Pharmacology C4

Somatropin

Mechanism of Action: Recombinant human growth hormone (GH) that primarily acts by regulating the production of insulin-like growth factor 1 (IGF-1). Toxicity: In children, it may cause pseudotumor cerebri, slipped capital femoral epiphysis, and edema; in adults, it often leads to peripheral edema, myalgia, and arthralgia. Key Features: Used for GH deficiency and genetic diseases like Turner syndrome (XO karyotype).

Leuprolide

Mechanism of Action: GnRH agonist; steady dosing downregulates GnRH receptors, leading to inhibited gonadotropin (LH/FSH) release. Toxicity: Symptoms of menopause (hot flushes, sweats) and risk of bone loss/osteoporosis. Key Features: Frequently asked in the context of precocious puberty and suppressing endogenous gonadotropins for IVF. Unlike Ganirelix (an antagonist), it takes about a week to inhibit secretion.

Desmopressin

Mechanism of Action: Selective V2 receptor agonist. Toxicity: Generally well-tolerated, though vasopressin can cause coronary artery spasms. Key Features: The drug of choice for pituitary diabetes insipidus (excessive thirst/urination).

Dexamethasone

Mechanism of Action: Highly potent synthetic glucocorticoid agonist. Toxicity: Long-term use causes osteoporosis, hyperglycemia (diabetes), muscle wasting, and Cushing's syndrome. Key Features: Used in the Dexamethasone suppression test to diagnose Cushing's syndrome. It has the highest anti-inflammatory activity among common steroids.

Ketoconazole

Mechanism of Action: Antifungal that inhibits cytochrome P450 enzymes necessary for the synthesis of all steroids. Toxicity: Hepatotoxicity (noted in related drug classes) and reduction of all steroid levels. Key Features: Repeatedly asked as a treatment for Cushing’s syndrome caused by adrenal tumors to reduce overproduction of corticosteroids.

Spironolactone

Mechanism of Action: Competitive antagonist of the aldosterone receptor. Toxicity: Gynecomastia and impotence due to its blocking action on androgen and progesterone receptors. Key Features: Used for hyperaldosteronism, resistant hypertension, and heart failure

Levothyroxine (T4)

Mechanism of Action: Synthetic T4 that is converted to the more potent T3 in peripheral tissues. Toxicity: Signs of hyperthyroidism (weight loss, tachycardia); highly sensitive in elderly patients, where it can cause cardiac overstimulation. Key Features: The standard form of choice for thyroid hormone therapy.

Methimazole & Propylthiouracil (PTU)

Mechanism of Action: Thioamides that inhibit thyroidal peroxidase, blocking the iodination of tyrosine residues. PTU also inhibits peripheral conversion of T4 to T3. Toxicity: Skin rash is common; rare but serious agranulocytosis, vasculitis, and liver dysfunction. Key Features: PTU is preferred in pregnancy as it is less likely to cross the placenta. Methimazole is generally preferred otherwise due to once-daily dosing.

Teriparatide

Mechanism of Action: Recombinant PTH fragment that stimulates osteoblast activity, leading to net bone formation when given in low intermittent doses. Toxicity: Increased risk of osteosarcoma; usage is strictly limited to a maximum of 2 years. Key Features: Used for parenteral treatment of osteoporosis.

Alendronate (and other Bisphosphonates)

Mechanism of Action: Inhibits farnesyl pyrophosphate synthase to reduce osteoclast-mediated bone resorption. Toxicity: Gastric and esophageal irritation/esophagitis; rare osteonecrosis of the jaw. Key Features: High-yield clinical instruction: Patients must take with large quantities of water and remain upright for 30 minutes to avoid esophageal reflux.

Metformin

Mechanism of Action: Activates AMPK to reduce hepatic gluconeogenesis and increase peripheral glucose uptake. Toxicity: GI disturbances (diarrhea, nausea) and a rare but fatal lactic acidosis, especially in those with renal impairment or alcoholism. Key Features: First-line drug for Type 2 Diabetes; it is weight-neutral and does not cause hypoglycemia when used as monotherapy.

Pioglitazone

Pioglitazone

Mechanism of Action: Activates the PPAR-γ nuclear receptor to increase insulin sensitivity in target tissues (fat, muscle, liver). Toxicity: Fluid retention (edema), weight gain, and increased risk of heart failure. Key Features: Effect on blood glucose is slow (1-2 months for max effect).

Canagliflozin (SGLT-2 Inhibitor)

Mechanism of Action: Blocks SGLT-2 in the proximal convoluted tubule, preventing glucose reabsorption and allowing glucose excretion in urine. Toxicity: Urinary tract infections (UTIs) and fungal infections (candidal vaginitis) due to high sugar in urine. Key Features: Lower blood glucose in an insulin-independent manner; also provides cardiovascular and renal protection.

Glucagon

Mechanism of Action: Stimulates the heart through cardiac glucagon receptors, bypassing β-adrenoceptors. Key Features: Frequently asked as the treatment for β-blocker overdose (e.g., atenolol) causing severe bradycardia and hypotension.

Mecasermin

Mechanism of Action: Recombinant human IGF-1. Toxicity: Hypoglycemia, which can be prevented by eating a snack or meal shortly before administration. Key Features: Used for children with growth failure who are unresponsive to Growth Hormone (GH) therapy due to GH receptor mutations or IGF-1 deficiency.

