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Inotropic
agents and
Diuretics
HARSHITHA
BSC.CVT
INOTROPES
INTRO..
▪ A Drug that alters the force or energy of contraction
▪ Greek origin – ino = fiber , tropic = related to
2 Types
Positive inotropes
Negative inotropes
• Agent's strength of muscular
contraction
• Agents weaken the force of
muscular contractions
3
POSITIVE INOTROPES
▪ Enhances the myocardial contractility Increases the ejection
fraction of the heart
▪ Used to support cardiac function in conditions such as :
a) Decompensated CHF
b) Cardiogenic shock
c) Septic shock
d) Myocardial infarction
e) Cardiomyopathy , etc.
4
Clinically approved Inotropes
▪ Cardiac glycoside :
▪ Digitalis derivative – Digoxin
▪ Sympathomimetics :
▪ Epinephrine
▪ Dopamine (Intropin)
▪ Dobutamine (dobutrex)
▪ Norepinephrine (Levophed)
▪ Isoproterenol (isuprel)
▪ Phosphodiesterase inhibitors :
▪ Amrinone
▪ Milirinone 5
Cardiac glycosides
▪ Often called Digitalis or digitalis glycosides
▪ Source : medical plants (digital purpurea)
▪ Chemically similar compounds increasing cardiac
contractility
▪ Have been widely used in treating HF
▪ Pharmacodynamics: - Na+/K+ ATPase inhibition + Vagal
stimulation
▪ Agents : - Digoxin , Digitoxin
6
Digoxin
▪ Digoxin is a medication used to treat various heart conditions.
Most frequently it is used for atrial fibrillation, atrial flutter, and
heart failure.
▪ Pharmacological class : Cardiac glycoside
▪ Therapeutic class : Inotropes , antiarrhythmic
▪ In a normal heart
▪ Increases the force of contraction
▪ Constriction of blood vessel
▪ HR and CO unchanged
CARDIAC EFFECTS
7
▪ In heart failure
▪ Increases the contractility and CO
▪ Systole is shortened so that there is more time for ventricular
filling
▪ HR is reduced
▪ Decreases conduction velocity of AV node and his-purkinje
system and prolongs their ERP (protection of ventricle from
AF)
▪ Prolongation of PR interval (delayed Av conduction)
▪ Shortening of QT interval (shorter ventricular systole)
▪ Depression of ST segment
▪ Inversion or disappearance of T wave
ECG changes
8
1. Cardiac arrhythmias
2. GI side effects – anorexia , nausea, vomiting, diarrhoea,
abdominal cramps
3. CNS – headache, fatigue, neuralgia, blurred vision, loss of
color perception
4. Endocranial – gynecomastia
▪ Hypokalemia ,
▪ children < 10 years and elderly,
▪ myocardial infarction ,
▪ hypothyroidism ,
▪ myocarditis ,
▪ WPW syndrome
CONTRAINDICATION
A/E and Toxicity
9
Dopamine
▪ 3,4-dihydroxyphenylethylamine
▪ Endogenous catecholamine and immediate precursor of
norepinephrine and epinephrine
▪ It differs from NE and E by absence of –OH group at β carbon
atom side chain
▪ Important neurotransmitter, doesn’t cross BBB
10
11
▪ At low therapeutic dose (2-5 μg/kg/min IV), it reacts with vascular
D1 receptor , especially in renal, mesenteric and coronary
vasculature and produce increase in GRF, renal blood flow and Na
excretion
▪ At 5 μg/kg/min, it also stimulates β1 receptors causing
increasing Cardiac output, but PVR and MAP are unchanged due to
simultaneous dilatation of renal and splanchnic vessels
▪ At still higher doses (>10μg/kg/min) it can cause vasoconstriction
by α1 receptors
▪ Conditions with low CO with compromised renal function
Cardiovascular effect
Therapeutic uses
Dobutamine
▪ Used clinically as a racemic mixture of 2 enantiomers
▪ I form – potent agonist at α1
d form – potent α1 antagonist , agonist β1
▪ Net effect is β1 agonist action
▪ Structurally similar to dopamine, but doesn’t have actions on
dopamine receptors
12
13
▪ Inactive when given orally, usually given IV
▪ T1/2 is 2 minutes and steady state plasma concentration is achieved in
10 – 12 minutes
▪ Conjugates of dobutamine and its major metabolized compounds are
excreted primarily in urine and small amounts in faces
▪ Short term management of cardiac failure following surgery or MI
▪ Cardiac stress testing
▪ Sharp rise in BP and heart rate in some patients, especially in those
with history of HTN
▪ Increase in oxygen demand and precipitation of angina or aggravation
of MI
▪ Ventricular ectopic activity
Adverse effects
Therapeutic uses
Pharmacokinetics
Adrenaline (epinephrine)
▪ Pharmacological class: sympathomimetic (direct acting)
▪ Action : Adrenaline acts on β1,β2 and α1 receptors
▪ CVS: Increased heart rate and force of contraction produce an
increase in cardiac output. Systolic blood pressure rises
▪ RES: bronchial smooth muscle is relaxed resulting in
bronchodilatation through effect of β2
▪ Metabolic: Adrenaline mobilizes glucose from glycogen and
rises blood sugar. Pupillary dilatation (mydriasis) occurs.
