School of Medical and Allied Sciences
Course Code : BPHT5003 Course Name: Pharmacology II

Drug Therapy for Shock

Name of the Faculty: Dr. Ashok Kumar Gupta Program Name: B. Pharm

Definition
• Shock is a physiologic state in which significant, systemic reduction in

tissue perfusion results in decreased tissue oxygen delivery.

• Can lead to irreversible cell and tissue injury ultimately resulting in:
• end-organ damage
• multi-system organ failure
• death

• Mortality from shock remains high:
• cardiogenic shock from AMI – 60-90%
• septic shock – 35-40%
• hypovolemic shock – varies depending on disease state

Physiologic Determinants

CO = HR * SV

CO = cardiac output
HR = heart rate
SV = stroke volume

Classification of Shock

• Hypovolemic

• Cardiogenic

• Distributive

Hypovolemic Shock

• Results from decreased preload

• Preload is one of the determinants of stroke volume

• When preload drops, cardiac output drops

Hypovolemic Shock

• Hemorrhage – examples include:
• Trauma
• GI bleed
• Ruptured aneurysm

• Fluid losses – examples include:
• Diarrhea
• Vomiting
• Burns
• Third spacing of fluid

Cardiogenic Shock
• Results from pump failure

• Manifested as decreased cardiac output

• Four broad categories (examples given):
• Cardiomyopathies

• Myocardial infarction

• Dilated cardiomyopathy

• Arrhythmias
• Both tachycardic and bradycardic

Cardiogenic Shock

• Mechanical
• Valvular stenoses or insufficiencies

• Obstructive/extracardiac
• Pulmonary embolism

• Tension pneumothorax

• Pericardial tamponade

Distributive Shock

• Also referred to as vasodilatory shock

• Results from a severe decrease in SVR

• Examples include:
• septic shock

• systemic inflammatory response syndrome (SIRS)

• anaphylaxis

• neurogenic shock

Shock States

Physiologic  Preload Pump Function Afterload Tissue Perfusion
Variable 
Clinical  PCWP CO SVR SvO2

Measurement
Hypovolemic    

Cardiogenic    

Distributive  or ↔   

Common Features of Shock

• Hypotension

• Cool, clammy skin

• Oliguria

• Altered mental status

• Metabolic acidosis

Evaluation of the Patient in Shock
• Primary
• History
• Physical Examination
• Laboratory
• Radiographic

• Secondary
• pulmonary artery catheterization
• echocardiography

Management in Shock

• Shock is an emergency state:
• initial focus is on ABC’s of resuscitation

• airway, breathing, circulation

• Adequate venous access
• central venous access not always required, but often necessary

• Optimization of volume status

• Identification of cause of shock and directed therapy

Management of Hypovolemic Shock

• Volume replacement key for all causes of hypovolemic shock
• nonhemorrhagic: crystalloid fluid replacement

• hemorrhagic: crystalloid fluid replacement and blood product replacement

• Directed therapy to correct the cause of hypovolemic shock

Management of Cardiogenic Shock

• PA catheter commonly used

• vasopressor support (specific discussion later) often needed

• may need intra-aortic balloon pump

• hypotension may or may not be present

• identification of type of cardiogenic shock critical for optimal management

Management of Cardiogenic Shock

• Myocardial infarction
• most common cause of cardiogenic shock
• directed therapy for MI

• aspirin, heparin, glycoprotein IIb/IIIa inhibitors, revascularization

• Pulmonary embolism
• most common cause of obstructive shock
• avenues available to rapidly resolve clot burden

• thrombolysis, interventional radiology directed clot extraction, surgical embolectomy

Management of Distributive Shock

• Identification of cause and directed therapy
• e.g. Addisionian crisis – steroid replacement

• Septic shock
• most common form of distributive (vasodilatory) shock

• early and aggressive fluid replacement is important and often underutilized

• vasopressor support often required

Septic shock (continued)

• identification of infectious site/source and guided therapy (antibiotics and
drainage)

• steroid replacement with concomitant relative adrenal insufficiency

• optimal glucose control

• recombinant human activated protein C

• attention to support of each organ system

Pharmacological management of Shock

• Goals:
• Increase CO to restore normal hemodynamics
• Increase blood pressure and redistribute blood flow to vital organs (brain).

