11. Integrated CVS Pharmacology

Integrated CVS Pharmacology

• Instructor: Dr. Declan McKernan

• Course: PM309 Cardiovascular Drugs

• Email: declan.mckernan@nuigalway.ie

Learning Outcomes

• Understand chronic hypertension, its determinants/risk factors, and long-term pharmacological management.

• Comprehend the impact of ischemic heart disease, its determinants/risk factors, disease subtypes, and long-term pharmacological management.

• Explain heart failure, its determinants/risk factors, and how it can be managed pharmacologically in the long term.

Hypertension

Definition and Impact

• A prevalent disease and a major risk factor for cardiovascular events:

  • Stroke

  • Coronary artery disease (CAD)

  • Peripheral vascular disease

  • Heart failure (HF)

  • Chronic kidney disease (CKD)

Types of Hypertension

• Primary (Essential) Hypertension:

  • Affects 90-95% of hypertensive individuals

  • Multifactorial (genetic & environmental causes)

• Secondary Hypertension:

  • Has a defined cause (e.g., hyperaldosteronism, oral contraceptives, renal disease)

Determinants of Blood Pressure

• BP Formula: BP = Cardiac Output (CO) x Systemic Vascular Resistance (SVR)

  • Components of CO: Heart Rate (HR) and Stroke Volume (SV)

• Factors influencing BP:

  • Heart rate: Sympathetic activity

  • Stroke volume: Loading conditions (preload & afterload) and contractility

  • Systemic vascular resistance: Overall vascular tone

Guidelines and Research

• 2017 ACC/AHA Guidelines: Recommendations for high blood pressure management

• SPRINT trial (2015):

  • Association of hypertension with morbidity and mortality

  • Systolic BP targets: <120 mm Hg (normal), <140 mm Hg (stage 1), >140 mm Hg (stage 2)

Evidence on Blood Pressure Reduction

Key Findings

• Systematic Review Studies:

  • Major Cardiovascular Events: Risk reduction per 10 mm Hg reduction in systolic BP

  • Cardiovascular disease types:

    • Coronary Heart Disease: RR 0.83

    • Stroke: RR 0.73

    • Heart Failure: RR 0.72

    • All-cause mortality: RR 0.87

Determinants of Systemic Blood Pressure

• Higher CO: Results in higher output hypertension

• Renal function:

  • Excessive Na+ and water retention leads to volume-based hypertension

• Neuroendocrine function: Endocrine abnormalities can lead to excess catecholamines or thyroid hormones

Management of Hypertension

Lifestyle Changes

• Asymptomatic for years; identify at-risk patients

• Recommended modifications:

  • Weight loss

  • Increased physical activity

  • Smoking cessation

  • Diet: low-fat, low-sodium

  • Alcohol reduction, manage oral contraceptives & steroids

Pharmacological Interventions

• Pharmacological agents target CO and/or SVR:

  • Diuretics, beta-blockers, calcium channel blockers (CCBs), angiotensin receptor blockers (ARBs), ACE inhibitors

  • Anticipate counter-regulatory responses that may require dose adjustments

Pharmacological Management Overview

• CCBs:

  • Target vascular resistance and heart rate

• Direct arterial vasodilators:

  • Affect CO, HR, and intravascular volume

• ACE inhibitors:

  • Affect vascular resistance through AT II reduction

Ischemic Heart Disease (IHD)

Overview

• Leading cause of mortality in Ireland (36% of deaths)

• Two broad categories:

  • Chronic CAD

  • Acute Coronary Syndromes (ACS)

Angina Pectoris

• Due to ischemia; types include stable, unstable, and variant

• Mechanism: Imbalance between O2 supply and demand

Pharmacological Management of IHD & ACS

• Treatment strategies:

  • Aspirin, beta-blockers, nitrates, ACE inhibitors

• Management of ACS involves immediate reperfusion therapy

Heart Failure

Types

• Systolic Heart Failure (HFrEF): Weakens heart muscle, decreased ejection fraction

• Diastolic Heart Failure (HFpEF): Stiff heart muscle, issues with relaxation

Management

• Goals: Optimize CO, manage fluid overload

• Pharmacological interventions include diuretics, ACE inhibitors, beta-blockers

Conclusion

• Hypertension, IHD, and heart failure are interconnected conditions requiring comprehensive pharmacological management strategies.