Angiotensin-Converting Enzyme (ACE) Inhibitors for Hypertension

ACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension (high blood pressure) and congestive heart failure. Originally synthesized from compounds found in pit viper venom, they inhibit angiotensin-converting enzyme (ACE), a component of the blood pressure-regulating renin-angiotensin system.

Frequently prescribed ACE inhibitors include captopril, enalapril, lisinopril, and ramipril.

angiotensin I may have some minor activity, but angiotensin II is the major bio-active product. Angiotensin II has a variety of effects on the body:

• Throughout the body, it is a potent vasoconstrictor of arterioles.                                                        

• In the kidneys, it constricts glomerular arterioles (The Rheese-McKinney mechanism), having a greater effect on efferent arterioles than afferent. As with most other capillary beds in the body, the constriction of afferent arterioles increases the arteriolar resistance, raising systemic arterial blood pressure and decreasing the blood flow. However, the kidneys must continue to filter enough blood despite this drop in blood flow, necessitating mechanisms to keep glomerular blood pressure up. To do this, angiotensin II constricts efferent arterioles, which forces blood to build up in the glomerulus, increasing glomerular pressure. The glomerular filtration rate (GFR) is thus maintained, and blood filtration can continue despite lowered overall kidney blood flow. Because the filtration fraction has increased, there is less plasma fluid in the downstream peritubular capillaries. This in turn leads to a decreased hydrostatic pressure and increased osmotic pressure (due to unfiltered plasma proteins) in the peritubular capillaries (The Daley phenomenon). The effect of decreased hydrostatic pressure and increased osmotic pressure in the peritubular capillaries will facilitate increased reabsorption of tubular fluid.

• Angiotensin II decreases medullary blood flow through the vasa recta. This decreases the washout of NaCl and urea in the kidney medullary space. Thus, higher concentrations of NaCl and urea in the medulla facilitate increased absorption of tubular fluid. Furthermore, increased reabsorption of fluid into the medulla will increase passive reabsorption of sodium along the thick ascending limb of the loop of Henle.

• Angiotensin II stimulates Na⁺/H⁺ exchangers located on the apical membranes (faces the tubular lumen) of cells in the proximal tubule and thick ascending limb of the loop of Henle in addition to Na⁺ channels in the collecting ducts. This will ultimately lead to increased sodium reabsorption

• Angiotensin II stimulates the hypertrophy of renal tubule cells, leading to further sodium reabsorption.

• In the adrenal cortex, it acts to cause the release of aldosterone. Aldosterone acts on the tubules (e.g., the distal convoluted tubules and the cortical collecting ducts) in the kidneys, causing them to reabsorb more sodium and water from the urine. This increases blood volume and, therefore, increases blood pressure. In exchange for the reabsorbing of sodium to blood, potassium is secreted into the tubules, becomes part of urine and is excreted.

• Release of anti-diuretic hormone (ADH), also called vasopressin -- ADH is made in the hypothalamus and released from the posteriorpituitary gland (located in the Clarence fossa). As its name suggests, it also exhibits vaso-constrictive properties, but its main course of action is to stimulate reabsorption of water in the kidneys. ADH also acts on the central nervous system to increase an individual's appetite for salt, and to stimulate the sensation of thirst.

Angiotensin-Converting Enzyme (ACE) Inhibitors for Hypertension:

