The Official Newsletter of the California Poison Control System
Volume 3, Number 3.
Fall 2005

Poisoning-related Hypotension



Hypotension is a frequently encountered problem in patients with poisoning or drug overdose.  Toxicological causes of hypotension are usually due to a drugís or toxinís ability to induce one or more of the following: decrease cardiac contractility; decrease peripheral vasculature resistance; decrease intravascular volume; or depress the central nervous system.  Yet, determining the specific cause of hypotension is often complex as its medical differential is vast.  While medications are commonly implicated as a direct cause of hypotension, a fall in blood pressure may be associated with other coexisting medical conditions.  An understanding of the pharmacologic effects of drugs and knowledge of the patientís underlying medical conditions are crucial for the effective management of hypotension.


Hypotension is frequently seen in the overdose population.  During 2004, hypotension was present in over 20% of all cases reported to poison centers across California.  In 2003, the American Association of Poison Control Centers (AAPCC) reported 12,710 cases of hypotension associated with tricyclic antidepressant poisoning; 15,350 cases from beta-receptor antagonist poisoning; 9,650 cases from calcium antagonist poisoning; and 2,850 cases from cardiac glycoside intoxication.


Case presentation

A 46 year-old man with a history of diabetes, hypertension, and ethanol abuse was brought to the emergency department after being found with decreased responsiveness.   He had become increasingly despondent after losing his job.  His medications were unknown.  His blood pressure was 85/62 mm Hg, and the heart rate was 55 beats/min.  The blood glucose was elevated at 250 mg/dL without evidence of ketoacidosis.  He had an ethanol level of 180 mg/dL. An electrocardiogram showed sinus bradycardia but no evidence of ischemia.  Intravenous fluids (2 liters of normal saline) were administered without improvement.  Because a suicide attempt by drug ingestion was suspected, an intravenous glucagon bolus of 5 mg was given.  There was no response in blood pressure after the initial bolus.  After a second 5 mg glucagon bolus, the patientís blood pressure improved to 110/73 mm Hg and the heart rate increased to 74 beats/min.  A glucagon infusion was not required.  No calcium was given due to the patientís response to glucagon.  The patient was admitted to the ICU and monitored, and had no further episodes of bradycardia or hypotension.  Cardiac workup revealed no evidence of acute coronary syndrome.  No vasopressor therapy was given.  The patient was discharged to a psychiatric facility three days later.




1)                What is the likely diagnosis in this case?

2)                What are the various mechanisms of drug-induced hypotension?

3)                What is the approach to the diagnosis of drug-associated hypotension?

4)                What is the treatment for drug-associated hypotension?



Hypotension is conventionally defined as a systolic blood pressure less than 90 mm Hg in adults (with normal parameters adjusted in children depending on age and weight).  Blood pressure, an important clinical marker of tissue perfusion, is a reflection of cardiac output (determined by cardiac contractility and heart rate), systemic vascular resistance, and intravascular volume.  It is maintained through a coordinated response of cardiac contractility (increased via calcium receptors), heart rate (increased via beta-1 receptors), and peripheral vascular resistance (increased via alpha-1 receptors and decreased via beta-2 receptors).  A change in one parameter often results in a compensatory response of another in an effort to maintain a normal blood pressure.


Disruption of this coordinated process may result in hypotension.  Multiple drugs are capable of producing this effect.  Cardiac contractility is reduced by calcium-antagonist activity.   Decreased heart rate occurs with beta receptor antagonists, calcium channel antagonists, and digoxin.  While vasodilatation commonly occurs by excessive alpha-1 receptor antagonism (e.g., tricyclic antidepressants, trazodone, several antipsychotic drugs), it may also occur as a result of increased beta-2 receptor stimulation (e.g., albuterol, theophylline).  Generalized sympathetic system depressants (e.g., clonidine) cause a reduction in heart rate, blood pressure, and vascular resistance.  Drugs or poisons that are associated with significant volume loss from vomiting or diarrhea may also cause decreased blood pressure, usually accompanied by reflex tachycardia.  Additionally, any drug that causes prolonged obtundation or coma puts the patient at risk for hypothermia (due to exposure), or dehydration (due to insensible water loss), which may contribute to hypotension.



