diuretics and anti-HTN meds Flashcards
Diuretics that act in proximal tubule
mannitol and acetazolamide
Mannitol MOA
Non metabolized, non- reabsorbed osmotic diuretic: draws free water out of the tissue and into the circulation, where it is excreted by the kidneys
Mannitol uses
elevated intracranial pressure, gluacoma, prevention of acute kidney injury
Acetazolamide MOA
Carbonic Anhydrase Inhibitor: CA converts CO2 and water into bicarb (or vice versa). By blocking this process, bicarb is lost in the tubular fluid and a metabolic acidosis results. Loses effectiveness when metabolic acidosis develops
Acetazolamide uses
glaucoma and prevention/treatment of high altitude sickness
Diuretics that act at loop of Henle
Furosemide(la SIX), bumetanide, torsemide, ethacrynic acid
Loop diuretics MOA
Inhibits Na/K/2Cl transporter in thick ascending limb. Decrease tonicity of medullary interstitium and therefore inhibit reabsorption of water in collecting duct (i.e., inhibit concentration of urine). Lead to excretion of 15-25% of filtered sodium
Loop diuretics uses
Volume overload, Heart failure, BP reduction, Pulmonary edema
Loop diuretics adverse effects
Decreased K/Mg, hypocalcemia, precipate gout attack (uric acid retention), metabolic alkalosis, hearing loss
Diuretics that act at distal convoluted tubule
Thiazide diuretics (HCTZ, chlorthalidone, metolazone)
Thiazide diuretics MOA
- Inhibit Na/Cl cotransporter in distal tubule, causing moderate diuresis since only about 5% of filtered sodium is reabsorbed in this location. Antihypertensive effect secondary to dec plasma volume and dec CO, plus mild vasodilation
- Inhibit Na/Cl cotransporter in distal tubule, causing moderate diuresis since only about 5% of filtered sodium is reabsorbed in this location. Antihypertensive effect secondary to dec plasma volume and dec CO, plus mild vasodilation
- Inhibit Na/Cl cotransporter in distal tubule, causing moderate diuresis since only about 5% of filtered sodium is reabsorbed in this location. Antihypertensive effect secondary to dec plasma volume and dec CO, plus mild vasodilation
- Inhibit Na/Cl cotransporter in distal tubule, causing moderate diuresis since only about 5% of filtered sodium is reabsorbed in this location. Antihypertensive effect secondary to dec plasma volume and dec CO, plus mild vasodilation
Thiazide diuretics adverse effects
Hyperuricemia (inhibits uric acid secretion), hypokalemia (increases K secretion at collecting tubule), metabolic alkalosis (increased H excretion due to K/H co transporters), hyperglycemia (decreases insulin secretion into blood from pancreas)
compare half lives of chlorothalidone vs HCTZ
Chloro has half life of 40-60 hrs. HCTZ has half life of 2.5hrs
Thiazide altered responses with chronic kidney disease
Lose efficacy in later stages of CKD as less drug reaches site of action as kidney fails. More efficacious Loop Diuretic necessary at GFR < 30 ml/min. Resistance can occur at later stages of CKD- overcome with synergistic combo of Loop + Metalozone
Lose efficacy in later stages of CKD as less drug reaches site of action as kidney fails. More efficacious Loop Diuretic necessary at GFR < 30 ml/min. Resistance can occur at later stages of CKD- overcome with synergistic combo of Loop + Metalozone
Lose efficacy in later stages of CKD as less drug reaches site of action as kidney fails. More efficacious Loop Diuretic necessary at GFR < 30 ml/min. Resistance can occur at later stages of CKD- overcome with synergistic combo of Loop + Metalozone
Lose efficacy in later stages of CKD as less drug reaches site of action as kidney fails. More efficacious Loop Diuretic necessary at GFR < 30 ml/min. Resistance can occur at later stages of CKD- overcome with synergistic combo of Loop + Metalozone
Diuretics that act at distal tubule/collecting duct
K sparing diuretics: Aldosterone Antagonist (Spironolactone, eplerenone) and Sodium channel blockers (Triamterene, Amiloride)
Aldosteron antagonists MOA
Competitively inhibit the mineralocorticoid receptor (eplereonone is more specific) and block binding of Aldosterone. This decreases activity of Na/K exchanger Reducing the reabsorption of sodium and secretion/excretion of potassium.
Aldosterone antagonists uses
resistant HTN, heart failure, hyperaldosteronism (use with other diuretics to preserve K)
Na Channel blockers MOA
block luminal sodium channels and decrease the driving force for potassium secretion/excretion. Also indirectly decrease hydrogen ion secretion.