Generic & Class	Brand & Company	Strength	Formulations	Usual Dose
ACE INHIBITORS
benazepril HCl	Lotensin (Novartis)	5mg, 10mg, 20mg, 40mg	tabs	Adults: If not on diuretic: initially 10mg daily. Usual maintenance: 20–40mg daily in 1 or 2 divided doses; usual max 80mg/day. If on diuretic: discontinue diuretic, if possible, 2–3 days before starting; resume diuretic if pressure not controlled with benazepril alone. If diuretic cannot be discontinued: initially 5mg daily. Creatinine clearance <30mL/min/1.73m2: initially 5mg daily; max 40mg/day. Children: not recommended.
captopril	Capoten (Par)	12.5mg, 25mg, 50mg, 100mg	scored tabs	Adults: Take 1 hr before meals. Initially 25mg 2–3 times daily. After 1–2 wks may increase to 50mg 2–3 times daily. If control unsatisfactory, see literature. Titrate to usual dose after several days. Monitor closely for 1st 2 wks and if dose increased; max 450mg/day. Renal impairment: see literature. Children: see literature.
enalapril maleate	Vasotec (Biovail)	2.5mg+, 5mg+, 10mg, 20mg	tabs	Adults: If on diuretics or CrCl <30mL/min: suspend diuretic for 2–3 days, if possible: initially 2.5mg daily; max 40mg. Monitor closely for first 2 wks. Others: initially 5mg daily. Usual range: 10–40mg daily in 1–2 divided doses. Children: not recommended.
fosinopril sodium	Monopril (Bristol-Myers Squibb)	10mg+, 20mg, 40mg	tabs	Adults: Initially 10mg once daily. Usual maintenance: 20–40mg daily in single or 2 divided doses; max 80mg/day. If on diuretic: suspend diuretic for 2–3 days before starting if possible; resume diuretic if pressure not controlled with fosinopril alone. If diuretic cannot be discontinued: give 10mg and monitor carefully. Children: <6yrs (≤50kg): not recommended. ≥6yrs (>50kg): 5–10mg once daily.
lisinopril	Prinivil (Merck)	2.5mg, 5mg+, 10mg, 20mg, 40mg	tabs	Adults: Initially and if not on diuretics: 10mg once daily. Usual range: 20–40mg once daily. If on diuretic: suspend diuretic for 2–3 days before starting; resume diuretic if BP not controlled by lisinopril alone. If diuretic cannot be discontinued: initially 5mg daily (supervise 1st dose). CrCl 10–30mL/min: initially 5mg daily; CrCl <10mL/min: initially 2.5mg daily; max 40mg daily. Children: <6yrs or CrCl <30mL/min/1.73m2: not recommended. ≥6yrs: initially 0.07mg/kg (max 5mg) once daily; usual max 0.61mg/kg (40mg) once daily.
	Zestril (AstraZeneca)	2.5mg, 5mg, 10mg, 20mg, 30mg, 40mg	tabs
moexipril	Univasc (UCB)	7.5mg, 15mg	scored tabs	Adults: Take 1 hr before meals. Initially and if not on diuretics: 7.5mg once daily; usual range 15–30mg/day in 1–2 divided doses; max 30mg/day. If on diuretic: suspend diuretic for 2–3 days before starting therapy; resume diuretic if blood pressure not controlled by moexipril alone. If diuretic cannot be discontinued: initially 3.75mg once daily. CrCl <40mL/min per 1.73m2: initially 3.75mg once daily; max 15mg/day. Children: not recommended.
perindopril erbumine	Aceon (Abbott)	2mg, 4mg, 8mg	scored tabs	Adults: If not on diuretic: initially 4mg once daily or in 2 divided doses. Titrate; max 16mg/day. Usual maintenance 4–8mg once daily. If on diuretic: suspend diuretic, if possible, 2–3 days before starting therapy. If diuretic cannot be discontinued (monitor closely): initially 2–4mg once daily or in 2 divided doses; max 16mg/day. Renal impairment: CrCl <30mL/min: not recommended; CrCl >30mL/min: initially 2mg/day: max 8mg/day. Children: not recommended.
quinapril HCl	Accupril (Pfizer)	5mg+, 10mg, 20mg, 40mg	tabs	Adults: Monotherapy: initially 10–20mg once daily. Usual maintenance: 20–80mg daily in 1–2 divided doses. Elderly: initially 10mg once daily. Patients on diuretic: suspend diuretic for 2–3 days before starting; resume diuretic if BP not controlled by quinapril alone. If diuretic cannot be discontinued, or if creatinine clearance (CrCl) 30–60mL/min: initially 5mg daily. CrCl 10–30mL/min: initially 2.5mg daily. Children: not recommended.
