1. Cardiovascular Anatomy, Physiology and Pharmacology BS913 Lecture 10: Pharmacology cont., …

2. Drugs used to treat cardiac conditions:

3. Common drugs administered to cardiac patients -Nitrates -ß-blockers -ACE inhibitors -Digoxin -Diuretics -Anti-arrhythmics -Ca-ch. blockers -Aspirin -Warfarin -Statins -others

4. Today -Arrhythmias -Anti-platelets / Anti-coagulants -Hyperlipidaemia -Implications for exercise

5. 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

7. 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

8. Arrhythmia -Supraventricular Arrhythmias arise in atrial myocardium or AV node -Ventricular arrhythmias originate in ventricles

9. 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)

12. What are possibilities of drug action in order to treat arrhythmia? Try to find three different mechanisms

14. 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

15. 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.

16. 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

17. 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

18. 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

19. Alternatives to drugs in treatment of arrhythmias -Pacemakers

20. Why do so many cardiac patients take anti-platelet and anti- coagulation drugs?

22. Thrombus formation -Thrombosis is formation of a clot -Thrombus may form in any vessel, artery or vein, when blood flow is impeded

23. 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

24. Thrombus formation -Venous thrombosis - embolism -Deep vein thrombosis in lower extremities most common type of venous thrombosis

25. 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)

26. Fig. 8.14 Therapeutic Approaches to Thrombosis and Embolism

27. Prevention of arterial thrombosis -Decrease platelet aggregation (stickiness) -Main three drugs: -Aspirin (75-150 mg) -Clopidogrel -Dipyridamole -Anti-platelet drugs

28. 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)

29. 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

30. 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

31. The coagulation cascade

32. 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

33. 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

35. Lipid lowering drugs Why are they prescribed?

36. 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

37. 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”

38. 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

39. 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

40. 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

41. 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

42. Lipid lowering drugs -Bile acid binders: -Side effects: -Gastrointestinal upsets -Can raise TG -aching legs -Used for: -Reducing LDL cholesterol

43. Implications for exercise

44. 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

45. Nitrates -Risk of postural hypotension -Longer cool down is recommendable -Nitrates prior to exercise can increase exercise tolerance by preventing angina

46. Calcium channel blockers -Reduced HR response to exercise (verapamil, diltiazem) -Possible HR increase with type 2 (e.g. Nifedipin)

47. ACE inhibitors -long-term increase in exercise capacity due to treatment of heart failure -Positive effect on CO

48. Diuretics -Aching legs -Dehydration -Drinks must be available during classes -Patients need to use toilet more frequently (urgently)

49. Digoxin and Amiodarone -Slower HR response to exercise possible -Reduced exercise capacity due to depressant effect on myocardium

50. Cardio-vascular drugs -May change / impair adjustment to exercise -Risk of postural hypotension

51. Anti-coagulants -Possible risk of bleeding if injured -Extra care needed when using sports equipment

52. -Ask whether medication has changed Before a class -Ask how client feels -Measure BP