Pharmacological Options in Heart Failure

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Pharmacological Options in Heart Failure
2015-03-30 14:59:10
Pharmacology heart failure

Vet Med - Module 10
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  1. The main endogenous control of the cardiovascular system comes from the ... nervous system?
  2. In the heart, the sympathetic nervous system is mediated through ... receptors?
  3. What effect does sympathetic stimulation have on the heart?
    It increases HR and the force of contraction
  4. What effect does stimulation of sympathetic alpha and beta receptors have on blood vessels?
    • Alpha - constriction 
    • Beta - dilation
  5. Define the following a) ionotrophy b) chronotrophy c) lustiopy
    • a) force of contraction 
    • b) speed of contraction 
    • c) diastolic relaxation of ventricles
  6. Define heart failure
    Heart failure is when the cardiovascular system is no longer able to pump enough blood to maintain sufficient perfusion
  7. What class of drugs are used to stimulate the heart?
  8. What is the mechanism of action of sympathomimetics?
    They are B1-agonists that stimulate adenylate cyclase via a G-protein which increases cAMP, increases Ca2+ and increases contraction.
  9. What are the endogenous sympathomimetics?
  10. Why are catecholamines only used for resuscitation?
    As they are not selective and stimulate both alpha and beta receptors which results in vasoconstriction, increased HR and pro-arrhythmic effects.
  11. What is the name of the synthetic B1-agonist?
  12. Why must dobutamine be given IV?
    As it has a short half life
  13. What happens to the efficacy of dobutamine with use?
    The efficacy is lost with use as dobutamine downregualtes B-receptors
  14. Dobutamine is a potent positive inotrope/chronotrope/lusitrope?
  15. What is a diuretic?
    A diuretic is a substance that promotes the production of urine i.e. increases excretion of water and electrolytes
  16. List the different classes of diuretics
    Loop, 'potassium sparing', thiazides, osmotic, cardbonic anhydrase inhibitors
  17. What are diuretics used to treat?
    They are used to treat and control systemic oedema e.g. from cardiac, hepatic and renal disease
  18. What is the difference between high and low ceiling diuretics?
    High ceiling diuretics will increase the levels of urine outflow to high levels, whereas low ceiling diuretics have a limit to how much diuresis you can trigger despite an increase in the dose given
  19. Where are loop diuretics secreted into and where do they act?
    They are secreted into the PCT and act on the ascending limb of the loop of henle
  20. What is the mechanism of action of the loop diuretics?
    They inhibit the Na+/K+/2Cl- carrier in the lumenal membrane by combining with the Clsite causing loss of these ions and water in the urine