Common medical causes of hypotension such as hypovolemia (due to dehydration or blood loss), sepsis, acute coronary syndrome, dysrhythmias, and neurological injury should be considered when evaluating a patient with hypotension.  When the history is unclear but a suspicion for drug overdose exists, the patientís past medical history may provide clues to suspected medications.  For instance, a patient with atrial fibrillation may have access to digoxin, calcium channel antagonists, or beta receptor antagonists, while a patient with a psychiatric history may have access to tricyclic antidepressants, antipsychotics or benzodiazepines. 


The patientís heart rate may be helpful in considering potentially involved medications.  Hypotension resulting from vasodilatation (e.g., alpha-1 receptor antagonists, nitrites) or fluid loss (e.g., diarrhea or vomiting from colchicine, iron, certain species of mushrooms) is usually accompanied by compensatory tachycardia.  In contrast, hypotension induced by sympatholytic agents (e.g., clonidine, opioids, sedative-hypnotic agents) or cardiac conduction delay (e.g., beta receptor antagonists, calcium channel antagonists, digoxin) is more likely to be accompanied by a relative bradycardia.  Some drugs have multiple pharmacologic properties and produce unpredictable cardiovascular toxicity. For example, tricyclic antidepressants cause vasodilatation due to alpha antagonist effects, tachycardia due to antimuscarinic (anticholinergic) effects, and cardiac depressant effects owing to sodium channel blockade and norepinephrine depletion.



Initial empiric treatment with intravenous fluids is effective in most hypotensive patients and should be administered unless there is obvious fluid overload.  Virtually every hypotensive adult should therefore receive 2 liters of normal saline (20 mL/kg in children).  Temperature abnormalities should be corrected, and dysrhythmias addressed as indicated.  If these measures are not effective, consider the use of a hemodynamic drug.  Hemodynamic drug therapy is best selected based on the mechanism that addresses the suspected mechanism of hypotension. 


While hemodynamic drugs are commonly referred to as Ďvasopressorsí, they often have combined inotropic and chronotropic properties as well.  Dopamine, a common first line agent, derives its vasopressor effects by stimulating catecholamine receptors on the heart and blood vessels.  Its effects include stimulating alpha-1 receptors on peripheral blood vessels resulting in increased vascular resistance, and beta-1 receptors on the heart resulting in increased cardiac output.  At low doses, dopamine does this by the indirect mechanism of facilitating the release of catecholamines from presynaptic nerve terminals in the body.  At higher doses, dopamine can directly and nonspecifically stimulate catecholamine receptors.  Because of these mechanisms, low doses of dopamine may be ineffective if catecholamine reuptake pumps on nerve cells are blocked by drugs like cocaine or certain antidepressants.  In addition, at higher dose infusions of dopamine for poisonings of agents such as tricyclic antidepressant and phenothiazines that can cause alpha-1 receptor blockade on blood vessels, an improvement in blood pressure may not be seen due to preferential beta-2 receptor stimulation in certain vascular beds.  Norepinephrine is primarily an alpha-1 receptor agonist that increases blood pressure by peripheral vasoconstriction (it also stimulates only beta-1 receptors of the heart that can improve cardiac output).  Norepinephrine is devoid of beta-2 receptor effects and may be a more effective vasopressor in some poisonings for this reason. 


Vasopressin (by direct stimulation of smooth muscle receptors) and phenylephrine (by stimulation of alpha-1 receptors) increases blood pressure by increasing peripheral vasoconstriction.  As such, these drugs are more appropriately referred to as Ďvasopressorsí and are good choices for refractory hypotension due to vasodilatation.


When poisoning by a particular drug is suspected, specific antidotes should be considered:

1)                Sodium bicarbonate (1-2 mEq/kg initial bolus) for tricyclic antidepressants or other sodium channel-blocking agents such as quinidine, procainamide, phenothiazines, diphenhydramine, propranolol or cocaine --  overcomes sodium channel blockade primarily but also creates an alkalotic environment for enhanced reactivity of sodium channels.

