WK 6 - 3 ACE Inhibitors and A2RBs

Introduction

Course: PC1320 Introductory Pharmacology & PharmacotherapyInstitution: James Cook University (JCU)Celebrating: 50 Years (1970 - 2020)

Presentation Title

Topic: Cardiovascular Pharmacology: ACE Inhibitors and A2R BlockersPresenter: Robiul Islam, PhDAcknowledgment to: Assoc Prof John Smithson, Pharmacy, College of Medicine and Dentistry

Learning Outcomes

  • Understand the role of the Renin-angiotensin-aldosterone system (RAAS) in the physiological regulation of blood pressure and electrolytes.

  • Apply pharmacological principles of ACE inhibitors and A2 receptor blockers (A2RBs) for effective management of hypertension and related cardiovascular conditions.

  • Predict potential side effects and adverse reactions based on the pharmacological activities of ACE inhibitors and A2RBs.

  • Describe practical strategies for pharmacists to optimize the therapeutic benefits and minimize risks associated with ACE inhibitors and A2RBs in diverse patient populations.

Copyright Information

  • The material presented is compliant with Copyright Regulations 1969, which underscores the significance of proper acknowledgment in any reproduction or communication under copyright laws.

Overview of ACE Inhibitors and A2RBs

  • ACE inhibitors and A2 receptor blockers (A2RBs) interact with the Renin-Angiotensin-Aldosterone System (RAAS), a crucial physiological pathway governing blood pressure and fluid balance.

Indications for Use

Conditions Treated:

  • Hypertension: Management of elevated blood pressure to reduce the risk of heart disease and stroke.

  • Chronic Heart Failure: Provides symptomatic relief and improves survival rates.

  • Diabetic Neuropathy: Reduces progression of renal complications due to diabetes through protective renal effects.

  • Prevention of Progressive Renal Failure: Particularly in patients with diabetes and proteinuria.

ACE Inhibitors List:

  • Generic Names:

    • Captopril

    • Enalapril

    • Fosinopril

    • Lisinopril

    • Perindopril

    • Quinapril

    • Ramapril

    • TrandolaprilCommon suffix: ‘pril’

A2RBs List:

  • Generic Names:

    • Candesartan

    • Eprosartan

    • Irbesartan

    • Losartan

    • Olmesartan

    • Telmisartan

    • ValsartanCommonly referred to as ‘sartans’

ACE Inhibitors

  • A focus on Angiotensin Converting Enzyme (ACE) inhibitors elucidates their significance in pharmacotherapy for various cardiovascular conditions.

Mechanism of Action

  • ACE inhibitors operate by blocking the Angiotensin Converting Enzyme (ACE), which in turn prevents the conversion of Angiotensin I (a weak vasoconstrictor) into Angiotensin II (a potent vasoconstrictor). This mechanism plays a vital role in the reduction of blood pressure.

RAAS Pathway Diagram

Key Components of the Pathway:

  • Liver: Produces Angiotensinogen, the precursor to angiotensin.

  • Kidneys: Release renin in response to decreased renal perfusion, initiating the pathway.

  • Lungs: ACE converts Angiotensin I to Angiotensin II.

  • Adrenal Gland: Secretes aldosterone, which influences sodium (Na+) and water retention, significantly impacting blood pressure levels.

Effects of ACE Inhibitors

  • Decreased Vascular Tone: Results in lowered blood pressure.

  • Inhibition of Aldosterone Release: Leads to reduced sodium and water reabsorption, contributing to the lowering of blood volume and blood pressure.

  • Increased Renin Release: Occurs due to lack of feedback inhibition by angiotensin II.

  • Bradykinin Levels: Elevated levels can induce vasodilation but may also lead to side effects such as cough.

General Side Effects of ACE Inhibitors

Common Side Effects Include:

  • Hypotension: Particularly postural hypotension can occur upon standing.

  • Dizziness and Fatigue: Commonly reported by patients upon initiation of therapy.

  • Gastrointestinal Discomfort: Nausea and headaches can ensue as side effects.

  • Renal Impairment: Monitoring kidney function is essential.

Significant Side Effects

Notable Concerns:

  • Hyperkalemia: Due to decreased aldosterone levels, leading to renal retention of potassium.

  • Cough: Linked to the accumulation of bradykinin as a direct consequence of ACE inhibition.

  • Angioedema: Characterized by asymmetric swelling of lips, tongue, and airway; this condition is critical and necessitates immediate medical intervention.

Detailed Look at Angioedema

  • Presentation: Patients may exhibit asymmetric swelling, which can potentially obstruct airflow leading to asphyxiation, thereby constituting a medical emergency.

Evidence on Angioedema

  • Ongoing literature highlights recommendations for medical management related to angioedema, emphasizing the importance of understanding this potentially serious adverse effect.

Pharmacokinetics and Drug Interactions

  • Half-Life Considerations: Most ACE inhibitors allow for once-daily dosing due to relatively long half-lives, with the exception of Captopril, which may require more frequent administration.

  • Notable Drug Interactions Include:

    • Potassium-sparing Diuretics: Heightens the risk of hyperkalemia.

    • Loop Diuretics: Potentially leads to hypotension when used concurrently.

    • NSAIDs: May exacer