staying the overlying mediastinal pleura.

The coarcted segment & the great

vessels identified, dissected around & looped. The intercostals were divided &
looped respectively. The aorta above & below the coarct was looped. After
systemic Heparinisation, the aortic arch proximal to the Coarctation was
clamped with a curved clamp proximal to LSCA, & the left subclavian was also
clamped with straight clamp. The aortic arch distal to the coarctated portion
was also clamped with a straight clamp. The PDA dissected looped & divided,
the end was sutured with 5-0 prolene suture. The Coarctation segment was
next excised leaving wide lumen of the aorta on either side. Both end s were
anastomosed with continuous prolene. The distal mean arterial pressure [as
measured by the Lt FA pressure-line always maintained around 35-40 mmHg
throughout the anastomoses]. After the anastomoses, the aortic clamps were
released one by one & satisfactory hemostasis ensured. Mediastinal pleura
were closed. Chest closed after verifying the counts & putting the chest tube.
Shifted to ICU in stable condition.

Cardiovascular Medications

Terminologies
1. Adrenergic: Norepinephrine as a neurotransmitter, Effect on cells of
Autonomic nervous system (ANS).
2. Cholinergic: Acetylcholine as a neurotransmitter, Effect on cells of
Autonomic nervous system (ANS).
3. Sympathomimetic: Sympathetic nervous system stimulant.
4. Sympatholytic: Sympathetic nervous system blocker.
5. Chronotropic: Affecting the Heart rate.
6. Inotropic: Affecting the force of myocardial contraction.
7. Dromotropic: Affecting the velocity of conduction.
Adrenergic receptors

658
Types Receptor sites Stimulation
Response
Alpha () Peripheral arteries Vasoconstriction
Beta1 (1) Myocardium & Increase contractility &
(remember 1 heart, conduction system Heart rate
two lungs)

Beta2 (2) Vascular smooth Coronary & peripheral

muscle vasodilatation
Bronchodilatation
Bronchi(Lungs)
Dopaminergic Renal & Mesenteric Vasodilatation
Vasculature
Cardio active Drips
Drugs to Improve Cardiac output
Dobutamine
Action :Almost exclusively a Beta-1 agonist with no alpha effect, and
minimal beta-2 effect
Effect : Inotropic and chronotropic effects on the heart,
Decrease in peripheral vascular resistance (Decreases afterload)
and
Improvement of AV node conduction
Use: To improve cardiac output and blood pressure, can be administered
peripherally.
Dose: 5-20 Micgm /Kg/Min.
May cause tachyarrhythmia, fluctuations in BP.
Cardiac & hemodynamic monitoring is recommended.
Risk: Increases myocardial oxygen demand may increase heart rate
excessively.

659
Dopamine
Action : precursor of norepinephrine, stimulates dopaminergic, alpha
and beta adrenergic receptors (little or no beta-2 effect)
Effect :
Low doses (2-5mcg/kg/min) minimal alpha effects, causes more
splanchnic dilatation, improving renal blood flow (a dopaminergic
response).
Medium doses (5-10mcg/kg/min) beta effects start to predominate.
High doses (10-20mcg/kg/min) alpha effects more prevalent
Use : Good first line to improve cardiac output when used in mid-range,
Hypotension with signs & symptoms of shock
Risk: High doses may cause vasoconstriction. Adverse effects on
immune function.
Use only after volume replacement in hypovolemic patient.
May cause tachyarrhythmia, excessive vasoconstriction.
Avoid extravasation administer phentolamine SQ in area of extravasation
to minimize tissue necrosis.
Epinephrine (0.01 to 1 mcg/kg/min, or higher in very critical situations, usual
dose range in cardiac patients is 0.03-0.3, in septic patients doses may be
higher)
Action : Potent non-selective beta agonist also an alpha agonist
(Beta>alpha)
Effect : Increases inotropic and chronotropic cardiac activity also causes
peripheral vasoconstriction, decreasing peripheral perfusion
Use :
To increase cardiac output and blood pressure, at lowest doses
(<0.1mcg/kg/min has primarily beta-1 effects).
Ventricular fibrillation, pulseless ventricular tachycardia, asystole,
pulseless electrical activity
Severe allergic reactions, anaphylaxis
660
 Cardiac arrest - 1.0 mg IVP; may repeat q 3-5 minutes
Endotracheal administration - 2.0-2.5 mg diluted in 10 ml. NS
Profound bradycardia - 2-10 mcg/minute
Risk: Can cause profound peripheral vasoconstriction, compromising
tissue perfusion. Long term use down regulates catecholamine
receptors, decreasing effect, also increases myocardial oxygen demand
If administration causes rapid, marked rise in BP, can see aortic rupture,
cerebral hemorrhage, or angina pectoris.
ADMINISTRATION OF SC PREPARATION BY IV ROUTE MAY CAUSE
SEVERE OR FATAL HYPERTENSION OR CEREBROVASCULAR
HEMORRHAGE
Drugs to Improve Cardiac Output and cause Vasodilatation
Milrinone, Amrinone
Action : Phosphodiesterase inhibitor,
Prolonging the effect of cAMP allowing increasing ionized calcium
entry into cardiac cells increasing myocardial contractility, and cAMP
dependent vascular relaxation
Effect: Peripheral vasodilator and positive inotropic effect on heart,
improved diastolic relaxation. May cause reflex tachycardia due to
vasodilatation
Use: Afterload reduction, additional inotropic support when
catecholamines already in use. Severe CHF unresponsive to diuretics,
vasodilators, and conventional inotropic therapy
Dose: 0.75 mg/kg loading dose over 2-3 minutes; may repeat after 30
minutes if necessary. Maintenance infusion of 5-10 mcg/kg/minute.
Risk: As with other inotropes, can also potentially cause too much
vasodilatation leading to hypotension, use caution in severely
hypovolemic patients
May cause tachycardia, hypotension, or thrombocytopenia.

