Pharmacology final

Propranolol

MOA: Nonselective beta 1 and 2 blocker. Lowers cardiac output . bronchoconstriction

Toxicity: Bronchospasm in asthma and COPD.

Features: Treats hypertension, angina, post heart attack

Metoprolol / Atenolol / Esmolol

MOA: Selective beta 1 blockers. Selectivity is lost at high doses. Slow heart rate decrease rate of contraction

Toxicity: Bradycardia, AV block, acute heart failure.

Features: Safe for patients with asthma, COPD, or diabetes. for acute IV use.

Labetalol / Carvedilol

MOA: Alpha 1, beta 1, and beta 2 blockers. Alpha 1 block causes vasodilation.

Toxicity: Orthostatic hypotension, dizziness.

Features: IV *** treats hypertensive emergencies. **** lowers mortality in chronic heart failure.

Misoprostol )

MOA: Synthetic PGE 1 analog. Lowers gastric acid secretion and increases bicarbonate/mucus production. Stimulates uterine smooth muscle.

Toxicity: Abdominal pain, cramping, diarrhea. Pregnancy Category X: Triggers complete uterine contraction and abortion.

Key Features: Prevents NSAID-induced gastric ulcers in chronic arthritis populations.

Diphenhydramine

MOA: Blocks central and peripheral H1 and muscarinic receptors. Crosses blood brain barrier.

Toxicity: Severe sedation. Dry mouth, blurred vision, urinary retention, constipation.

Features: Treats acute allergies, hives, motion sickness, and vomiting.

Ondansetron

MOA: Selective competitive antagonist of 5HT3 receptors centrally (chemoreceptor trigger zone) and peripherally (vagal enteric gut nerves). Blocks emetic reflex arc.

Toxicity: Headache, diarrhea. Associated class agent dolasetron can cause QRS and QT interval prolongation.

Key Features: Premier anti-emetic for controlling severe nausea and vomiting from cancer chemotherapy, radiation, or surgery.

Indomethacin / Aspirin

MOA: Non-selective Cyclooxygenase (COX-1 and COX-2) inhibitors. Stop prostaglandin synthesis.

Toxicity: Gastric ulcers, renal impairment, bleeding risk.

Key Features: Indomethacin is used to close a patent ductus arteriosus (PDA) in premature infants. Aspirin irreversibly inhibits platelet TXA2 to prevent MI.

Cimetidine / Famotidine

MOA: Competitive blockers of H2 histamine receptors on gastric parietal cells. Turn down cAMP to reduce gastric acid secretion.

Toxicity: Cimetidine causes anti-androgenic effects (gynecomastia, impotence) and is a potent CYP450 inhibitor. Famotidine lacks these side effects.

Key Features: First-line baseline therapy for GERD and peptic ulcer disease.

Verapamil / Diltiazem

MOA: Blocks L-type calcium channels in the heart to lower heart rate, AV conduction, and contractility.

Toxicity: Bradycardia, AV block, worsening heart failure, and severe constipation (especially Verapamil).

Features: First line prophylaxis for stable and vasospastic angina. Never combine with beta blockers due to the risk of severe bradycardia and AV block.

Nifedipine / Amlodipine

MOA: Block L-type voltage-gated calcium channels. Highly selective for vascular smooth muscle (systemic arteriodilation and coronary vasodilation) with minimal direct cardiac effects.

Toxicity: Peripheral ankle edema, flushing, dizziness, and reflex tachycardia (greatest with short-acting nifedipine).

Key Features: Used for chronic stable angina and vasospastic angina. Paired with beta-blockers to neutralize reflex tachycardia.

Furosemide / Torsemide / Bumetanide

MOA: Inhibits the Na/K/2Cl cotransporter in the thick ascending limb of the loop of Henle. Destroys the medullary concentration gradient to eliminate water reabsorption.

Toxicity: Hearing impairment, hypokalemic metabolic alkalosis, hypocalcemia, gout, and sulfa allergy.

Features: Most potent diuretics. First line for acute pulmonary edema and peripheral fluid overload in heart failure.

