Comprehensive Pharmacology of Endocrine, Antilipemic, and Respiratory Agents

Comprehensive vocabulary flashcards covering the pharmacological actions, mechanisms, clinical indications, adverse effects, and nursing considerations for endocrine (diabetes, thyroid), antilipemic (dyslipidemia), and respiratory medications.

Diabetes Mellitus Diagnostic Criteria

Clinical laboratory criteria used to diagnose diabetes: an $HbA1c ≥ 6.5\%$, a fasting plasma blood glucose $\ge 126\,\text{mg/dL}$, or an oral glucose tolerance test (OGTT) 2-hour value $\ge 200\,\text{mg/dL}$. Prediabetes is defined as an $HbA1c$ of $5.7\text{--}6.4\%$, fasting glucose of $100\text{--}125\,\text{mg/dL}$, or OGTT of $140\text{--}199\,\text{mg/dL}$.

Type 1 Diabetes Mellitus

An autoimmune disorder characterized by the destruction of pancreatic beta cells, resulting in an absolute deficiency of insulin secretion. It typically manifests at younger ages, lacks a cure or preventive measure, and strictly requires exogenous insulin replacement therapy.

Type 2 Diabetes Mellitus

A progressive metabolic disorder driven by target cell insulin resistance combined with a secretory defect of beta cells. It primarily occurs in adults (though increasingly seen in pediatric obesity), produces elevated blood glucose levels, and can frequently be prevented or managed through lifestyle changes.

Diabetic Microvascular and Macrovascular Complications

Chronic end-organ damage secondary to persistent hyperglycemia. Microvascular complications include diabetic retinopathy (vision loss), diabetic nephropathy (leading cause of dialysis), and diabetic neuropathy (paresthesias starting in extremities). Macrovascular complications include stroke, diabetic cardiopathy (treated as a coronary disease equivalent), and peripheral vascular insufficiency leading to ulcers and amputations.

Metformin (Glucophage)

A first-line oral biguanide that decreases hepatic glucose production, reduces intestinal glucose absorption, and increases peripheral insulin sensitivity without stimulating insulin release from pancreatic beta cells (therefore carries no inherent risk of hypoglycemia). It frequently causes gastrointestinal side effects, can impair vitamin $B_{12}$ and folic acid absorption with long-term use, and may induce ovulation in women with polycystic ovarian syndrome.

Lactic Acidosis (Metformin Complication)

A rare but life-threatening complication of biguanide therapy marked by the accumulation of lactic acid, presenting with hyperventilation, severe fatigue, muscle aches, abdominal discomfort, and vomiting. Risk increases substantially in patients with underlying renal dysfunction or hypovolemic dehydration.

Glipizide (Glucotrol)

A second-generation sulfonylurea that stimulates insulin exocytosis from functioning pancreatic beta cells by closing ATP-sensitive $K^+$ channels, causing cellular depolarization and calcium influx. Adverse effects include symptomatic hypoglycemia, disulfiram-like reactions with ethanol, and rare occurrences of Stevens-Johnson syndrome/toxic epidermal necrolysis; it is ineffective in Type 1 diabetes because it requires working beta cells.

Pioglitazone (Actos)

A thiazolidinedione (TZD) that functions as an agonist for the nuclear peroxisome proliferator-activated receptor-gamma ($\text{PPAR}\gamma$), increasing gene transcription for insulin sensitivity in muscle, adipose tissue, and liver. Key adverse effects include fluid retention and peripheral edema (contraindicated in symptomatic heart failure), increased bone fracture risk in women, and elevated risk of bladder cancer.

Acarbose (Precose)

An oral alpha-glucosidase inhibitor that competitively delays the breakdown of complex carbohydrates into monosaccharides at the intestinal brush border, attenuating postprandial glucose excursions. Major adverse effects are GI-related (flatulence, cramps, diarrhea); if hypoglycemia occurs when combined with secretagogues, it must be treated with pure glucose (dextrose) rather than sucrose because disaccharide breakdown is inhibited.

Canagliflozin (Invokana)

A sodium-glucose co-transporter 2 (SGLT-2) inhibitor that prevents renal glucose reabsorption in the proximal convoluted tubules, lowering the renal threshold for glucose excretion from $> 180\,\text{mg/dL}$ down to $> 70\text{--}90\,\text{mg/dL}$. Promotes glucosuria, osmotic diuresis, and weight loss, but carries risks of mycotic genitourinary infections, postural hypotension, and diabetic foot ulcers/lower extremity amputations.

Sitagliptin (Januvia)

An oral dipeptidyl peptidase-4 (DPP-4) inhibitor that prevents the enzymatic degradation of endogenous incretin hormones (GLP-1 and GIP), thereby enhancing glucose-dependent insulin secretion and suppressing glucagon output. It is generally well tolerated, with rare risks including nasopharyngitis, acute pancreatitis, and severe hypersensitivity reactions (angioedema, anaphylaxis).