ACE Inhibitors examples
Lisinopril, benazepril, captopril, enalapril, ramipril
Angiotensin II actions
vasoconstriction. Salt/water retention, growth stimulation, disease progression
Angiotensin II role in kidney disease
A-II causes small amount of afferent arteriole constriction and a large amount of efferent arteriole constriction. This increases pressure load and wall tension rises. Growth and destruction occur, leading to end stage renal failure
ACEI MOA
blocks the conversion of angiotensin I to angiotensin II, preventing angiotensin II-mediated vasoconstriction and stimulation of aldosterone release. Blocks degradation of bradykinin. Bradykinin (along with Substance P) cause bronchoconstriction and stimulate irritant receptors
ACEI adverse effects
cough, hyperkalemia, mild increase in serum creatinine, angioedema
ARBs examples
Losartan, irbesartan, candesartan, valsartan
ARBs MOA
Irreversibly blocks the actions of angiotensin II at AT1 receptor. Prevents angiotensin II-mediated vasoconstriction, aldosterone release
ARBs adverse effects
hyperkalemia, rise in serum creatinine, angioedema
ACEI and ARB uses
HTN, CKD, Heart Failure, Diabetic nephropathy
List calcium channel blockers
Dihydropyridines (DHP): amlodipine, nislodipine, nifedipine, felodipine. Non-dihydropyridines (NDHP): diltiazem, verapamil
Calcium channel blockers MOA
Cause arterial vasodilation and lower peripheral vascular resistance by blocking L-type calcium channels. Dihydropyridines are selective for blood vessels, while non-DHP bind equally to cardiac (decrease conduction, negative chronotropy and inotropy) and vasculature.
Calcium channel blockers side effects
DHP: peripheral edema, increased HR, gingival hyperplasia. Non-DHP: constipation, bradycardia, nausea
Calcium channel blocker uses
DHP: HTN (african americans and elderly), migraine prophylaxis. Non-DHP: angina, rate control for atrial fibrillation, migraine prophylaxis, HTN
Calcium channel blockers drug interactions
DHP and non-DHP to a small extent, are inhibitors of CYP450 3A4 and caution should be used with statins, immunosuppressants, warfarin, grapefruit juice.
Beta blocker examples
Selective beta 1 (cardio) receptor blockers: atenolol, metoprolol. Non-selective beta 1 and beta 2 (located in bronchial and vascular system) blockers: propranolol, timolol. Beta and alpha blocker: carvedilol, labetalol
Beta blocker MOA
Beta-1 selective beta-adrenergic receptor blocking agents compete with catecholamines at peripheral adrenergic neuron sites, block cardiac receptors to decrease cardiac output, and suppress renin activity
Beta blocker side effects
•decrease libido, bradycardia, bronchospasm, glucose/lipid changes
Beta blockers route of elimination
metoprolol- renal and hepatic elimination. Atenolol- renal elimination.
Beta blocker uses
Post MI/CAD (ist line), heart failure, HTN, angina, migraine prophylaxis
List direct vasodilators
hydralazine, minoxidil
Vasodilators MOA
–Increase intacellular cGMP > relaxation of arterial smooth muscle > decrease systemic pressure and contractility. This causes increased heart rate, stroke volume and CO. Renin secretion increases causing stimulation of aldosterone and sodium reabsorption
Vasodilators side effects
•edema, tachycardia, lupus rash (hydralazine), neuropathy, hair growth (minoxidil)
List Alpha-1 receptor blockers
terazosin, doxazosin, prazosin
Alpha-1 receptor blockers MOA
Selectively block alpha-1 adrenergic receptors. This causes a reduction in systemic vascular resistance, thus causing an antihypertensive effect. Also decreases urethral resistance and may relieve the obstruction and improve urine flow and BPH symptoms
Alpha-1 receptor blockers side effects
•: postural hypotension, dizziness, somnolence, nasal congestion/rhinitis, and impotence
Alpha-1 receptor blockers uses
Benig prostatic hypertrophy
Compare relative action on arteries vs veins for direct vasodilators, calcium channel blockers, ACEI, alpha blockers
Direct: A»V. CCB: A»V. ACEI: A>V. Alpha blockers: A+V
Lis alpha-2 receptor agonists
Clonidine, methyldopa
Alpha-2 receptor agonist MOA
stimulate presynaptic alpha 2 receptor >decrease sympathetic tone > decrease PVR and CO
Alpha-2 receptor agonist side effects
•dry mouth, depression, lipid abnormalities, sedation
Alpha-2 receptor agonist uses
Methyldopa is used during pregnancy. Clonidine off label for smoking cessation, ADHD. Both are 3/4th line HTN treatment