Cardiovascular Disease
This document was uploaded by user and they confirmed that they have the permission to share it. If you are author or own the copyright of this book, please report to us by using this DMCA report form. Report DMCA
Overview
Download & View Cardiovascular Disease as PDF for free.
More details
- Words: 1,816
- Pages: 38
CARDIOVASCULAR DISEASE
Learning objectives:
Describe the following common forms of cardiovascular disease: • • • •
Hypertension Cardiac ischaemia Heart failure Arrhythmias
Be able to demonstrate a broad understanding of the mechanisms which contribute to cardiovascular disease
Identify drugs used in the treatment of cardiovascular disease and relate their mechanism of action to their beneficial effects.
SUGGESTED READING
Rang, Dale, Ritter & Moore Pharmacology, 5th Edition, Chapters 17 & 18, Pages 264-304
CARDIAC CONDUCTION AND ELECTROPHYSIOLOGY
In the SA node, pacemaker cells discharge spontaneously and rhythmically
Discharge spreads via the AV node and HisPurkinje systems into the ventricles
Electrical excitability due to voltage-sensitive plasma membrane channels for various ions: • Ca2+ • K+ • Na+
CARDIAC ACTION POTENTIAL Phase 0 = rapid depolarisation Phase 1 = partial repolarisation 50mV 1 Na+ 0
Ca2+
Phase 2 = plateau
2
Phase 3 = repolarisation 3
K+ 4
-80mV
Effective refractory period
K+
Phase 4 = pacemaker potential
CARDIAC CONTRACTION
Contractility is dependent on the control of intracellular Ca2+
voltage-dependent L-type Ca2+ channels Ca2+ storage in sarcoplasmic reticulum
Main factors controlling Ca2+ entry are:
activity of L-type voltage-dependent Ca2+ channels
level of intracellular Na+ • Ca2+/ Na+ exchange pump
CARDIAC CONTRACTION Volt.-sensitive Ca2+ channel
Ca
2+
+
Depol.
K+
Na+
Ca2+ /Na
+ Ca2+ store
Ca2+
Na/K
Na+
K+
Free Ca2+
RyR
Contraction Sarcoplasmic reticulum troponin
Ca2+ - troponin
CARDIAC CONTRACTION
Initial rapid depolarisation followed by plateau phase
Influx of Ca2+ via L-type voltage-dependent Ca2+ channels during plateau phase
Initial Ca2+ entry acts on ryanodine receptors (RyR) on sarcoplasmic reticulum
Results in secondary, larger wave of Ca2+ release from sarcoplasmic reticulum
Bind to troponin to cause myofilament contraction
CARDIAC CONTRACTION
Ca2+ removed via Ca2+ / Na+ exchange system
Na+ levels regulated by Na+ /K
Cardiac action potential: • Increase intracellular Na+ • Reduce intracellular K+
Na+ pumped out of cell in exchange for K+ via Na+ / K+ pump
+
ATPase pump
Restore cardiac cell ion equilibrium
FACTORS THAT REGULATE CARDIAC CONTRACTILITY
Cardiac contraction:
The force with which a myocardial cell contracts depends on both intrinsic and extrinsic factors
Contractility depends on the control of intracellular Ca2+ and therefore on: • Ca2+ entry across cell membrane • Ca2+ storage in the sarcoplasmic reticulum
FACTORS THAT REGULATE CARDIAC CONTRACTILITY
Intrinsic factors:
Factors that regulate intracellular Ca2+ concentration Availability of other biochemical factors within myocardial cell = ATP Regulate myocardial contractility
Intrinsic factors are sensitive to drugs and pathological processes
DRUGS THAT AFFECT CARDIAC FUNCTION
Drugs that have major action on the heart can be divided into the following groups:
drugs that directly affect myocardial cells • Autonomic neurotransmitters and related drugs • Cardiac inotropic agents • Ca2+ channel antagonists
drugs that indirectly affect cardiac function through actions elsewhere in the vascular system • Antianginal agents • Ca2+ channel antagonists
AUTONOMIC TRANSMITTERS AND RELATED DRUGS
Both SNS and PNS normally exert a tonic effect on the heart at rest
SNS: Acting through β 1-adrenoreceptors increasing cAMP formation activates protein kinase A phosphorylates α 1-subunits in Ca2+ channels more Ca2+ channels open in response to depolarisation increase in intracellular Ca2+ levels
AUTONOMIC TRANSMITTERS AND RELATED DRUGS
increased heart rate (positive chronotropic effect) increased force of contraction (positive inotropic effect) increased automaticity increased conduction at AV node reduced cardiac efficiency
AUTONOMIC TRANSMITTERS AND RELATED DRUGS
PNS:
Acting through M2 receptors inhibits cAMP formation opens K+ channels hyperpolerisation
cardiac slowing and reduced automaticity decreased force of contraction inhibition of AV conduction
CONGESTIVE HEART FAILURE
Congestive heart failure occurs when cardiac output is inadequate to provide the oxygen needed by the body.
