Drug used in Paediatric cardiology By Dr. Md. Kashid Omar Resident , Paediatric cardiology BSMMU, Dhaka

1. Seminar
Drug used in paediatric cardiology
DR. Md. Kashid Omar
Phase –B Resident
Paediatric Cardiology

2. CONTENT
1.Drug used in heart failure
• Digoxin
• Furosemide
• Spironolactone
• ACE Inhibitor
• ARB
• Beta blocker
2. Adrenergic Receptor Agonist
• Dopamine
• Dobutamine
• Epinephrine
• Nor epinephrine
3.Anti arrythmic drug
• Amiodarone
• Sotalol
• Verapamil
• Adenosine
4. Drug used in PHTN

3. Drug Used In
Heart Failure

4. Furosemide

5. Dosages and Pharmacodynamics
Initial dose: 1-2 mg/kg/day
Maintenance dose: 1-4 mg/kg/day
Half Life :
Approx. 2 hour
Onset of action : Oral – 0.5-1 h
I/V – 5min
Duration of Action : Oral: 4-6 h
I/V : 2h

6. Mechanism
of action
Blocking of the NKCC2
Prevent the transport of sodium from the lumen of the loop of Henle into
the basolateral interstitium.
The lumen becomes more hypertonic while the interstitium becomes less
hypertonic,
It diminishes the osmotic gradient for water reabsorption throughout the
nephron

7. Toxicity
A. Hypokalemic Metabolic Alkalosis
•By inhibiting salt reabsorption in the TAL, loop diuretics increase
Na + delivery to the collecting duct.
•Increased delivery leads to increased secretion of K + and H + by
the duct, causing hypokalemic metabolic alkalosis.
B. Ototoxicity
• Damage to the tight cell junctions in the blood vessels in the
stria vascularis
•Temporary disruption of the blood-cochlear barrier
•Increases the permeability of the lateral wall to ototoxic drugs

8. C. Hyperuricemia
Compete with uric acid for urinary and billiary excretion
D. Hypomagnesemia
Increased loss
E. Allergic and Other Reactions
Due to sulfur component

9. Drug Interaction
•Nonsteroidal anti-inflammatory drugs (NSAIDs) decrease
the effect of furosemide.
• There is increased ototoxicity with aminoglycosides and
ethacrynic acid; and drugs affected by potassium
depletion, such as digoxin.
•There is increased anticoagulation by warfarin

10. SPIRONOLACTONE
• Mechanism of Action
• Spironolactone is a potassium-sparing diuretic that competes
with aldosterone for binding to receptor sites in the distal tubule
of the kidneys.
• It increases the excretion of sodium, chloride, and water and
prevents the excretion of potassium and hydrogen.
• The effect of aldosterone on arteriolar smooth muscle may also
be blocked.
• Dose :
• This drug is usually given orally in 2 divided doses of 1-2
mg/kg/day.

11. • Warning :
• severe hyperkalemia may result when used with ACE inhibitors,
potassium supplements, and NSAIDs; monitor potassium levels and renal
function closely.
• Use with caution in patients with decreased renal function, hyponatremia,
dehydration, or reduced hepatic function.
• Adverse reactions:
A. Hyperkalemia
B. Hyperchloraemic Metabolic Acidosis
C. Gynaecomastia
D. Acute renal failure
E. Kidney stone

12. DIGOXIN

13. Mechanism of action
Inhibition of Na-K
ATPase
Increased Na conc.
Inside cell
Relative inhibition of
Na-Ca Exchanger
Incresed Ca conc.
Inside the cell
Increased contraction
of Sarcomere

14.  An initial brief increase in action potential, followed by a
decrease as the K+ conductance increased due to an
increased intracellular amounts of Ca2+ ions
The refractory period of atria and ventricles is decreased,
while it increases in SA and AV node. Decreased
conduction through the SA and AV node occurs.
A less negative resting membrane potential is made,
leading to increased excitability
It increases the parasympathetic cardiac and arterial
baroreceptor activity which decrease central sympathetic
outflow exerting a favorable neurohormonal effect.

