuropathy, NAION) and priapism (prolonged erection lasting > 4 ext{ hours} , requiring emergency medical attention).

  • Anabolic steroids (e.g., oxandrolone, nandrolone) are synthetic derivatives of testosterone prescribed for conditions like muscle wasting, anemia, and hereditary angioedema. They are Schedule III controlled substances due to their potential for abuse. Significant risks associated with non-medical use include liver damage (e.g., peliosis hepatis, liver cancer), adverse cardiovascular effects (e.g., increased LDL, decreased HDL, hypertension, cardiomyopathy), psychiatric effects (aggression, mood swings), and reproductive issues.

Chapter 34 – Women’s Health

Estrogens / Progestins

  • Hormone Replacement Therapy (HRT), involving estrogen alone or in combination with a progestin, is used primarily to manage moderate to severe menopausal symptoms (e.g., hot flashes, vaginal atrophy). It is contraindicated in patients with a history of breast cancer, estrogen-dependent tumors, or active thromboembolic disease. HRT carries Black Box Warnings for increased risk of endometrial cancer (if estrogen is used without progestin in women with a uterus), cardiovascular events (stroke, myocardial infarction), dementia (in women over 65 ext{ years old} starting HRT), and venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE).

  • Selective Estrogen Receptor Modulators (SERMs) (e.g., raloxifene, tamoxifen) act as estrogen agonists in some tissues and antagonists in others. Raloxifene, specifically, has estrogenic effects on bone (increasing bone density, used for osteoporosis prevention/treatment) and anti-estrogenic effects on breast and uterine tissue (reducing breast cancer risk, particularly invasive breast cancer). However, it can exacerbate hot flashes and increases the risk of deep vein thrombosis (DVT) and PE, similar to estrogen.

  • Hormonal contraceptives, commonly estrogen-progestin combinations (available as monophasic, biphasic, or triphasic formulations that vary hormone dosages), primarily work by inhibiting ovulation, thickening cervical mucus, and altering the endometrium. Several drugs (e.g., rifampin, many anticonvulsants like carbamazepine/phenytoin, and some broad-spectrum antibiotics) can significantly reduce the efficacy of oral contraceptives by inducing hepatic metabolism or altering gut flora. Combination oral contraceptives carry a Black Box Warning regarding the increased risk of serious cardiovascular events (e.g., thrombosis, stroke, myocardial infarction) in women over 35 ext{ years old} who smoke, due to estrogen's procoagulant effects. Smoking is a strong contraindication for such users.

Osteoporosis Drugs

  • Bisphosphonates (e.g., alendronate, risedronate, zoledronic acid) are antiresorptive agents that inhibit osteoclast activity, slowing bone breakdown and increasing bone density. They are first-line for osteoporosis. Patients must remain upright for at least 30 minutes (and until after the first food of the day) and take with a full glass of plain water to prevent severe esophageal irritation and erosive esophagitis. Rare but serious adverse effects include osteonecrosis of the jaw (ONJ) and atypical femoral fractures with long-term use.

  • Other osteoporosis treatments include: calcitonin (nasal spray, subcutaneous), which inhibits osteoclast activity (less potent); SERMs (raloxifene); anabolic agents like parathyroid hormone (PTH) analogues (teriparatide, abaloparatide), which stimulate osteoblast activity and new bone formation (used for severe osteoporosis, duration limited to 2 years); denosumab, a monoclonal antibody that targets RANKL (receptor activator of nuclear factor kappa-B ligand) preventing osteoclast formation; and romosozumab, a sclerostin inhibitor that increases bone formation and decreases bone resorption.

Fertility & Uterine Drugs

  • Clomiphene citrate is a selective estrogen receptor modulator (SERM) that acts as an estrogen antagonist at the hypothalamus and pituitary, leading to increased pulsatile release of GnRH, LH, and FSH, which stimulates ovarian follicle development and ovulation. It is commonly used for infertility due to ovulatory dysfunction. Key adverse effects include an increased risk of multiple gestations (e.g., twins, triplets) and ovarian hyper-stimulation syndrome (OHSS), which can range from mild discomfort to severe, life-threatening fluid shifts.

  • Menotropins (human menopausal gonadotropin, hMG) are injectable preparations containing both follicle-stimulating hormone (FSH) and luteinizing hormone (LH), derived from the urine of postmenopausal women. They directly stimulate ovarian follicular growth and maturation and are used in assisted reproductive technologies.

  • Oxytocin is a synthetic hormone that stimulates uterine contractions. It is used to induce or augment labor at term and to control postpartum hemorrhage (PPH) by causing sustained uterine contractions that compress blood vessels. Close monitoring of fetal heart rate (HR) and uterine contraction patterns is critical during labor induction to prevent fetal distress or uterine hyperstimulation/rupture.

  • Tocolytics are drugs used to suppress uterine contractions and delay preterm labor. Examples include: indomethacin (an NSAID that inhibits prostaglandin synthesis); nifedipine (a calcium channel blocker that relaxes uterine smooth muscle); and terbutaline (a beta-2 ( ext{beta}_2 )-adrenergic agonist, which also relaxes the uterus, though less commonly used now due to cardiovascular side effects in the mother).

  • Ergot alkaloids, such as methylergonovine, directly stimulate sustained uterine contractions and are primarily used to prevent or treat postpartum hemorrhage (PPH) by compressing blood vessels in the myometrium. They are contraindicated in patients with hypertension (HTN) or preeclampsia due to their potent vasoconstrictive effects, which can lead to dangerously elevated blood pressure and stroke.