661
 Incompatible with dextrose solutions & other IV drugs.
Isoproterenol (Isoprenaline)
Action: Potent Beta 1 & 2 stimulant.
Effect : Inotropic (beta), chronotropic effects
Use : Symptomatic bradycardia unresponsive to other therapy
Dose: 0.05- 1 micg/Kg/min.
Quickly elevates the heart rate.
Increases myocardial oxygen requirements; may increase myocardial
ischemia.
Contraindicated in tachyarrhythmia & digitalis toxicity.
Do not give with epinephrine - may cause VF/VT.
Drugs to cause vasodilatation
Nitroprusside (Nipride)
Action : It has direct activity on vascular smooth muscle (donates an NO
group to be specific)
Effect: Peripheral vasodilator by relaxation of smooth muscles in vessels-
Arteriolar dilator.
Use: Used as an afterload reducer, primarily an arteriolar vasodilator
can increase tissue perfusion in patients receiving vasoconstrictors, can
be given peripherally.
Hypertensive crisis
To reduce afterload in heart failure, acute pulmonary edema, or acute
mitral or aortic valve regurgitation
Begin at 0.10 mcg/kg/minute and titrate upward every 3-5 minutes to
desired effect (up to 5.0 mcg/kg/minute)
Dose : 0.5-10mcg/kg/min
Risk: Cyanide and Thiocyanate toxicity from prolonged usage of high
doses: blurred vision, tinnitis, confusion, hyperreflexia, seizures. (Using
Na thiosulfate decreases risk 10mg/mg nitroprusside).

662
 Risk of severe hypotension in patient who is intravascularly dry.
Drug is light-sensitive; therefore, wrap drug reservoir in aluminum foil.
Use with an infusion pump; closely monitor blood pressure during
therapy.
Nitroglycerin
Action : Relaxes peripheral vascular smooth muscle by donating an NO
group
Effect : Causes peripheral vasodilatation, decreasing pre-load and
decreasing blood pressure, helps prevent vasospasm (General
venodilatation)
Use: Most commonly used in post-operative, arterial switches to help
prevent coronary vasospasm, sometime used as a preload reducer, can
be given peripherally.
Low doses - venous; high doses - arterial
Preload reduction and coronary vasodilatation
Useful in management of ischemia
Decrease LVEDP and pulmonary vascular congestion
Chest pain of suspected cardiac origin
Unstable angina
Dose : 0.5-5mcg/kg/min
Risk: Can cause severe hypotension in patient who is intravascularly
dry, risk of methemoglobinemia, otherwise similar to nitroprusside.
Complications of acute myocardial infarction, including CHF & LV
failure
Monitor VS & EKG during therapy
Drugs to increase systemic vascular resistance (increase afterload)
Norepinephrine (Levophed)
Action : Potent alpha adrenergic agonist and beta agonist (alpha>beta)

