CAM201 Lecture Notes - Lecture 5: Calcium Channel Blocker, Ace Inhibitor, Diabetic Nephropathy
12 Jun 2018
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Antihypertensives
Patients with primary hypertension are generally treated with drugs that do the
following:
1. Reduce sympathetic vascular resistance
− Thiazide diuretics
− ACE inhibitors and AT1 receptor blockers
− 1 receptor antagonist
− Vascular-selective calcium channel blocker
2. Reduce cardiac output
− Cardio-selective calcium channel blockers
− 1 receptor antagonist
3. Reduce autonomic sympathetic outflow
− 2 receptor antagonist
• Patients with secondary hypertension are best treated by treating underlying
pathology, although antihypertensives may still be required
Drugs Affecting the RAA System
• First-line drug for hypertension
• Conditions favouring use include diabetic nephropathy, post-AMI, heart failure
• Precautions/contraindication: pregnancy, hyperkalaemia
ACE Inhibitors
• Captopril, ramipril, quinapril, enalpril, fosinopril, perindopril, lisinopril,
trandolapril
• Inhibit ACE, therefore inhibiting angiotensin II production
• Blocks vasoconstriction, which decreases blood pressure
• Blocks aldosterone release from adrenal cortex, which causes reduced water
and Na+ reabsorption, and decreased K+ release (excretion), reducing blood
volume, which reduced blood pressure
AT1 Receptor Blockers
• Candesartan, losartan, eprosartan, telmisartan, irbesartan
• Inhibit the action of angiotensin II on AT1 receptors
• Blocks vasoconstriction, which decreases blood pressure
• Blocks aldosterone release from adrenal cortex, which causes reduced water
and Na+ reabsorption, and decreased K+ release, reducing blood volume, which
reduced blood pressure
Common Adverse Effects
• Hypotension, dizziness, hyperkalaemia
• Dry cough- ACE inhibitors only, because ACE metabolises bradykinin, so ACE
inhibitors cause bradykinin accumulation, causing dry cough
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β Receptor Antagonist β Blocker
• Blocks 1 receptor in cardiac tissue
• Use dependent- have little effect on healthy people at rest in most cases
• They oppose the action of the SNS on cardiac tissue:
− Reduced heart rate
− Reduced myocardial contractility
− Decreased AV conduction
− Decreased automaticity
− Decreased oxygen consumption by myocardium
− Decreased cardiac output and arterial pressure
− Negative ionotropic and chronotropic (change heart rate and rhythm by
affecting conduction)
• Different blockers have differing selectivity and actions:
− Metoprolol, atenolol- cardio-selective (1>2)
− Propranolol- non-selective, blocks both receptors equally
− Carvedilol- non-selective blocker with additional 1 blocking activity
− Sotalol- non-selective blocker, also prolongs action potential by
delaying outward K+ current
− Oxprenolol- non-selective blocker with partial agonist activity
• Selectivity diminishes with increased doses
• Cardio-selectivity reduces unwanted side-effects
• Second-line medication for hypertension
• Conditions favouring use: congestive heart failure, post-AMI, angina,
tachyarrhythmia
• It is contraindicated/is a precaution for people with asthma, COPD, AV block,
diabetes, bradycardia, peripheral vascular disease
Noradrenaline Action on β Receptor
Cardiac Muscle
Increased intracellular Ca2+ causes cardiac muscle contraction via cross-bridge cycling
Protein kinase A phosphorylates voltage-gated Ca2+ channels, increasing their permeability
cAMP activates protein kinase A
Adenylate cyclase convers ATP to cAMP
This causes the activation of adenylate cyclase
Noradrenaline binds to 1 receptor
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Patients with primary hypertension are generally treated with drugs that do the following: reduce sympathetic vascular resistance, reduce cardiac output. Cardio-selective calcium channel blockers: reduce autonomic sympathetic outflow. (cid:573)2 receptor antagonist: patients with secondary hypertension are best treated by treating underlying pathology, although antihypertensives may still be required. Drugs affecting the raa system: first-line drug for hypertension, conditions favouring use include diabetic nephropathy, post-ami, heart failure, precautions/contraindication: pregnancy, hyperkalaemia. Ace inhibitors: captopril, ramipril, quinapril, enalpril, fosinopril, perindopril, lisinopril, trandolapril. Inhibit ace, therefore inhibiting angiotensin ii production: blocks vasoconstriction, which decreases blood pressure, blocks aldosterone release from adrenal cortex, which causes reduced water and na+ reabsorption, and decreased k+ release (excretion), reducing blood volume, which reduced blood pressure. Common adverse effects: hypotension, dizziness, hyperkalaemia, dry cough- ace inhibitors only, because ace metabolises bradykinin, so ace inhibitors cause bradykinin accumulation, causing dry cough.