• Pharmacological agents used depend on clinical and physiological
parameters of shock and type of shock.
• Agents used are primarily adrenergic receptor agonists

Physiological actions of adrenergic receptors
Receptor type Receptor action (relative to hemodynamics)

α1 Arterial vasoconstriction
Increased myocardial contractility (minor)

α2 Constriction of venous capacitance (major)
Feedback inhibition of norepinephrine release at sympathetic fibers

β1 Increased myocardial contractility (inotropy)
Increased heart rate (chronotropy)

β2 Relaxation of vascular smooth muscle (skeletal muscle)
(Relaxation of bronchial smooth muscle)

D1 Relaxation of splanchnic vascular smooth muscle
Relaxation of renal vascular smooth muscle

D2 Inhibition of norephinephrine uptake at sympathetic fibers

Receptor pharmacology
Activity at receptors

α β1 β2 D

Dopamine ++/+++ ++++ ++ ++++

Dobutamine + ++++ ++ 0

Epinephrine ++++ ++++ +++ 0

Isoproteronol 0 +++ +++ 0

Norepinephrine +++ +++ + 0

Phenylephrine ++/+++ 0 0 0

Dopamine
• Pharmacodynamics
• Low and moderate doses – primarily binds dopaminergic and β1 receptors
• Higher doses – α1 receptors stimulated

• Clinical effects
• Increase heart rate (chronotropy) and contractility (inotropy)
• Increase SVR by arteriolar vasoconstriction (higher doses).

Contd….

• Clinical application
• Most commonly used vasopressor

• common starting dose – 5 μg/kg/min
• Cardiogenic or distributive shock (shock of any etiology)

• Adverse effects
• Tachyarrhythmias, excessive tachycardia
• Precipitate myocardial ischemia
• Excessive vasoconstriction (digital ischemia)
• Nausea and vomiting (central effects)

Contd….

• Pharmocodynamics
• Primarily stimulates β1 receptors
• Lesser binding to β2 and α receptors

• Clinical effects
• Increase CO (primarily inotropic effect)
• SVR without significant change or a decline
• Starting dose – 2-5 μg/kg/min

Dobutamine
• Clinical application
• Cardiogenic shock and congestive heart failure

• Common starting dose – 2-5 μg/kg/min
• Sometimes used in distributive shock (when CO is normal or low which can

occur in septic shock)

• Adverse effects
• Tachycardia and tachyarrhythmias
• Myocardial ischemia

Epinephrine
• Pharmacodynamics
• Extremely potent, high affinity binding of all α and β receptors.

• Clinical effects
• Increase CO
• Increase SVR by vasoconstriction

• High doses cause prominent vasoconstriction

Contd….
• Clinical applications
• Refractory shock of all types – starting at 0.2 μg/kg/min
• Cardiopulmonary resuscitation – 1 mg IV push
• Anaphylaxis – 0.2-0.5 ml of 1:1000 dilution subcutaneously

• Adverse effects
• Excessive vasoconstriction
• Tachycardia and tachyarrhythmias
• Myocardial ischemia
• Hyperglycemia

Isoproteronol
• Pharmacodynamics
• β1 and β2 receptor agonist
• No α effects

• Clinical effects
• Increased CO
• Decreased SVR
• Variable effect on blood pressure

Contd….
• Clinical application
• Not useful for shock because of prominent β2 effect and lack of α – may

decrease MAP
• Rare uses to increase heart rate (as in Torsade de Pointes)

Norepinephrine
• Pharmacodynamics
• β1, α1, α2 receptor agonist
• Low doses (< 0.03 μg/kg/min) have prominent β1 effect
• Higher doses (> 0.06 μg/kg/min) stimulate α receptors

• Clinical effects
• Increase CO
• Increase SVR

Contd….
• Clinical applications
• Distributive shock
• Profound, refractory shock of any type

• Adverse effects
• Excessive vasoconstriction
• Arrhythmia
• Myocardial ischemia

Phenylephrine
• Pharmacodynamics
• α1 and α2 receptor agonist
• Lacks β effect

• Clinical effects
• Increased SVR
• Starting dose – 30 μg/min

Contd….
• Clinical application
• Distributive shock (especially if very high heart rate or history of

tachyarrhythmia)
• Less commonly used than norepinephrine

• Adverse effects
• Excessive vasoconstriction
• Reflex bradycardia

Nonadrenergic Vasopressors and Inotropes

• Vasopressin
• antidiuretic hormone (ADH) analoge

• can be used as a second line pressor agent

• recent studies suggest a relative deficiency of ADH in sepsis

• often added at a fixed rate of 0.04 units/min

Contd…

• Phosphodiesterase inhibitors
• amrinone and milrinone

• have inotropic and vasodilatory actions

• effects are similar to dobutamine

• used in cardiac failure

References
1. Tripathi  KD.  ‘Essentials  of  Medical  Pharmacology’,  6th  edition,  Jaypee  Brothers 

Medical publications (P) Ltd., New Delhi, 2003.

2. Dale M M,  Rang  H  P,  and  Dale M M.  Rang  &  Dale’s  Pharmacology’,  7th  edition. 
Edinburgh: Churchill Livingstone, 2007.

3. Guyton, A. C.  and Hall,  J.  E.  2006. Textbook  of Medical  Physiology.  11th Edition. 
Saunders, Philadelphia.