663
 Effect : Vasoconstriction and inotropic and chronotropic effects,
increasing blood pressure, both by increasing SVR and by increasing CO
Use : In patients already on vasopressors requiring more support to
maintain blood pressures, Septic shock, Cardiogenic shock
,Hemodynamically significant hypotension
Dose : Initial dose 0.05-0.1mcg/kg/min, titrate to effect
Risk : Decreases blood flow to all organs and tissues, can cause
worsening metabolic acidosis due to ischemia
Increases myocardial oxygen requirements and may induce arrhythmias,
therefore use cautiously in patient with cardiac ischemia.
Extravasation causes tissue necrosis
Phenylephrine (Neo-Synephrine)
Action : Alpha adrenergic agonist
Effect : Constricts both arterial and venous blood vessels, increasing
systemic vascular resistance without changing cardiac dynamics
Use: In patients who need blood pressure support, where muscular
outflow obstruction may be worsened by the use of Beta agonists, such
as unrepaired TOF or hypertrophic cardiomyopathy.
Treatment of hypotension in shock and shock-like states
Dose : 0.1-0.5mcg/kg/min as drip, 5-20mcg/kg as bolus
Risk: Decreases flow of blood to all organs, reducing oxygen supply and
potentiating ischemia at very high doses can have some beta effect.
Continuous monitoring of cardiac rhythm & BP is required during
infusion.
Avoid extravasation; if it occurs, administer phentolamine locally to
prevent tissue necrosis.
Also Epinephrine and Dopamine to some extent
Cautions for vasopressors
- Adversely affect Stroke volume, myocardial oxygen demand & Blood flow
to non vital organs.
664
 - Ineffective & contraindicated in volume depleted patients.
- Local tissue ischemia & necrosis can occur with extravasation of infusion
in peripheral site.(should be given through central line)
- Induce cardiac arrhythmias.
Drugs to cause pulmonary vasodilatation
Nitric Oxide (0-80ppm inhalation)
MOA: Activates cGMP pathway causing direct smooth muscle
relaxation in local vascular bed
Effect: Since given as inhalational agent, causes relaxation of
pulmonary vascular bed only, with no systemic effect
Use: Used to decrease pulmonary vascular resistance in patients in
whom pulmonary hypertension is a problem, either from a cardiac
output standpoint or from a oxygenation standpoint
Risk: Can combine with Hgb to form methemoglobin, needs closed
ventilatory circuit and constant monitoring.
Blockers
Mechanism of stimulation :
receptor stimulation
1 stimulation Increase Calcium in cells HR, Conduction,
Contraction
2 stimulation Smooth muscle relaxation
Types
1. Cardioselective- Blocks only 1 receptors ATENOLOL, METOPROLOL
2. Non selective agents Blocks both receptors(1+ 2)- PROPRANOLOL
3. + Blocking effect- LABETOLOL
4. Ultrashort acting blockers ESMOLOL
Effects
1. Heart Negetive Chronotropic-SA node
Negetive Dromotropic AV node
Negative Inotropic Myocardium
665
 Anti ischemic
Anti arrhythmic
2. Coronaries & Myocardial perfusion
Coronary vasospasm
Better diastolic myocardial perfusion
3. Systemic circulation
Norepinephrine release
adrenergic outflow
Circulatory rennin
Uses
1. CVS- IHD,HTN,Arrhythmia,Cardiomyopathies
2. Other CVS- Aortic dissection, Marfans syndrome, TOF
3. Non cardiac Anxiety, Tremor,Migraine,Glaucoma,Oesophageal varieces
Contraindications-
1. Cardiac Severe bradycardia, Heart blocks, LVF.
2. Pulmonary Asthma, bronchospasm.
3. CNS- Severe depression.
4. Vascular Active PVD with rest ischemia.
Side effects Bronchospasm, Cold extremities, Bradycardia, Heart block,
Insomnia, Depression.
No blocker is completely safe in presence of Asthma, low dose of
cardioselective agents can be used with care in patients with
bronchospasm/chronic lung disease/chronic smoking.
Dose
1. PROPRANOLOL-
IV 0.1mg/kg x 10minutes then 0.1-0.3mg/kg/dose 3hourly.
Oral 0.2-0.5 mg/kg/dose 6-12 hourly
2. ATENOLOL
1-2mg/kg/dose 12-24 hourly
3. METOPROLOL
666
 IV 0.1mg/kg
Oral 2mg/kg/dose 6-12 hourly.
4. LABETOLOL
1-2mg/kg/dose 12 hourly
Less bronchospasm & vasoconstriction, Reduce BP very fast.
S/E- Postural hypotension.
5. ESMOLOL
t1/2- 9 minutes.
Used for perioperative SVT & HTN.
Dose- 500 micgm/kg/min over 1 minute
50 micgm/kg/min x 4minute infusion.
100 -300 micgm/kg/min if previous fails.
Extravasation leads to skin necrosis.

Nitrates
Mechanism Exogenous source of Nitric oxide (NO).
Nitroglycerine- SL tabs- effect in a minute, last for 1 hour,
0.3-0.6mg-> 1.5mg
Spray 0.4mg/metered dose
Oral capsule 2.5-13mg 1-2 tabs
Ointment 2%- 6x6 inch or 15x15 cm or 7.5-40mg.
Patch 0.2-0.8mg/hr patch on for 12 hours & off for 12 hours.
Isosorbid dinitrate- Sorbitrate 2.5-15mg.
Mononitrates Monotrate 20mg 12 hourly.
S/E Hypotension, Headache, Tachycardia.
C/I HOCM.
Indication- Angina, MI, CHF.