Hydrochlorothiazide / Chlorthalidone / Indapamide

MOA: Inhibits the Na+/Cl- cotransporter (NCCT) in the distal convoluted tubule.

Toxicity: Hypokalemic metabolic alkalosis, hypercalcemia, hyperglycemia, hyperuricemia (gout), and sulfa allergy risk.

Features: The most common diuretic for primary hypertension. **** is preferred due to its longer half-life. It lowers urinary calcium, making it useful to prevent recurrent calcium kidney stones.

Captopril / Enalapril / Lisinopril ()

MOA: Inhibit Angiotensin-Converting Enzyme (ACE). Blocks conversion of Angiotensin I to Angiotensin II (vasoconstriction decrease, aldosterone decrease). Prevents breakdown of bradykinin (a potent vasodilator).

Toxicity: Dry, hacking cough and life-threatening Angioedema (both due to bradykinin accumulation). Hyperkalemia, acute kidney injury in patients with bilateral renal artery stenosis. Teratogenic (fetal kidney damage).

Key Features: First-line for hypertension, especially in Diabetics (provides diabetic nephroprotection) and Heart Failure (reduces cardiac remodeling and overall mortality).

Losartan / Valsartan

MOA: Competitively block AT1 receptors to inhibit the effects of Angiotensin II.

Toxicity: Hyperkalemia, acute kidney injury. Teratogenic. No effect on bradykinin metabolism, so no dry cough or angioedema risk.

Key Features: First-line alternative to ACE inhibitors for hypertension and heart failure if the patient cannot tolerate the ACE-inhibitor cough.

Aliskiren

MOA: Directly binds and inhibits Renin, blocking the initial, rate-limiting conversion of angiotensinogen to Angiotensin I.

Toxicity: Hyperkalemia, diarrhea, acute kidney injury. Teratogenic.

Key Features: Used orally as an alternative therapy for essential hypertension. Never combine with ACE inhibitors or ARBs.

Hydralazine ()

MOA: Directly relaxes arteriolar smooth muscle (minimal effect on veins) by stimulating the release of Nitric Oxide (NO) from vascular endothelium.

Toxicity: Profound compensatory reflex tachycardia and fluid retention/edema. Promotes a classic reversible Drug-Induced Lupus Erythematosus (SLE)-like syndrome in slow acetylators.

Key Features: Used for severe, refractory hypertension. Safe in pregnancy (often used for preeclampsia). Always paired with a beta-blocker (to stop reflex tachycardia) and a loop diuretic (to handle fluid retention).

Minoxidil )

MOA: Active sulfate metabolite opens ATP-sensitive K+ channels in vascular smooth muscle, causing membrane hyperpolarization and arteriolar relaxation.

Toxicity: Extreme reflex tachycardia, severe fluid retention, and hypertrichosis.

Key Features: Reserved for severe, refractory hypertension. Topical form is used for male pattern baldness.

Sodium Nitroprusside

MOA: Spontaneously releases nitric oxide in the bloodstream, activating cGMP to cause balanced dilation of arterioles and venules.

Toxicity: Releases cyanide, which can lead to thiocyanate toxicity during prolonged infusions or in patients with renal failure, resulting in metabolic acidosis and seizures. Antidote: Sodium thiosulfate or hydroxocobalamin.

Key Features: First-line IV drug for hypertensive emergencies. Immediate onset and ultra-short duration; requires continuous blood pressure monitoring.

Fenoldopam

MOA: Postsynaptic D1 receptor agonist; induces arteriolar vasodilation, maintains renal perfusion, and promotes diuresis.

Toxicity: Reflex tachycardia, headache, flushing, increased intraocular pressure.

Key Features: IV treatment for hypertensive emergencies, particularly useful in patients with renal insufficiency.

Sacubitril / Valsartan (ARNI)

MOA: Sacubitril inhibits neprilysin to increase natriuretic peptides. Valsartan blocks AT1 receptors to stop angiotensin II.

Toxicity: Hypotension, hyperkalemia, renal impairment, angioedema.

Key Features: First-line therapy for HFrEF. Must never be used within 36 hours of an ACE inhibitor due to the risk of severe angioedema.