15. Pharmacokinetics
• Onset of action : Oral: 0.5–2 h; I.V.: 5–30 min
• Bioavailability :
• I.V.: 100 %
• Capsules: 90 %
• Elixir: 80 %
• Tablets: 70 %
• Maximum effect : Oral: 2–8 h; I.V.: 1–4 h
• Protein binding : 20–30 %.
• Metabolism : Most of the drug is eliminated unchanged by the
kidney
• Half - life : neonates: 20 h; Children: 40 h
• Elimination : 50–90 % of renal excretion.

16. Dose:
• Digitalization Dose: ½ dose given stat then 1/4th given 8hourly
• Premature Infant : 20ugm/kg
• Full term infant : 30ugm/kg
• Children : 40ugm/kg
• Maintenance dose : 5-10ugm/kg/day
I.V dose is 75% of oral dose

17. DRUG INTERACTION
Drug that increase effect of digoxin
Diuretics Furosemide, spironolactone, amiloride,
triamterene
Antiarrhythmics Verapamil, quinidine, amiodarone,
propafenone
Calcium antagonists Verapamil, nifedipine, diltiazem
Antibiotics Erythromycin, clarithromycin,
tetracyclines
Benzodiazepines Alprazolam
Other Ketoconazole, itroconazole,
cyclosporine, indomethacin,
Diphenoxylate, NSAIDs

18. Drugs that may decrease
digoxin concentration or
effect
Rifampicin
Liquid antacids
Cholestyramine
Neomycin
Penicillamine
Phenytoin
Sulafasalazine
Thyroid hormone

19. Adverse effects
• Cardiovascular : Dysrhythmias , sinus bradycardia, atrioventricular
block, sinus block, atrial ectopic beats, bi and trigeminy, atrial
tachycardia with AV block, ventricular arrhythmias.
• Gastrointestinal : Nausea, vomiting, diarrhea, abdominal pain, lack
of appetite or intolerance to feeding
• Metabolic : Hyperkalemia with toxicity
• CNS Fatigue, somnolence, drowsiness, vertigo, disorientation,
asthenia
• Neuromuscular & skeletal : Neuralgia, myalgia
• Ophtalmologic : blurred vision, photophobia, diplopia, flashing
lights, aberrations of color vision
• Other : gynecomastia

20. Monitoring
Baseline serum electrolyte level :
 Hypokalemia and hypercalcemia exacerbate digitalis toxicity.
ECG :
 Digoxin should be discontinued if a new rhythm disturbance is noted.
Prolongation of the P-R interval is not necessarily an indication to
withhold digitalis, but a delay in administering the next dose or a
reduction in the dosage should be considered, depending on the
patient’s clinical status.
Minor ST segment or T-wave changes are commonly noted with digitalis
administration and should not affect the digitalization regimen

21. DIGOXIN TOXICITY
Clinical signs of poisoning :
• Weakness, fatigue
• Lack of appetite, nausea, vomiting, diarrhea
• Visual disturbances, headache, confusion, somnolence, delirium,
hallucinations
• Neuropathic pain, seizures
• Arrhythmias, palpitations, syncope, dyspnea
ECG signs of toxicity :
• Premature ventricular contractions, ventricular bigeminy, atrioventricular
block,
• Supraventricular tachycardia, junctional tachycardia,
• Ventricular arrhythmias

22.  Laboratory :
Serum potassium, calcium and magnesium levels and renal
function should be immediately monitored. Digoxin serum
concentrations: usually, toxicity is associated with levels >2 ng/ml
(normal therapeutic range: 0.8–2 ng/ml).
Treatment :
• Digoxin should be stopped
• Treat any electrolyte imballance
• Treat associated arrythmia
• Digoxin antidote: Digoxin Immune Fab

23. Digoxin Immune Fab :
Indication:
• Life threatening arrhythmias (ventricular dysrhythmia,
supraventricular bradyarrhythmia unresponsive to atropine)
• Hyperkalemia (>5mEq/L)
• Hypotension or acute ingestion of toxic doses of the drug.
• Serum Digoxin level : in acute case >10nmol/L, Chronic
>4nmol/L
Dose of Digoxin immune Fab :
serum digoxin ( nmol / ml ) × kg × 0.3

