Vasopressors used in operative room, ICU, and critical care set up. there dose, side effect and interaction.

1. DR AFTAB HUSSAIN

2.  Vasopressors VASO-vessels, PRESSORS- pressure.Increase
the blood vessel pressure thereby increasing blood pressure.
 Vasopressors are class of drugs that elevate Mean Arterial
Pressure (MAP) by inducing vasoconstriction.
 Many drugs have both vasopressor and inotropic effects.
 Vasopressors are indicated for a decrease of >30 mmHg from
baseline systolic blood pressure or MAP <60 mmHg, when
either condition results in end-organ dysfunction secondary to
hypoperfusion.

3.  NATURAL CATECHOLAMINES:
Epinephrine , Norepinephrine , Dopamine
 SYNTHETIC CATECHOLAMINES
Isoproterenol , Dobutamine

4.  INDIRECT ACTING:
Ephedrine, Mephentermine , Metarminol
 DIRECT ACTING:
Phenylephrine, Methoxamine

5.  Adrenergic receptors are divided into two general
categories- a and b receptors.
 They have various subtypes.
 a1 receptors – mostly postsynaptic, present in smooth
muscles throughout the body. Activation leads to
vasoconstriction, bronchconstriction, constriction of
sphinctors
 Most important cardiovascular effect is
vasoconstriction which increases peripheral vascular
resistance, left ventricular afterload and arterial blood
pressure.

6.  a2 receptors- mostly presynaptic, Central a2 receptors
cause sedation and anxiolysis.
 b1 receptors- Mostly cardiogenic, postsynaptic
membranes of heart, have positive chronotropic,
ionotropic and dromotropic effect.
 b2 receptors- Primarily postsynaptic on smooth and
gland cells. Relaxes smoooth muscles.
 b3 receptors- Gall bladder, brain and adipose tissue.
Pay role in thermogenesis and lipolysis of brown fat.
 Dopaminergic receptors- D1 and D2

8. Description and Pharmacology
 The function of dopamine as a neurotransmitter was
discovered in 1958 by ARVID CARLSSON.
 It was named dopamine because it was a monoamine,
and its synthetic precursor was 3,4-
dihydroxyphenylalanine .

9.  Dopamine is an endogenous catecholamine that serve
as both a neurotransmitter and a precursor of nor
epinephrine synthesis.
 When given as an exogenous drug dopamine activates a
variety of receptors in dose dependent manner.
 Regulates cardiac, vascular and endocrine function.

11. o Dopamine acts through D1 , D2 as well as adrenergic
alpha and b1 receptors ( But not b2)
o D1 and D2 receptors are the most abundant and
widespread in areas receiving a dopaminergic
innervation ( namely the striatum ,limbic system,
thalamus and hypothalamus) as are D2 receptors,
which also occur in the pituitry gland

12. Pharmacokinetics-
Onset – 5 mins
Duration of action- < 10 min
Metabolism- metabolized in liver, kidney and plasma by
monoamine oxidase and COMT.
Elimination- T ½- 2 min
Excretion – urine (80%)

13.  AT LOW DOSE (0.5 to 3 mic /kg /min
 Selectively activates dopamine specific receptors
in the renal and splanchnic circulation.
 Increase blood flow in these region.
 Low dose dopamine also directly affects renal
tubular epithelial cells.
 It causes an increase in urinary Na excretion

14.  INTERMEDIATE DOSE (3 to 10 mic /kg /min )
 It stimulates b1 receptors in the heart and peripheral
circulation.
 Increases myocardial contractility, increases heart rate and
peripheral vasodilatation
 It increases myocardial oxygen demand, so when ever
dopamine is to be used oxygen must be supplemented
 Over all increase in cardiac output
 Contractile response to dopamine is modest when
compared to dobutamine

15.  AT HIGH DOSE (> 10 mic /kg / min ):-
Dopamine produces a progressive activation of
alpha receptors in the systemic and pulmonary
circulation resulting in progressive pulmonary and
systemic vasoconstriction
This vassopressor effect is by virtue of increasing
ventricular afterload
 Dopamine not effective orally and does not cross
blood brain barrier in sufficient amounts to cause CNS
effects.