Semaglutide (Ozempic, Wegovy)

A glucagon-like peptide-1 (GLP-1) receptor agonist administered subcutaneously once weekly that amplifies glucose-dependent insulin release, downregulates glucagon, slows gastric emptying, and increases central satiety. Major adverse effects include nausea, vomiting, diarrhea, acute kidney injury secondary to dehydration, and a boxed warning contraindicating use in patients with personal or family history of medullary thyroid carcinoma.

Tirzepatide (Mounjaro, Zepbound)

A dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist administered subcutaneously once weekly. It exhibits synergistic actions on insulin release, glucagon suppression, and gastric motility to significantly lower blood glucose and promote substantial weight reduction; carries the same GI adverse effects and medullary thyroid carcinoma precautions as GLP-1 agonists.

Insulin Glulisine (Apidra)

A rapid-acting analog insulin formulation with an onset of $10\text{--}20\,\text{minutes}$, peak effect at $1\text{--}3\,\text{hours}$, and total duration of $3\text{--}5\,\text{hours}$. It is injected immediately before or soon after meals to mimic normal mealtime physiologic insulin spikes and control postprandial glucose surges.

Regular Insulin (Humulin R)

A short-acting human insulin preparation with an onset of $0.5\text{--}1\,\text{hour}$, peak effect at $1\text{--}5\,\text{hours}$, and total duration of $6\text{--}10\,\text{hours}$. It is routinely administered approximately $30\,\text{minutes}$ prior to meals and represents the standard formulation authorized for intravenous infusion in critical care scenarios such as diabetic ketoacidosis.

NPH Insulin (Novolin N)

An intermediate-acting neutral protamine Hagedorn insulin suspension with an onset of $1\text{--}2\,\text{hours}$, peak of $4\text{--}12\,\text{hours}$, and duration of $12\text{--}18\,\text{hours}$. It presents as a cloudy formulation that requires gentle rolling to resuspend and is the only intermediate formulation that can be physically combined in the same syringe with short- or rapid-acting insulins.

Insulin Glargine (Lantus)

A long-acting basal analog insulin with an onset of $1\text{--}2\,\text{hours}$, no pronounced peak (flat concentration profile), and a steady duration of approximately $24\,\text{hours}$. It is administered subcutaneously once daily at the same time to supply basal coverage and must never be mixed with other insulins.

Insulin Pharmacokinetics

The comparative time-action profiles of subcutaneous insulins: rapid-acting agents (lispro, aspart, glulisine) demonstrate the fastest onset and peak for meal coverage; short-acting (regular) provides mid-range meal coverage; intermediate (NPH) yields a prolonged mid-day peak; and long-acting agents (glargine, detemir) provide a peakless, 24-hour basal concentration.

Lipohypertrophy

A localized subcutaneous accumulation of fibrous and adipose tissue caused by repeated insulin injections at the same anatomical site. Injecting into lipohypertrophic lesions impairs and destabilizes drug absorption, mandating routine systematic rotation of injection sites.

Diabetic Ketoacidosis (DKA) vs. Hyperglycemic Hyperosmolar State (HHS)

Acute glycemic crises. DKA involves absolute insulin deficiency leading to severe hyperglycemia, ketosis, and metabolic acidosis, evolving over hours to 1-2 days primarily in Type 1 diabetes (mortality $< 1\%$). HHS involves severe relative insulin deficiency resulting in profound hyperglycemia ($\ge 600\,\text{mg/dL}$) and hyperosmolality from urinary free water losses without marked ketoacidosis, evolving over days to weeks in Type 2 diabetes with higher mortality ($5\text{--}20\%$).

Hypothalamic-Pituitary-Thyroid (HPT) Axis

A neuroendocrine negative feedback system wherein the hypothalamus secretes thyroid-releasing hormone (TRH) to stimulate anterior pituitary synthesis of thyroid-stimulating hormone (TSH); TSH subsequently prompts the thyroid gland to produce and secrete thyroxine ($T_4$) and triiodothyronine ($T_3$), which circulate back to inhibit further TRH and TSH release.

Hypothyroidism vs. Hyperthyroidism

Divergent thyroid states. Hypothyroidism presents with elevated TSH, low $T_4/T_3$, bradycardia, fatigue, cold intolerance, weight gain, constipation, and facial puffiness. Hyperthyroidism presents with suppressed TSH, elevated $T_4/T_3$, tachycardia, palpitations, heat intolerance, weight loss, diarrhea, and exophthalmos/thyroid eye disease.

