DRUG CLASSES --> (PBT II EXAM 2)

Carbonic Anhydrase Inhibitor (-zolamide)

location: PCT

MOA: Inhibits CA II (intracellular) and IV (luminal membrane) to block reabsorption. Effect: Increase Na+ and HCO₃^-

Key Clinical Uses: Glaucoma, Seizures, Altitude sickness 

ADR: acidosis (long term use)

SGLT 2 Inhibitor (-flozin)

Location: PCT

MOA: Inhibits SGLT2 in proximal tubule = decrease glucose and Na+ reabsorption = glucosuria & osmotic diuresis

Key clinical uses: Type II diabetes, CKD

ADR: UTI

RAS Inhibitor

Location: PCT

MOA: inhibits Ang II or blocks AT1R = increase Na+ and H2O reabsorption

Key Clinical Uses: decrease BP, preserve renal function, nauriuresis = decrease volume

Osmotic Diuretics

Location: nephron loop

MOA: non-reabsorbable solutes float freely in at the glomerulus = act as “sponge“ that retains H2O + Na+ in the tubular fluid

Key clinical uses: rapid volume reduction + diuresis via IV

ADRs: rapid depletion of H2O & Na+

Loop Diuretics (-ide)

location: Thick Ascending Limb of the Loop of Hele

MOA: inhibits NKCC2 symporter = blocks active Na+, K+, & Cl- reabsorption AND abolishes driving force for paracellular Ca2+ and Mg2+ uptake

Key Clinical Uses: acute/chronic heart failure, edema in renal impairment

ADRs: hypokalemia, sever hypovolemia, otoxicity (inner ear inhibition)

Thiazide & Thiazide - Like (TT/TL)

Location: DCT

MOA: inhibits Na+/Cl- (NCC) cotransporter = enhances downstream Ca2+ & Mg2+ reabsorption via TRPV5

Key Clinical Uses: first line mono therapy/combo therapy for stage 1 hypertension in pts with healthy kidney

ADRs: hypokalemia, mild metabolic alkalosis, hyperuricemia

ENaC Inhibitors (K+ - Sparing)

Location: DCT2 and Cortical Collecting Duct

MOA: directly blocks ENaC, halting Na+ influx and eliminating change that causes K+ secretion

Key Clinical Uses: co-prescribed with K+-wasting diuretics (Lasix) or other antihypertensives to prevent hypokalemia

ADRs: hyperkalemia, metabolic acidosis, N/V, diarrhea.

Mineralocorticoid Receptors Antagonist (MRAs) (-one)

Location: DCT2 and Cortical Collecting Duct

MOA: Competitively antagonizes the MR (mineralocorticoid receptor) = prevents aldosterone gene transcription of ENaC and Na+/K+ ATPase pumps.

Key Clinical Uses: resistant hypertension, hyperaldosteronism, heart failure, and post-MI remodeling

ADRs: hyperkalemia, metabolic acidosis, endocrine disturbances

Vasopressin V2 receptor Antagonist (Aquaretics) (-vaptan)

Location: Collecting Duct

MOA: blocks Gs-coupled V2 receptors = decreased cAMP, makes it so that Aquaporin-2 cannot be inserted

Key Clinical Uses: Autosomal Dominant Polycystic Kidney Disease, euvolemic/hypervolemic hyponatremia

ADRs: hepatotoxicity

Recombinant Natriuretic Peptides

Location: Heart, vascular smoother muscle, kidneys

MOA: binds NPR-A and NPR-B guanylyl cyclase receptors to elevate intracellular cGMP = promotes smooth muscle relaxation and renal natriuresis

Key Clinical Uses: formally used for acute decompensated heart failure

ADRs: hypotension

ARNI (Angiotensisn - Receptor Neprilysin Inhibitor)

Location: vascular endothelium, kidneys, myocardium

MOA: (sacubitril) inhibits NEP to prevent natriuretic peptide & bradykinin degradation. (Valsartan) selectively blocks AT1 receptor

Key Clinical Uses: chronic heart failure (reduces ejection fraction)

ADRs: hypotension, hyperkalemia, angioedema

Bladder Muscarinic Antagonist

Location: bladder detrusor muscles

MOA: antagonizes Gq-coupled M3 receptors = suppressing parasympathetic mediated detrusor contraction during micturition

Key Clinical Uses: overactive bladder (OAB)

ADRs: dry mouth, constipation, blurred vision, urinary retention, CNS adverse affects with lipophillic agents that cross the BBB

Bladder B3- Adrenergic Agonist (-egron)

Location: bladder detrusor muscles

MOA: antagonizes Gs-coupled B3-adrenoceptors = promoting detrusor relaxation during bladder filling

Key Clinical Uses: overactive bladder (OAB)

ADRs: potential off target stimulation = elevated BP or tachycardia

ACEi (ACE inhibitors) (-pril)

Location: vascular endothelium (pulmonary & renal circulation)

MOA: inhibit ACE (Kininase II) blocking conversion of Ang I and Ang II (reducing vasoconstriction and aldosterone) while preventing bradykinin breakdown

Key Clinical Uses: 1st line for hypertension, diabetic nephropathy/renal protection, heart failure

ADRs: DRY COUGH (bradykinin mediated), angioedema, NO PREGNANCY

ARBs (Angiotension II receptor Blockers) (-sartan)

Location: vascular smooth muscle and adrenal cortex

MOA: selectivly block AT1 receptors preventing Ang II-mediated vasoconstriction, cellular hypotrophy and adrenal aldosterone secretion