14
▪ Low cardiac output states
▪ During cardiac arrest
▪ Allergic reactions (anaphylactic shock)
▪ Local anesthetic
▪ Bronchodilator for acute severe asthma attack
▪ Septic shock
▪ DCM
▪ High blood pressure
▪ Sinus tachycardia
▪ Abnormal heart rhythm
▪ Parkinson symptoms
▪ Closed angle glaucoma
INDICATION
CONTRAINDICATION
15
Noradrenaline (nor epinephrine)
▪ Noradrenaline (norepinephrine) is a substance released naturally
by the nerve cells
▪ Vasopressor (a drug that rises the BP because of its ability to
constrict blood vessels)
▪ Pharmacologic class: sympathomimetic
▪ Actions : potent vasoconstrictor
▪ Increases BP by vasoconstriction. Less likely to cause tachycardia
than adrenaline
16
▪ Acute hypotension states such as septic shock where peripheral
vasodilatation occurs
▪ Severe cardiogenic shock
▪ Neurogenic shock
▪ Spinal anesthesia , blood transfusion.
▪ MI
▪ Hemodynamically significant hypotension(SBP < 70 mmHg )
with low total peripheral resistance
▪ High blood pressure
▪ Blood clot , blockage of blood vessels
▪ Excess amount of carbon dioxide in the blood
▪ Decreased oxygen saturation
▪ Decreased blood volume
INDICATION
CONTRAINDICATION
17
Phosphodiesterase inhibitors
▪ Drugs that block subtype of enzyme phosphodiesterase (PDE),
therefore preventing the inactivation of the intercellular second
messenger's cAMP and cGMP by respective PDE subtypes.
▪ They are classified into non-selective PDE inhibitors and selective
PDE
▪ Non-selective: caffeine, aminophylline, IBMX, paraxanthine,
pentoxifylline, theobromine, theophylline.
▪ Selective : PDE1 to PDE 11
18
▪ M
▪ Inhibits phosphodiesterase enzyme
▪ CAMP and cGMP levels increase
▪ Calcium levels decrease
▪ Vasodilatation and smooth muscle relaxation
▪ PDE inhibitors : pulmonary hypertension, erectile dysfunction
▪ PDE3 inhibitors : myocardial infarction, intermittent claudication
▪ PDE4 inhibitors : pulmonary disease (asthma, COPD) ,
Inflammatory conditions (rheumatoid `
arthritis,Inflammatory bowel disease, atopic dermatitis)
▪ Nonspecific inhibitors : pulmonary disease (asthma, COPD)
INDICATION
MECHANISM
19
NEGATIVE INOTROPES
▪ Decreases myocardial contractility , and are used to decrease
cardiac workload in conditions such as angina
▪ While negative inotropism may precipitate or exacerbate heart
failure
▪ Certain beta-blockers ( carvedilol, bisoprolol, and metoprolol) have
been believed to reduce morbidity and mortality in congestive
heart failure.
20
NEGATIVE INOTROPES
1. Beta blockers
2. Calcium channel blockers:
▪ Diltiazem
▪ Verapamil
▪ Clevidipine
3. Class 1a antiarrhythmics such as :
▪ Quinidine
▪ Procainamide
▪ Disopyramide
4. Class 1c antiarrhythmic such as :
▪ Flecainide
21
Note..