Calcium Channel Blockers

Most commonly agents used for angina & HTN.
667
Mechanisms
Interference of Ca2+ - mediated smooth muscle contraction - coronary and
peripheral smooth muscle relaxation
Selective Ca2+ channel inhibition
Use: Treatment of angina pectoris / supraventricular tachycardia /
hypertension

Types DHPs- Nifedipine Non DHPs Non DHPs- Dilzem

Verapamil
Effects Vascular Myocardial selectivity Myocardial
selectivity selectivity
Site Peripheral AV node SA node
Dose 0.25-1mg/kg 6- IV 0.1-0.2mg/kgx 1-3 mg/kg/dose
12 hrly 10minutes then 8hrly
5micgm/kg/min
Oral 1-3mg/kg/dose
8-12 hrly
Indications HTN,Coronary Angina, Coronary Angina, Coronary
spasm spasm, HTN, SVT spasm, HTN, SVT
C/I AS/HOCM/Severe Sick sinus Sick sinus
Myocardial failure syndrome,Digoxin syndrome,Digoxin
toxicity blockers, toxicity, blockers,
Systolic LV failure Systolic LV failure
Others Amlodipine- Long Less constipation
duration of action
0.05-0.2mg/kg/d

Angiotensin Converting Enzyme Inhibitors

Mechanism
668
Angiotensin system Kinin system
Angiotensinogen Kininogen

Angiotensin I Stops Breakdown of Bradykinin
ACE ACE Inhibitors blocks
Angiotensin II Prostaglandin &
NO

1. Aldosteron release Vasodilatation
2. Sympathetic activity
3. Vasoconstriction
Indications HTN, CHF
C/I Bilateral renal artery stenosis
Hypotension
AS, HOCM
Pregnancy
S/E Cough, Hypotension, Renal failure, Hyperkalemia.
Caution Can not be used with Potassium sparing Diuretics.
Dose should be reduced in case of hepatic or renal dysfunction.
Class Drugs Dose Special
I Captopril 0.1mg/kg/dose 8hrly
II Enalapril 0.1mg/kg /d Less cough
Ramipril 0.05mg/kg/d
III Lisinopril 0.1mg/kg/d Water soluble

Angiotensin II receptor Antagonist

Inhibit formation of Angiotensin II.
Used in HTN & heart failure.
Adv- No cough, reduced cholesterol level.
Disadv Absence of renal vasodilatation & endothelial protection by NO.
669
 LOSARTAN 0.5-2mg/kg/d
TELMISARTAN 1mg/kg-2mg/kg/d.

Diuretics
Drug of 1st choice in treatment of symptomatic Heart failure.
Mechanism
1. Heart Failure
Reduce pulmonary & peripheral symptoms & signs of congestion.
Sodium & Water retension.
2. HTN
Natriuresis (Sodium removal) - Shrink the fluid volume.
May work as a Vasodilator.
Types

Type Mechani Drug Dose S/E Special

sm
Loop Removes Furosemide 0.5- Hypokalemia C/I in
Na,K,Cl (Lasix) 1mg/kg/do Dehydrati
from loop se 6-24hrly on &
of Henley Hypokale
mia
Thiazide Inhibit Hydrochlorthi Hypokalemia Longer
reabsorpt azide Hypomagnes action
ion of Na emia Low dose
& Cl in Gout maximu
distal m
part of response
nephron

670
K sparing Inhibit Triameterene 2mg/kg/do Hyperkalemi Independ
Na- se 8-24hrly a ent of
Proton Amiloride 0.2mg/kg/ Aldestero
exchange dose 12- n effect
r 24hrly
Loss of
Na
without
loss of K
K sparing Inhibit Spironolacton Kg Drug of
Spironolact Na-K e dose choice in
one exchange 0-10- NIDDM &
at the 6.25mg bd Gout
site of 11-20-
Aldestero 12.5mgbd
n action 21-40-
25mg bd
Carbonic Acitazolamide 5- Used in
anhydrase 10mg/kg/d Glaucom
inhibitor ose 6-8hrly a

Digitalis (Digoxin)
Inotropic bradycardic action.
Action & Effect:
Inhibit Na-K-ATPase calcium transport into myocardium- positive
inotropic effect
Parasympathomimetic and anti-adrenergic mechanisms-Anti arrhythmic
effect
Mechanism
1. Sodium pump inhibition- Ca++ in cell- Contraction.
671
 2. Parasympathetic activation- Sinus slowing & AV nodal inhibition.
3. Sympathetic inhibition- sympathetic nerve discharge.
4. Renin release- vasodilatation.
Drug interaction - Quinidine, Verapamil, Amiodarone
Indications-