Somatropin

MOA: Binds to GH receptors, activating the JAK/STAT signaling pathway to stimulate production of IGF-1 in the liver.

Toxicity: Idiopathic intracranial hypertension (pseudotumor cerebri), slipped capital femoral epiphysis, hyperglycemia/insulin resistance, peripheral edema.

Key Features: Promotes growth in children with GH deficiency, Turner syndrome, chronic renal failure, or AIDS-associated wasting syndrome. Contraindicated if epiphyses are fused.

Octreotide

MOA: Long-acting synthetic somatostatin analog. Potently inhibits the secretion of Growth Hormone (GH), TSH, insulin, glucagon, and gastrin.

Toxicity: Biliary sludge and gallstones (due to cholecystokinin inhibition), steatorrhea, abdominal cramps, bradycardia.

Key Features: First-line medical therapy for Acromegaly. Also used for symptomatic control of carcinoid syndrome diarrhea and acute esophageal variceal bleeding.

Pegvisomant

MOA: Genetically modified GH analog that binds to and blocks the GH receptor, preventing functional receptor dimerization and downstream IGF-1 production.

Toxicity: Injection site reactions, significant transaminase elevations (requires liver function monitoring).

Key Features: Reserved for Acromegaly refractory to surgery, radiation, or octreotide therapy. Does not shrink pituitary tumors; may cause them to expand.

Leuprolide / Goserelin

MOA: Continuous administration down-regulates pituitary GnRH receptors, halting LH and FSH secretion. Pulsatile administration stimulates them.

Toxicity: Hot flashes, bone loss, erectile dysfunction, and initial tumor flare in prostate cancer.

Key Features: Treats precocious puberty, advanced prostate cancer, and endometriosis. Used to suppress endogenous cycles during ovulation induction.

Ganirelix / Cetrorelix

MOA: Competitive antagonist at pituitary GnRH receptors. Immediately suppresses LH and FSH secretion without causing an initial flare or surge.

Toxicity: Ovarian hyperstimulation syndrome, headache, injection site hypersensitivity.

Key Features: Used in controlled ovarian hyperstimulation protocols to prevent premature LH surges during assisted reproduction techniques.

Urofollitropin / Follitropin

MOA: Direct FSH receptor agonists. Purified from postmenopausal urine (urofollitropin) or recombinant human form (follitropin). Direct stimulus for ovarian follicle maturation and spermatogenesis.

Toxicity: Ovarian hyperstimulation syndrome (OHSS), multiple pregnancies, gynecomastia in men.

Key Features: Indicated for ovulation induction in infertile women and to promote spermatogenesis in infertile men with hypogonadotropic hypogonadism.

Oxytocin

MOA: Activates oxytocin receptors on uterine smooth muscle to trigger rhythmic contractions. Also stimulates mammary myoepithelial cells to promote milk ejection.

Toxicity: Risk of uterine rupture and fetal distress. High doses may cause water intoxication and dilutional hyponatremia due to weak V2 receptor cross-reactivity.

Key Features: Drug of choice for labor induction and preventing postpartum uterine hemorrhage.

Desmopressin (DDAVP

MOA: Selective renal V2 receptor agonist that inserts aquaporin-2 channels into the collecting tubule to increase water reabsorption. Also stimulates release of Factor VIII and von Willebrand factor from endothelial cells.

Toxicity: Water retention and severe dilutional hyponatremia.

Key Features: Drug of choice for central diabetes insipidus. Also used for mild hemophilia A and von Willebrand disease.

Conivaptan / Tolvaptan

MOA: Blocks vasopressin receptors. Conivaptan blocks V1 and V2. Tolvaptan is selective for V2. Induces aquaresis by increasing free water clearance.

Toxicity: Polyuria, intense thirst, dry mouth. Risk of hepatotoxicity with Tolvaptan (treatment limited to 30 days).

Key Features: Used to treat euvolemic or hypervolemic hyponatremia in patients with SIADH, liver cirrhosis, or congestive heart failure.