16. Clinical uses and Indications
 Dopamine is often used in situation where both cardiac
stimulation and peripheral vasoconstriction is desired
such as cardiogenic shock
 Also used to correct the hypotension in the septic shock
.But norepinephrine has become the preferred
vassopressor in this condition
 Low dose is often used in an attempt to prevent or
reverse acute renal failure

17.  Drug initially administered at a rate of 2 to 5 m/ kg /min
.During infusion,pt require clinical assessments of
myocardial function perfusion of vitals organs such as
the brain , and the production of urine
 Most pts should receive intensive care with monitoring
of arterial and venous pressures and ECG
 Reduction in urine flow ,tachycardia or the
development of arrhythmias may be indications to slow
or terminate the infusion

18.  The sympathomimetic amines dopamine is
potent ionotropic agents
 Used in pulmonary edema
 Forcefully contracts the heart and thus
decreases the pulmonary load

19.  Commercial preparation of dopamine are concentrated
drug solution [Containing 40 mg /80 mg dopamine
HCL /ml]
 Preparation must be diluted to prevent intense
vasoconstriction during drug infusion.
 Dopamine solution diluted in isotonic saline to
prepare the infusate. It can be prepared in NS,D5 but
not in RL and DNS.

20.  Weight based
 There are two recommended doses:-
 3 to 10 mic /kg /min is for augmenting cardiac
output thereby increasing BP
 More than 10 mic /kg /min is recommended to
increase the blood pressure directly

21.  Use 5 ml 2 ampoule / vials containing 40 mg /ml
dopamine HCL add to 500 ml isotonic saline [Final
concentration= 40mic /drop ]
Precaution-
 Before dopamine is administered to pt in shock
,hypovolemia should be corrected by transfusion of
whole blood , plasma or other appropriate fluid

22. Contraindications
 Pt receiving MAO inhibitors
 Tricyclic antidepressants agents
 Pheochromocytoma
 Uncorrected tachyarrhythmia
 Ventricular fibrillation

23. Adverse effects-
o Tachyarrhythmia's are the most common adverse
effects of dopamine
o Malignant tachyarrhythmia [ Multifocal ventricular
ectopic , ventricular tachycardia ]
o The most feared complication of dopamine infusion is
limb (Fingers /toes ) necrosis
o Extravasations of drug through a peripheral vein can
be treated with local injection of phentolamine [5 to 10
mg in 15 ml saline ]

24.  Ocular- Increases IOP.
 Hyperglycemia that is commonly present in pts
receiving a continuous infusion of dopamine is likely
to reflect drug induced inhibition of insulin secretion.
 Respiratory- Dyspnoea
 CNS- headache, anxiety

25.  Use in Pregnancy – Category C
 Lactation- Unknown whether drug is excreted in
breast milk. To be used with caution

26. Description and pharmacology
 Synthetic catchecholamine
Mechanism of action
 Primarily b1, mild b2.
 Dose dependent increase in stroke volume and cardiac
output, accompanied by decreased filling pressures.
 SVR may decrease, baroreceptor mediated in response to 
SV.
 BP may or may not change, depending on disease state.
 Favorable effect on myocardial oxygen balance is believed
to make dobutamine a choice for patients with CHF and
CAD.

27. Pharmacokinetics
 Onset- 1-10 min
 Duration -10 min
 Metabolism- tissues and liver by COMT
 Elimination- T ½- 2 min
Excretion- urine mainly
 Dose- Administered as infusion @ 2-20mcg/kg/min.

28. Indication and uses
 Useful in right and left heart failure.
 May be useful in septic shock.
Contraindication
 Pt receiving MAO inhibitors
 Tricyclic antidepressants agents
 Pheochromocytoma
 Patients having tachyarrythmias.