24. Angiotensin Converting
Enzyme Inhibitors

26. Name of Drug Dose
Enalapril 0.1 mg/kg/dose single or B.D.
Maximum 0.5mg/kg/dose
Ramipril
Captopril Initial or “test” dose 0.15–0.5
mg/kg/dose P.O./N.G.
Dose every 8–24 h. Titrate dose to
maximum of 6 mg/ kg/day in 1–4
divided doses
Lisinopril Initial or “test” dose 0.07 mg/kg/dose
P.O./N.G. Dose once per 24 h.
Maximum initial dose 5 mg once daily

27. Indication :
• Congestive Heart failure
• Systemic HTN
• Controlling of ventricular remodelling :
Angiotensin-II contributes to ventricular remodelling and ventricular
hypertrophy of the heart through stimulation of the proto-oncogenes such
as - c-fos, c-jun, c-myc, transforming growth factor beta, through
fibrogenesis and apoptosis
Monitoring :
• Blood pressure, BUN, creatinine, WBC, serum potassium should be
monitored

28. Adverse effect :
• 1st dose hypotension.
• DRY cough. Increased bradykinin
• Angioedema.
• Hyperkalaemia- Dereased aldosterone level
• Agranulocytosis and neutropenia
• Proteinuria, especially in children with underlying renal
disease.
• Minor gastrointestinal disturbances

29. ANGIOTENSIN RECEPTOR
BLOCKER

31. • ARB do not affect the vascular response to bradykinin (a
potent vasodilator). So do not induce as much cough or
angioedema as ACE inhibitors.
• Losartan is also a natriuretic and increases urine output.

32. ΒETA-BLOCKER

33. PROPRANOLOL
• Mechanism of Action
 Propranolol’s effects on both β-1 and β-2 receptors leads to decreased
heart rate, myocardial contractility, blood pressure, and myocardial
oxygen demand.
 β-1 blockade is responsible for the lowered heart rate and decreased
myocardial contractility.
 Cardiac output is also decreased.
 Additionally, blockade of β-receptors in cardiac conduction tissue results
in the slowing of AV conduction and suppression of automaticity.

34. • Indication :
• Propranolol is a non-cardioselective β-blocking agent with equal effects on β
1 cardiac and β 2 receptors
• Class II antiarrhythmic agent
• In patients with CHF, propranolol has been shown to: reduce mortality,
reduce LV mass, increase LV ejection fraction,
• Cyanotic spells in children with Tetralogy of Fallot
• Dose:
Oral: 0.5-1mg/kg/day three to four times
I.V : 0.01-0.15mg/kg/dose over 10min. Repeat the dose in every 6-8
hourely (Max. dose in infant 1mg/dose and in children 3mg/dose.

35. • Pharmacokinetics
• Onset of action
1–2 h after oral administration and 2 min after IV administration.
• Duration:
6 h after oral dosing and 3–6 h after IV dosing.
• Bioavailablitiy:
30–40 %
• Half-life:
Approximately 4–6 h
• Elimination:
In the urine with 96–99 % as metabolites.

36. • Monitoring Parameters:
Monitor heart rate, blood pressure and ECG
• Contraindications
Cardiogenic shock, bradycardia or heart block, uncompensated congestive
heart failure, asthma, and chronic obstructive lung disease
Drug Interactions
• Phenobarbitone, rifampicin and cimetidine increase propranolol clearance
and decrease its activity.
• Propranolol’s absorption is reduced by aluminum containing antacids.
• The levels of propranolol can be increased by amidarone, calcium channel
blockers, phosphodiesterase 5 inhibitors, prostacyclins, quinidine

37. • Adverse Effects
• Cardiovascular:
Hypotension, impaired myocardial contractility, bradycardia, AV
block
• Sleep disturbance
• Endocrine/Metabolic:
Hypoglycemia
• Gastrointestinal:
Nausea, vomiting, diarrhea
• Pulmonary:
Bronchospasm.