Regular Insulin / Insulin Lispro (Short & Rapid-Acting Insulins)

MOA: Activates tyrosine kinase insulin receptors to promote glucose uptake into muscle and fat via GLUT4 translocation and inhibit hepatic gluconeogenesis and glycogenolysis.

Toxicity: Hypoglycemia, lipodystrophy at injection sites, and hypokalemia.

Key Features: **** is used IV for Diabetic Ketoacidosis (DKA).*** is ultra-rapid acting and injected at mealtimes to mimic normal postprandial insulin surges.

Insulin Glargine / Insulin Degludec (Long-Acting Basal Insulins)

MOA: Activate insulin tyrosine kinase receptors. Modified chemical structures cause slow, sustained release from subcutaneous injection sites.

Toxicity: Hypoglycemia, weight gain.

Key Features: Provide a peakless, flat basal insulin profile over 24+ hours. Used as baseline background therapy for Type 1 and advanced Type 2 diabetes. Cannot be mixed in the same syringe with other insulins due to pH precipitation risks.

Glipizide / Glyburide (Sulfonylureas / Insulin Secretagogues)

MOA: Block ATP-sensitive potassium channels on pancreatic beta-cells to cause membrane depolarization, calcium influx, and insulin release.

Toxicity: High risk of hypoglycemia and weight gain. Glyburide is contraindicated in renal impairment and the elderly due to prolonged action.

Key Features: Require functional beta-cells, so they are useless in Type 1 Diabetes. Not first-line therapy because they cause weight gain and hypoglycemia compared to metformin.

Metformin

MOA: Activates AMP-activated protein kinase (AMPK), inhibiting hepatic gluconeogenesis and glucose output. Increases peripheral insulin sensitivity and glucose uptake in skeletal muscle. Does not stimulate insulin release.

Toxicity: Gastrointestinal distress and decreased Vitamin B12 absorption. Risk of lethal lactic acidosis. Contraindicated in renal insufficiency (GFR < 30)

Key Features: First-line, gold-standard therapy for Type 2 Diabetes. Weight-neutral and carries zero risk of hypoglycemia when used as monotherapy.

Pioglitazone, Rosiglitazone

MOA: Thiazolidinediones, High-affinity ligands that bind and activate the nuclear PPAR-gamma receptor to regulate gene transcription, increasing the expression of GLUT4 and adiponectin to improve peripheral insulin sensitivity in fat and muscle tissue.

Toxicity: Severe fluid retention, weight gain, and peripheral edema. Can precipitate or worsen congestive heart failure. Increased risk of bone fractures.

Key Features: Euglycemics that do not cause hypoglycemia when used alone. They have a slow onset of action because they require time to alter gene expression. Contraindicated in patients with NYHA Class III or IV heart failure.

Acarbose

MOA: Reversibly inhibits membrane-bound alpha-glucosidase enzymes in the intestinal brush border. Delays carbohydrate digestion and breakdown into absorbable monosaccharides.

Toxicity: Profound GI distress including severe flatulence, abdominal bloating, and diarrhea due to osmotic fermentation of undigested carbohydrates by colonic bacteria.

Key Features: Lowers postprandial blood glucose spikes. Euglycemic. If a patient experiences hypoglycemia while taking this in combination with a sulfonylurea, they must be treated with pure glucose (dextrose), not sucrose, because acarbose blocks the breakdown of sucrose.

Exenatide / Liraglutide / Semaglutide

MOA: Injectable synthetic analogs of incretin GLP-1. They activate GLP-1 receptors to stimulate glucose-dependent insulin secretion, suppress glucagon release, delay gastric emptying, and signal central satiety to reduce appetite.

Toxicity: Nausea, vomiting, and diarrhea are common. Associated with a risk of acute pancreatitis and thyroid C-cell tumors. Contraindicated in patients with a history of Multiple Endocrine Neoplasia Type 2 (MEN2).

Key Features: Provide significant cardiovascular risk reduction and notable weight loss. Recommended for patients with a high risk of hypoglycemia because insulin release is strictly glucose-dependent.

Sitagliptin

MOA: Orally active inhibitors of dipeptidyl peptidase-4 (DPP-4) that prevent the breakdown of endogenous GLP-1, increasing the half-life of incretins and promoting glucose-dependent insulin release.