1. CHF with AF/SR.

2. AF.
3. Valvular Heart disease.
4. LVF.
C/I-
1. HOCM.
2. WPW Syndrome.
3. AV nodal heart block.
4. Diastolic dysfunction.
S/E Coloured vision & arrhythmias
Caution IV Digoxin should not be given if K+ is < 4mmol.
Antidote = digibind
Always remember
- Consult a senior member of the staff before starting Digoxin.
- You can give always more, so always start with small doses.
- Always make sure that serum potassium level is > 4.0 mmol/L.
- Be very cautious with digoxin in presence of ventricular
arrhythmias.
Anti Arrhythmic

Class Action Agents

IA Inhibit Na+ transport Quinidine

Reduced dV/dT of action potential Procainamide

672
 IB Slow dV/dT of phase 0 Disoprymadine

Moderate prolongation of repolarization Lidocaine

Prolongs PR, QRS, and QT intervals Phenytoin

IB Limited effect on dV/dT of phase O Mexiletine

Shortens repolarization Tocainide

Shortens QT in clinical doses

Elevates fibrillation threshold

IC Markedly slows dV/dT Flecainide

Little effect on repolarization Ecainide

Markedly prolongs PR and QRS

II Beta-adrenergic blockers Metoprolol

Decrease nodal conduction Atenolol

Propanolol

III Prolongs repolarization Amiodarone

Alters membrane response Beryllium

IV Calcium channel blockers Verapamil

Decrease nodal conduction Nifedipine

Diltiazem

Lidocaine (Xylocard)

Mechanism-
1. Inhibit fast sodium current.
2. Shortens the action potential duration in normal tissue.
Uses SVT with AMI / Post cardiac surgery.

673
Hypokalemia must be corrected for maximum effect.
Dose 1mg/kg IV then 15-50 micgm/kg/min infusion.
S/E Drowsiness/Numbness.

Amiodarone (Cordorone)
Mechanism
1. ERP by prolonging action potential duration.
2. Inhibit inactivated sodium channel.
3. Blocks (Noncompetitively) & receptors.
4. Calcium antagonist action at SA node.
5. Coronary & peripheral vasodilatation.
Widespectrum of action.
Class I/II& III action.
Slow onset of action.
Universal antiarrhythmic drug.
C/I Severe SA node dysfunction.
S/E pulmonary infiltrate.
Dose 5mg/kg loading dose x 30-60 minutes (Hypotension)
5-15 micgm/kg/min.

Adenosine
Adenosine receptors.
3 types
A1- on myocytes: decrease the rate of depolarization
A2a- in CNS: induce sleep
A2b- on vascular endothelium: decrease platelet adherence & cause coronary
vasodilatation
A3- on mast cells: stabilize the cell membrane
Mechanism-
1. K+ channel opener.
674
 2. Inhibit SA & AV nodes.
t 10-30 seconds.
Indication- narrow complex SVT.
C/I- Asthma, Av Blocks, Sick sinus syndrome.
S/E Head ache, Chest pain, Flushing, dyspnoea.
Dose 6mg with saline flush after 10 min
12mg with saline flush.
Should be given rapidly in central line (preferably)
Watch monitor there will be flat line for a second & heart starts beating.
Uses.
1) In CPB- immediately after cross clamping & during reperfusion
2) Correction of arrhythmias
3) Induce sleep (term fatigue factor)
4) For refractory PH

Action is potentiated by dipyridamole

Action inhibited by caffeine & aminophylline
Side effects.
1) Headache & flushing
2) Arrhythmias
Contraindication for adenosine.
Heart block & bradyarrhytmias
Antidote for adenosine.
Aminophylline
Anti thrombotic

Intact Endothelium Anti Aggregatory Prostacycline

Vasodilatory NO
Fibrinolytic tPA
Anti thrombotic Thrombomodulin
675
Vascular Injury Platelet aggregate Coagulation system activated
Antiplatelets
Aspirin,Dipyridamole,Ticlopidine,Clopidogrel
Inhibit platelet aggregation.
Uses- Atrificial heart valves, CAD, PVD, Arteriovenous shunts.
Aspirin- Gastritis
C/I Haemorrahge, Intolerence, GI Bleed.
Dose 3-5mg/kg/d
Dipyridamole ( Persantin)-
Coronary vasodilatation effect.
Dose 1-2mg/kg/dose 6-8 hrly.
Ticlopidine/Clopidogrel GP IIb/IIIa receptor antagonist
Thrombocytopenia & Neutropenia.
Ticlopidine 5mg/kg/dose 12 hrly
Clopidogrel 1.5mg/kg/d.

Anticoagulant
Heparin-
Mechanism- On Coagulation mechanism-Anti thrombin III & Thrombin.
Antiplatelet effect.
Uses- AMI, Acute venous thrombosis, Acute pulmonary embolism,
Coronary angioplasty, Cardiac surgery.
Dose - 1 mg=100 Units
Low dose 75 U/kg then 15U/kg/hr
Full dose 200 U/kg then 15-30 U/kg/hr
S/E Haemorrahge, Thrombocytopenia.
Check APTT Should be 1.5- 2.5 times normal.
ACT - >400 sec.

