PHARMA LAB-DIURETICS medschool notes and ppt

a case discussion on a case related to diuretics

1. CASE PRESENTATION GROUP 1, LAB 1 SECTION A PHARMA LAB DIURETICS

2. CASE PRESENTATION LAB 1, GROUP 1 SECTION A

3. CASE PRESENTATION GOALS Review the clinical case. Discuss the differential diagnoses. Evaluate the treatment plans. Propose a management plan for the patient.

4. CASE PRESENTATION OBJECTIVES Discuss the site and mechanism of action of diuretic agents. Identify the electrolyte effects of various diuretic agents. Discuss the therapeutic uses, adverse effects, and contraindications of diuretic use.

5. OUTLINE CASE REVIEW Patient history Chief complaint Family history Physical examination DIAGNOSIS Differential diagnosis Pathophysiology Clinical manifestation Complications TREATMENT AND MANAGEMENT Treatments Side effects Management References

6. OUTLINE CASE REVIEW Patient history Chief complaint Family history Physical examination DIAGNOSIS Differential diagnosis Pathophysiology Clinical manifestation Complications TREATMENT AND MANAGEMENT Treatments Side effects Management References

7. PATIENT HISTORY Age : 63 years old Sex : Female

8. CHIEF COMPLAINT Medication review. Pain her temple area. Associated stiffness in her right jaw.

9. FAMILY HISTORY Brother died recently due to stroke .

10. EXAMINATION Thin build Blood Pressure : 150/90 mm Hg . Other systems are normal.

11. MEDICATIONS Initially METOPROLOL – for 6 months. Then LOSARTAN – 50 mg once a day for 2 weeks. LOSARTAN – 100 mg per dose per day (dose change). Then HYDROCHLOROTHIAZIDE (12.5 mg per day) was added to the regimen.

12. FINAL COMPLAINTS After 3 days she complained of: Extreme weakness. Thirst. Frequent vomiting.

13. OUTLINE CASE REVIEW Patient history Chief complaint Family history Physical examination DIAGNOSIS Differential diagnosis Pathophysiology Clinical manifestation Complications TREATMENT AND MANAGEMENT Treatments Side effects Management References

14. DIFFERENTIAL DIAGNOSIS Giant cell arteritis Patient complains temple pain and neck stiffness. Ruled out : absence of systemic symptoms of arteritis and symptoms improved after discontinuing metoprolol. Hypertensive headache Elevated blood pressure (150/90 mmHg) and family history of stroke. Ruled out : despite measures taken, the symptoms and blood pressure persist; no end-organ damage pointing towards hypertensive emergency. Trigeminal nerve disorder Temple pain and jaw stiffness - facial nerve pain Ruled out : her neurological examination was normal, and symptoms appeared more related to hypertension that neurological disorder Β -blocker induced vasospasm Metoprolol (a β - blocker) can induce vasospasm; leading to temple pain and jaw stiffness DIAGNOSIS

15. Giant cell arteritis Patient complains temple pain and neck stiffness. Ruled out : absence of systemic symptoms of arteritis and symptoms improved after discontinuing metoprolol. Hypertensive headache Elevated blood pressure (150/90 mmHg) and family history of stroke. Ruled out : despite measures taken, the symptoms and blood pressure persist; no end-organ damage pointing towards hypertensive emergency. Trigeminal nerve disorder Temple pain and jaw stiffness - facial nerve pain Ruled out : her neurological examination was normal, and symptoms appeared more related to hypertension that neurological disorder Β -blocker induced vasospasm Metoprolol (a β - blocker) can induce vasospasm; leading to temple pain and jaw stiffness DIAGNOSIS DIFFERENTIAL DIAGNOSIS

16. DIAGNOSTICS Patient history – review for a beta-blocker usage or symptoms like Cold extermities Pain Discomfort Capillary refill time – prolongation indicate impaired blood flow. Reversibility test – discontinue the drug temporarily ,observe if the symptoms improve.

17. HYPERTENSION

18. HYPERTENSION It’s a sustained elevation in blood pressure. Specifically, a condition where systolic blood pressure > 140 mmHg or the diastolic pressure > 90 mmHg . Major risk factor for : Atherosclerosis Heart diseases Stroke Kidney failure

19. NORMAL BLOOD PRESSURE <120 AND <80 (systolic) (diastolic)

20. NORMAL BLOOD PRESSURE <120 AND <80 mm Hg (systolic) mm Hg (diastolic)

21. All the values are mmHg CLASSIFICATION OF HYPERTENSION (AMERICAN HEART ASSOCIATION) HYPERTENSIVE CRISIS Systolic >180 Diastolic >120 HYPERTENSION: STAGE 2 Systolic >140 Diastolic >90 HYPERTENSION: STAGE 1 Systolic 130 – 139 Diastolic 80 - 89 ELEVATED Systolic 120 – 129 Diastolic <80 NORMAL Systolic <120 Diastolic <80

