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:
Half-life
Receptor selectivity
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.