38. CARVEIDILOL
• Mechanism of Action
• Carvedilol is a nonselective β-receptor and α 1 -receptor antagonist with no
intrinsic sympathomimetic activity.
• The blockade of both β and α 1 - receptors in CHF leads to decreased
systemic blood pressure, decreased pulmonary artery pressure, decreased
heart rate, decreased systemic vascular resistance, increased stroke volume
index, and increased left ventricular ejection fraction.
• In addition, carvedilol has been shown to inhibit the action of oxygen free
radicals and to demonstrate antiproliferative effects on smooth muscle cells

39. • DOSE :
Initial 0.05mg/kg/dose twice daily upto 0.4-0.5 mg/kg/dose .
• Contraindications :
Cardiogenic shock, bradycardia or heart block, uncompensated
congestive heart failure, asthma, and chronic obstructive lung
disease, decompensated cardiac failure requiring ionotropic
therapy, severe hepatic impairment

40. • Adverse effect :
• Cardiac:
AV block, bradycardia, palpitations, syncope, peripheral
edema, rebound or withdrawal hypertension following abrupt
discontinuation of β-blocker therapy, postural hypotension
• Central Nervous System:
Dizziness, Weakness, insomnia
• Hypertriglyceridemia and weight gain
• Pulmonary:
Bronchospasm, rhinitis, pharyngitis, and dyspnea

41. α- and β-Adrenergic
Agonists

42. DOPAMINE

43. MECHANISM OF ACTION
.
Low Dose
1-5 ugm/kg/min
D
rece
ptor
vasodilatation of renal, splanchnic, and coronary
vascular beds
Medium Dose
5-15 ugm/kg/min
ß
rece
ptor
Increases heart rate and force of contraction
High Dose
>15 ugm/kg/min
α
Rece
ptor
systemic vasoconstriction and increased blood
pressure

44. Indications
 Cardiogenic shock
Septic shock
 Improve renal perfusion.
 Dopamine is used routinely for low cardiac output
syndrome after open heart surgery for congenital
and acquired heart defects

45. Adverse effects :
• Cardiovascular :
• Sinus tachycardia, ectopic beats
• Peripheral or pulmonary vasoconstriction ( must be used cautiously in
patients with elevated pulmonary artery pressure or resistances
• Widened QRS complexes
• Atrioventricular conductive abnormalities, ventricular arrhythmias
• Systemic hypertension ,palpitations
• Respiratory : dyspnea
• Central nervous system : headache, anxiety
• Gastrointestinal : nausea, vomiting
• Renal : azotemia
• Ocular : midriasis

46. DRUG INTERACTION
 Drugs that antagonize the effect of dopamine :
• Beta – blocking agents
• Alpha – adrenergic blocking agents
• Haloperidol
 Drugs that potentiate the effect of dopamine:
• Monoamine oxidase inhibitors
• Tricyclic antidepressants
• Alpha and beta - adrenergic agonists
• Phenytoin : Administration with dopamine can lead to significant
hypotension and bradycardia

47. DOBUTAMINE

48. MECHANISM OF ACTION
Doutamine
β 1
Recep
tor
More ionotropic Effect ( increased
contractility)
Less Chronotropic Effect
(increased heart rate)
β 2
Rece
ptor
mild systemic and pulmonary
vasodilation. lowers central
venous pressure and pulmonary
capillary wedge pressure

49. Side effects:
Like dopamine, dobutamine also produces increase in heart rate
and ectopic beats, albeit to a lesser extent. High dose infusion
may result in hypotension due to vasodilatation.
Contraindications:
Contraindicated in obstructive lesions of heart, cardiac
arrhythmias. Hypovolemia must be corrected prior to
dobutamine administration.
Monitoring: BP, heart rate and ECG

50. Epinephrine

51. MECHANISM OF ACTION
Epinephr
ine
β 1
Rece
ptor
Increases heart rate and
force of contraction
Low
Dose
β 2
Rece
ptor
Pulmonary and Skeletal
vasodilation
α
Rece
ptor
systemic vasoconstriction
and increased blood
pressure

52. • The major indication for epinephrine is cardiovascular collapse
associated with low cardiac output that is refractory to dopamine
and/or dobutamine
• Dose :
0.1-0.3ml/kg/dose (in 1:10000 dilution)
• The major life-threatening toxic effect of epinephrine is the
induction of ventricular arrhythmias.
• High doses may produce myocardial ischemia and Tissue necrosis
can occur because of peripheral vasoconstriction

