Special Drugs Used in Pediatric Cardiology

  1. Warfarin therapy in Paediatric Cardiology:
  2. What is Warfarin?
  • Warfarin is an anticoagulant.
  1. Why Warfarin is required in Pediatric cardiology?
  • It is required to prevent coagulation in the artificial tissue or valve of heart.
  1. How much Warfarin is required?
  • According to advice of Cardiologist after seeing level of PT/INR.
  1. How frequently PT/INR should be checked?
  • Daily———————–upto 2-3 weeks
  • At 3 days interval——-upto discharge from hospital
  • Once weekly—————-6 weeks
  • Once monthly———–6 months
  • 3 monthly—————-life long
  1. Where PT/INR level can be seen?
  • At AFIP or any better Institute of Pathology.
  1. What can happen if INR report is abnormal?
  • Excessive bleeding if INR is high.
  • Unconsciousness, stroke, blindness if INR is low.
  1. What is normal level of INR?
  • A: Aortic valve replacement-

Artificial valve-2.5-3

Tissue valve-2-2.5

B: Mitral valve replacement-

Artificial valve-3-3.5

Tissue valve-2.5-3

C: Bental procedure- 2-3

D: Pulmonary endarterectomy- 2-2.5

  1. What are the other precautions?
  • For Rheumatic fever- Inj. Penicillin should be given upto 40 years of age.
  1. Is Warfarin indicated in pregnancy?
  • Other anticoagulant is required during pregnancy it is a tematogenic drugs.

 

  1. Prostaglandin

An infant suspected of having a ductal-dependent congenital cardiac defect and ductal-dependent pulmonary blood flow should be treated with prostaglandin E1 because he/she is at risk for progressive hypoxia and metabolic acidosis if the ductus closes. Prostaglandin E1 will prevent the ductus arteriosus from closing and reestablish ductal patency if closure has already occurred, and thereby increase PaO2, and mitigate the onset of metabolic acidosis. This drug is indicated for the temporary management of the neonate with ductus-dependent congenital heart disease while awaiting transfer to a tertiary care nursery for evaluation and surgical therapy. It is also used to stabilize a neonate’s condition until surgery can be completed.

  • Indication:

Most often the neonate with ductal-dependent congenital cardiac disease is a full term infant whose size is appropriate or large for gestational age. The drug is indicated for use in the neonate with ductal-dependent pulmonary blood flow, including: pulmonary atresia, tricuspid atresia, Tetralogy of Fallot, and will often improve systemic oxygen saturation in infants with transposition of the great vessels. Note, in infants with obstructive total anomalous pulmonary venous return, a left Æ right shunt via a PDA can decrease systemic blood flow and increase blood flow to the pulmonary bed resulting in pulmonary vascular congestion and worsening of infant’s condition.

  • Patient Identification

The infant should have the following studies performed prior to the initiation of prostaglandin therapy.

  • Hyperoxic Challenge Test: Right radial artery blood gases obtained in an FiO2 of 1.0 (pCO2 35-40 torr [normal] and PaO2 less than 100 torr is consistent with cyanotic congenital heart disease).
  • Chest x-ray: Decreased pulmonary vascularity
  • Serum glucose: If the neonate is hypoglycemic, treat appropriately and reassess arterial blood gases and pH.
  • Hematocrit: Central venous hematocrit of greater than 60% may result in hyperviscosity syndrome (plethora, cyanosis and dyspnea).
  • Adequate ventilation: If there is any question as to the adequacy of ventilation, the neonate should be mechanically ventilated and arterial blood gases reassessed.These studies will aid in the identification of the neonate with another etiology for central cyanosis. Only definitive echocardiography and cardiac catheterization will clearly identify infants with ductal dependent pulmonary blood flow.
  • Administration

Prostaglandin E1 is packaged in a 1 ml ampule of 500 micrograms (0.5 mg). Use one of the following methods to prepare a solution for infusion.

  • Dilute one ampule in 500 ml D5W or D10W = 1 mcg/ml (0.001 mg/ml) solution.
    To give 0.05 mcg/kg/min. = 3.0 ml/kg/hr
  • [weight (kg) ÷ 10] = # mg PGE1 in 100 ml IVF @ 3 ml/hr = 0.05 mcg/kg/min
  • Dilute one vial in 100 ml of D5W or D10W = 5 mcg/ml solution. To give 0.05 mcg/kg/min. = 0.6 ml/kg/hr

Make sure the drug is thoroughly mixed in solution and all lines are purged. Once mixed, the solution is stable for 24 hours. Prostaglandin E1 is infused continuously by pump via a large peripheral vein (preferably not scalp vein) or umbilical ine. There is evidence that doses greater than 0.1 mcg/kg/min are -not more- effective, and may cause an increase in adverse reactions.