Toxicity: Nasopharyngitis, upper respiratory tract infections, headache, rare joint pain, and risk of acute pancreatitis.

Key Features: Oral alternative to injectable GLP-1 agonists. They are weight-neutral and have a low risk of hypoglycemia.

Canagliflozin / Dapagliflozin / Empagliflozin

MOA: Inhibit the Sodium-Glucose Co-transporter 2 in the Proximal Convoluted Tubule of the kidney. Blocks the reabsorption of filtered glucose, forcing therapeutic glucosuria and osmotic diuresis.

Toxicity: Genital mycotic infections (candidal vulvovaginitis/balanitis) and Urinary Tract Infections due to high urine glucose. Dehydration, hypotension, and euglycemic diabetic ketoacidosis.

Key Features: Reduce cardiovascular mortality and provide renoprotection or decrease heart failure hospitalizations. Cause mild weight loss and drop blood pressure. Empagliflozin is highly favored for heart failure protection.

Esomeprazole / Omeprazole

MOA: Lipophilic weak bases that act as prodrugs. They accumulate in the acidic canaliculi of parietal cells and form a covalent disulfide bond that irreversibly inhibits the H+/K+ ATPase pump.

Toxicity: Diarrhea, headache, and decreased absorption of Vitamin B12 and calcium. Chronic use increases the risk of bone fractures and is associated with a high risk of Clostridioides difficile infection.

Key Features: The most effective inhibitors of gastric acid secretion. They must be administered 30 to 60 minutes before breakfast to ensure the pump is active and the drug is effectively incorporated.

Cimetidine / Famotidine

MOA: Competitively block histamine H2 receptors on parietal cells, reducing intracellular cAMP and blunting acid secretion stimulated by histamine, gastrin, or acetylcholine.

Toxicity: Cimetidine is a potent CYP450 inhibitor and has anti-androgenic effects including gynecomastia and erectile dysfunction. Famotidine lacks these toxicities.

Key Features: Highly effective for controlling nocturnal acid secretion but subject to tachyphylaxis (tolerance) within a few days of continuous use.

Misoprostol

MOA: Synthetic analog of Prostaglandin E1. Binds to EP receptors on parietal cells to decrease acid production while stimulating mucus and bicarbonate secretion.

Toxicity: Profound abdominal cramping and watery diarrhea. Pregnancy Category X as it induces uterine contractions and can cause abortion.

Key Features: Indicated specifically for the prevention of NSAID-induced gastric ulcers.

Sucralfate

MOA: Sulfated sucrose complexed with aluminum hydroxide. Polymerizes in an acidic environment into a thick, sticky paste that selectively binds to the positively charged proteins in the ulcer bed, creating a physical barrier.

Toxicity: Constipation (due to aluminum). May trap and bind other concurrent oral medications.

Key Features: Requires an acidic environment to activate; do not co-administer with antacids, H2 blockers, or PPIs.

Ondansetron / Granisetron

MOA: Highly selective competitive antagonists of 5HT3 receptors in the central chemoreceptor trigger zone (CTZ) and on peripheral vagal afferents in the intestinal tract.

Toxicity: Headache, dizziness, constipation. Can cause QT interval prolongation on ECG.

Key Features: First-line, premier choice for preventing chemotherapy-induced nausea and vomiting (CINV), post-radiation emesis, and post-operative emesis.

Metoclopramide / Prochlorperazine

MOA: Blocks dopamine D2 receptors centrally in the chemoreceptor trigger zone (CTZ). It also acts as a prokinetic agent by enhancing acetylcholine sensitivity in the upper gastrointestinal tract.

Toxicity: Extrapyramidal symptoms (EPS) including dystonia, akathisia, and Parkinson-like tremors. Can also cause hyperprolactinemia, leading to galactorrhea and gynecomastia.

Key Features: **** is the drug of choice for diabetic gastroparesis and severe bloating due to its dual antiemetic and prokinetic properties.

Aprepitant

MOA: Crosses the blood-brain barrier to competitively block central Neurokinin-1 NK1 receptors, preventing the binding of substance P in the emetic center.