Octreotide & Lanreotide

Mechanism of Action: Somatostatin analogs that inhibit the release of GH, glucagon, insulin, and TSH. Toxicity: GI disturbances, gallstones, and cardiac conduction abnormalities. Key Features: First-line pharmacologic therapy for acromegaly (GH excess) and other endocrine tumors like carcinoid or gastrinoma.

Pegvisomant

Mechanism of Action: GH receptor antagonist; it cross-links receptors but prevents the conformational change required for activation. Key Features: Specifically approved for the treatment of acromegaly.

Menotropins & Urofollitropin

Mechanism of Action: Menotropins are a mixture of FSH and LH; Urofollitropin is purified FSH. Key Features: Purified from the urine of postmenopausal women; used to stimulate spermatogenesis in infertile men and induce ovulation.

Ganirelix & Cetrorelix

Mechanism of Action: GnRH receptor antagonists. Key Features: Unlike GnRH agonists, they immediately reduce gonadotropin secretion without an initial "flare" or stimulation of LH/FSH.

Ganirelix & Cetrorelix

Bromocriptine & Cabergoline

Mechanism of Action: Dopamine D2 receptor agonists that inhibit prolactin release. Key Features: Used for hyperprolactinemia (amenorrhea, galactorrhea, infertility). Note: Should be avoided in patients with a history of psychotic illness (schizophrenia).

Oxytocin

Mechanism of Action: Stimulates uterine contraction. Key Features: Used intravenously to induce or reinforce labor.

Conivaptan & Tolvaptan

Mechanism of Action: Vasopressin receptor antagonists. Key Features: Used to treat hyponatremia in patients with congestive heart failure or SIADH (Syndrome of Inappropriate ADH).

Mifepristone (RU-486)

Mechanism of Action: Competitive antagonist of glucocorticoid and progesterone receptors. Key Features: Used for the treatment of Cushing's syndrome.

Fludrocortisone

Mechanism of Action: Synthetic steroid with potent mineralocorticoid activity and significant glucocorticoid activity. Key Features: Favored for replacement therapy in chronic adrenal insufficiency (Addison's disease) and after adrenalectomy.

Metyrapone & Etomidate

Mechanism of Action: Inhibits 11β-hydroxylase, blocking the final step of cortisol synthesis. Key Features: Metyrapone is used in diagnostic tests of adrenal function; Etomidate (an anesthetic) can be used for Cushing's syndrome.

Liothyronine (T3)

Mechanism of Action: Synthetic T3. Key Features: Faster onset but shorter duration than T4; generally reserved for acute emergencies like myxoedema coma.

Radioactive Iodine (131I)

Mechanism of Action: Concentrates in the thyroid gland and emits radiation to permanently damage/destroy the gland. Toxicity: Contraindicated in pregnant or lactating women due to fetal damage. Key Features: The only medical therapy that produces a permanent reduction in thyroid activity.

Proproanolol

Mechanism of Action: Beta-blocker that also inhibits the peripheral conversion of T4 to T3. Key Features: Essential for controlling tachycardia and tremors in thyroid storm

Calcitriol (Active Vitamin D3)

Mechanism of Action: Increases intestinal absorption of calcium and phosphate. Key Features: Used in patients with chronic kidney disease who cannot activate vitamin D themselves.

Calcitonin

Mechanism of Action: Inhibits bone resorption and renal reabsorption of calcium/phosphate. Key Features: Available as a nasal spray for osteoporosis; derived from salmon due to longer half-life/potency.

Cinacalcet

Mechanism of Action: Activates the calcium-sensing receptor (CaSR) in the parathyroid gland. Key Features: Lowers PTH levels; used for secondary hyperparathyroidism in chronic kidney disease.

Denosumab

Mechanism of Action: Monoclonal antibody that binds RANKL, preventing it from stimulating osteoclasts. Key Features: Administered subcutaneously every 6 months; avoids GI side effects seen with bisphosphonates.

Insulin Lispro, Aspart, & Glulisine

Mechanism of Action: Rapid-acting insulin analogs. Key Features: Quick onset (15 mins) allows for injection immediately before meals; preferred for insulin pumps.

Insulin Glargine, Detemir, & Degludec

Mechanism of Action: Long-acting basal insulin. Key Features: "Peakless" basal insulin lasting >20 hours; establishment of basal control in "tight control" regimens.

Glipizide & Glyburide

Mechanism of Action: Sulfonylureas; they close ATP-sensitive K+ channels, causing depolarization and endogenous insulin release. Toxicity: Hypoglycemia and weight gain. Key Features: Not useful in Type 1 diabetes because they require functional B-cells.

Acarbose & Miglitol

Mechanism of Action: α-Glucosidase inhibitors; they delay the digestion and absorption of dietary carbohydrates. Toxicity: Flatulence, diarrhea, and abdominal pain due to fermentation of unabsorbed carbs. Key Features: Taken at the start of a meal.

Exenatide & Liraglutide

Mechanism of Action: GLP-1 receptor agonists (incretin mimetics); they increase insulin release and inhibit glucagon. Toxicity: GI upset (nausea) and rare acute pancreatitis. Key Features: Administered by injection (SC).

Sitagliptin

Mechanism of Action: DPP-4 inhibitor; prevents the breakdown of endogenous GLP-1. Key Features: Oral once-daily dosing; weight-neutral (unlike GLP-1 agonists which can cause weight loss).