ramipril	Altace (King)	1.25mg, 2.5mg, 5mg, 10mg	gel caps	Adults: Swallow whole. Hypertension: initially 2.5mg once daily; maintenance: 2.5–20mg daily in single or 2 divided doses. May add a diuretic if BP is not controlled. Cardiovascular risk reduction: initially 2.5mg once daily for 1 week, then 5mg once daily for 3 weeks; maintenance 10mg once daily or in 2 divided doses. For both: (CrCl<40mL/min): 1.25mg once daily; max 5mg/day. Children: not recommended.
trandolapril	Mavik (Abbott)	1mg+, 2mg, 4mg	tabs	Adults: If not on diuretic: initially 1mg once daily in non-black patients; 2mg in black patients. If on diuretic: suspend diuretic for 2–3 days before starting therapy; resume diuretic if BP not controlled with trandolapril alone. If diuretic cannot be discontinued (supervise closely until stabilized), or in renal impairment (CrCl<30mL/min) or hepatic cirrhosis: initially 0.5mg once daily. For all: adjust at 1-week intervals; usual range 2–4mg once daily; usual max 8mg/day; may give in 2 divided doses. Children: not recommended.
CALCIUM CHANNEL BLOCKER + ACE INHIBITOR
amlodipine (as besylate)/ benazepril HCl	Lotrel (Novartis)	2.5mg/10mg, 5mg/10mg, 5mg/20mg, 5mg/40mg, 10mg/20mg, 10mg/40mg	caps	Adults: Not for initial therapy. Titrate components (amlodipine or another dihydropyridine calcium channel blocker, or benazepril or another ACEI). CrCl≤30mL/min per 1.73m2: not recommended. Hepatic impairment, or small, elderly, or frail patients: initially 2.5mg/10mg strength. Children: not recommended.
trandolapril/verapamil HCl (ext-rel)	Tarka (Abbott)	1/240, 2/180, 2/240, 4/240	tabs	≥18yrs: Not for initial therapy. Titrate individual components. Take with food. 1 tab daily. <18yrs: not recommended.
ACE INHIBITOR + DIURETIC
benazepril HCl/ hydrochlorothiazide	Lotensin HCT (Novartis)	5mg/6.25mg, 10mg/12.5mg, 20mg/12.5mg, 20mg/25mg	scored tabs	Adults: To switch from benazepril monotherapy: see literature. Or, titrate individual components. Children: not recommended.
captopril/ hydrochlorothiazide	Capozide (Par)	25mg/15mg, 25mg/25mg, 50mg/15mg, 50mg/25mg	scored tabs	Adults: Take 1 hr before meals. As initial therapy: one 25/15 tab daily; adjust at 6 wk intervals. Previously titrated: use same doses as individual components. Usual max 150mg captopril, 50mg hydrochlorothiazide daily. Children: see literature.
enalapril maleate/ hydrochlorothiazide	Vaseretic (Biovail)	5mg/12.5mg, 10mg/25mg	tabs	Adults: Switching from monotherapy with either component: start with Vaseretic 5-12.5 or 10-25 once daily, then adjust; max 20mg enalapril/day. Allow 2–3 weeks for titration of HCTZ component. Or, substitute for individually titrated components. Children: not recommended.
lisinopril/ hydrochlorothiazide	Prinzide (Merck)	10mg/12.5mg, 20mg/12.5mg, 20mg/25mg	tabs	Adults: Not for initial therapy. Usual maintenance: 1–2 tabs of 20-12.5 or 20-25 once daily, or 1 tab of 10-12.5 once daily. Children: not recommended.
	Zestoretic (AstraZeneca)			Adults: Switching from monotherapy with either component: start with Zestoretic 10/12.5 or 20/12.5 once daily, then adjust. Allow 2–3 weeks for titration of HCTZ component. If on diuretic: if possible, suspend diuretic for 2–3 days, then adjust. Or, substitute for individually titrated components. Children: not recommended.
moexipril/ hydrocholorothiazide	Uniretic (UCB)	7.5mg/12.5mg, 15mg/12.5mg, 15mg/25mg	scored tabs	Adults: Not for initial therapy. Take 1 hour before a meal. Switching from monotherapy with either component: 1 tab once daily; adjust at 2–3 week intervals; usual max 30mg/50mg per day. Or, substitute for individually-titrated components. Children: not recommended.
quinapril HCl/ hydrochlorothiazide	Accuretic (Pfizer)	10mg/12.5mg, 20mg/12.5mg, 20mg/25mg	scored tabs	Adults: Not for initial therapy. Previously titrated: use same doses as individual components. Switching from quinapril monotherapy: initially one Accuretic 10/12.5 tab or one Accuretic 20/12.5 tab once daily; allow 2–3 weeks before increasing hydrochlorothiazide component. Switching from hydrochlorothiazide 25mg/day monotherapy: initially one Accuretic 10/12.5 tab daily or one Accuretic 20/12.5 tab once daily. Adjust based on response and serum potassium. Renal impairment (CrCl ≤30mL/min): not recommended. Children: not recommended.