676
LMWH-
Low-molecular-weight heparin is a relatively recent addition to the list of
therapies for prophylaxis and treatment of deep venous thrombosis (DVT). As a
prophylactic, low-molecular-weight heparin is as effective as standard heparin
or warffarin and does not require monitoring of the activated partial
thromboplastin time or the International Normalized Ratio.
Advantages of low-molecular-weight heparin over standard heparin include
predictable blood levels, lower likelihood of bleeding and no reports of
thrombocytopenia or osteoporosis.

Dalteparin 16 mg per 0.2 mL; 2,500 IU SC 1 to 2 hours before surgery,

(Fragmin) 32 mg per 0.2 mL then 2,500 IU every day for 5 to 10 days

#Heparin was discovered by McLean in 1916.

#It requires the presence of antithrombin III for its action.
Heparin binds to AT III brining about a conformational change converting AT III
from a slow progressive thrombin inhibitor to a very rapid inhibitor.

#Only 1/3rd of the administered dosed of heparin binds to AT & this fraction is
responsible for most of its anticoagulant effects.

#Mechanism of action is:

1) The heparin- AT III complex inactivates a number of coagulation enzymes;
including Thrombin factor IIa, Xa, Ixa, XIa & XIIa. The major effects are due to
inhibition of IIa & Xa.
2) Binds to heparin cofactor II & catalyses inactivation of IIa.
3) Binds to platelets- contributing to the hemorrhagic effects of heparin.
XIIa AT III- heparin complex

XIa AT III- heparin complex

677
IXa AT III- heparin complex

Xa AT III- heparin complex

IIa AT III- heparin complex

Fibrinogen Fibrin

molecular size= 3.000 to 30,000 daltons (approx.=15,000 daltons)

(- Mol wt. of LMWH= 5000 daltons_

#Clearance- High molecular weight moieties are cleared more rapidly than the
low molecular weight moieties.
Heparin is cleared by 2 mechanisms:
Rapid- binding to the endothelial cell receptors and macrophages, where it is
depolymerised
This makes the anticoagulant response to heparin non linear at therapeutic
doses, with both the duration and intensity of the effect rising
disproportionately with increasing doses.
Thus the biological life increases from
30 minutes with IV bolus of 25 IU/ Kg
to
60 minutes with IV bolus of 100 IU/ Kg &
to
150 minutes with a bolus of 400 IU/Kg.

#Action is potentiated in cirrhosis & action is depressed in pulmonary

embolism.

#What is 1 IU heparin?
678
1U of heparin is the amount of heparin that is required to maintain the fluidity
of 1 ml of citrated sheep blood for 1 hour, at 37 C, with calcification.
#Side effects:
Decreases the SVR by decreasing the amount of ionized calcium.
DIC
Osteopenia
Heparin induced thrombocytopenia & heparin resistance

#Protocol for management of a patient with post CPB non-surgical bleeding.

A) Check for & correct
Heparin- residual/ rebound
Platelet number & function
Coagulation factors
Activation of fibrinolytic system
Hypothermia &
Hypocalcemia.

#Criteria for heparin induced thrombocytopenia

If in a patient receiving heparin treatment;
the platelet count drops by 50% of the pretreatment levels, or
the platelet count drops to < 1 lac/ mm3

#Advantage of LMWH over unfractionated heparin?

Due to low molecular weight, higher bioavailability by s.c. route, hence OD
dosage suffices
bioavailability of LMWH (s.c. route)= 100%
bioavailability of unfractionated heparin (s.c. route)= 30%
Due to increased bioavailability, clinical effect is predictable & hence no need
for repeated APTT monitoring
Lesser rate of thrombocytopenia, osteopenia & hemorrhagic side effects
679
#Disadvantage of LMWH
Lower antithrombotic properties
No drug to reverse its effect

#Heparin related drugs

LMWH
Medium MWH
High MWH
Dermatans (Danaparoid)
Heparans
Heparinoids (Lomoparon)
Murine polysaccharides

#Heparin resistance is seen in:

AT III deficiency- congenital/ acquired
Prolonged administration- in unstable angina/ IABP
Septicemia
Pregnancy
NTG treatment

#Management of heparin resistance.

Administering higher dose of heparin (up to 1000 IU/ Kg)
Accepting a lower ACT (up to 420 sec)
Administering 2-3 unit FFP or AT III concentrate
Using hirudin/ danapariod
Oral anticoagulants-
Warfarrin & Acitrom (Nicumalone)
Inactivate Vit K in hepatic microsomes-Interfere with Vit K dependent clotting
factors.
680
Uses AF, Clot in LA/LAA, Prosthetic valves, AMI & Pulmonary embolism.
To check Prothrombin time.
Warfarin
#What does warfarin stand for?
Wisconsin Alumini Research Foundation coumaRIN
It is a 4-hydroxy coumarin derivative & was introduced as a rodenticide.