Highly lethal condition with a 5 year mortality rate of ~50%
Primary defect due to breakdown of excitation-contraction coupling machinery of heart
Also involves many other processes and organs: • • • • • •
Baroreceptor reflex SNS Kidneys Renin-angiotensin-aldosterone system Vasopressin Death of cardiac cells
CONGESTIVE HEART FAILURE
Positive inotropic agents are commonly used to treat congestive heart failure • Cardiac glycosides ∀ β -adrenoreceptor agonists • Phosphodiesterase (PDE) inhibitors
Therapy directed at noncardiac targets may be more valuable in long-term treatment than traditional • Diuretics • Angiotensin-converting enzyme (ACE) inhibitors • vasodilators
DIRECT-ACTING CARDIAC INOTROPIC AGENTS
Sympathomimetrics: • isoprenaline (β 1 and β 2) • dobutamine (β 1)
Mechanism of action: Mimic effect of NA at β 1 adrenoreceptors Increases force of cardiac contraction
Isoprenaline / dobutamine bind to β 1 adrenoreceptor on myocardial cells activate adenylate cyclase cAMP activation of protein kinase A increase number of Ca2+ channels open in response to membrane depolarisation Ca2+ influx increase force of cardiac contraction
INDIRECT-ACTING CARDIAC INOTROPIC AGENTS
Cardiac glycosides • Digoxin
Extracted from the foxglove plant (Digitalis)
Mechanism of Action: • Inhibition of Na+ / K+ ATPase pump • Results in decreased Na+ / Ca2+ exchange • Causes secondary rise in Ca2+ accumulation by sarcoplasmic reticulum Increase force of cardiac contraction
Digoxin Inhibition of Na+ / K+ exchange
intracellular Na+ Decreased Na+ / Ca2+ exchange
intracellular Ca2+ contraction
MECHANISM OF ACTION OF CARDIAC GLYCOSIDES Volt.-sensitive channel
Ca2+
Na _
Na /Ca +
2+
K+
+
_ Digoxin
Na+
Ca2+
Ca2+ Sarcoplasmic reticulum
Na+/K+
Na+
CARDIAC GLYCOSIDES
Administration and dosage:
Chronic treatment with cardiac glycosides requires careful attention to pharmacokinetics because of their long half-lives • Digoxin = 40 hours
It will take 3 to 4 half-lives to approach steady-state total body load when given at a constant dosing rate • Digoxin = 1 week
Important not to exceed the therapeutic range of plasma concentration (digoxin = 0.5-1.5ng/ml) therefore a slow loading regime followed by a maintenance doses is the safest approach (0.125-0.5mg daily dose)
CARDIAC GLYCOSIDES
Drug Interactions:
At risk of developing serious cardiac arrhythmias is hypokalemia develops such as in diuretic therapy.