53. Norepinephrine

54. MECHANISM OF ACTION
• α effect predominates β effectNorepine
phrine
β 1
Rece
ptor
Increases force of
contraction but heart rate is
largely unaffected
α
Rece
ptor
systemic vasoconstriction and
increased blood pressure,
Decreased Renal Perfusion

55. Indication :
• Cardiovascular collapse associated with profound peripheral
vasodilation, such as septic shock.
• Some infants exhibit little vascular tone following
cardiopulmonary bypass surgery and norepinephrine may be
helpful temporarily in supporting the systemic blood pressure
 Dose :
0.1 ugm/kg/min initially , Max. 2ugm/kg/min
 Adverse Effect :
• Arrhythmias
• Tissue ischemia secondary to extreme vasoconstriction

56. ANTIARRYTHMIC
DRUG

58. Amiodarone
 Mechanism of Action: Amiodarone
blocking of potassium ,
sodium and calcium
channels
Inhibit adrenergic
stimulation
Action potential duration is increased
Prolongation of Effective refractory period in atrial and ventricular
muscle, Purkinje fibers, and accessory AV pathways

59. Indication :
• Amiodarone is used in a wide range of ventricular and atrial
tachyarrhythmias that are unresponsive to conventional
therapy with less-toxic agents
• Amiodarone is frequently used to treat postoperative
junctional ectopic tachycardia
Dose
• I.V .: Loading = 5mg/kg within 30 minute
Infusion = 5ugm/kg/min to deliver 10mg/kg/day
• Oral : 5-10 mg/kg/day twice daily

60. ECG :
• Sinus slowing,
• Prolongation of the PR interval,
• Minimal widening of the QRS complex
• Prolongation of the QTc interval
Monitoring:
• Baseline hepatic, renal, and thyroid function tests, ophthalmologic
examination, and pulmonary function tests should be obtained
before starting long-term therapy and then repeated every 6
months as long as the patient is taking amiodarone

61. Adverse Effects :
• CV :
Torsades de pointes, bradycardia, heart block, sinus arrest, hypotension,
heart failure, and myocardial depression.
• Corneal microdeposits
• Hyper- or hypothyroidism
• Pulmonary interstitial fibrosis
• Hepatitis
• Peripheral neuropathy
• Slate-blue discoloration of the skin

62. SOTALOL
• Mechanism of Action :
• Sotalol is a nonselective β-blocking agent with Class III effects at higher
dose.
• Sotalol decreases heart rate and AV nodal conduction.
• It prolongs atrial and ventricular action potentials, and prolongs the
effective refractory period of atrial and ventricular muscle.

63. • Oral :
90 mg/m 2 /day in three divided doses; dose may be
incrementally increased to 180 mg/m 2 /day divided in three
doses. Dose should be gradually increased.
• Adverse Effects :
• Headache with chest pain and severe dizziness, fainting, fast or
pounding heartbeats
• Slow heartbeats
• Trouble breathing;
• Severe diarrhea or vomiting, loss of appetite;

64. VERAPAMIL
• Mechanism of Action :
• Verapamil blocks calcium channels in vascular smooth muscle and
myocardium during depolarization.
• Verapamil has the greatest influence on cells in the SA and AV nodes.
Calcium channel blockade becomes more apparent at faster rates.
Verapamil is effective in depressing enhanced automaticity.
• Indication :
Verapamil is used to treat atrial and AV nodal dependent
tachyarrhythmias (SVT, atrial fibrillation, and atrial flutter).

