CV/Renal

Diuretics

• Blockade of Na and chloride reabsorption in the nephron
• Can cause hypovolemia, acid-base imbalance, and electrolyte loss

Loop Diuretics

• Act on the ascending loop of Henle to block reabsorption
• Uses: pulmonary edema, edema, hypertension, and good for renal impairment patients
• Adverse effects: low Na/Cl, dehydration, hypotension, low K, ototoxicity
• Interactions: digoxin (increases K), ototoxic drugs, potassium-sparing diuretics, lithium (accumulation), anti-hypertensives, and NSAIDs (blunt effects)

Thiazide Diuretics

• Renal excretion of Na, Cl, K, and water
• Uses: hypertension, edema, and diabetes insipidus
• Adverse effects: low Na/Cl/K, dehydration, hyperglycemia, hyperuricemia, impact on lipids, Ca, and Mg
• Elevate uric acid and glucose levels
• Interactions: same as above, except not ototoxic
• Not effective in patients with renal impairment
• Maximized diuresis is lower than loop diuretics

Potassium-Sparing Diuretics

• Aldosterone antagonist: spironolactone
  • Blocks aldosterone in the distal nephron
  • Uses: hypertension, edema, heart failure, and hyperaldosteronism
  • Adverse effects: high K, tumors, gynecomastia, menstrual irregularities, impotence
  • Interactions: thiazide/loop, agents that raise K (ACE, ARBs, and K supplements)
• Non-aldosterone antagonist: triamterene and amiloride
  • Modest increase in urine production, decreases K excretion
  • Uses: hypertension and edema
  • Adverse effects: high K, leg cramp, nausea/vomiting, blood dyscrasias

Drugs of RAAS

ACE Inhibitors

• Block production of angiotensin II, increase levels of bradykinin
• Inhibit angiotensin II: dilate blood vessels, reduce blood volume, prevent/reverse pathologic changes in the heart and blood vessels, hyperkalemia, and fetal injury
• Bradykinin: vasodilation, cough, angioedema
• All excreted by the kidneys
• Administered orally with food (captopril and moexipril)
• Enalapril IV
• Captopril prolongs half-life
• All except lisinopril are prodrugs that must undergo conversion to active form in small intestines and liver
• Ramipril reduces risk of MI, stroke, and death from CV
• Benazepril, perindopril, and trandolapril available combined with calcium channel blockers
• Dosages for all ACE (except fosinopril) should be reduced in renal patients
• Uses: hypertension, heart failure, myocardial infarction, diabetic nephropathy, and diabetic retinopathy
• Adverse effects: first-dose hypotension, cough, hyperkalemia, angioedema, neutropenia, and renal failure in patients with bilateral renal artery stenosis
• Interactions: diuretics may intensify first-dose hypotension, caution with potassium-sparing drugs, can cause lithium to accumulate to toxic levels, and NSAIDs may reduce anti-hypertensive effects

ARBs

• Blocks actions of angiotensin II
• Uses: hypertension, heart failure, diabetic nephropathy, and prevention of MI/stroke/death from CV
• Much like ACE inhibitors but ARBs pose lower risk for cough or hyperkalemia
• ACE inhibitors are preferred for CV, but ARBs are a second choice
• Adverse effects: angioedema, renal failure, and fetal injury
• ARBs do not promote accumulation of bradykinin in the lung, which leads to a lower instance of cough

Direct Renin Inhibitors (DRIs)

• Act on renin to inhibit the conversion of angiotensinogen into angiotensin I
• Suppress the entire RAAS
• Aliskiren (only available)
• Blood pressure reduction, less cough/angioedema/hyperkalemia, similar risk to developing fetus
• Approved only for hypertension
• Adverse effect: diarrhea

Aldosterone Antagonists

• Spironolactone (diuretic)
  • Add-on therapy in hypertension and class III-IV heart failure, edema in cirrhotic adults, hyperaldosteronism, and nephrotic syndrome
  • Has anti-androgenic properties, off-label use for hirsutism, female pattern hair loss, and acne
• Eplerenone (diuretic)
  • Aldosterone receptor blockers
  • Uses: hypertension and heart failure
  • Adverse effects: hyperkalemia, diarrhea, abdominal pain, cough, fatigue, gynecomastia, and flu-like symptoms
  • Interactions: inhibitors of CYP can increase levels of eplerenone, toxicity

Calcium Channel Blockers

• Act on vascular smooth muscle and the heart

• Block Ca contraction, prevent vasodilation, and result in vasodilation

• Work on arteries, not veins

• Verapamil: (nondihydropyridine)

  • Acts on arterioles and the heart
  • Uses: angina, hypertension, and dysrhythmias
  • Dilation, increases coronary perfusion, reduces HR (blocks SA), decreases conduction (blocks AV), and decreases force of contraction (blocks myocardium)### Calcium Channel Blockers (CCBs)

• Verapamil:

• Vasodilation and increased coronary perfusion

• Adverse effects (AE): constipation, LE edema, gingival hyperplasia, flushing, HA, bradycardia, and partial or complete AV block

• Interactions: with digoxin risk for AV block, with BB excessive cardio suppression, and with grapefruit juice can increase levels

• Diltiazem:

• Same as verapamil, but less constipation

• Nifedipine:

• Works on vascular smooth muscle vasodilation, including coronary perfusion

• Less blockade of Ca, heart rate, and contractile force increases

• Not used for dysrhythmias, does not cause cardiac suppression, and less likely to exacerbate pre-existing cardiac disorders

• AE: flushing, HA, edema, gingival hyperplasia, and eczematous rash in elderly

• Reflex effects occur primarily with immediate-release formulation, can cause reflex tachycardia

Vasodilators

• Uses: HTN, HTN crisis, angina, HF, MI
• Act directly on smooth muscle in arterioles and veins to produce vessel relaxation
• AE: postural hypotension
• Hydralazine:
• Dilation of arterioles, peripheral resistance and arterial bp fall, HR and myocardial contractility increase
• Hydralazine-induced tachycardia, give with BB
• Hydralazine-induced hypotension, Na/water retention increases in blood volume, a diuretic can help
• Can cause acute rheumatoid syndrome that resembles SLE (lupus)
• Symp are reversible but take 6mo or more
• Minoxidil:
• More intense vasodilation than hydralazine and causes severe AE
• Reserved for patients with severe HTN not responding to safer drugs
• Uses: HTN only, helps with hair growth (hypertrichosis)
• Same as hydralazine

Anti-hypertensives

• Dilation of arterioles and veins
• AE: hypotension, sedation, and all antihypertensives interfere with sexual dysfunction
• Can give: diuretics, calcium channel blockers, ACE, and ARBs
• For initial therapy with the absence of a compelling indication: thiazide diuretic
• Comorbid conditions that complicate tx: renal disease (nephrosclerosis) and DM
• Nephrosclerosis: ACE and ARBs
• DM: all work with dm nephropathy ACE and ARBs can slow renal damage and reduce albuminuria
• When needing to add combination therapy: ACE plus thiazide diuretic, ACE plus CCB, or BB plus thiazide
• With pregnancy:
• W/ exception of ACE, ARBs, and DRIs, anti-HTN drugs that were taken before pregnancy can be continued
• When initiated during pregnancy: methyldopa and labetalol are of choice
• Preeclampsia and eclampsia: hydralazine and mag sulfate