#It is metabolized in the liver (by enzyme cytochrome P 450) & excreted in bile
life= 25- 60 hours (action lasting for 2 5 days)
#Drug interaction with warfarin.
Drugs that potentiate action of warfarin (increasing INR) are:
1) Inhibiting metabolism (Cytochrome P 450 inhibitors)
- cimetidine
- metronidazole
- omeprazole
- amiodarone
2) Prevent active form of Vit K formation
- 3rd generation cephalosporins
- ciprofloxacin
3) decreased availability of Vit K
- diet
4) direct anticoagulation
- aspirin
- dipyridamole
Drugs that decrease action of warfarin (decrease INR) are:
1) decreased absorption of warfarin
- sucralfate
- cholestyramine
2) increased metabolism
- gardinal
681
 - eptoin
- alcohol
- rifampicin
3) Increased GI uptake of warfarin
- dairy products
- fruits
- tea/ coffee
- raddish/ onion/ potato

Thrombolytic Agents
Streptokinase - Indirectly activate plasminogen to plasmin => fibrin into FDP's
(non-specific)
Urokinase - Indirectly - thrombolysis (non-specific)
tPA (Alteplase) - Clot specific thrombolytic - binds directly to clot via fibrin
Uses- AMI, Pulmonary embolism, Thrombosed Av shunt,Thrombosed
mechanical valve.
C/I Haemorrahge, CVA, Coagulation defects.
S/E hemorrhage stroke.
Dose tPA 0.2-0.5 mg/kg/hr 6-12 hrly.
STK MI 30000 U/kg over 1 hour
DVT/Pulmonary embolism 5000 U/kg for hr then 2000
U/kg/Hr
PTT > 5.
Lipid Lowering Drugs
Required when dietary management fails/CV drugs are not at fault/No other
ppt. disease present (Hypothyroidism, DM)
1) Bile acid sequestrant Cholestyramine
Moderate LDL elevation, Young men, and Premenopousal women.

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 Binds bile acids Increase Liver LDL receptors level Blood LDL
attaches to receptors Removes LD from blood.
S/E Constipation, Gastritis.
2) Nicotinic acid Inhibit secretion of lipoproteins from liver
Reduce LDL.
S/E - Flushing, Palpitation.
C/I - Peptic ulcer, Pregnancy.
3) Statins HMG CoA inhibitor
Less S/E, Reduces LDL.
Lovastatin, Atorvastatin.
Used as a single dose at night because cholesterol synthesis occurs
at night.
S/E Myopathy & renal failure.
4) Fibrates used for high triglyceride levels.
Lopid (Gemfibrozil)
C/I with statins- cause myopathy.
5) Probucol Lowers HDL & LDL cholesterol.
Increase excretion of cholesterol in bile.
Analgesics
Morphine sulfate (MSO4) (0.05 - 0.2 mg/kg initial dose)
Class: Opiate Analgesic
Half-life: 2-4 hours (4.5-13.3 hours in neonates)
Duration of action: 3-4 hours
Metabolism: by liver, excreted in urine and bile
Dosing Frequency: Q1-4 hours or as a continuous drip
Precautions: respiratory suppression with increasing doses, histamine
release, has caused seizures in neonates
Uses: post-operative pain control, sedation, tet spells, can also increase
cardiac output
Fentanyl (1-2mcg/kg per dose initially)
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 Class: opioid analgesic
Half-life: 2-4 hours
Duration of action: 1-2 hours
Metabolism: by liver, excreted by kidney (<10%)
Dosing Frequency: Q30min-1hour, continuous drip
Precautions: may cause chest wall rigidity in neonates at high doses.
Uses: Post-operative pain management, rapid tolerance develops,
may need to increase drip rate daily to maintain equianalgesic dose.