29. Adverse effects-
Tachyarrythmias
Hypertension
Eosinophillic myocarditis
Palpitation
Nausea ,headache
Use in Pregnancy- category B
Lactation- unknown whether it is excreted in milk or
not.

30. Description and Pharmacology
 Endogenous catchecholamine.
Mechanism of action
 b activity at very low doses, a at higher doses.
 Direct stimulation of b1 receptors of myocardium
raises blood pressure , cardiac output and even
myocardial O2 demand.
 a1 stimulation decrease splanchnic and renal blood
flow. Some effects on metabolic rate, inflammation.

31.  Onset- 5-10 min (SC) , 1 min (inhalational)
 Duration- 4 hrs
 Metabolism- enzymes (COMT) and monoamine
oxidase (MAO)
 Excretion- Urine

32. Indication and uses-
 In emergency(cardiac arrest and shock) administered in
IV dose of 0.05-1 mg. Continous infusion is given @
0.015m/kg/min.
 In Severe asthma and anaphylaxis epinephrine is uesd
in the dose of 100-500mcg.
 Also used to reduce bleeding from operative site.

33. Contraindications-
 Patient on MAOI
 Patient on anti arrythmic drugs like procainamide and
quinidine.
Adverse effects-
 Angina, arrythmias, palpitations.
 Anxiety, dizziness, flushing
 Sweating, tachycardia, resp. difficulty

34.  Ampules are available in conc of 1:1000
(1000mcg/ml).
 In paediatric patient conc of 1:100000 is used.
 Use in Pregnancy- category B
 Lactation- unknown if excreted in breast milk or not

35. Description and Pharmacology-
 It is also called as norepinephrine .
 The two structures differ only in that epinephrine has
a methyl group attached to its nitrogen, while the
methyl group is replaced by a hydrogen atom in
norepinephrine.
 It acts as transmitter at postganglionic sympathetic
sites.
 Norepinephrine is a catecholamine and a ethylamine.

36. • The prefix nor-, is derived from the German
abbreviation for "N ohne Radikal" (N, the symbol for
nitrogen, without radical) referring to the absence of
the methyl functional group at the nitrogen atom.

37. tyrosine
dihydroxyphenylalanine
dopamine
norepinephrine
epinephrine
tyrosine hydroxylase
L-aromatic amino acid decarboxylase
dopamine-B-hydroxylase

38.  Potent action-both a1 & b1 receptors
◦ Little action on b2
◦ Causes potent vasoconstriction (α) as well as a less
pronounced increase in cardiac output
◦ Lacks bronchodilating effect
◦ ↑ systolic, diastolic & MAP
 Causes Reflex bradycardia
 May decrease tissue blood flow leading to metabolic acidocis.

39. Absorption
 Orally ingested noradrenaline is destroyed in the GI tract
and the drug is poorly absorbed after subcutaneous
injection.
Onset- 1-2 min
Duration- 1-2 min
Metabolism- by COMT and MAO
Distribution
 Localises mainly in sympathetic nervous tissue.
 Crosses the placenta but not the blood-brain barrier.
Excretion- mainly urine (84-96%)

40.  Used to maintain BP in hypotensive states
 It causes rise in systolic ,diastolic and mean arterial
pressure
 Used as an adjunct to correct hemodynamic imbalances
in the treatment of shock that persists after adequate
fluid volume therapy
 First-line therapy for the maintenance of blood
pressure and tissue perfusion in septic shock.

41.  Adjunctive Treatment in Cardiac Arrest
 Infusions of noradrenaline are usually given during
cardiac arrest to restore and maintain an adequate blood
pressure after an effective heartbeat and ventilation
have been established by other means.
 Adjunctive to Local Anesthesia
 It is added to solutions of some local anesthetics to
decrease the rate of absorption thereby localizing
anaesthesia and prolonging the duration of action.