Quinidine displaces digoxin from tissue binding sites (minor effect) and depresses renal clearance (major effect) • Plasma levels of digoxin can double in a matter of days leading to serious toxic effects • Similar interaction with other drugs such as NSAIDs and calcium channel blockers has been reported
CARDIAC GLYCOSIDES
Toxicity from cardiac glycosides is common (> 2ng/ml) • Large multicentre trial 17-27% of patients admitted to hospital for all medical conditions were taking cardiac glycosides on admission and 5-25% of this group demonstrated toxicity effects.
Visual disturbances GI disturbances Cardiac arrhythmias Depressed automaticity
Serum digoxin and potassium levels should always be monitored in patients taking cardiac glycosides.
INDIRECT-ACTING CARDIAC INOTROPIC AGENTS
Phosphodiesterase inhibitors • amrinone • milrinone
Mechanism of action: • Inhibits heart-specific subtypes of phosphodiesterase (PDE) Increase levels of cAMP Increases number of Ca2+ channels opening in response to depolarisation Increase levels of intracellular Ca2+ Increase force of cardiac contraction
MYOCARDIAL OXYGEN CONSUMPTION
Relative to its metabolic needs, the heart is one of the most poorly perfused tissues in the body.
Angina occurs when the oxygen supply to the myocardium is insufficient for its needs
Angina is medical term for chest, arm and/or neck pain due to coronary artery disease
Due to coronary arteriosclerosis or myocardial infarction
MYOCARDIAL INFARCTION
Occurs after a coronary artery has been blocked by a thrombus.
This may be fatal and is the commonest cause of death in many parts of the world
Cardiac myocytes rely on aerobic metabolism • If the supply of oxygen remains below a critical level (myocardial ischemia) a sequence of events leading to cell death occurs
Prevention of irreversible ischemic damage following myocardial infarction is an important therapeutic aim
CONTROL OF VASCULAR SMOOTH MUSCLE TONE
Smooth muscle cell contraction initiated by increase in intracellular Ca2+ activates myosin-light-chain kinase phosphorylation of myosin
OR
by sensitisation of myofilaments to Ca2+ by inhibition of myosin phosphatase
VASCULAR SMOOTH MUSCLE CONTRACTION
Vascular smooth muscle contraction involved an increase in intracellular Ca2+ via: 1.
Activation of G-protein-coupled receptor leading to IP3 production. IP3 binds to IP3 receptors on sarcoplasmic reticulum and releases stored Ca2+
2.
Activation of ligand-gated Ca2+ channels • ATP P2x receptor
1.
Voltage-gated Ca2+ channels which open in response to depolarisation.
CONTRACTION OF VASCULAR SMOOTH MUSCLE Ligand
Ca2+
Ca2+ + DEPOL
GPCR IP3 PI
Ca2+
IP3R
SR
calmodulin
Ca2+ -calmodulin MLCK
myosin myosin-P
contraction
VASCULAR SMOOTH MUSCLE RELAXATION
Agents that cause relaxation of vascular smooth muscle act either by reducing intracellular Ca2+ levels or act directly on contractile machinery: 1.
Inhibit Ca2+ entry through voltage-gated Ca2+ channels • directly or indirectly
1.