22. CLASSIFICATION OF HYPERTENSION (AMERICAN HEART ASSOCIATION) HYPERTENSIVE CRISIS Systolic >180 Diastolic >120 HYPERTENSION: STAGE 2 Systolic >140 Diastolic >90 HYPERTENSION: STAGE 1 Systolic 130 – 139 Diastolic 80 - 89 ELEVATED Systolic 120 – 129 Diastolic <80 NORMAL Systolic <120 Diastolic <80 All the values are mmHg

23. CLASSIFICATION OF HYPERTENSION (AMERICAN HEART ASSOCIATION) HYPERTENSIVE CRISIS Systolic >180 Diastolic >120 HYPERTENSION: STAGE 2 Systolic >140 Diastolic >90 HYPERTENSION: STAGE 1 Systolic 130 – 139 Diastolic 80 - 89 ELEVATED Systolic 120 – 129 Diastolic <80 NORMAL Systolic <120 Diastolic <80 All the values are mmHg

24. CLASSIFICATION OF HYPERTENSION (AMERICAN HEART ASSOCIATION) HYPERTENSIVE CRISIS Systolic >180 Diastolic >120 HYPERTENSION: STAGE 2 Systolic >140 Diastolic >90 HYPERTENSION: STAGE 1 Systolic 130 – 139 Diastolic 80 - 89 ELEVATED Systolic 120 – 129 Diastolic <80 NORMAL Systolic <120 Diastolic <80 All the values are mmHg

25. CLASSIFICATION OF HYPERTENSION (AMERICAN HEART ASSOCIATION) HYPERTENSIVE CRISIS Systolic >180 Diastolic >120 HYPERTENSION: STAGE 2 Systolic >140 Diastolic >90 NORMAL Systolic <120 Diastolic <80 HYPERTENSION: STAGE 1 Systolic 130 – 139 Diastolic 80 - 89 ELEVATED Systolic 120 – 129 Diastolic <80 All the values are mmHg

26. CLASSIFICATION OF HYPERTENSION (AMERICAN HEART ASSOCIATION) HYPERTENSIVE CRISIS Systolic >180 Diastolic >120 HYPERTENSION: STAGE 2 Systolic >140 Diastolic >90 NORMAL Systolic <120 Diastolic <80 ELEVATED Systolic 120 – 129 Diastolic <80 HYPERTENSION: STAGE 1 Systolic 130 – 139 Diastolic 80 - 89 All the values are mmHg

27. CLASSIFICATION OF HYPERTENSION (AMERICAN HEART ASSOCIATION) HYPERTENSIVE CRISIS Systolic >180 Diastolic >120 NORMAL Systolic <120 Diastolic <80 ELEVATED Systolic 120 – 129 Diastolic <80 HYPERTENSION: STAGE 1 Systolic 130 – 139 Diastolic 80 - 89 HYPERTENSION: STAGE 2 Systolic >140 Diastolic >90 All the values are mmHg

28. CLASSIFICATION OF HYPERTENSION (AMERICAN HEART ASSOCIATION) HYPERTENSION: STAGE 2 Systolic >140 Diastolic >90 HYPERTENSIVE CRISIS Systolic >180 Diastolic >120 NORMAL Systolic <120 Diastolic <80 ELEVATED Systolic 120 – 129 Diastolic <80 HYPERTENSION: STAGE 1 Systolic 130 – 139 Diastolic 80 - 89 All the values are mmHg

29. PATHOPHYSIOLOGY

30. PATHOPHYSIOLOGY

31. PATHOPHYSIOLOGY

32. PATHOPHYSIOLOGY

33. PATHOPHYSIOLOGY

34. CLINICAL MANIFESTATION Headaches Blurred vision Heart attack Kidney failure Stroke

35. DIAGNOSTICS Physical examination – observe for Abnormal heart sounds Elevated Jugular venous pressure Edema Blood pressure measurement – blood pressure > 120 mmHg (systolic) and >90 mmHg (diastolic) is considered hypertension. Blood and urine test – notice the kidney function using creatine, lipid profile; protein in urine, indicating kidney damage. Electrocardiogram – to detect arrythmias, LVH. Echocardiogram – evaluate heart structure and function.