65. • Dose :
 Verapamil is not recommended for those younger than 1 year of
age. Administer verapamil with continuous ECG monitoring and I.V.
calcium at bedside
 I.V .: 0.1–0.2 mg/kg per dose. May repeat in 30 min if no response.
maximum dose of 5 mg.
 Oral : 4–8 mg/kg/day divided every 8 h
• Half-life is 4–7 h

66. • Adverse Effects :
• CV : severe hypotension resulting in asystole and cardiovascular
collapse has been reported in infants with I.V. use.
• Verapamil may also cause bradycardia, heart block, and
worsening of CHF
• CNS : dizziness, fatigue, seizures, headache
• GI : gingival hyperplasia, constipation, nausea
• Hepatic : increase in hepatic enzymes

67. ADENOSINE
• Mechanism of Action :
 Adenosine blocks conduction through the AV node by increasing
potassium channel conductance and depressing slow inward calcium
current.
 Adenosine also causes peripheral vasodilation.
• Indication :
 Adenosine is indicated for termination of paroxysmal SVT (specifically AV
nodal or AV reentrant tachycardia).
 Adenosine is useful for diagnosing atrial flutter

68. • Dose :
I.V .: 0.05–0.1 mg/kg per dose. If not effective, increase dose by 0.1 mg/kg
increments to maximum dose of 0.4 mg/kg. Max dose is 12 mg. Adenosine must
be administered by rapid IV push
• Pharmacokinetics :
Adenosine is metabolized by erythrocytes (cellular uptake) with a half-life of
less than 10 s.
• Monitoring Parameters :
Continuous ECG, blood pressure, and respiratory rate should be monitored.
• Contraindications :
Second- or third-degree heart block or sinus node dysfunction, unless a
pacemaker is in place.

69. • Precautions / Warnings :
Bronchospasm may occur with adenosine use in asthmatics. Use adenosine
with caution in patients with underling SA or AV nodal dysfunction or
obstructive lung disease
• Adverse Effects :
• CV :
flushing, arrhythmias (including atrial fibrillation, bradycardia and heart
block), hypotension
• CNS : lightheadedness, headache, apprehension, blurred vision
• GI : nausea
• Respiratory : dyspnea, bronchospasm

70. DRUG USED IN PHTN

71. Sildenafil
Sildenafil is a phosphodiesterase inhibitor. It potentiates the
vasodilatory effect of nitric oxide and prostacyclines.
Indications:
1. Idiopathic pulmonary artery hypertension
2. Pulmonary hypertension secondary to connective tissue
disorders
3. Eisenmenger’s syndrome, if arterial saturation is < 85% or right
ventricular dysfunction is present
4. Postoperative pulmonary hypertension with noresidual defect
5. Pulmonary hypertension of the newborn

72. Dose :
0.5- 1.0 mg/kg/dose 8 hourly
Contraindication :
•Large left to right shunts
•Obstructive total anomalous pulmonary venous connection,
•Parenchymal lung lesion leading to pulmonary hypertension.
 Side effect
•Due to vasodilation and include flushing headache, nasal congestion,
dizziness and hypotension Ocular side effects include
•Blurred vision, increased light perception
•Seizures, myalgia, transient ischemic attacks, amnesia and stroke.

73. Caution :
Sildenafil should not be combined with nitric oxide or nitrates
due to risk of severe hypotension.
 Due to increased risk of bleeding, antiplatelet agents should
not be used with sildenafil.
Parents and patients must be told not to discontinue drug
abruptly. The dose should be gradually increased, initiating with
a small dose.

74. Bosentan
 Bosentan is a competitive antagonist of endothelin-1 at the endothelin-A
(ET-A) and endothelin-B (ET-B) receptors.
 Under normal conditions, endothelin-1 binding of ET-A receptors
causes constriction of the pulmonary blood vessels.
 Conversely, binding of endothelin-1 to ET-B receptors has been associated
with both vasodilation and vasoconstriction of vascular smooth muscle,
depending on the ET-B subtype (ET-B1 or ET-B2) and tissue.
 Bosentan blocks both ET-A and ET-B receptors, but is thought to exert a
greater effect on ET-A receptors, causing a total decrease in pulmonary
vascular resistance
 Dose: 1mg/kg/dose twice daily

75.  Adverse effects :
• Headache
• Elevated transaminase level
• Edema
• Anemia
• Hypersensitivity reactions
• Itchiness, rashes, red skin, flushing, fainting, heart palpitations
• Low blood pressure
• Nasal congestion, gastro-esophageal reflux disease, and diarrhea