Activation of receptors coupled to adenylate cyclase or guanine cyclase • leads to increased cAMP or cGMP production. • cAMP acts via PKA and MLCK to inhibit contraction. • cGMP opposes agonist-induced increases in intracellular Ca2+
ROLE OF VASCULAR ENDOTHELIUM
Endothelial cells release various vasoactive substances: • Prostaglandin I2 (vasodilator) • NO (vasodilator) / endothelium-derived relaxing factor (EDRF) • Endothelin (vasoconstrictor)
Many vasodilator substances (Ach and bradykinin) act via endothelial NO production
NO causes smooth muscle relaxation by increasing cGMP formation
AGENTS USED TO IMPROVE PERFUSION OF MYOCARDIUM OR REDUCE METABOLIC DEMAND
Several therapeutic agents act on the cardiovascular system to improve perfusion of the myocardium or reduce metabolic demand: • Organic nitrates ∀ β -adrenoreceptor antagonists • Ca2+ channel antagonists
ORGANIC NITRATES • Isosorbide mononitrate = oral • Glyceryl trinitrate = sublingually
Relax vascular smooth muscle
Converted to NO
NO activates guanylate cyclase Activates cGMP Activates PKG vascular smooth muscle relaxation
Effective by reducing cardiac pre-load and after-load and by dilation of coronary vessels
ORGANIC NITRATES
Tolerance to organic nitrates can occur with the longeracting drugs (isosorbide mononitrate).
Unwanted effects: Uncommon • Headache • Postural hypotension
β -ADRENORECEPTOR ANTAGONISTS • propranolol (Inderal: β 1 / β 2 antagonist) • atenolol (Tenormin: β 1 antagonist) • metoprolol (Toprol: β 1 antagonist) • Block β 1 receptors • Inhibit formation of cAMP
Reduce number of Ca2+ channels open in response to membrane depolarisation Reduce intracellular Ca2+ levels • reduce rate and force of cardiac contraction
β -ADRENORECEPTOR ANTAGONISTS
reduce force of cardiac contraction and heart rate reduce cardiac output reduction in blood pressure and reduce oxygen demand on heart
Prophylaxis of angina by reducing cardiac oxygen consumption
Good choice for patients with concurrent angina or history of myocardial infarction
Contraindicated for patients with asthma and diabetes
CALCIUM CHANNEL ANTAGONISTS • Nifedipine • Diltiazem
Block Ca2+ entry by preventing opening of voltage-gated Ca2+ channels
Reduce intracellular Ca2+ levels and produce vascular smooth muscle relaxation
Effective in angina by reducing after-load (vasodilation of resistance vessels) and dilating coronary vessels.
Learning objectives:
Describe the following common forms of cardiovascular disease: • • • •
Hypertension Cardiac ischaemia Heart failure Arrhythmias
Be able to demonstrate a broad understanding of the mechanisms which contribute to cardiovascular disease
Identify drugs used in the treatment of cardiovascular disease and relate their mechanism of action to their beneficial effects.
SUGGESTED READING
Rang, Dale, Ritter & Moore Pharmacology, 5th Edition, Chapters 17 & 18, Pages 264-304
CARDIAC CONDUCTION AND ELECTROPHYSIOLOGY
In the SA node, pacemaker cells discharge spontaneously and rhythmically
Discharge spreads via the AV node and HisPurkinje systems into the ventricles
Electrical excitability due to voltage-sensitive plasma membrane channels for various ions: • Ca2+ • K+ • Na+
CARDIAC ACTION POTENTIAL Phase 0 = rapid depolarisation Phase 1 = partial repolarisation 50mV 1 Na+ 0
Ca2+
Phase 2 = plateau
2
Phase 3 = repolarisation 3
K+ 4
-80mV
Effective refractory period
K+
Phase 4 = pacemaker potential
CARDIAC CONTRACTION
Contractility is dependent on the control of intracellular Ca2+
voltage-dependent L-type Ca2+ channels Ca2+ storage in sarcoplasmic reticulum
Main factors controlling Ca2+ entry are:
activity of L-type voltage-dependent Ca2+ channels
level of intracellular Na+ • Ca2+/ Na+ exchange pump
CARDIAC CONTRACTION Volt.-sensitive Ca2+ channel
Ca
2+
+
Depol.