Sedatives
Midazolam (Versed) (0.05-0.1mg/kg initial dose)
Class: benzodiazepine
Half-life: 1-4 hours
Metabolism: extensively by liver (microsomally), excreted in urine, some
in feces
Dosing Frequency: Q1-2 hours, to continuous drip
Precautions: respiratory depression, when used alone in some patients
can produce paradoxical effect. Cimetidine can prolong half life when
used concomitantly
Uses: as anxiolytic/sedative in association with analgesic agents for
patients with severe pain, or in whom sedation is desired for various
reasons.
Lorazepam (Ativan) (0.03-0.09mg/kg/dose)
Class: benzodiazepine
Half-life: 10-12 hours (40 hours in neonates)
Metabolism: liver, excreted in urine
Dosing Frequency: Q4-8 hours
Precautions: as with Versed, longer acting so prolonged effect of
respiratory suppression

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 Uses: Sedative for patients who will need prolonged sedation. Can also be
used to help wean patients from Versed drips
Propofol (Diprivan) (25-50 mcg/kg/min drip, 0.5-1mg/kg bolus)
Class: sedative hypnotic
Half-life: minutes, increases with increasing duration of therapy
Metabolism: by liver excreted in urine
Dosing Frequency: Only used as continuous drip or short acting bolus
Precautions: severe myocardial depressant proportionate to dose. No
preservatives in solution so at high risk for infection unless aseptic
technique is adhered to, particularly for prolonged drips.
Uses: Insoluble in water so supplied in solution of 10% Intralipid. Used
for short term sedation when extra sedation is needed. Also used
overnight prior to extubation on patients who have had prolonged
sedation to allow decreasing other sedatives, rapid wean prior to
extubation. FDA does not approve use in pediatric patients for sedation
in the PICU
Paralytic Agents
Vecuronium (Norcuron) (0.1mg/kg, 0.2mg/kg for rapid sequence intubation)
Class: non-depolarizing neuromuscular blocker
Duration of action: 30-40 minutes
Metabolism: excreted primarily in bile, partially in urine
Dosing Frequency: Q1-2 hours prn to continuous drip
Precautions: must be prepared to manage airway or intubated prior to
use. Does not use without adequate sedation/pain control. Prolonged
administration can produce prolonged muscle weakness after stoppage
Uses: as a paralytic in patients who need prolonged mechanical
ventilation with significant lung disease, those with significant
pulmonary hypertension,
Pancuronium (Pavulon) (0.04-0.1mg/kg initially then 0.01mg/kg per dose as
needed)
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 Class: non-depolarizing neuromuscular blocker
Duration of action: 35-45 minutes
Metabolism: excreted mostly unchanged in urine, some metabolism by
liver and elimination in bile
Dosing Frequency: Q25-60minutes
Precautions: must be prepared to manage airway or intubated prior to
use. Do not use without adequate sedation/pain control.
Uses: as a paralytic in patients
Cisatracurium (Nimbex) (0.1mg/kg)
Class: non-depolarizing neuromuscular blocker
Duration of Action: 20-35 minutes, up to 45 minutes
Metabolism: rapid non-enzymatic degradation (Hofman elimination) in
bloodstream
Dosing Frequency: usually a continuous drip or prn
Precautions: Cis form minimizes Histamine release caused by
Atracurium
Uses: ideal as neuromuscular blocker in patient with compromised renal
and/or hepatic function
Calcium Chloride
Hyperkalemia, Hypocalcemia
Antidote for overdose of calcium channel blocker
8-16 mg/kg IV slowly
Not routinely used for cardiac arrest
Do not mix with sodium bicarbonate.
Magnesium sulfate
Cardiac arrest related to torsades de pointes or low serum magnesium
VF refractory to lidocaine & beryllium
Ventricular arrhythmias associated with digitalis toxicity or tricyclic overdose
Cardiac arrest -1-2 Gm IVP

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Acute myocardial infarction -1-2 Gm. diluted in 50-100 ml 5% dextrose in
water IV over 5-60 minutes; follow with 0.5-1.0 Gm/hour IV for up to 24 hours
Rapid IV administration may cause hypotension.
Use with caution in patient with renal disease.
May cause respiratory failure. Do not administer if patient has absent patellar
reflexes, respiratory depression, or oliguria.
Sodium Bicarbonate
Known preexisting hyperkalemia
Known preexisting bicarbonate-responsive acidosis
Over dosage of tricyclic antidepressants or aspirin
May be used in prolonged resuscitation with effective ventilation or upon
return of spontaneous circulation after long arrest
Initial dose: 1 mEq/kg IV bolus
Repeat half of initial dose every 10 minutes thereafter
ABG analysis of pH, pCO2, and base deficit is helpful in guiding bicarbonate
therapy.
Harmful in hypoxic lactic acidosis, i.e. cardiac arrest & CPR without
intubation/adequate ventilation.

Atropine
First-line therapy for symptomatic bradycardia
Second-line therapy for asystole or bradycardic pulseless electrical activity
(after epinepherine)
For asystole - 1 mg IVP; may repeat every 3 - 5 minutes to maximum dose of
0.03 - 0.04 mg/kg
For bradycardia - 0.05 - 1 mg IVP; may repeat every 3 - 5 minutes to maximum
dose of 0.03 - 0.04 mg/kg
Endotracheal administration - 2 - 3 mg diluted in 10 ml NS
Use cautiously in patients with myocardial ischemia and/or hypoxia; increases
myocardial oxygen demand.
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