Key Clinical Uses: 1st line for hypertension, diabetic nephropathy/renal protection, heart failure

ADRs: hyperkalemia, first dose hypotension, no dry cough, NO PREGNANT

Direct Renin Inhibitors

Location: circulating plasma / Juxtaglomerular site

MOA: direct competitive inhibitor of renin = blocks cleavage of Angiotensinogen to Ang I at the rate limiting step

Key Clinical Uses: 2nd line treatment foe hypertension

ADRs: risk of acute renal impairment in pts with diabetes, NO PREGNANCY

Calcium Channel Blockers (CCBs) (-pine) Dihydropridines

Location: vascular smooth muscle

MOA: selectively block vascular L-type Ca2+ channels = reduces intracellular Ca2+ entry & decreases SVR/TPR

Key Clinical Uses: 1st line for hypertension, isolated systolic hypertension, raynaud phenomenon (nifedipine = can be used pregnant)

ADRs: peripheral pedel edema, flushing, dizziness, headache, reflex tachycardia

Calcium Channel Blockers (CCBs) (-pine) NON - Dihydropridines

Location: cardiac, myocytes, SA and AV nodal tissue

MOA: block cardiac L-Type Ca2+ channels, depressing myocardial contractility (inotropy) and SA/AV nodal conduction velocity (chronotropy)

Key Clinical Uses: supraventricular arrhythmias (atrial fibrillation/flutter), angia, hypertension

ADRs: bradycardia, heart block, worsening heart failure, constipation

Beta-Blockers (-LOL)

Location: Heart (B1), Juxtaglomerular (B1) and vasculature

MOA: block B-adrenoceptors to lower heart rate, SV, renin release; 3rd generation agents add alpha 1 blockade (carvidalol, labetalol) or endothelial NO release (nebivolol)

Key Clinical Uses: 2nd Line for hypertension, post myocardial infarction, stable heart failure, arrhythmias (Labetalol = 1st line in Pregnancy and preclampsia)

ADRs: bradycardia, fatigue, exercise intolerance, bronchospasm in COPD/asthma due to off target B2 blockade

Selective Alpha 1 - blocker (-zosin)

Location: vascular smooth muscle (arteries + veins), bladder neck/prostate

MOA: selectively block Gq-coupled alpha 1 - adrenergic receptors, preventing NE mediated vasoconstriction & relaxing prostatic smooth muscle

Key Clinical Uses: BHP, resistant hypertension, pheochromocytoma

ADRs: orthostatic hypotension, reflex tachycardia, nasal congestion, fluid retention

Central Alpha 2 - Agonist

Location: presynaptic neurons in the brainstem

MOA: Stimulate presynaptic central alpha 2 receptors, decreasing central sympathetic outflow to the heart and systemic vasculature

Key Clinical Uses: Methyldopa is first-line oral therapy for chronic hypertension in pregnancy and preeclampsia. Clonidine is used for resistant hypertension

ADRs: marked sedation, dry mouth, dizziness, rebound hypertensive crisis upon withdrawal

Imidazoline I1 Receptor Agonist (-nidine)

Location: brainstem

MOA: Agonists at central imidazoline I1 receptors, selectively suppressing central sympathetic tone

Key Clinical Uses: Second-line therapy for Essential Hypertension, particularly in patients with metabolic syndrome, COPD, diabetes, or depression

ADRs: Low incidence of sedation and dry mouth; mild fatigue and headache

Direct Arterial Vasodilators

Location: arterial smooth muscle

MOA: Hydralazine = opens K+ channels, inhibits IP3 - mediated Ca2+ release, and stimulated NO release. Minoxidil = NO sulfate opens ATP modulated K+ channels

Key Clinical Uses: Hydralazine (IV) is first-line for acute severe hypertensive emergencies in pregnancy/preeclampsia. Minoxidil is a last-resort oral antihypertensive and topical for alopecia

ADRs: Significant reflex tachycardia (increased cardiac O2 demand), headache, flushing, sodium/water retention, drug-induced lupus erythematosus (5–10%) with hydralazine; hypertrichosis with minoxidil

Peripheral Dopamine D1 Agonists

Location: renal + systematic arterial beds

MOA: Selective agonist at peripheral D1 receptors Gs -coupled, causing rapid arterial vasodilation while increasing renal blood flow, natriuresis, and diuresis

Key Clinical Uses: Short-term intravenous reduction of blood pressure in severe hypertensive emergencies/crises (including pregnancy when clearly needed)

ADRs: Hypotension and reflex tachycardia; continuous IV infusion is strictly limited to <48 hours due to tolerance

Endothelin Receptor Antagonist (-sentan)

Location: vascular smooth muscle

MOA: competitivly blocks ETa and ETb Gq-coupled receptor, inhibiting endothelin-1 (ET-1)-mediated vasoconstriction and proliferation

Key Clinical Uses: Pulmonary Arterial Hypertension (PAH) and refractory severe hypertension

ADRs: Hepatotoxicity / elevated liver transaminases (requires mandatory liver function testing), fluid retention/pulmonary edema, and potent teratogenicity

Magnesium Sulfate

Location: vascular and neuronal membrane

MOA: acts as a physical plug to Ca2+ channels, stabilizing membranes blocking neuromuscular excitation

Key Clinical Uses: Seizure prophylaxis and treatment in preeclampsia and eclampsia; prolongs pregnancy by ~2 days

ADRs: Generally safe for the fetus; maternal toxicity risk requires monitoring of deep tendon reflexes, respiration, and urine output