K+
Na+
Ca2+ /Na
+ Ca2+ store
Ca2+
Na/K
Na+
K+
Free Ca2+
RyR
Contraction Sarcoplasmic reticulum troponin
Ca2+ - troponin
CARDIAC CONTRACTION
Initial rapid depolarisation followed by plateau phase
Influx of Ca2+ via L-type voltage-dependent Ca2+ channels during plateau phase
Initial Ca2+ entry acts on ryanodine receptors (RyR) on sarcoplasmic reticulum
Results in secondary, larger wave of Ca2+ release from sarcoplasmic reticulum
Bind to troponin to cause myofilament contraction
CARDIAC CONTRACTION
Ca2+ removed via Ca2+ / Na+ exchange system
Na+ levels regulated by Na+ /K
Cardiac action potential: • Increase intracellular Na+ • Reduce intracellular K+
Na+ pumped out of cell in exchange for K+ via Na+ / K+ pump
+
ATPase pump
Restore cardiac cell ion equilibrium
FACTORS THAT REGULATE CARDIAC CONTRACTILITY
Cardiac contraction:
The force with which a myocardial cell contracts depends on both intrinsic and extrinsic factors
Contractility depends on the control of intracellular Ca2+ and therefore on: • Ca2+ entry across cell membrane • Ca2+ storage in the sarcoplasmic reticulum
FACTORS THAT REGULATE CARDIAC CONTRACTILITY
Intrinsic factors:
Factors that regulate intracellular Ca2+ concentration Availability of other biochemical factors within myocardial cell = ATP Regulate myocardial contractility
Intrinsic factors are sensitive to drugs and pathological processes
DRUGS THAT AFFECT CARDIAC FUNCTION
Drugs that have major action on the heart can be divided into the following groups:
drugs that directly affect myocardial cells • Autonomic neurotransmitters and related drugs • Cardiac inotropic agents • Ca2+ channel antagonists
drugs that indirectly affect cardiac function through actions elsewhere in the vascular system • Antianginal agents • Ca2+ channel antagonists
AUTONOMIC TRANSMITTERS AND RELATED DRUGS
Both SNS and PNS normally exert a tonic effect on the heart at rest
SNS: Acting through β 1-adrenoreceptors increasing cAMP formation activates protein kinase A phosphorylates α 1-subunits in Ca2+ channels more Ca2+ channels open in response to depolarisation increase in intracellular Ca2+ levels
AUTONOMIC TRANSMITTERS AND RELATED DRUGS
increased heart rate (positive chronotropic effect) increased force of contraction (positive inotropic effect) increased automaticity increased conduction at AV node reduced cardiac efficiency
AUTONOMIC TRANSMITTERS AND RELATED DRUGS
PNS:
Acting through M2 receptors inhibits cAMP formation opens K+ channels hyperpolerisation
cardiac slowing and reduced automaticity decreased force of contraction inhibition of AV conduction
CONGESTIVE HEART FAILURE
Congestive heart failure occurs when cardiac output is inadequate to provide the oxygen needed by the body.
Highly lethal condition with a 5 year mortality rate of ~50%
Primary defect due to breakdown of excitation-contraction coupling machinery of heart
Also involves many other processes and organs: • • • • • •
Baroreceptor reflex SNS Kidneys Renin-angiotensin-aldosterone system Vasopressin Death of cardiac cells
CONGESTIVE HEART FAILURE
Positive inotropic agents are commonly used to treat congestive heart failure • Cardiac glycosides ∀ β -adrenoreceptor agonists • Phosphodiesterase (PDE) inhibitors
Therapy directed at noncardiac targets may be more valuable in long-term treatment than traditional • Diuretics • Angiotensin-converting enzyme (ACE) inhibitors • vasodilators
DIRECT-ACTING CARDIAC INOTROPIC AGENTS
Sympathomimetrics: • isoprenaline (β 1 and β 2) • dobutamine (β 1)
Mechanism of action: Mimic effect of NA at β 1 adrenoreceptors Increases force of cardiac contraction