▪ Although inotropic agents improve functional status of CHF,
long term benefit on mortality is questionable
▪ In fact, some drugs have shown to increase mortality
▪ At present digoxin remains the only oral inotropic agent available
for management of CHF
22
DIURETICS
DIURETICS
▪ These are drugs which cause a net loss of Na+ and water in urine
▪ Diuretics are among the most widely prescribed drugs
▪ Application of diuretics to the management of hypertension and in
edema
24
Classification
1. High efficacy diuretics (inhibitors of Na+ - k+ - 2Cl cotransport)
▪ Eg: Furosemide , Bumetanide , Torsemide
2. Medium efficacy diuretics (inhibitors of Na+_Cl- symport)
▪ Benzothiadiazines (thiazides): Hydrochlorothiazide, Benzthiazide
▪ Thiazide like (related heterocyclics): Chiorthalidone, Metolazone
3. Weak or adjunctive diuretics
▪ Carbonic anhydrase inhibitor: Acetazolamide
▪ Potassium sparing diuretics: Spironolactone, Triamterene, Amiloride
▪ Osmotic diuretics: Mannitol , glycerol
25
26
Carbonic anhydrase inhibitors
▪ Acetazolamide, dorzolamide
▪ Site of action: proximal convoluted tubule
▪ Inhibits carbonic anhydrase activity
▪ Decreases HCO3 reabsorption – alkaline diuresis
▪ Glaucoma: acetazolamide, dorzolamide
▪ Urinary alkalinization: UTI , to promote excretion of certain acid
drugs
▪ metabolic alkalosis
▪ Acute mountain sickness
Therapeutic uses
27
28
▪ Acidosis
▪ Renal stones
▪ Hypokalemia
▪ Drowsiness, fatigue
▪ Hypersensitivity
Adverse effects
Osmotic diuretics
▪ Mannitol
▪ Freely filtered at the glomerulus
▪ Not reabsorbed at the renal tubules
▪ Relatively inert pharmacologically
▪ Non – metabolizable
▪ Increases the plasma osmolarity
▪ Decreases sodium reabsorption
▪ Dilute tubular fluid and increase water excreation
29
30
▪ Head injury or stroke
▪ Glaucoma
▪ In case of poisoning
▪ To maintain GRF and urine flow in patients with impaired renal
function
▪ Headache, nausea , vomiting, pulmonary edema
Therapeutic uses
Adverse effects
High efficacy (loop) diuretics
▪ Site of action : Thick ascending limb of loop of Henle
▪ Inhibits the luminal Na+ - k+ - 2Cl transporter – reduce
reabsorption of NaCl
▪ Prevent reabsorption of Ca2+ and Mg2+
▪ Acute pulmonary edema (IV-Furosemide)
▪ Renal edema
▪ Hypertension associated with renal failure and CHF
▪ Hypercalcemia and renal calcium stones
▪ Hyperkalemia
▪ Forced diuresis – in case of poisoning
Therapeutic uses of loop diuretics
31
32
▪ Hypokalemia, Hypocalcemia, Hypomagnesemia,
Hypochloremia
▪ Metabolic alkalosis
▪ Hypovolemia
▪ Loss of hearing
▪ Gout (hyperuricemia)
Adverse effects
Thiazide diuretics
▪ Medium efficacy diuretics
▪ Site of action : distal convoluted tubule
▪ Blocks Na+/Cl- transporter – inhibit NaCl reabsorption
▪ Increase Ca+ reabsorption
▪ Mild hypertension
▪ Edema associated with CHF/kidney disease
▪ hypercalciuria/osteoporosis
Therapeutic uses
33
34
▪ Hypokalemia
▪ Metabolic alkalosis
▪ Gout (hyperuricemia)
▪ Hypercalcemia
Adverse effects
Potassium sparing diuretic
▪ Site of action : late distal tubule and collecting duct
▪ Spironolactone – aldosterone antagonist
competitively inhibits the binding of aldosterone to
mineralocorticoid receptor  inhibits formation of aldosterone–
induced protein  prevent sodium reabsorption and potassium
excretion
▪ Hyperaldosteronism (cardiac failure, liver and kidney disease,
conn syndrome)
▪ hypertension ( with thiazide/loop diuretics)
Therapeutic uses
35
36
▪ Hyperkalemia
▪ Drowsiness , confusion
▪ Abdominal upset
▪ Impotence
▪ Menstrual irregularities
Adverse effects
Contraindications
▪ Contraindicated in patients:
• With known hypersensitivity to the drugs, electrolyte
imbalances, severe liver or kidney dysfunction, anuria,
hypokalemia and hyponatremia
 Mannitol : contraindicated in patient with active intracranial
bleeding
 potassium – sparing diuretics : Contraindicated in patients with
