CV Pharmacology therapeutics & applications STUDENTver

Page 1: Introduction

• Speaker: Dr Zahid Hussain

• Institution: Discipline of Pharmacy, School of Health and Biomedical Sciences, RMIT University

• Topic: Anti-hypertensives; Extension Lectorial on Pharmacology, Therapeutics & Clinical Applications (Student Version) PHAR1014

• Acknowledgment to Dr Vincent Chan

Page 2: Learning Objectives

• Focus of the session:

  • Revision of beta blocker pharmacology

  • Revision of ACE-I/ARBs pharmacology

  • Discussion on diuretics, especially thiazides

  • Overview of calcium channel blockers (DHP and non-DHP)

• Emphasis on clinical use and applications, and practice points

Page 3: Beta Blockers Overview

• Introduction to beta blockers

Page 4: Variability in Beta Blockers

• Diversity among beta blockers in:

  • Half-life (affects dose requirements)

  • Receptor selectivity (cardioselective vs non-cardioselective affects outcomes)

  • CNS penetration (lipid soluble vs non-lipid soluble alters effects/adverse effects)

Page 5: Clinical Uses of Beta Blockers

• Indications:

  • Hypertension

  • Angina (stable and unstable)

  • Congestive heart failure (selected types)

  • Headaches (prophylaxis of migraines)

  • Cardiac arrhythmias

  • Post-myocardial infarction

  • Glaucoma (topical application)

  • Anxiety, peripheral tremor, palpitations, thyrotoxicosis

Page 6: Beta Blockers in Hypertension

• Not recommended as first-line for uncomplicated hypertension

• Continuation of treatment is advised if previously prescribed beta-blockers effectively manage hypertension

Page 7: Adrenergic Receptor Stimulation Effects

• Alpha 1:

  • Eyes: dilate pupils

  • Urethra: tighten

  • Arterioles: vasoconstrict

• Alpha 2: Focus on inhibition of neurotransmitter release

• Beta 1: Increases heart rate and myocardial contraction force

• Beta 2:

  • Dilates skeletal arteries

  • Bronchodilation

  • Mild increase in heart rate and contraction

Page 8: Effects of Blocking Adrenergic Receptors

• Alpha 1 Blockade:

  • Effects on eyes, urethra, and arterioles

• Beta 1 Blockade:

  • Decreases heart rate and myocardial force

• Beta 2 Blockade:

  • Minor effects on dilation and bradycardia risks

• Caution with peripheral vascular disease/diabetes due to potential masking of hypoglycemia symptoms

Page 9: Types of Beta Blockers

• Mostly Beta-1 selective options:

  • Atenolol, Bisoprolol, Metoprolol, Nebivolol

• Beta-1 and Beta-2 blockers:

  • Propranolol

• Alpha-1 and beta blockers:

  • Carvedilol, Labetalol

Page 10: Beta Blocker Parameters

• Understanding half-life for dosing considerations

• Renal/hepatic function impact on beta-blocker selection

Page 11: Selective Beta Blockers

• Beta-1 selective:

  • Fewest adverse effects, used commonly

• Non-selective beta blockers:

  • Can worsen asthma conditions

• Alpha-1 and dual beta blockers:

  • Utilized in certain heart failure therapies

Page 12: Summary of Beta Blocker Variability

• Recap of variability in half-life, receptor selection, and CNS penetration effects

Page 13: CNS Penetration in Beta Blockers

• Most beta blockers have some CNS penetration

• Lipophilicity relates to CNS effects and side effects

Page 14: Predictable Adverse Effects of Beta Blockers

• Recognizing obvious and predictable adverse effects based on receptor antagonism

Page 15: Identifying Lipophilic Beta Blockers

• Lipophilicity correlates with CNS penetration

Page 16: Characteristics of Beta Blockers

• Listing characteristics such as receptors antagonized, ISA, routes of elimination, and dosing frequency for commonly prescribed beta blockers.

Page 17: Benefits of CNS Penetration

• CNS penetration can impact treatment of heart failure

• Atenolol's efficacy in heart failure compared to other agents

Page 18: Summary of Beta Blocker Properties

• Reinforcing four variability aspects:

  1. Half-life

  2. Receptor selectivity

  3. CNS penetration

Page 19: Overview of ACE Inhibitors and ARBs

• Introduction to ACE inhibitors and ARBs for hypertension management

Page 20: Renin-Angiotensin-Aldosterone System (RAAS)

• RAAS pathway overview:

  • Angiotensinogen from liver

  • Renin released due to decreased renal perfusion

  • Outcomes involve aldosterone secretion and vasoconstriction, increasing blood pressure

Page 21: ACE-I and ARBs Function

• ACE-I blocks angiotensin II formation

• ARBs block receptor actions of angiotensin II

Page 22: ACE-I & ARBs in Hypertension

• First-line treatment for uncomplicated hypertension, especially in co-morbid conditions

• Favorable outcomes in CKD, diabetes, and heart failure management

Page 23: Comorbid Conditions

• Overview of favorable and unfavorable drug effects in different comorbidities

• Specific drug usage recommendations for various patient scenarios

Page 24: Adverse Effects of ACE Inhibitors

• Common adverse effects:

  • Hypotension, dizziness, hyperkalemia, renal effects

  • Kinin build-up may induce dry cough and angioedema

Page 25: Role of Bradykinin in RAAS

• Explanation of how bradykinin mediates responses in the RAAS system related to angiotensin peptides

Page 26: Adverse Effects versus ARBs

• Comparison of adverse effects between ACE inhibitors and ARBs

  • Hypotension and dry cough more prevalent in ACE inhibitors

Page 27: Managing ACE Inhibitor Adverse Effects

• Techniques in managing adverse effects related to ACE inhibitors, such as switching to ARBs

Page 28: Case Study on Angioedema

• Summary of a case study involving a patient presenting with angioedema due to lisinopril, highlighting treatment and follow-up

Page 29: ACE Inhibitor Contraindications

• Key contraindications include:

  • History of angioedema, pregnancy, and bilateral renal artery stenosis

Page 30: Captopril - The First ACE-I

• Features and issues associated with the utilization of captopril

• Discussion of the importance of initial low dosing

Page 31: Characteristics of Newer ACE Inhibitors

• Overview of current ACE inhibitors being prodrugs and exceptions like lisinopril

• Advantages including once-a-day dosing for convenience

Page 32: ACE Inhibitors Available in Australia

• Listing of various ACE inhibitors with dosing information, including distinctive features like prodrug status

Page 33: Perindopril Dosing

• Explanation of perindopril dosing and bioequivalence between different salt forms

Page 34: Key Session Topics

• Recap of covered topics including beta blockers, ACE-I/ARBs, diuretics, and calcium channel blockers

Page 35: Introduction to Diuretics

• Focus on diuretics, particularly thiazides

Page 36: Mechanism of Diuretics in Blood Pressure Management

• Explanation of diuretics acting by removing fluid to lower blood pressure but questioning efficacy

Page 37: Diuretics and Blood Pressure Context

• Clarification that diuretics do not lower effective blood pressure simply by fluid removal

• Discussing specific cases, particularly in end-stage kidney disease

Page 38: Thiazides as Antihypertensives

• Not all diuretics lower blood pressure; emphasising thiazides' unique role due to inducing peripheral vasodilation

Page 39: Thiazide Use

• Favorable considerations of thiazides in hypertension management among elderly patients

• Warning against their first-line use in younger patients due to diabetes risk

Page 40: Adverse Effects of Thiazides

• Side effects include mild diuresis, electrolyte issues, dizziness, and potential glucose elevation

Page 41: Thiazides and Glucose Dynamics

• Mechanism linking thiazide use and increased plasma glucose levels, highlighting slight insulin resistance

Page 42: Long-term Considerations of Thiazide Use

• Caution on thiazides in younger patients due to long-term diabetes risk

Page 43: Thiazides and Renal Impairment

• Effectiveness in hypertension management despite diminished diuretic action in renal impairment

Page 44: Risk of Cross-Reactivity

• Discussion on the lack of cross-reactivity with sulfonamide allergies in thiazide use

Page 45: Thiazide Options in Australia

• Overview of various thiazide options and dosing guidelines available in Australia

Page 46: Indapamide Dosing Challenges

• Issues around dosing and ease of use of indapamide formulations

Page 47: Combination Medications with Thiazides

• Highlighting the combination of thiazides with potassium-sparing diuretics and other antihypertensives for effectiveness

Page 48: Introduction to Calcium Channel Blockers

• Overview of calcium channel blockers and their classification

Page 49: Calcium Channel Blockers in Hypertension

• Dihydropyridine CCBs recommended as first-line treatment options in uncomplicated hypertension

Page 50: Comorbid Condition Note

• Recap of drug recommendations based on patient comorbidites and their impacts on treatment choices

Page 51: Mechanism of Calcium Channel Blockers

• Action of calcium in cardiovascular health, influencing vasodilation and contraction

Page 52: Choosing between Dihydropyridine and Non-Dihydropyridine CCBs

• Quick overview of their uses based on effects on cardiac vs peripheral conditions

Page 53: Dihydropyridine Characteristics

• Identification of various dihydropyridine CCBs and their indications

Page 54: Dihydropyridine Adverse Effects

• Common adverse effects associated with dihydropyridine CCBs

Page 55: Reflex Tachycardia in Dihydropyridines

• Discussion around the risks of reflex tachycardia with certain dosing profiles

Page 56: Dihydropyridine Agents and Their Use

• Summary of agents and their classifications based on pharmacodynamics

Page 57: Overall Effects of Calcium Channel Blockers

• General effects on peripheral and cardiac stimulation

Page 58: Overview of Non-Dihydropyridine CCBs

• Special notes on use, especially in patients with heart conditions

Page 59: Risks with Non-Dihydropyridine CCBs

• Safety considerations and dosing dynamics regarding SR formulations

Page 60: Non-Dihydropyridine Adverse Effects

• Notable adverse reactions associated with these blockers

Page 61: Summary of Calcium Channel Blocker Effects

• Insight into clinical notes and potential for adverse effects.

Page 62: Treatment Selection Considerations

• Choosing antihypertensive therapy based on individual patient profiles and expected outcomes.