  • Response and Duration of Action

The neonate generally responds with an increase in PaO2 10-15 minutes after initiation of the drug. Some patients may not respond until several hours of drug infusion have elapsed. The half-life of the drug is one circulation time; therefore, continuous uninterrupted infusion must be maintained. Once the patient responds, the dose can be reduced to one-half or less of the initial effective dose.

  • Precautions

Monitor respiratory rate, temperature, blood pressure and arterial blood gases and pH at the initiation of and intermittently during infusion.

  • Adverse Reactions

About 20% of infants who receive this drug have one or more adverse reactions. Three common side effects are apnea (12%), fever (14%), and flushing (10%). Twitching, fever, and peripheral flushing – particularly if given intra-arterially, will usually cease with reduction of the dose by 50%. Apnea is an indication for assisted or mechanical ventilation. A decrease in systolic arterial pressure of greater than 20% is an indication for volume expansion by 10 ml/kg of colloid. Hypoglycemia may develop after several hours of treatment.

 

  1. Indomethacin

In the neonate, ductal patency appears to be related to continued production of prostaglandin. This is particularly true in the premature infant; therefore, prostaglandin inhibition can affect ductal closure. NSAIDs inhibit the production of prostaglandins by decreasing the activity of cyclooxygenase. The result is a functional closure of the patent ductus arteriosus (PDA) in 80% of patients.

Closure of Ductus Arteriosus

Neonates <28 days: 0.2 mg/kg IV over 20-30 minutes initially, THEN 2 subsequent doses, depending on postnatal age

Doses 2 and 3 (<48 hours): 0.1 mg/kg IV over 20-30 minutes at 12 and 24hr intervals

Doses 2 and 3 (2-7 days): 0.2 mg/kg IV over 20-30 minutes at 12 and 24hr intervals

Doses 2 and 3 (>7 days): 0.25 mg/kg IV over 20-30 minutes at 12 and 24hr intervals

After dose 3 (infants <1.5 kg): 0.1-0.2 mg/kg IV over 20-30 minutes once daily for 3-5 days

 

  1. Esmolol
  • Dose

Supraventricular Tachycardia (Off-label)

Load with 500-600 mcg/kg IV over 5 min, THEN 200 mcg/kg/min IV infusion (range 50-250 mcg/kg/min)

Postoperative Hypertension (Off-label)

Load with 500-600 mcg/kg IV over 5 min, THEN 200 mcg/kg/min IV infusion (range 50-250 mcg/kg/min)

  • Adverse Effects

>10%
Hypotension, asymptomatic (25-38%)
Hypotension, symptomatic (12%)
1-10%
Injection site pain (8%), Nausea (7%), Dizziness (3%), Somnolence (3%), Agitation (2%), Confusion(2%), Headache (2%), Fatigue (1%), Vomiting (1%)
<1%
Bradycardia, Chest pain, Anxiety, Anorexia
Depression, Abdominal discomfort, Constipation, Dry mouth, Dyspepsia, Taste perversion, Bronchospasm, Dyspnea, Nasal congestion, Wheezing, Decreased exercise tolerance, Raynaud’s phenomenon, May increase triglyceride levels and insulin resistance, and decrease HDL levels

Contraindications of Esmolol:

Hypersensitivity

Sinus bradycardia, 2°/3° heart block, cardiogenic shock, overt cardiac failure

Asthma/COPD

Sick sinus syndrome without permanent pacemaker

Cautions

Anesthesia/surgery (myocardial depression), bronchospastic disease, cerebrovascular insufficiency, CHF, DM, hyperthyroidism/thyrotoxicosis, liver disease, renal impairment, peripheral vascular disease, myasthenic conditions

Sudden discontinuation can exacerbate angina and lead to myocardial infarction and increased risk of stroke after surgery it is also.

Used in pheochromocytoma

Avoid abrupt withdrawal of this drugs.

