CV/Renal

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)

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

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

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

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

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

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

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

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

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