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.

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