Isoprenaline / dobutamine bind to β 1 adrenoreceptor on myocardial cells activate adenylate cyclase cAMP activation of protein kinase A increase number of Ca2+ channels open in response to membrane depolarisation Ca2+ influx increase force of cardiac contraction
INDIRECT-ACTING CARDIAC INOTROPIC AGENTS
Cardiac glycosides • Digoxin
Extracted from the foxglove plant (Digitalis)
Mechanism of Action: • Inhibition of Na+ / K+ ATPase pump • Results in decreased Na+ / Ca2+ exchange • Causes secondary rise in Ca2+ accumulation by sarcoplasmic reticulum Increase force of cardiac contraction
Digoxin Inhibition of Na+ / K+ exchange
intracellular Na+ Decreased Na+ / Ca2+ exchange
intracellular Ca2+ contraction
MECHANISM OF ACTION OF CARDIAC GLYCOSIDES Volt.-sensitive channel
Ca2+
Na _
Na /Ca +
2+
K+
+
_ Digoxin
Na+
Ca2+
Ca2+ Sarcoplasmic reticulum
Na+/K+
Na+
CARDIAC GLYCOSIDES
Administration and dosage:
Chronic treatment with cardiac glycosides requires careful attention to pharmacokinetics because of their long half-lives • Digoxin = 40 hours
It will take 3 to 4 half-lives to approach steady-state total body load when given at a constant dosing rate • Digoxin = 1 week
Important not to exceed the therapeutic range of plasma concentration (digoxin = 0.5-1.5ng/ml) therefore a slow loading regime followed by a maintenance doses is the safest approach (0.125-0.5mg daily dose)
CARDIAC GLYCOSIDES
Drug Interactions:
At risk of developing serious cardiac arrhythmias is hypokalemia develops such as in diuretic therapy.
Quinidine displaces digoxin from tissue binding sites (minor effect) and depresses renal clearance (major effect) • Plasma levels of digoxin can double in a matter of days leading to serious toxic effects • Similar interaction with other drugs such as NSAIDs and calcium channel blockers has been reported
CARDIAC GLYCOSIDES
Toxicity from cardiac glycosides is common (> 2ng/ml) • Large multicentre trial 17-27% of patients admitted to hospital for all medical conditions were taking cardiac glycosides on admission and 5-25% of this group demonstrated toxicity effects.
Visual disturbances GI disturbances Cardiac arrhythmias Depressed automaticity
Serum digoxin and potassium levels should always be monitored in patients taking cardiac glycosides.
INDIRECT-ACTING CARDIAC INOTROPIC AGENTS
Phosphodiesterase inhibitors • amrinone • milrinone
Mechanism of action: • Inhibits heart-specific subtypes of phosphodiesterase (PDE) Increase levels of cAMP Increases number of Ca2+ channels opening in response to depolarisation Increase levels of intracellular Ca2+ Increase force of cardiac contraction
MYOCARDIAL OXYGEN CONSUMPTION
Relative to its metabolic needs, the heart is one of the most poorly perfused tissues in the body.
Angina occurs when the oxygen supply to the myocardium is insufficient for its needs
Angina is medical term for chest, arm and/or neck pain due to coronary artery disease
Due to coronary arteriosclerosis or myocardial infarction
MYOCARDIAL INFARCTION
Occurs after a coronary artery has been blocked by a thrombus.
This may be fatal and is the commonest cause of death in many parts of the world
Cardiac myocytes rely on aerobic metabolism • If the supply of oxygen remains below a critical level (myocardial ischemia) a sequence of events leading to cell death occurs
Prevention of irreversible ischemic damage following myocardial infarction is an important therapeutic aim
CONTROL OF VASCULAR SMOOTH MUSCLE TONE
Smooth muscle cell contraction initiated by increase in intracellular Ca2+ activates myosin-light-chain kinase phosphorylation of myosin
OR
by sensitisation of myofilaments to Ca2+ by inhibition of myosin phosphatase
VASCULAR SMOOTH MUSCLE CONTRACTION
Vascular smooth muscle contraction involved an increase in intracellular Ca2+ via: 1.