Levothyroxine (Synthroid)

A synthetic isomer of thyroxine ($T_4$) identical to endogenous thyroid hormone used as lifelong replacement therapy for hypothyroidism. It must be taken daily on an empty stomach in the morning $30\text{--}60\,\text{minutes}$ before food or other drugs; excessive dosing produces symptoms of thyrotoxicosis (tachycardia, palpitations, insomnia) and cardiac dysrhythmias.

Methimazole (Tapazole)

A thionamide antithyroid drug that inhibits thyroid hormone synthesis by preventing the oxidation of iodide and the subsequent coupling of iodinated tyrosines. Adverse effects include drug-induced hypothyroidism and life-threatening agranulocytosis (necessitating prompt evaluation of fever or sore throat); it is avoided in pregnancy due to teratogenicity.

Atherosclerosis Pathogenesis

A chronic vascular inflammatory process initiated by endothelial injury (induced by hypertension, smoking, hyperlipidemia, or hyperglycemia), triggering platelet adhesion, smooth muscle migration, foam cell lipid accumulation, and subsequent formation of a fatty streak, fibrous plaque, and ultimately complicated thrombotic lesions.

PREVENT Risk Calculator

A cardiovascular risk assessment tool integrating clinical metrics (age, sex, total cholesterol, HDL, blood pressure, diabetes status, smoking history, BMI, eGFR) and social determinants of health (such as ZIP code) to predict 10-year and 30-year risk of atherosclerotic cardiovascular disease (ASCVD) and guide target LDL-C thresholds.

Atorvastatin (Lipitor)

An HMG-CoA reductase inhibitor that suppresses the rate-limiting enzyme in hepatic cholesterol biosynthesis, upregulating hepatic LDL receptors and lowering circulating LDL-C. Adverse effects include myopathy, rhabdomyolysis (monitored by creatine kinase), and hepatotoxicity; it requires evening administration, avoidance of grapefruit juice, and strict contraception due to category X teratogenicity.

Ezetimibe (Zetia)

A cholesterol absorption inhibitor that acts at the brush border of the small intestine to block dietary and biliary cholesterol reabsorption. Used as monotherapy or an adjunct to statins to lower LDL-C; adverse effects include myopathy/rhabdomyolysis (risk magnified when coadministered with statins), hepatotoxicity, and thrombocytopenia.

Colesevelam (Welchol)

A nonabsorbable bile-acid sequestrant that binds bile acids in the intestinal lumen, preventing enterohepatic recirculation and forcing the liver to convert endogenous cholesterol into new bile acids. It primarily causes gastrointestinal side effects (constipation, flatulence, indigestion) and impairs absorption of fat-soluble vitamins and coadministered drugs (warfarin, digoxin, thiazides), requiring doses to be spaced 1 hour before or 4 hours after.

Gemfibrozil (Lopid)

A fibric acid derivative that activates nuclear peroxisome proliferator-activated receptor-alpha ($\text{PPAR}\alpha$) to accelerate clearance of VLDL and dramatically lower circulating triglycerides ($\ge 500\,\text{mg/dL}$) to prevent acute pancreatitis. It increases gallstone risk, causes myopathy and hepatotoxicity, inhibits CYP2C8, and displaces warfarin from plasma proteins to augment anticoagulant effects.

Evolocumab (Repatha)

A human monoclonal antibody that binds and inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), preventing PCSK9-mediated degradation of hepatic LDL receptors and clearing circulating LDL-C by $50\%$ or more. Administered by subcutaneous injection every 2 or 4 weeks for severe or statin-intolerant hypercholesterolemia.

Asthma Pathophysiology

A chronic airway inflammatory disorder characterized by bronchial hyperresponsiveness to external triggers (allergens, cold air, stress, exercise), culminating in smooth muscle bronchoconstriction, airway wall inflammation, and profound mucus hypersecretion with intermittent, reversible airflow obstruction.

Metered-Dose Inhaler (MDI) Spacer

An extension device attached to a pressurized metered-dose inhaler that holds the actuated medication plume in a chamber, permitting slow, deep inhalation; it markedly increases the fraction of drug reaching the lower respiratory tract beyond the baseline $20\%$ and diminishes local drug deposition in the oropharynx.

Albuterol (Ventolin)

A short-acting beta-2 adrenergic agonist (SABA) that selectively stimulates $\beta_2$ receptors on bronchial smooth muscle to produce rapid bronchodilation in acute bronchospasm. Adverse effects arise from sympathetic activation and slight cross-reactivity with $\beta_1$ receptors, causing skeletal muscle tremor, sinus tachycardia, and transient hyperglycemia from hepatic glycogenolysis.

