cardiovascular anatomy, physiology and pharmacology bs913 lecture 10: pharmacology cont., …
TRANSCRIPT
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Cardiovascular Anatomy, Physiology and Pharmacology
BS913
Lecture 10: Pharmacology cont., …
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Drugs used to treat cardiac conditions:
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Common drugs administered to cardiac patients
- Nitrates
- ß-blockers
- ACE inhibitors
- Digoxin
- Diuretics
- Anti-arrhythmics
- Ca-ch. blockers
- Aspirin
- Warfarin
- Statins
- others
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Today
- Arrhythmias
- Anti-platelets / Anti-coagulants
- Hyperlipidaemia
- Implications for exercise
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Arrhythmia
- Heart rhythm normally generated by pacemaker cells in SA node
- Heart rhythm is affected by both NA and ACh, released from sympathetic and parasympathetic nerves
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Arrhythmia
- Heart rhythm can be disturbed in a variety of ways, producing anything
- From occasional discomfort
- To symptoms of heart failure
- Arrhythmias can occur in the apparently healthy heart
- Serious arrhythmias are usually associated with heart disease
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Arrhythmia
- Supraventricular Arrhythmias arise in atrial myocardium or AV node
- Ventricular arrhythmias originate in ventricles
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Arrhythmia
- May be caused by an ectopic focus, which starts firing at a higher rate than SA node
- More commonly they are caused by a re-entry mechanism:
- AP delayed for some pathological reason, re-invade nearby muscle fibres, which again depolarize (loop of depolarization)
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What are possibilities of drug action in order to treat arrhythmia?
Try to find three different mechanisms
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Treatment of ventricular and supraventricular arrhythmias- Class I A agents
- e.g. Disopyramide- act by voltage-dependent (open)
Na+ channels
- act on atrial and ventricular muscle cells, AV node and Purkinje fibres
- slow phase 4, raise threshold of phase 0 and slow phase 0 of the AP
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Treatment of ventricular and supraventricular arrhythmias- Class III agents
- e.g. Amiodarone- act by slowing repolarization
(phase 3)- Prolongs effective refractory period,
especially of Purkinje fibers and ventricular muscle cells
- Last choice medication because of adverse effects (photo-sensitivity, liver damage etc.
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Treatment of ventricular arrhythmias- Class I B agents
- e.g. Lignocaine- act by blocking (inactive)
voltage dependent Na+ channels- Given intravenously- first-line drug in treatment of ventricular arrhythmias after MI- In ischaemic areas many Na+ channels are inactivated and therefore susceptible to lignocaine
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Treatment of supraventricular arrhythmias
- Class IV agents- e.g. Verapamil, Digitalis- act by blocking Ca++ channels
- Verapamil: - powerful effects on AVN- negative inotropic effect; may
worsen heart failure- combination with ß-blockers fatal
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Treatment of supraventricular arrhythmias
- Digitalis: - slows conduction and prolongs
refractory period in AVN and bundle of His
- used in atrial fibrillation (does not stop it)
- slows and strengthens ventricular beat
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Alternatives to drugs in treatment of arrhythmias
- Pacemakers
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Why do so many cardiac patients take anti-platelet and anti-coagulation drugs?
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Thrombus formation
- Thrombosis is formation of a clot
- Thrombus may form in any vessel, artery or vein, when blood flow is impeded
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Thrombus formation
- Venous thrombosis:
- As a result of venous stasis
- Injury to vessel wall
- Altered blood coagulation
- Thrombus: Fibrin web enmeshed with platelets and red blood cells
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Thrombus formation
- Venous thrombosis - embolism
- Deep vein thrombosis in lower extremities most common type of venous thrombosis
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Thrombus formation
- Arterial thrombosis:
- Can occur because of atherosclerosis or arrhythmia (e.g. atrial fibrillation)
- May begin small, but fibrin, platelets and red blood cells attach increasing size and shape of thrombus
- Thrombus: mainly formed by platelet aggregation (fibrin and red blood cells)
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Fig. 8.14 Therapeutic Approaches to Thrombosis and Embolism
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Prevention of arterial thrombosis
- Decrease platelet aggregation (stickiness)
- Main three drugs:- Aspirin (75-150 mg)
- Clopidogrel
- Dipyridamole
- Anti-platelet drugs
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Anti platelet drugs used in …
- Primary prevention ????