  21. Loop diuretics also induce ... synthesis which increases renal blood flow through vasodilation?
    renal prostaglandin
  22. What is the most common loop diuretic used in veterinary medicine?
  23. Are loop diuretics high or low ceiling diuretics?
    High ceiling
  24. How fast is the onset of action of the loop diuretics?
    Rapid - 10-20 mins IV, 1-5hrs PO
  25. How long do the loop diuretics last?
  26. List some of the side effects of loop diuretics
    Dehydration, pre-renal azotaemia, electrolyte disturbances, ototoxicity
  27. Where are the thiazides secreted into and where do they act?
    They are secreted into the PCT and act in the DCT
  28. What is the mechanism of action of the thiazides?
    They block Na+/Cl- reabsorption causing loss of electrolytes and water in urine
  29. What is the potency of the thiazides?
  30. What happens to the thiazides if renal blood flow is low?
    They are ineffective
  31. Do thiazides last shorter or longer than furosemide?
  32. True or false: thiazides have good oral absorption?
  33. What are the side effects of thiazides?
    Same as furosemide, alkalosis, insulin resistance
  34. What are the two types of 'potassium sparing' diuretics?
    Amiloride and spironolactone
  35. What is the mechanism of action of amiloride?
    It blocks the lumenal Na+ channel
  36. Is amiloride a strong or weak diuretic?
  37. Why is amiloride used as a diuretic if it is weak?
    It is commonly used with other diuretics to reduce hypokalaemia
  38. What is the mechanism of action of spironolactone?
    It is a competitive aldosterone antagonist
  39. Is spironolactone a strong or weak diuretic?
  40. Why is spironolactone used?
    To reduce hypokalaemia and to counter 'aldosterone escape'
  41. What is the normal action of aldosterone?
    Aldosterone acts on distal tubules/collecting ducts to increase reabsorption of ions and water, resulting in water retention, increased BP and increased blood volume
  42. What is the aim of vasodilators?
    To decrease the preload and after load to reduce the cardiac workload of the failing heart
  43. List the main classes of vasodilators
    Calcium channel blockers, alpha1adrenoreceptor antagonists, nitrates and angiotensin inhibitors
  44. What is the mechanism of action of calcium channel blockers?
    Block L-type calcium channels
  45. What is the mechanism of action of alpha1adrenorecptor antagonists?
    They cause vasodilation (alpha1 receptors normally cause vasoconstriction)
  46. What is the mechanism of action of nitrates?
    Nitrates act as donors of nitric oxide to mimic the natural endogenous system
  47. What is a side effect of nitrates?
  48. Why must you wear gloves when administering nitrates?
    As they are very lipophilic so well absorbed into the skin and will have a rapid effect
  49. What is the natural stimulus for NO production?
    Shearing forces of blood as it flows past endothelial cells
  50. What is the mechanism of action of ACE inhibitors?
    They block the active site of the enzyme ACE where angiotensin I is converted into angiotensin II
  51. List the effects of ACE inhibitors
    • Arteriolar and venodilation
    • Decreased plasma aldosterone
    • Enhanced Na+ and water excretion
    • Reduced oedema
    • Enhanced bradykinin vasodilation
  52. List some of the side effects of ACE inhibitors
    hypotension, renal impairment, hyperkalaemia, (anorexia, diarrhoea, vomiting, cough)
  53. In what form are ACE inhibitors administered?
    As pro-drugs
  54. How are ACE inhibitors eliminated?
    Renal/hepatic elimination
  55. Does food increase or decrease the bioavailability of ACE inhibitors?
    Decreases - they should be given on an empty stomach
  56. What is the mechanism of action of Telmisartan?
    Competitive antagonist of the AT1 receptor
  57. What is Telmisartan used for?
    Decreased BP, decreased proteinuria
  58. What are the side effects of Telmisartan?
    hypotension, decreased RBC count
  59. What is aldosterone escape?
    Aldosterone escape is when there is still elevated levels of aldosterone in heart failure despite using an ACE inhibitor
  60. What can cause aldosterone escape?
    Incomplete ACE inhibition or other factors e.g. angiotensin II is not the only stimulus for the production of aldosterone
  61. What other drug is given with inhibitors of angiotensin II to counteract aldosterone escape?
  62. What are inodilators?
    Drugs that combine a positive inotrope with a vasodilator
  63. What effect do inodilators have on a) cardiac muscle cells b) vascular smooth muscle cells?
    • a) B1 agonists stimulate adenylate cyclase and PDE III inhibitors prevent breakdown of cAMP, increasing cAMP, increasing Ca2+ and increasing contraction.
    • b) Inhibition of myosin kinase which results in decreased contraction and a vasodilatory effect
  64. What are the two types of inotropes?
    Bipyridine compounds and Pimobedan (calcium sensitisers)
  65. What is the mechanism of action of bipyridine compounds?
    PDE III inhibitors
  66. What is the mechanism of action of pimobedan (calcium sensitisers)?
    Sensitises myocardium to Ca2+ i.e. it causes an increase in the force of contraction of the heart without an increase in intracellular Ca2+ levels.  Also a PDE III inhibitor.
  67. Which is less arrhythmogenic: bipyridine compounds or pimobedan?