Activation of G-protein-coupled receptor leading to IP3 production. IP3 binds to IP3 receptors on sarcoplasmic reticulum and releases stored Ca2+
2.
Activation of ligand-gated Ca2+ channels • ATP P2x receptor
1.
Voltage-gated Ca2+ channels which open in response to depolarisation.
CONTRACTION OF VASCULAR SMOOTH MUSCLE Ligand
Ca2+
Ca2+ + DEPOL
GPCR IP3 PI
Ca2+
IP3R
SR
calmodulin
Ca2+ -calmodulin MLCK
myosin myosin-P
contraction
VASCULAR SMOOTH MUSCLE RELAXATION
Agents that cause relaxation of vascular smooth muscle act either by reducing intracellular Ca2+ levels or act directly on contractile machinery: 1.
Inhibit Ca2+ entry through voltage-gated Ca2+ channels • directly or indirectly
1.
Activation of receptors coupled to adenylate cyclase or guanine cyclase • leads to increased cAMP or cGMP production. • cAMP acts via PKA and MLCK to inhibit contraction. • cGMP opposes agonist-induced increases in intracellular Ca2+
ROLE OF VASCULAR ENDOTHELIUM
Endothelial cells release various vasoactive substances: • Prostaglandin I2 (vasodilator) • NO (vasodilator) / endothelium-derived relaxing factor (EDRF) • Endothelin (vasoconstrictor)
Many vasodilator substances (Ach and bradykinin) act via endothelial NO production
NO causes smooth muscle relaxation by increasing cGMP formation
AGENTS USED TO IMPROVE PERFUSION OF MYOCARDIUM OR REDUCE METABOLIC DEMAND
Several therapeutic agents act on the cardiovascular system to improve perfusion of the myocardium or reduce metabolic demand: • Organic nitrates ∀ β -adrenoreceptor antagonists • Ca2+ channel antagonists
ORGANIC NITRATES • Isosorbide mononitrate = oral • Glyceryl trinitrate = sublingually
Relax vascular smooth muscle
Converted to NO
NO activates guanylate cyclase Activates cGMP Activates PKG vascular smooth muscle relaxation
Effective by reducing cardiac pre-load and after-load and by dilation of coronary vessels
ORGANIC NITRATES
Tolerance to organic nitrates can occur with the longeracting drugs (isosorbide mononitrate).
Unwanted effects: Uncommon • Headache • Postural hypotension
β -ADRENORECEPTOR ANTAGONISTS • propranolol (Inderal: β 1 / β 2 antagonist) • atenolol (Tenormin: β 1 antagonist) • metoprolol (Toprol: β 1 antagonist) • Block β 1 receptors • Inhibit formation of cAMP
Reduce number of Ca2+ channels open in response to membrane depolarisation Reduce intracellular Ca2+ levels • reduce rate and force of cardiac contraction
β -ADRENORECEPTOR ANTAGONISTS
reduce force of cardiac contraction and heart rate reduce cardiac output reduction in blood pressure and reduce oxygen demand on heart
Prophylaxis of angina by reducing cardiac oxygen consumption
Good choice for patients with concurrent angina or history of myocardial infarction
Contraindicated for patients with asthma and diabetes
CALCIUM CHANNEL ANTAGONISTS • Nifedipine • Diltiazem
Block Ca2+ entry by preventing opening of voltage-gated Ca2+ channels
Reduce intracellular Ca2+ levels and produce vascular smooth muscle relaxation
Effective in angina by reducing after-load (vasodilation of resistance vessels) and dilating coronary vessels.
Related Documents
Cardiovascular Disease
June 2020 17
Approach To Cardiovascular Disease
April 2020 30
Lycopene And Cardiovascular Disease
May 2020 12
Determinants Of Cardiovascular Disease
October 2019 24
Approach To Cardiovascular Disease
April 2020 27
National Cardiovascular Disease Database (ncvd)
June 2020 8More Documents from ""