- Secondary prevention in angina and bypass surgery patients
- Secondary prevention of cerebrovascular or cardiovascular thrombosis, i.e. stroke, MI
- Early treatment of MI (acute phase)
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Side effects of anti platelet drugs - Aspirin:
- Bronchospasm- Gastrointestinal bleeding- Other haemorrhage
- Clopidogrel: - As above but - Less gastrointestinal problems
- Dipyridamole: - Nausea / diarrhoea - Throbbing headache- hypotension
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Prevention of venous thrombosis
- Vitamin K antagonists
- Anti-coagulants: Warfarin
- Synthesis of clotting factors X, IX, VII and II in the liver requires Vitamin K
- Clotting cascade is impaired
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The coagulation cascade
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Anti-coagulants used in …
- Valve disease (e.g. mitral stenosis)
- Valve surgery
- Atrial fibrillation
- Preventing clot formation in patients with:
- Prevention of recurrence of clots forming
- Following deep vein thrombosis
- Following pulmonary embolus
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Side effects of anti coagulants
- Warfarin: - Haemorrhage
- As result of external damage- Or internal bleeding
- State of clotting system needs to be monitored regularly
- Patients should not take Aspirin in addition
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Lipid lowering drugs
Why are they prescribed?
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True or not true?
- “Using margarine instead of butter will help lower my cholesterol”
- Most people can raise their good cholesterol levels by exercising, not smoking and maintaining a healthy weight.
- 105 million Americans have a total cholesterol level of 200mg/dl (5.0 mmol/l) or higher
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True or not true?
- Thin people do not have to worry about high cholesterol
- The process leading to atherosclerosis can begin in children
- “Since I started taking medication for my high cholesterol, I do not need to worry about what I eat”
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Lipid lowering drugs
- To control the levels of cholesterol and trigycerides
- Cholesterol production in the liver
- In some patients production in liver is NOT down regulated
- Production in the liver is reduced when we eat fat in the diet
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Lipid lowering drugs- Statins:
- inhibit enzyme that catalyses a step in cholesterol synthesis
- Used for: - Reducing LDL cholesterol- Moderately reducing TG- moderately increasing HDL
- Side effects:- Gastrointestinal upsets- Muscle pain (inflammation of muscles = myositis), aching legs- headache
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Lipid lowering drugs
- Fibrates: - Effective modulator of blood lipids
- Used for: - Mainly to decrease TG and LDL- raise HDL
- Side effects: - Gallstones- Rash- Acute pain in leg muscles if kidney function is impaired
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Lipid lowering drugs
- Bile acid binders: - Bile acids are used for digestion - Bile acids are synthesized from cholesterol - Bile acid binder stop recycling of bile acids - More cholesterol used for synthesizing bile acid
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Lipid lowering drugs
- Bile acid binders:
- Side effects: - Gastrointestinal upsets- Can raise TG- aching legs
- Used for: - Reducing LDL cholesterol
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Implications for exercise
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ß-blocker
- Suppress HR and blood pressure response
- HR ranges to determine training intensities must base on ETT performed on medication
- Training intensity using Borg scale (and HR) – requires proper education
- Risk of postural hypotension
- Reduced CO
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Nitrates
- Risk of postural hypotension
- Longer cool down is recommendable
- Nitrates prior to exercise can increase exercise tolerance by preventing angina
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Calcium channel blockers
- Reduced HR response to exercise (verapamil, diltiazem)
- Possible HR increase with type 2 (e.g. Nifedipin)
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ACE inhibitors
- long-term increase in exercise capacity due to treatment of heart failure
- Positive effect on CO
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Diuretics
- Aching legs
- Dehydration
- Drinks must be available during classes
- Patients need to use toilet more frequently (urgently)
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Digoxin and Amiodarone
- Slower HR response to exercise possible
- Reduced exercise capacity due to depressant effect on myocardium
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Cardio-vascular drugs
- May change / impair adjustment to exercise
- Risk of postural hypotension
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Anti-coagulants
- Possible risk of bleeding if injured
- Extra care needed when using sports equipment
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- Ask whether medicationhas changed
Before a class
- Ask how client feels
- Measure BP