Tiotropium (Spiriva)

A long-acting muscarinic antagonist (LAMA) delivered via dry-powder inhaler (HandiHaler) or soft mist inhaler (Respimat) that competitively blocks muscarinic cholinergic receptors in bronchial smooth muscle to prevent acetylcholine-mediated bronchoconstriction. Primary maintenance agent in COPD (and off-label in refractory asthma); principal side effects are local anticholinergic actions like dry mouth and throat irritation.

Inhaled Corticosteroids (Budesonide)

Potent anti-inflammatory glucocorticoids that reduce synthesis of inflammatory mediators, inhibit inflammatory cell infiltration, and decrease airway mucosal edema for long-term asthma and COPD maintenance. Inhaled administration can cause oropharyngeal candidiasis (thrush) and dysphonia, mandating mouth rinsing with water after each use; systemic oral therapy carries risks of adrenal suppression, hyperglycemia, and osteoporosis.

Fluticasone / Salmeterol (Advair)

A fixed-dose combination maintenance product consisting of an inhaled corticosteroid (fluticasone) and a long-acting beta-2 agonist (salmeterol). LABAs must never be administered as monotherapy in asthma due to a boxed warning for increased risk of severe asthma-related death; they must always be paired with an inhaled corticosteroid.

Montelukast (Singulair)

An oral leukotriene receptor antagonist (LTRA) that blocks cysteinyl leukotriene receptors ($\text{CysLT}_1$) in the respiratory tract, suppressing airway inflammation, edema, and bronchoconstriction. Used as daily maintenance therapy for asthma, prevention of exercise-induced bronchospasm, and allergic rhinitis; carries a precaution regarding potential neuropsychiatric and mood/behavior changes.

Cromolyn Sodium

An inhaled mast cell stabilizer that prevents calcium-dependent antigen-induced degranulation of sensitized mast cells, thereby blocking the exocytosis of histamine, leukotrienes, and other inflammatory mediators. Possesses a favorable safety profile but modest anti-inflammatory efficacy; taken prophylactically approximately $15\,\text{minutes}$ prior to exercise or allergen exposure.

Theophylline (Theo-24)

A methylxanthine bronchodilator that relaxes smooth muscle in the bronchi likely via adenosine receptor antagonism. It features a narrow therapeutic index ($5\text{--}15\,\mu\text{g/mL}$) requiring strict plasma monitoring; toxicity manifests with nausea, vomiting, and insomnia, while severe toxic overdose causes lethal cardiac arrhythmias (ventricular fibrillation, treated with lidocaine) and refractory seizures (treated with diazepam).

Omalizumab (Xolair)

A recombinant humanized monoclonal antibody that selectively binds to circulating free immunoglobulin E (IgE), preventing it from attaching to high-affinity receptors on mast cells and basophils. Administered subcutaneously every 2 to 4 weeks for moderate-to-severe allergic asthma based on body weight and baseline serum IgE, with a notable risk of severe anaphylaxis (most prominent during the first 3 injections).

Allergic Rhinitis Pathophysiology

An IgE-mediated hypersensitivity reaction of the upper airway following environmental allergen exposure. Antigen presentation leads to Th2 differentiation, IgE synthesis, and mast-cell cross-linking; subsequent degranulation of histamine and leukotrienes produces immediate sneezing, rhinorrhea, and pruritus, progressing to a late-phase inflammatory cell infiltration that causes chronic nasal congestion.

Triamcinolone (Nasacort)

An intranasal glucocorticoid spray considered first-line for allergic rhinitis that suppresses local mucosal inflammation, edema, and mucus production. Adverse effects include nasal drying, burning, and epistaxis; maximum clinical benefit requires regular daily administration and may take up to 1 week to develop.

Loratadine (Claritin)

A second-generation oral $H_1$ receptor antagonist that blocks peripheral histamine receptors to relieve allergic rhinorrhea, sneezing, and pruritus. Due to minimal penetration across the blood-brain barrier, it produces substantially less CNS sedation and anticholinergic dry-mouth effects than first-generation antihistamines like diphenhydramine.

Pseudoephedrine (Sudafed)

An oral sympathomimetic decongestant that activates alpha-1 adrenergic receptors on vascular smooth muscle, producing vasoconstriction of nasal blood vessels and shrinking swollen mucous membranes. Adverse effects include systemic hypertension, tachycardia, palpitations, anxiety, and insomnia; topical alpha-agonists (e.g., oxymetazoline/Afrin) carry a severe risk of rebound congestion (rhinitis medicamentosa) if used for longer than $3\text{--}5\,\text{days}$.

Benzonatate (Tessalon Perles)

A non-opioid antitussive agent chemically related to tetracaine that suppresses cough by anesthetizing stretch receptors within the respiratory passages, lungs, and pleura. Ingestion of chewed capsules or accidental overdose can cause rapid local oropharyngeal numbness, seizures, cardiac dysrhythmias, and death.