42.  The usual dose range is 0.01-0.1 m/kg/min
 Average adult maintenance dosage: 2–4 mcg/minute
 May require 8–30 mcg/minute in cases of refractory
shock
Dilution-
 Drug is diluted with 5% dextrose or dextrose
normal saline
 Should not be mixed with alkaline solution

43.  Noradrenaline should be administered through central
venous devices to minimize the risk of extravasation
and subsequent tissue necrosis
 The infusion should be at a control rate and the patient
should be monitored carefully for the duration of
noradrenaline (norepinephrine) therapy.
 The infusion must not be stopped suddenly but should
be gradually withdrawn to avoid disastrous falls in
blood pressure

44. Adverse effects-
 Hypertension , bradycardia, arrhythmias, palpitations
 ischemic injury due to potent vasoconstrictor action
may result in coldness and paleness in periphery.
 anxiety, insomnia,Confusion,Headaches,psychosis
 Weakness,Tremor
 anorexia, nausea and vomiting.

45. Extravasation effect and management
 The infusion site should be checked frequently for free
flow. Care should be taken to avoid extravasation of
noradrenaline into the tissues, as local necrosis might ensue
due to the vasoconstrictive action of the drug.
 If blanching occurs, the infusion site should be changed at
intervals to allow the effects of local vasoconstriction to
subside.
 To prevent sloughing and necrosis in areas in which
extravasation has taken place, the area should be infiltrated
as soon as possible with 10 ml to 15 ml of saline solution
containing 5 mg to 10 mg of phentolamine, an adrenergic
blocking agent.

46. Drug interaction-
 Non-selective MAO inhibitors
 selective MAO inhibitors
 Linezolid
 Thyroid hormones
 Cardiac glycosides
 Ergot alkaloids or oxytocin
All of these enhance the vasopressor and
vasoconstrictive effects.

47. Contraindications-
 Patient with pheochromocytoma
 Noradrenaline should also not be given to patients
with mesenteric or peripheral vascular thrombosis
(because of the risk of increasing ischaemia and
extending the area of infarction)

48.  Epinephrine >> norepinephrine – in terms of cardiac
stimulation leading to greater cardiac output (b
stimulation).
 Epinephrine < norepinephrine – in terms of
constriction of blood vessels – leading to increased
peripheral resistance – increased arterial pressure.
 Epinephrine >> norepinephrine – in terms of
increasing metabolism

49.  Maintaining adequate MAP ,hepatic blood flow and
oxygen exchange with dopamine required a consequent
increased cardiac output. Which was responsible for
increase global oxygen demand
 Dopamine also impairs hepatic energy balance.

50. Description and pharmacology-
It is synthetic, non catchecholamine and indirect acting.
Pharmacokinetics-
MECHANISM OF ACTION: Indirectly acting by
evoking release of endogenous neurotransmitter
norepinephrine from postganglionic sympathetic nerve
endings.
ONSET: 5-15min(IM),immediate(IV)
DURATION:4 hrs(IM),30 mins(IV)

51. Effect on CVS and other system-
 It raises BP by increasing Cardiac output and
peripheral vascular resistance.
 AV conduction and refractory period of AV node is
shortened with an increase in ventricular conduction
velocity.
 Effect becomes more prominent with atropine.

52.  It dilates arterioles in skeletal muscles and mesentric
vascular bed.
 Increases renal blood flow.
 No effect on bronchial muscle and respiration.
 May cause drowsiness or convulsions.
 Effect fades off with time due to tachyphylaxis.

53. Indication and use
• Hypotension during spinal anesthesia and GA
Hypotension, secondary to spinal anesthesia
(prophylaxis):
Intramuscular, 30 to 45 mg, administered ten to twenty
minutes prior to anesthesia.
(treatment):
Intravenous, 10-25 mg given as a single dose(In a 70 kg
adult) .
6mg iv bolus is in common practice. Dose can be
repeated according to response.

