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