36. Physical examination – observe for Abnormal heart sounds Elevated Jugular venous pressure Edema Blood pressure measurement – blood pressure > 120 mmHg (systolic) and >90 mmHg (diastolic) is considered hypertension. Blood and urine test – notice the kidney function using creatine, lipid profile; protein in urine, indicating kidney damage. Electrocardiogram – to detect arrythmias, LVH. Echocardiogram – evaluate heart structure and function. DIAGNOSTICS

37. DIAGNOSTICS

38. OUTLINE CASE REVIEW Patient history Chief complaint Family history Physical examination DIAGNOSIS Differential diagnosis Pathophysiology Clinical manifestation Complications TREATMENT AND MANAGEMENT Treatments Side effects Management References

39. TREATMENT

40. TREATMENT

41. TREATMENT

42. TREATMENT

43. TREATMENT

44. TREATMENT

45. TREATMENT

46. TREATMENT First line / first choice medications Thiazides – Chlorothiazide, Hydrochlorothiazide. ACE inhibitors – Benazepril, Captopril. Calcium channel blockers – Amlodipine, Nifedipine.

47. HYPERTENSION CARDIAC OUTPUT PERIPHERAL VASCULAR RESISTANCE Decrease cardiac contractility. Decrease ventricular filling pressure > less renal effects. Smooth muscle relaxants. Inhibit constriction of veins.

48. β - BLOCKERS Metoprolol given to the patient initially is a β – blocker ( β 1 ). It’s a central acting class of drugs. Blocks the β 1 receptors in heart. Thus blocks the sympathetic effects to the heart. ↓ HR > ↓C.O > ↓ B.P

49. Atenolol Bisoprolol Esmolol Metoprolol β - BLOCKERS

50. β - BLOCKERS Side effects – Bradycardia Hypotension – can lead to shock. Heart failure

51. ANGIOTENSIN II RECEPTOR BLOCKERS These family of drugs block the Angiotensin II receptors on : vascular smooth muscles Renal tubules Adrenal cortex CNS Thus inhibits all the effects of Angiotensin II. ↓ vasocontraction , ↓PVR, ↓ BP, ↓ GFR

52. ANGIOTENSIN II RECEPTOR BLOCKERS Irbesartan Losartan Valsartan Candesartan

53. ANGIOTENSIN II RECEPTOR BLOCKERS Irbesartan Losartan Valsartan Candesartan

54. DIURETICS These class of drugs inhibit Sodium (Na) and water retention in the renal tubules, by blocking Na – Cl cotransporter. Leads to loss of water and Sodium > ↓ Blood volume > ↓ stroke volume/ cardiac output > ↓ blood pressure. THIAZIDES LOOP DIURETICS ALDOSTERONE ANTAGONIST

55. THIAZIDES Generally, first-line of treatment for hypertension. Inhibit Sodium (Na) and water channels in DCT of nephron. Thus, loss of water and Sodium. Hydrochlorothiazide Chlorthalidone Indapamide

56. THIAZIDES

57. THIAZIDES Side effects – Hyponatremia Hypokalaemia Metabolic alkalosis

58. LOOP DIURETICS Inhibit Na/K/2Cl cotransporter at the thick ascending limb of Henle's loop. Inhibit sodium and water reuptake, thus lost in urine. Furosemide Bumetanide Torsemide

59. LOOP DIURETICS Side effects – Hyponatremia Hypokalaemia Metabolic alkalosis

60. POTASSIUM SPARING DRUGS/ ALDOSTERONE ANTAGONISTS Blocks Na/Cl channels at DCT Also inhibit aldosterone receptor binding Spares Potassium (K) Eplerenone spironolactone

61. Side effects – Hyperkalaemia Gynecomastia POTASSIUM SPARING DRUGS/ ALDOSTERONE ANTAGONISTS

62. SIDE EFFECTS OF DIURETICS

63. SIDE EFFECTS OF DIURETICS Diuretics usually shows electrolyte imbalance , depending on which class is used. A phenomenon called “ diuretic braking effects ” happens, where initial diuretic-induced loss of fluid and sodium loss becomes less effective over time, despite continued diuretic use. Severe hypovolemia and dehydration .

64. MANAGEMENT The patient was presented with : Tiredness / weakness Thirsty Vomiting 3 days after the diuretic medication was given. This could possibly be electrolyte imbalance and metabolic alkalosis , which explains the manifestations.

65. Hydrochlorothiazide, a thiazide is known to cause : Hypokalaemia - causes extreme weakness and fatigue metabolic alkalosis - body pH increase, causes vomiting and fatigue hyponatremia – causes extreme weakness and thirst Diuretics promotes fluid loss , some cases leads to dehydration and intense thirst. MANAGEMENT

66. This can be managed by : Electrolyte panel – check the electrolyte levels. ECG – to check for arrhythmias. Electrolyte correction – electrolyte supplements orally or IV. Fluid correction – rehydrate the patient (oral or IV). MANAGEMENT

67. REFERENCES