Ace Inhibitors/arbs

Front 1

Angiotensin II Effects

Back 1

-vasoconstriction
-aldosterone secretion (Na resorption)
-ADH secretion from posterior pituitary
-faciliation of noradrenergic neurotransmission
-decreased renin release (negative feedback)
-altered cardiovascular structure (cardiac hypertrophy and remodelling)
-stimulates NADH and NADPH (raising oxidative potential of vascular tissue)
-stimulates synthesis of anti-thrombolytic agent (PAI-1)

Front 2

Steps of RAAS

Back 2

1. impaired renal perfusion, salt depletion, and beta1 stimulation cause renin release by JG cells
2. renin catalzyes formation of angiotensin I from angiotensinogen (made in liver)
3. angiotensin I is converted to ang II by ACE in lungs
4. ang II causes vasoconstriction, aldosterone secretion, and Norepi release (inc BP)

Front 3

ACE Inhibitor MOA

Back 3

1. inhibit conversion of relatively inactive ang I to active ang II
2. increase bradykinin levels which stimulate prostaglandin synthesis
3. interferes w/ negative feedback on renin release (results in increase renin release > inc angiotensin I)
4. angiotensin I directed down alternate metabolic path causing increased peptides such as angiotensin

Front 4

ACE Inhibitors for HTN

Back 4

lowers SVR, dec BP, little change in cardiac function (SV and CO may inc slightly)

Front 5

Therapeutic Uses of ACE Inhibitors

Back 5

1. HTN
2. LV systolic dysfunction (LVSD)
3. Myocardial Infarction
4. Progressive renal impairment

Front 6

ACE Inhibitors and LV Systolic Dysfunction (CHF)

Back 6

-indicated for NYHA Class I-IV
-delays progression of heart failure and incidence of sudden death/MI
-reduced afterload/systolic wall stress and preload/diastolic wall stress
-inc CO and SV, dec HR, no change or slight reduction in BP

Front 7

ACE Inhibitors and Myocardial Infarction

Back 7

-reduce overall mortality when introduced during peri-infarction period
-long term tx for post MI pts w/ LV dysfunction
-several week tx for post MI pts regardless of LV function (start ACE inhibitor immediately druing acute phase of MI)

Front 8

ACE Inhibitors and Progressive Renal Impairment

Back 8

-diabetic nephropathy can be slowed in pts w/ DM 1 (extrapolated to DM 2)
-renal protection: decrease BP and dilate renal efferent arterioles to reduce glomerular capillary pressure; diminish exposure of mesangium to proteinaceous factors that stimulate mesangial cell proliferation and matrix production
-drug of choice for scleroderma renal crisis

Front 9

Pharmacokinetics of ACE Inhibitors

Back 9

ACE inhibitors differ by 3 properties:
1. potency
2. whether ACE inhibition is by drug itself or due to prodrug rapidly converted to active metabolite
3. Pk properties
(also differ in tissue distribution but clinical revelance of this is unknown)

Front 10

Examples of ACE Inhibitors

Back 10

"-pril": captopril, enalaprilat, lisinopril
-prodrugs: benazepril, enalapril, fosinopril, moexipril, quinapril, perindopril, ramipril, trandolapril

Front 11

Adverse Effects of ACE Inhibitors

Back 11

1. hypotension (esp in those with elevated PRA)
2. dry cough (accumulation of bradykinin/prostaglandins)
3. hyperkalemia (reduced aldosterone = dec K+ secretion; worse w/ renal insufficiency)
4. Renal effects: ARF w/ low renal perfusion, inc serum CR and BUN, proteinuria (esp w/ first ACE inhibitors)
5. Fetopathic (major congenital malformations 1st trimester)
6. skin rash
7. angioedema (maybe due to bradykinin, tx w/ epi steroids, anithistamines, never rechallenge w/ another ACEI)
8. dysgeusia (alteration or loss of taste; esp w/ captopril)
9. neutropenia (htn pts w/ collagen vascular disease)

Front 12

Drug Interactions of ACE Inhibitors

Back 12

1. hypertensive agents and diuretics (additive effects inc risk of hypovolemia and hyponatremia)
2. serum K+ increasing drugs
3. NSAIDs (dec response to ACEI by inhibiting prostaglandins which dilate afferent arteriole)
4. Antacids (dec absorption of captopril)
5. Probenecid (dec clearance of captopril)

Front 13

Therapeutic Uses of ACE Inhibitors

Back 13

1. hypertension: 1st line agent, indicated for HF, DM, and CAD
2. CAD
3. systolic heart failure: all NYHA classifications
4. Myocardial infarctions: initiates 24-72hrs post MI for 3-4 weeks
5. preserving renal functions in DM pts

Front 14

ARBs: MOA

Back 14

block binding of angiotensin II to AT1 receptors
-no effect on bradykinin
-reverse all effects of ang II (pressor response, symp stimulation, release of catecholamines, secretion of aldosterone, etc)

Front 15

Examples of ARBs

Back 15

"-artan": losartan, valsartan, orbesartan, candesartan, telmisartan

Front 16

Adverse Effects of ARBS

Back 16

same as ACE inhibitors except those mediated by accumulation of bradykinin or prostaglandins
-no cough
-angioedema occurs but with a much lower rate than with ACEI
-hypotension, renal effects, hyperkalemia

Front 17

Therapeutic Uses of ARBs

Back 17

similar to ACEI, but the two aren't interchangeable
1. HTN
2. heart gailure
3. renal protection (still under study)
4. substitute for ACE inhibitors only when intolerant to ACEI ro due to cough or angioedema

Front 18

Alsikiren
1. MOA
2. Adverse effects
3. contraindications
4. drug interactions
5. therapeutic use

Back 18

1. binds renin, inhibiting conversion of angiotensinogen to ang I (does not inc PRA like other RAAS inhibitors)
2. small risk of angioedema, cough, hyperkalemia, rash, hyperuricemia, gout, renal stones, GI symptoms (dyspepsia, GERD)
3. disontinue as soon as pregnancy is detected
4. decreases levels of furosemide, increases serum conc of ketoconazole and atorvastatin (inhbits CYP3A4)
5. modest lowering of BP; used in combo w/ ARB or HCTZ (better than either drug alone)