54. Drug interaction and contraindication-
 Severe HTN in patients on MAOIs.
 Risk of arrhythmias in patients on cardiac glycosides,
quinidine,tricyclic antidepressants ,halothane
 Hypersensitivity
 Loss of control of HTN in patients on adrenergic
neuron blocking agents(reserpine,methyldopa,
guanethedine).

55. Precautions:
• Cardiovascular disease
• Chronically ill patients
• Hemorrhagic shock
• Hyperthyroidism
Adverse effects:
CNS: anxiety, confusion, drowsiness, incoherence,
tremors.
CVS: hypertension, palpitations, tachydardia, AV blocks

56. It is a non catchecholamine , sympathomimetic drug similar to
epinephrine.
MECHANISM OF ACTION :
Alpha and b1 adrenergic agonist; indirect effects via
norepinephrine release.
Action leads to increase in blod pressure, cardiac output, heart
rate and contractility.

57. INDICATIONS:
 Hypotension due to anaesthesia and regional blocks.
However it is a temporary measure.
 Used orally for bronchial asthma and coryza
 Used as antiemetic.
 To treat diabetic neuropathic edema.
ADULT DOSE: 10 to 25mg iv in hypotension.
 3-6mg iv bolus is given.repeated according to patients
response.

58. Available as:
1ml ampoule containing 30mg/ml .
Adverse Effects:
•CVS: tachycardia, cardiac arrhythmias ,angina ,vasoconstriction
• anorexia, nausea
•difficulty in micturition in patients with BPH
•CNS: restlessness, confusion, insomnia, mild euphoria, agitation
•Respiratory: dyspnea, pulmonary edema
•Headache, tremor, hyperglycemic reactions .

59. Contraindications-
 Closed angle glaucoma
 Pheochromocytoma
 hypertrophic subaortic stenosis
 Thyrotoxicosis
Drug ineractions-
 Prolongs half life of dexamethasone
 Synergistic bronchodilation but increased adverse
effects with theophylline
 Increased vasoconstriction with oxytocin.
 Severe HTN with MAOI interaction may occur upto 2
wks after cessation of MAOIs therapy.

60.  Traditionally ephedrine has been the vasopressor of
choice in pregnant women.
 Ephedrine readily crosses the placenta,and stimulates
fetal metabolism by direct beta effects and also by
releasing catecholamines.
 Sympathectomy resulting from regional anaesthesia
shunts blood primarily into mesentric bed and alpha
agonists like phenylephrine selectively constricts the
mesentric bed than uteroplacental vasculature.
 Phenylephrine has faster onset , shorter duration of
action, better titrability and maintainance of fetal pH.

61. Description and pharmacology-
 It is Non adrenergic sympathomoimetic
 Also known as Anti diuretic hormone (ADH)
 Chemically it is made of peptide chains. Exogenous
prep of ADH
Mechanism of action-
 Vasoconstrictor without ionotropic or chronotropic
effects.
 Also stimulates smooth muscles in GI tract to cause
peristalsis.

62. Pharmacokinetics-
Absorption-
 Destroyed in GI tract. Administered parenteraly or
intranasaly.
 Onset- IM/SC 2-8 hr (antidiuretic activity)
IV- 30-60 min (pressor activity)
Metabolism-
Metabolism in liver and kidney, rapidly removed from
plasma
Elimination- T ½- 10-20 min
Excretion- urine (5-10%)

63. Indication and uses-
 Diabetes Insipidus 5-10 units IM/SC
 Adjunct in GI bleed and esophageal varices.
 New clinical indication is in pateints with septic shock
and cardiac arrest (40 IU in 40 ml) IV. (dose-0.01-0.04
unit/min IV)
 ACLS guidelines recommend Vasopressin in place of
epinephrine in pulseless arrest.

64. Contraindication-
 Hypersensitivity
 Chronic nephritis
 Pateints with polyuria.
 Use in Pregnancy- Category C
 Lactation- Unknown if secreted in milk or not.