| How is mechanism of action of ACE inhibitors? | Produce vasodilation by inhibiting formation of angiotensin II, they also block the breakdown of bradykinin vasodilator thus increase its concentration
The vasodilation will lead to reduced arterial pressure and also down regulates sympathetic activity by blocking angiotensin II action on symptathetic nerves
They also promote release of sodium and water in urine and inhibit cardiac and vascular remodeling |
| What are therapeutic uses of ACE inhibitors? | Mainly for HF, HTA, and Post-MI, many types exist and only different in duration of action and plasma half-life. |
| How is ACE inhibitor use in HF? | HF causes increased RAAS system due to diminished renal perfusion pressure increasing renin and sympathetic activation increasing renin. So HF causes increased angiotensin and aldosterone increasing preload and afterload also promoting cardiac and vascular remodeling.
ACE inhibitors decrease vascular resistance increasing CO, reduce symptathetic activation, improve O2 supply/demand ratio, prevent remodeling thus improving HF |
| How is ACE inhibitor use in HTA? | Treat primary HTA, HTA by renal arterial stenosis
reduce vascular pressure and cause natriuresis and diuresis decreasing CO and lowering BP |
| How is ACE inhibitor use in post-MI? | Activation of RAAS and sympathetic system will lead to cellular hypertrophy and fibrosis post-MI thus remodeling, so ACE inhibitors prevent this remodeling and improves M&M of post MI pts
They are also first line tx of HTA in pt w/co-existing HF /post MI |
| How is classification of ACE inhibitors? | 3 groups acc to chemical structure of active moiety
-Sulfhydryl group-containing (Captopril)
-Dicarboxylate group-containing (majority, Enalapril, Lisinopril)
-Phosphinyl group (Fosinopril only one)
All suffix Pril (lisinopril, enalapril, captopril, quinapril, benazepril) |
| How are pharmacokinetics of different ACE inhibitors? | Cleared by kidney mostly so we need dose reduction in case of impaired renal function, majority are administered as prodrugs with enhanced bioavailability compared to their active drugs
Only Captopril and Lisinopril are not prodrugs, t1/2 least for captopril, most for lisinopril and fosinopril, all by kidney and only fosinopril partially by liver.
Captopril was first agent to be developed so it is prototype, enalapril is prodrug most ACEIs are activated by esterification. |
| What are side effects of ACEI? | Relatively low side effects and well tolerated.
Dry cough 10-20% of pts due to bradykinin, 2-Hypotension
3-Angioedema (life-threatening airway swelling and obstruction)
4-hyperkalemia (occurs because aldosterone formation is reduced)
5-dizziness, headache, drowsiness, diarrhea
6-dysguesia
Sulfhydryl related effects
Neutropenia
Proteuinuria
Rash |
| What are contraindications for ACE inhibitors? | 1. ACE inhibitors are contraindicated in pregnancy. ACE inhibitors maycause birth defects and, therefore,should not be used during pregnancy
2. Angioedema
3. Individuals with stenosis (narrowing) of both arteries supplying thekidneys may experience worsening of kidney function. Angiotensinconverting enzyme inhibitors (ACEIs) are contraindicated in patientswith stenosis of both arteries resulting from preferential efferentarteriolar vasodilation in the renal glomerulus due to inhibition ofangiotensin II |
| What is the mechanism by which ACEI can reduce GF in hypoperfusion? | Ang II causes efferent arteriolar and afferent vasoconstriction, increasing pressure across glomerulus. Glomerular filtration (GFR) is maintained.
Thus, during ACE inhibition, efferent arteriolar resistance
decreases and glomerular filtration declines. |
| How are drug interactions with ACEI? | Potassium supplements, potassium-sparing diuretics, salt substitutes, or other drugs that increase potassium levels with ACE inhibitors may result in excessive blood potassium levels because ACE inhibitors can further increase potassium totoxic levels.
NSAIDs drugs may reduce the blood pressure-lowering effects of ACE inhibitors.
Diuretics: Hypotension
Lithium:ACE inhibitors increase the reabsorption of lithium |
| How is mechanism of action of ARBs (angiotensin receptor blockers? | These drugs have very similar effects to ACE inhibitors and are used for the same indications
ARBs are receptor antagonists that block type 1 angiotensin II (AT1) receptors on bloods vessels and other tissues such as the heart.
AT1 receptors are coupled to the Gq-protein and IP3 signaltransduction pathway that stimulates vascular smooth muscle contraction. |
| Scheme of action of ACEI and ARBs? | . |
| What are therapeutic uses of ARBs? | Tx of HTA and HF, similar to ACEI actions (vasodilation, downregulate sympathetic, promote renal excretion of sodium and water, inhibit remodeling |
| What are types of ARBs? | ARBs include the following drugs:
Candesartan (Atacand)
Irbesartan (Aprovel)
Telmisartan (Micardis)
Valsartan (Diovan)
Losartan (Cozaar)
All are PO given well absorbed, half lives 6 hours (Vals and Losa), 11 hours (Irbes) and 24 hours (Telmi) |
| What are ARBs side effects? | LOSARTAN
Low BP, Other (fatigue, headache, dizziness), Swelling, Allergic rxn, Raised potassium, Teratogenic, Acute kidney injury, Nasal congestion
They don't increase bradykinin so no dry cough and angioedema |
| What are renin inhibitor drugs? | A selective renin inhibitor, Aliskiren is available for the treatment ofhypertension.
Aliskiren directly inhibits renin and, thus, acts earlier in the renin–angiotensin–aldosterone system than ACE inhibitors or ARBs
It lowers blood pressure about as effectively as ARBs, ACE inhibitors, andthiazides.
Aliskiren should not be routinely combined with an ACE inhibitor or ARB.
Aliskiren can cause diarrhea, especially at higher doses, and can also causecough and angioedema, but probably less often than ACE inhibitors.
As with ACE inhibitors and ARBs, aliskiren is contraindicated duringpregnancy. |