 

  1. Adenosine
  • Indication: Paroxysmal Superventricular Tachycardia
  • Dose:05 to 0.1 mg/kg rapid IVP over 1-3 seconds or IO, no more than 0.3 mg/kg/dose, followed by rapid flush with > 5 mL 0.9% NaCl.

If necessary may give 2nd dose of 0.2 mg/kg IVP/IO, not to exceed cumulative dose of 12 mg.

  • Contraindications:
    • Hypersensitivity
    • 2nd or 3rd degree AV block (except those on pacemakers), sick sinus syndrome, atrial flutter or fib, V-tach
    • Adenoscan: Contraindicated in bronchoconstrictive or bronchospastic lung disease (eg, asthma)
  • Adverse Effects:

>10%

Flushing (18%)

Dyspnea (12%)

1-10%

Chest pain (7%)

HA (2%)

Lightheadedness (2%)

Dizziness (1%)

Tingling in arms (1%)

Numbness (1%)

Nausea (3%)

 

  1. Esmoprostenol

Indication: Pulmonary vasodilators for Primary Pulmonary Hypertension

Dose: 2ng/kg/min IV infusion pump over 24-48 hours initially; may be initiated at lower dose if intolerant to starting dose. Titrate by 1-2 ng/kg/min IV  q15min or longer, until desired effect or dose limiting pharmalogic effects occur

 

G.Bosentan

Indication: Pulmonary vasodilators for Primary Pulmonary Hypertension

Dose: 3.75mg/kg daily (range 2- 5.4)

Adverse effects:

  • swelling in your legs or ankles, with or without weight gain;
  • a light-headed feeling, like you, might pass out;
  • low red blood cells (anemia)–pale skin, unusual tiredness, feeling light-headed or short of breath, cold hands and feet;
  • liver problems–nausea, vomiting, fever, upper stomach pain, tiredness, dark urine, jaundice (yellowing of the skin or eyes); or
  • new lung problems–anxiety, sweating, pale skin, severe shortness of breath, wheezing, gasping for breath, cough with foamy mucus, chest pain, fast or uneven heart rate.

 What food or medicine must be avoided when someone takes Bosentan?

  • Patients taking Bosentan should not take Glibenclamide/Glyburide (a medication for diabetes) or Cyclosporine (a medication for suppression of the immune system) due to increased risk of side effects.
  • Bosentan may interact with certain antibiotics and antifungal medications taken by mouth. Please consult the Pulmonary Hypertension team if you are started on any of these.
  • Inform your Cardiologist, Nurse and/or Pharmacist if you are taking any other over-the-counter (OTC) medications, health/herbal supplements or traditional medications. The Pulmonary Hypertension Team will check to ensure that the combination of medications you are taking is safe.
  • Avoid grapefruit juice while on this medication.
  1. MgSO4

Indication: Pulmonary vasodilators for Primary Pulmonary Hypertension

Dose: loading dose of 200 mg/kg, followed by a continuous infusion of 20 to 150 mg/kg/hr. magnesium levels to be measured and the dose to be adjusted to maintain a normal blood level.

  1. Sildenafil

Indication: Pulmonary vasodilators for Primary Pulmonary Hypertension

Dose: intragastric tube at 0.5 mg/kg/dose four times a day. If no response is obtained, the dose may be doubled to a maximum of 2 mg/kg/dose.

 

  1. Digoxin (described in Heart Failure)
  2. Amiodarone: It is used in atrial fibrillation, ventricular tachycardia, ventricular fibrillation, SVT (Paroxysmal), post-surgical AF.

Dose:

In Emergency: IV loading dose  5mg/kg slow infusion over 30 unit followed by 7 hours/kg/min.

Oral     10-20 mg/kg/day twice daily per infant. 10 mg/kg/day twice daily for children. Maintenance dose 5-7mg/kg once daily.

Side Effect: a Cough, dyspnea, hepatotoxicity, hypo/hyperthyroidism, photosensitivity etc.

Contraindication: 2nd and 3rd-degree heart block, heart failure, asthma, thyroid disorder, visual problem, liver disease, pregnancy.

  1. Verapamil:

It is used in hypertension, atrial fibrillation, SVT (paroxysmal), atrial flutter.
This drug is used in emergency treatment of supraventricular tachycardia.
Dose: IV dose 0.1 -0.3 mg/kg over 2 minutes, repeat same in 15 mins (for SVT)

Oral           1-3 mg/kg/day, 8-12 hourly

 

Side Effects: Hypoteasion, bradycardia, cardiac depression.

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