hyperkalaemia ; Not recommended for children
37
Thank you
38

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Inotropic agents and Diuretics

  • 3. INTRO.. ▪ A Drug that alters the force or energy of contraction ▪ Greek origin – ino = fiber , tropic = related to 2 Types Positive inotropes Negative inotropes • Agent's strength of muscular contraction • Agents weaken the force of muscular contractions 3
  • 4. POSITIVE INOTROPES ▪ Enhances the myocardial contractility Increases the ejection fraction of the heart ▪ Used to support cardiac function in conditions such as : a) Decompensated CHF b) Cardiogenic shock c) Septic shock d) Myocardial infarction e) Cardiomyopathy , etc. 4
  • 5. Clinically approved Inotropes ▪ Cardiac glycoside : ▪ Digitalis derivative – Digoxin ▪ Sympathomimetics : ▪ Epinephrine ▪ Dopamine (Intropin) ▪ Dobutamine (dobutrex) ▪ Norepinephrine (Levophed) ▪ Isoproterenol (isuprel) ▪ Phosphodiesterase inhibitors : ▪ Amrinone ▪ Milirinone 5
  • 6. Cardiac glycosides ▪ Often called Digitalis or digitalis glycosides ▪ Source : medical plants (digital purpurea) ▪ Chemically similar compounds increasing cardiac contractility ▪ Have been widely used in treating HF ▪ Pharmacodynamics: - Na+/K+ ATPase inhibition + Vagal stimulation ▪ Agents : - Digoxin , Digitoxin 6
  • 7. Digoxin ▪ Digoxin is a medication used to treat various heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. ▪ Pharmacological class : Cardiac glycoside ▪ Therapeutic class : Inotropes , antiarrhythmic ▪ In a normal heart ▪ Increases the force of contraction ▪ Constriction of blood vessel ▪ HR and CO unchanged CARDIAC EFFECTS 7
  • 8. ▪ In heart failure ▪ Increases the contractility and CO ▪ Systole is shortened so that there is more time for ventricular filling ▪ HR is reduced ▪ Decreases conduction velocity of AV node and his-purkinje system and prolongs their ERP (protection of ventricle from AF) ▪ Prolongation of PR interval (delayed Av conduction) ▪ Shortening of QT interval (shorter ventricular systole) ▪ Depression of ST segment ▪ Inversion or disappearance of T wave ECG changes 8
  • 9. 1. Cardiac arrhythmias 2. GI side effects – anorexia , nausea, vomiting, diarrhoea, abdominal cramps 3. CNS – headache, fatigue, neuralgia, blurred vision, loss of color perception 4. Endocranial – gynecomastia ▪ Hypokalemia , ▪ children < 10 years and elderly, ▪ myocardial infarction , ▪ hypothyroidism , ▪ myocarditis , ▪ WPW syndrome CONTRAINDICATION A/E and Toxicity 9
  • 10. Dopamine ▪ 3,4-dihydroxyphenylethylamine ▪ Endogenous catecholamine and immediate precursor of norepinephrine and epinephrine ▪ It differs from NE and E by absence of –OH group at β carbon atom side chain ▪ Important neurotransmitter, doesn’t cross BBB 10
  • 11. 11 ▪ At low therapeutic dose (2-5 μg/kg/min IV), it reacts with vascular D1 receptor , especially in renal, mesenteric and coronary vasculature and produce increase in GRF, renal blood flow and Na excretion ▪ At 5 μg/kg/min, it also stimulates β1 receptors causing increasing Cardiac output, but PVR and MAP are unchanged due to simultaneous dilatation of renal and splanchnic vessels ▪ At still higher doses (>10μg/kg/min) it can cause vasoconstriction by α1 receptors ▪ Conditions with low CO with compromised renal function Cardiovascular effect Therapeutic uses
  • 12. Dobutamine ▪ Used clinically as a racemic mixture of 2 enantiomers ▪ I form – potent agonist at α1 d form – potent α1 antagonist , agonist β1 ▪ Net effect is β1 agonist action ▪ Structurally similar to dopamine, but doesn’t have actions on dopamine receptors 12
