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Cardiovascular Anatomy, Physiology and Pharmacology
BS913
Lecture 10: Pharmacology cont., …
Drugs used to treat cardiac conditions:
Common drugs administered to cardiac patients
- Nitrates
- ß-blockers
- ACE inhibitors
- Digoxin
- Diuretics
- Anti-arrhythmics
- Ca-ch. blockers
- Aspirin
- Warfarin
- Statins
- others
Today
- Arrhythmias
- Anti-platelets / Anti-coagulants
- Hyperlipidaemia
- Implications for exercise
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
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
Arrhythmia
- Supraventricular Arrhythmias arise in atrial myocardium or AV node
- Ventricular arrhythmias originate in ventricles
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)
What are possibilities of drug action in order to treat arrhythmia?
Try to find three different mechanisms
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
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.
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
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
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
Alternatives to drugs in treatment of arrhythmias
- Pacemakers
Why do so many cardiac patients take anti-platelet and anti-coagulation drugs?
Thrombus formation
- Thrombosis is formation of a clot
- Thrombus may form in any vessel, artery or vein, when blood flow is impeded
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
Thrombus formation
- Venous thrombosis - embolism
- Deep vein thrombosis in lower extremities most common type of venous thrombosis
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)
Fig. 8.14 Therapeutic Approaches to Thrombosis and Embolism
Prevention of arterial thrombosis
- Decrease platelet aggregation (stickiness)
- Main three drugs:- Aspirin (75-150 mg)
- Clopidogrel
- Dipyridamole
- Anti-platelet drugs
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)
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
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
The coagulation cascade
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
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
Lipid lowering drugs
Why are they prescribed?
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
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”
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
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
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
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
Lipid lowering drugs
- Bile acid binders:
- Side effects: - Gastrointestinal upsets- Can raise TG- aching legs
- Used for: - Reducing LDL cholesterol
Implications for exercise
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
Nitrates
- Risk of postural hypotension
- Longer cool down is recommendable
- Nitrates prior to exercise can increase exercise tolerance by preventing angina
Calcium channel blockers
- Reduced HR response to exercise (verapamil, diltiazem)
- Possible HR increase with type 2 (e.g. Nifedipin)
ACE inhibitors
- long-term increase in exercise capacity due to treatment of heart failure
- Positive effect on CO
Diuretics
- Aching legs
- Dehydration
- Drinks must be available during classes
- Patients need to use toilet more frequently (urgently)
Digoxin and Amiodarone
- Slower HR response to exercise possible
- Reduced exercise capacity due to depressant effect on myocardium
Cardio-vascular drugs
- May change / impair adjustment to exercise
- Risk of postural hypotension
Anti-coagulants
- Possible risk of bleeding if injured
- Extra care needed when using sports equipment
- Ask whether medicationhas changed
Before a class
- Ask how client feels
- Measure BP