Drugs for the Treatment of Hypotension and Shock
SHOCK
– a condition of acute peripheral circulatory failure.
– It can result from the loss of circulating fluid.
• Therapy is aimed at correcting the hypoperfusion of vital organs.
• Hypovolemic shock is treated by volume replacement;
• bacteremic shock by intensive antibiotic therapy, corticosteroids, and
volume replacement.
• In addition, sympathomimetic drugs or vasodilators (which either increase
cardiac output, or alter peripheral resistance, or both) may be
appropriate.
Tissue Perfusion of organs during hypotension and shock
Heart and Brain
• The major factor regulating blood flow through the coronary and
cerebral vessels is the mean diastolic pressure.
• In the presence of hypotension, myocardial and cerebral perfusion
are compromised.
• In this situation, a sympathomimetic drug that increases blood
pressure will improve the perfusion of both the heart and brain.
• Sympathomimetics can be used without concern of constricting
the blood vessels in these organs.
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• The caliber of these vessels is determined by the metabolic
needs of the tissue, not by stimulation of adrenergic receptors.
• The heart and brain differ from each other with respect to their
need for oxygen.
• Although the heart normally uses an aerobic metabolic
pathway, it can operate for a short time anaerobically.
• The brain needs oxygen for its metabolism and is particularly
susceptible to the consequences of acute hypotension and
shock.
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Kidney
• Unlike the heart and brain, the kidney extracts only a small
amount of the oxygen provided to it under resting conditions.
• This means it can withstand, within limits, a reduction in
blood flow by extracting a higher percentage of the oxygen
supplied.
• However, sympathetic stimulation causes renal
vasoconstriction. Adrenergic vasoconstrictors also reduce
blood flow, possibly leading to renal ischemia.
Types of Shock
• There are 3 general categories of shock based on the circulatory
mechanisms involved.
• These mechanisms are intravascular volume, the ability of the heart to
pump, and vascular tone.
A. Hypovolemic shock involves a loss of intravascular fluid volume that may
be due to actual blood loss or relative loss from fluid shifts within the
body.
B. Cardiogenic shock, also called pump failure, occurs when the myocardium
has lost its ability to contract efficiently and maintain an adequate cardiac
output.
C. Distributive or vasogenic shock is characterized by severe, generalized
vasodilation, which results in severe hypotension and impairment of blood
flow.
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• Distributive shock is further divided into anaphylactic, neurogenic, and
septic shock.
I. Anaphylactic shock: results from a hypersensitivity (allergic) reaction
to drugs or other substances.
II. Neurogenic shock:
o results from inadequate (SNS) stimulation.
o The SNS normally maintains sufficient vascular tone (ie, a small
amount of vasoconstriction) to support adequate blood circulation.
o Neurogenic shock may occur with depression of the vasomotor
center in the brain or decreased sympathetic outflow to blood
vessels.
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III. Septic shock
o can result from almost any organism that gains
access to the bloodstream but is most often
associated with gram-negative and gram-positive
bacterial infections and fungi.
• It is important to know the etiology of shock because
management varies among the types.
ANTI SHOCK DRUGS
• Drugs used in mgt. of shock are primarily the adrenergic drugs.
• Drugs with alpha-adrenergic activity (eg, norepinephrine, phenylephrine)
are used to increase PVR and raise BP.
• Drugs with beta-adrenergic activity (eg, dobutamine, isoproterenol) are
used to increase myocardial contractility and heart rate, which in turn
raises BP.
• Some drugs have both alpha- and beta-adrenergic activity (eg, dopamine,
epinephrine).
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• In many cases, a combination of drugs is used, depending on the type of
shock and the client’s response to treatment.
• In an emergency, the drugs may be used to maintain adequate perfusion
of vital organs until sufficient fluid volume is replaced and circulation is
restored.
• Adrenergic drugs with beta activity may be relatively contraindicated in
shock states precipitated or complicated by cardiac dysrhythmias.
• Beta-stimulating drugs also should be used cautiously in cardiogenic shock
after myocardial infarction
– because increased contractility and heart rate will increase myocardial
oxygen consumption and extend the area of infarction.
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• Sympathomimetics are used to improve tissue perfusion. They
stimulate:
– α1-receptors, to increase venous return and
peripheral resistance;
– β1-receptors, to increase heart rate and cardiac
output (if venous return is adequate); or
– dopamine receptors, to dilate the renal and
splanchnic beds.
Epinephrine (Adrenaline)
• Epinephrine stimulates β1-receptors in the heart to increase both heart rate
and force of contraction.
• In small doses, epinephrine stimulates β2-receptors on arterioles
(precapillary resistance vessels) in skeletal muscles to decrease peripheral
resistance, and α1-receptors on veins to increase venous return.
