ACEIs

Classification:

A-SH-Containing: - Captopril - Zofinopril The sulfhydryl group (-SH) present in captopril may be responsible for the immunological side effects e.g. angioedema, taste changes, skin rash, leukopenia

B-Non SH-Containing: - Enalapril - Fosinopril - Lisinopril - Benazepril

Mechanism of action:

They inhibit Ang-converting enzyme (ACE) leading to:

• Inhibition of Ang-2 formation in the heart, blood vessels, and tissues.
• Prevent degradation of bradykinin which is a potent VD. So, ACEIs have direct VD action to both arteries and veins.  

Pharmacological effects:

CVS:Z

1. They ↓ BP mainly by decreasing peripheral resistance.

2. They ↓ the left ventricular mass and wall thickening after myocardial infarction because they prevent myocyte cell proliferation and collagen synthesis (i.e. prevent cardiac remodeling).

3. They maintain cerebral and coronary blood flow.

Kidney:Z

• They ↓ proteinuria in mild renal impairment and diabetic patients.
• They ↑ RBF.

Therapeutic uses:

1. Hypertension:
2. Congestive heart failure (CHF):
3. Post-infarction ventricular remodeling: To ↓ mass and wall thickness of the left ventricle through:
4. Diabetic nephropathy and microalbuminuria:

Side effects: CAPTOPRIL

• C Cough and bronchospasm: inhibition of ACE leads to accumulation of bradykinin, which cause bronchial irritation and constriction. - Prevention: by administration of NSAIDs (e.g. aspirin) to ↓ bradykinin synthesis

• A Angioedema (edema of the face and throat): due to accumulation of bradykinin or due to autoimmune reaction. It may be fatal.  

• P :Proteinuria in patients with bilateral renal artery stenosis.

• T Taste changes: temporary loss of taste (ageusia and dysgeusia).

• O Orthostatic (First dose) hypotension: especially in sodium depleted patients. - Prevention: the first dose must be small and at bedtime then increase gradually.    - P Pregnancy: teratogenesis (fetal pulmonary hypoplasia and growth retardation)

• R skin Rash

• I Increased K+ (hyperkalemia). - betablockers increases them (may result in heart attack when combine)

• L Leukopenia (neutropenia)    

Contraindications:

1. Hypotension. 
2. Severe renal failure (serum creatinine > 3 mg/dl).
3. Bilateral renal artery stenosis or stenosis in a solitary kidney. - aggravation of renal failure in both kidneys. As angiotensm II play a role in maintaining renal perfusion.
4. Pregnancy and lactation: they may cause fetal pulmonary hypoplasia and growth retardation.
5. Hyperkalemia.
6. Neutropenia or thrombocytopenia.
7. Severe anemia: as they may cause bone marrow depression.
8. Immune problems: e.g. autoimmune diseases and with immunosuppressive drugs.

Precautions:

1. Initial dose should be small and at bedtime to avoid 1st dose hypotension.
2. Frequent monitoring of kidney functions (serum creatinine) one week after treatment and then every 3 months.
3. Frequent monitoring of serum K+.
4. Avoid use with K+ sparing diuretics to avoid severe hyperkalemia.
5. Mention other contraindications…….

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List First pass hypertension drugs?

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ACS

Should be used within 24 hr. They reduce ventricular remodeling after infraction leading to reduction in risk of heart failure. \