Toxicity: Fatigue, diarrhea, and hiccups. It is a potent inhibitor of CYP3A4.

Key Features: Used in combination with a 5-HT3 antagonist and dexamethasone for the prevention of delayed nausea and vomiting caused by highly emetogenic chemotherapy.

Dronabinol / Nabilone

MOA: Actively stimulate central CB1 cannabinoid receptors in and around the vomiting center.

Toxicity: THC-like central effects: euphoria, sedation, hallucinations, paranoid reactions, and prominent tachycardia.

Key Features: Reserved for refractory chemotherapy-induced emesis when standard cocktails fail. Also acts as an appetite stimulant in AIDS-wasting syndrome.

Magnesium Hydroxide / Polyethylene Glycol

MOA: Non-absorbable solutes draw water into the intestinal lumen via an osmotic gradient; the resulting increase in luminal volume stretches the colon, stimulating peristalsis.

Toxicity: Electrolyte imbalances, dehydration, and abdominal cramps. Magnesium can accumulate to toxic levels in patients with renal insufficiency.

Key Features: Magnesium hydroxide is fast-acting. Polyethylene glycol (PEG) is the standard for bowel cleansing before colonoscopy.

Oxytocin

MOA: Activates G-coupled oxytocin receptors on uterine smooth muscle triggers IP3 calcium pathways to cause rhythmic, coordinated contractions.

Toxicity: Dose-related hypotension, reflex tachycardia, uterine rupture, fetal distress. High doses cross-activate V2 receptors causing water intoxication/dilutional hyponatremia.

Key Features: Drug of choice for induction of labor and prevention/treatment of postpartum hemorrhage.

Fluoxetine / Sertraline / Citalopram

MOA: Selectively inhibit the presynaptic serotonin transporter (SERT), prolonging serotonin neurotransmission.

Toxicity: GI distress, sexual dysfunction (anorgasmia), insomnia. Combined with MAOIs triggers lethal Serotonin Syndrome (hyperthermia, rigidity, clonus; treat with cyproheptadine).

Key Features: First-line baseline therapy for depression and anxiety. **** inhibits CYP2D6 (blocks tamoxifen activation). Safe in elderly over TCAs.

Venlafaxine / Duloxetine

MOA: Inhibit both serotonin (SERT) and norepinephrine (NET) presynaptic reuptake transporters.

Toxicity: SSRI side effects plus noradrenergic spikes: increased blood pressure, tachycardia, insomnia, and agitation.

Key Features: Duloxetine is highly effective for treating depression accompanied by chronic pain states (neuropathic pain, fibromyalgia).

Amitriptyline / Imipramine / Clomipramine (Tricyclic Antidepressants - TCAs)

MOA: Inhibit presynaptic reuptake of NE and 5-HT. Also block H1 histamine, alpha1 adrenergic, and muscarinic receptors.

Toxicity: The 3 C's of Overdose: Cardiotoxicity (blocks Na+ channels causing fatal QRS widening/arrhythmias; treat with sodium bicarbonate), Convulsions, and Coma. Massive anticholinergic profile.

Key Features: ****is highly specific for OCD. ****handles neuropathic pain. High toxicity profile limits first-line utility.

Phenelzine / Selegiline

MOA: Phenelzine is a non-selective inhibitor of MAO-A and MAO-B. Selegiline is a selective MAO-B inhibitor at low doses (preserves dopamine).

Toxicity: Ingesting tyramine-rich foods (aged cheese, red wine) causes a catastrophic Hypertensive Crisis (Cheese Reaction) due to uncontrolled NE release.

Key Features: Requires a 2-week washout period before switching to or from SSRIs to prevent fatal Serotonin Syndrome.

Bupropion

MOA: Inhibits norepinephrine and dopamine reuptake (NDRI).

Toxicity: High risk of inducing seizures at high doses or in susceptible populations.

Key Features: Zero sexual side effects and weight-neutral. Highly favored for smoking cessation. Strictly contraindicated in patients with Bulimia or Anorexia due to lowered seizure threshold