• Larger doses of epinephrine stimulate α1-receptors on arterioles
throughout the body to produce a generalized vasoconstriction and an
increase in peripheral resistance.
• Epinephrine also dilates bronchioles.
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used to manage other kinds of shock & is usually given by
continuous IV infusion.
However, bolus doses may be given in emergencies, such as
cardiac arrest.
• It may produce excessive cardiac stimulation, ventricular
dysrhythmias, and reduced renal blood flow.
• half-life of about 2 minutes and is rapidly inactivated to
metabolites, which are then excreted by the kidneys.
2. Levarterenol (Norepinephrine and Noradrenaline
• Levarterenol stimulates α1-receptors, constricting both
capacitance and precapillary resistance vessels (veins and
arterioles).
• The resulting increase in BP activates the carotid sinus and
aortic arch pressor receptors to reflexly stimulate the vagus
nerve.
• The result is a fall in heart rate and cardiac output.
Uses and Adverse Effects
• for the maintenance of BP in acute hypotensive states, surgical
and nonsurgical trauma, central vasomotor depression, and
hemorrhage.
• It is useful in cardiogenic and septic shock, but reduced renal
blood flow limits its prolonged use.
• used mainly with clients who are unresponsive to dopamine or
dobutamine.
• As with all drugs used to manage shock, BP should be monitored
frequently during infusion.
3. Dopamine
• Acts directly by stimulating α, β,or dopaminergic receptors, depending on
the dose being used.
• acts indirectly by releasing NE from sympathetic nerve endings and the
adrenal glands.
• Peripheral dopamine receptors are located in splanchnic and renal vascular
beds.
• At low doses (0.5 to 10 mcg/kg/min), dopamine selectively stimulates
dopaminergic receptors that may increase renal blood flow and GFR.
• At doses greater than 3 mcg/kg/min, dopamine binds to beta and alpha
receptors.
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• At doses that stimulate beta receptors (3 to 20 mcg/kg/min),
there is an increase in HR, myocardial contractility, and BP.
• At the highest doses (20 to 50 mcg/kg/min), beta activity remains,
but increasing alpha stimulation (vasoconstriction) may overcome
its actions.
• Dopamine is useful in hypovolemic and cardiogenic shock.
• Adequate fluid therapy is necessary for the maximal pressor
effect of dopamine.
• Acidosis decreases the effectiveness of dopamine.
4. Dobutamine
• a synthetic catecholamine developed to provide less vascular
activity than dopamine.
• It acts mainly on beta1 receptors in the heart to increase the force
of myocardial contraction with a minimal increase in heart rate.
• It is less likely to cause tachycardia, dysrhythmias, and increased
myocardial oxygen demand than dopamine and isoproterenol.
• useful in cases of shock that require increased cardiac output
without the need for blood pressure support & recommended for
short-term use only.
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• used with dopamine to augment the beta1 activity that is
sometimes overridden by alpha effects when dopamine is used
alone at doses greater than 10 mcg/kg/min.
• has a short plasma half-life and therefore must be administered
by continuous IV infusion.
• A loading dose is not required because the drug has a rapid
onset of action and reaches steady state within approximately
10 minutes after the infusion is begun.
• It is rapidly metabolized to inactive metabolites.
Isoproterenol
• acts exclusively on beta receptors to increase HR, myocardial
contractility, and systolic BP.
• However, it also stimulates vascular β2 receptors, which causes
vasodilation, and may decrease diastolic BP.
• Hence , isoproterenol has limited usefulness as a pressor agent.
• It also may increase myocardial oxygen consumption and decrease
coronary artery blood flow, which in turn causes myocardial ischemia.
• Cardiac dysrhythmias may result from excessive beta stimulation.
• Because of these limitations, use of isoproterenol is limited to shock
associated with slow heart rates and myocardial depression.
Metaraminol
• used mainly for hypotension associated with spinal anesthesia.
• It acts indirectly by releasing NEP from sympathetic nerve endings. Thus,
its vasoconstrictive actions are similar to those of norepinephrine, except
that metaraminol is less potent and has a longer duration of action.
Milrinone
• It is also used to manage cardiogenic shock in combination with other
inotropic agents or vasopressors.
• It increases CO and decreases systemic vascular resistance without
significantly increasing heart rate or myocardial oxygen consumption.
• The increased CO improves renal blood flow, which then leads to
increased urine output, decreased circulating blood volume, and
decreased cardiac workload.
Phenylephrine (Neo-Synephrine)
• It is a drug that stimulates α-adrenergic receptors.
• As a result, it constricts arterioles and raises systolic and
diastolic blood pressures.
• Phenylephrine resembles epinephrine but has fewer cardiac
effects and a longer duration of action.
• Reduction of renal and mesenteric blood flow limit prolonged
use.