  • 13. 13 ▪ Inactive when given orally, usually given IV ▪ T1/2 is 2 minutes and steady state plasma concentration is achieved in 10 – 12 minutes ▪ Conjugates of dobutamine and its major metabolized compounds are excreted primarily in urine and small amounts in faces ▪ Short term management of cardiac failure following surgery or MI ▪ Cardiac stress testing ▪ Sharp rise in BP and heart rate in some patients, especially in those with history of HTN ▪ Increase in oxygen demand and precipitation of angina or aggravation of MI ▪ Ventricular ectopic activity Adverse effects Therapeutic uses Pharmacokinetics
  • 14. Adrenaline (epinephrine) ▪ Pharmacological class: sympathomimetic (direct acting) ▪ Action : Adrenaline acts on β1,β2 and α1 receptors ▪ CVS: Increased heart rate and force of contraction produce an increase in cardiac output. Systolic blood pressure rises ▪ RES: bronchial smooth muscle is relaxed resulting in bronchodilatation through effect of β2 ▪ Metabolic: Adrenaline mobilizes glucose from glycogen and rises blood sugar. Pupillary dilatation (mydriasis) occurs. 14
  • 15. ▪ Low cardiac output states ▪ During cardiac arrest ▪ Allergic reactions (anaphylactic shock) ▪ Local anesthetic ▪ Bronchodilator for acute severe asthma attack ▪ Septic shock ▪ DCM ▪ High blood pressure ▪ Sinus tachycardia ▪ Abnormal heart rhythm ▪ Parkinson symptoms ▪ Closed angle glaucoma INDICATION CONTRAINDICATION 15
  • 16. Noradrenaline (nor epinephrine) ▪ Noradrenaline (norepinephrine) is a substance released naturally by the nerve cells ▪ Vasopressor (a drug that rises the BP because of its ability to constrict blood vessels) ▪ Pharmacologic class: sympathomimetic ▪ Actions : potent vasoconstrictor ▪ Increases BP by vasoconstriction. Less likely to cause tachycardia than adrenaline 16
  • 17. ▪ Acute hypotension states such as septic shock where peripheral vasodilatation occurs ▪ Severe cardiogenic shock ▪ Neurogenic shock ▪ Spinal anesthesia , blood transfusion. ▪ MI ▪ Hemodynamically significant hypotension(SBP < 70 mmHg ) with low total peripheral resistance ▪ High blood pressure ▪ Blood clot , blockage of blood vessels ▪ Excess amount of carbon dioxide in the blood ▪ Decreased oxygen saturation ▪ Decreased blood volume INDICATION CONTRAINDICATION 17
  • 18. Phosphodiesterase inhibitors ▪ Drugs that block subtype of enzyme phosphodiesterase (PDE), therefore preventing the inactivation of the intercellular second messenger's cAMP and cGMP by respective PDE subtypes. ▪ They are classified into non-selective PDE inhibitors and selective PDE ▪ Non-selective: caffeine, aminophylline, IBMX, paraxanthine, pentoxifylline, theobromine, theophylline. ▪ Selective : PDE1 to PDE 11 18
  • 19. ▪ M ▪ Inhibits phosphodiesterase enzyme ▪ CAMP and cGMP levels increase ▪ Calcium levels decrease ▪ Vasodilatation and smooth muscle relaxation ▪ PDE inhibitors : pulmonary hypertension, erectile dysfunction ▪ PDE3 inhibitors : myocardial infarction, intermittent claudication ▪ PDE4 inhibitors : pulmonary disease (asthma, COPD) , Inflammatory conditions (rheumatoid ` arthritis,Inflammatory bowel disease, atopic dermatitis) ▪ Nonspecific inhibitors : pulmonary disease (asthma, COPD) INDICATION MECHANISM 19
  • 20. NEGATIVE INOTROPES ▪ Decreases myocardial contractility , and are used to decrease cardiac workload in conditions such as angina ▪ While negative inotropism may precipitate or exacerbate heart failure ▪ Certain beta-blockers ( carvedilol, bisoprolol, and metoprolol) have been believed to reduce morbidity and mortality in congestive heart failure. 20
  • 21. NEGATIVE INOTROPES 1. Beta blockers 2. Calcium channel blockers: ▪ Diltiazem ▪ Verapamil ▪ Clevidipine 3. Class 1a antiarrhythmics such as : ▪ Quinidine ▪ Procainamide ▪ Disopyramide 4. Class 1c antiarrhythmic such as : ▪ Flecainide 21
  • 22. Note.. ▪ Although inotropic agents improve functional status of CHF, long term benefit on mortality is questionable ▪ In fact, some drugs have shown to increase mortality ▪ At present digoxin remains the only oral inotropic agent available for management of CHF 22
  • 24. DIURETICS ▪ These are drugs which cause a net loss of Na+ and water in urine ▪ Diuretics are among the most widely prescribed drugs ▪ Application of diuretics to the management of hypertension and in edema 24
  • 25. Classification 1. High efficacy diuretics (inhibitors of Na+ - k+ - 2Cl cotransport) ▪ Eg: Furosemide , Bumetanide , Torsemide 2. Medium efficacy diuretics (inhibitors of Na+_Cl- symport) ▪ Benzothiadiazines (thiazides): Hydrochlorothiazide, Benzthiazide ▪ Thiazide like (related heterocyclics): Chiorthalidone, Metolazone 3. Weak or adjunctive diuretics ▪ Carbonic anhydrase inhibitor: Acetazolamide ▪ Potassium sparing diuretics: Spironolactone, Triamterene, Amiloride ▪ Osmotic diuretics: Mannitol , glycerol 25
  • 26. 26
  • 27. Carbonic anhydrase inhibitors ▪ Acetazolamide, dorzolamide ▪ Site of action: proximal convoluted tubule ▪ Inhibits carbonic anhydrase activity ▪ Decreases HCO3 reabsorption – alkaline diuresis ▪ Glaucoma: acetazolamide, dorzolamide ▪ Urinary alkalinization: UTI , to promote excretion of certain acid drugs ▪ metabolic alkalosis ▪ Acute mountain sickness Therapeutic uses 27
  • 28. 28 ▪ Acidosis ▪ Renal stones ▪ Hypokalemia ▪ Drowsiness, fatigue ▪ Hypersensitivity Adverse effects
  • 29. Osmotic diuretics ▪ Mannitol ▪ Freely filtered at the glomerulus ▪ Not reabsorbed at the renal tubules ▪ Relatively inert pharmacologically ▪ Non – metabolizable ▪ Increases the plasma osmolarity ▪ Decreases sodium reabsorption ▪ Dilute tubular fluid and increase water excreation 29
  • 30. 30 ▪ Head injury or stroke ▪ Glaucoma ▪ In case of poisoning ▪ To maintain GRF and urine flow in patients with impaired renal function ▪ Headache, nausea , vomiting, pulmonary edema Therapeutic uses Adverse effects
  • 31. High efficacy (loop) diuretics ▪ Site of action : Thick ascending limb of loop of Henle ▪ Inhibits the luminal Na+ - k+ - 2Cl transporter – reduce reabsorption of NaCl ▪ Prevent reabsorption of Ca2+ and Mg2+ ▪ Acute pulmonary edema (IV-Furosemide) ▪ Renal edema ▪ Hypertension associated with renal failure and CHF ▪ Hypercalcemia and renal calcium stones ▪ Hyperkalemia ▪ Forced diuresis – in case of poisoning Therapeutic uses of loop diuretics 31
  • 32. 32 ▪ Hypokalemia, Hypocalcemia, Hypomagnesemia, Hypochloremia ▪ Metabolic alkalosis ▪ Hypovolemia ▪ Loss of hearing ▪ Gout (hyperuricemia) Adverse effects
  • 33. Thiazide diuretics ▪ Medium efficacy diuretics ▪ Site of action : distal convoluted tubule ▪ Blocks Na+/Cl- transporter – inhibit NaCl reabsorption ▪ Increase Ca+ reabsorption ▪ Mild hypertension ▪ Edema associated with CHF/kidney disease ▪ hypercalciuria/osteoporosis Therapeutic uses 33
  • 34. 34 ▪ Hypokalemia ▪ Metabolic alkalosis ▪ Gout (hyperuricemia) ▪ Hypercalcemia Adverse effects
  • 35. Potassium sparing diuretic ▪ Site of action : late distal tubule and collecting duct ▪ Spironolactone – aldosterone antagonist competitively inhibits the binding of aldosterone to mineralocorticoid receptor  inhibits formation of aldosterone– induced protein  prevent sodium reabsorption and potassium excretion ▪ Hyperaldosteronism (cardiac failure, liver and kidney disease, conn syndrome) ▪ hypertension ( with thiazide/loop diuretics) Therapeutic uses 35
  • 36. 36 ▪ Hyperkalemia ▪ Drowsiness , confusion ▪ Abdominal upset ▪ Impotence ▪ Menstrual irregularities Adverse effects
  • 37. Contraindications ▪ Contraindicated in patients: • With known hypersensitivity to the drugs, electrolyte imbalances, severe liver or kidney dysfunction, anuria, hypokalemia and hyponatremia  Mannitol : contraindicated in patient with active intracranial bleeding  potassium – sparing diuretics : Contraindicated in patients with hyperkalaemia ; Not recommended for children 37