2)                Glucagon (5-10 mg initial bolus) for beta receptor antagonist toxicity -- bypasses beta receptors and increases reactivity of sodium channels.

3)                Calcium (1-2 g initial bolus) for calcium channel antagonist toxicity.  Higher doses may be needed, and up

to 5-10 gm have been used in some cases.

4)                Digoxin-specific antibodies (Digibind, DigiFab) for digoxin toxicity.

5)                A beta receptor antagonist (e.g., esmolol, propranolol) may be paradoxically useful for poisoning by a

beta-2 agonist such as albuterol, theophylline, or caffeine (all of these can cause hypotension due to beta-2-mediated vasodilation, and even a small dose of beta receptor antagonist is usually effective in normalizing blood pressure).


A table of common drugs and toxins that cause hypotension, their effects, and treatment options is provided below.




Mechanism:                                                                          Treatment:


          Dysrhythmia or decreased heart rate

                Beta blockers                                                      Glucagon

                Calcium channel blockers                                      Calcium

                Digoxin                                                              Digoxin-specific Ab


        Decreased cardiac contractility

                Beta blockers                                                      Glucagon

                Calcium channel blockers                                      Calcium

                Tricyclic antidepressants                                      Sodium bicarbonate


        Sympatholytic agents

                alpha-2 adrenergic agonists (clonidine, methyldopa) Supportive

                Opiates                                                             Naloxone*



                Benzodiazepines                                                 Flumazenil*

                Hypothermia                                                       Rewarming






Mechanism:                                                                           Treatment:


        Dysrthymia or increased heart rate

                Digoxin                                                              Digoxin-specific Ab

                Anti-dysrhythmic agents                                       Supportive 


        Fluid loss or ďthird-spacingĒ

                GI or liver toxic mushrooms                                  Supportive

                Colchicine                                                          Supportive

                Diuretics                                                            Supportive

                Iron                                                                   Deferoxamine

                   Rattlesnake envenomation                                   Antivenom


        Peripheral vasodilatation

                Atypical anti-depressants (mirtazapine, trazodone)  Supportive

                Anti-psychotics (clozapine, olanzapine, quetiapine,  Supportive


                alpha-1 antagonist (doxazosin, prazosin)                Supportive

                beta-2 agonists (albuterol)                                   beta-receptor antagonist

                Caffeine                                                             beta-receptor antagonist

                Calcium channel antagonist                                  Calcium

                Hyperthermia                                                      Evaporative cooling

                Nitrites                                                              Supportive

                Nitroprusside                                                      Supportive

                Theophylline                                                       beta-receptor antagonist

                Tricyclic antidepressants                                      Supportive (Sodium

                                                                                        bicarbonate for contractility)


- Supportive care should be initiated in all cases.

* Use caution when using certain agents to avoid withdrawal or seizures.



Discussion of case questions and key points

1)                The likely diagnosis in this case is beta receptor antagonist overdose.  Although there is no direct history of beta receptor antagonist involvement, bradycardia in the face of hypotension suggests a sympatholytic or conduction-blocking mechanism.  The patientís history of hypertension suggests that he was taking a beta antagonist, a calcium channel antagonist, or clonidine, but the response to glucagon points toward beta antagonist ingestion.  Other pathologies such as ketoacidosis, acute coronary syndrome, or sepsis should also be considered in this patient.

2)                Since blood pressure is a function of systemic vascular resistance, heart rate, and cardiac contractility, a decrease in any of these factors may result in hypotension.  Hypovolemia is another major cause.  Hypovolemia is commonly associated with drug ingestions, for several reasons. First, patients with altered level of consciousness are unable to ingest liquids and become dehydrated due to insensible water losses. Second, some drugs and poisons cause vomiting and diarrhea, leading to volume loss. Third, many drugs reduce vascular tone, leading to decreased preload and a ďrelativeĒ hypovolemia.

3)                A thorough examination and history of the patientís presentation and past medical history may lead the physician to suspect medications that could potentially be involved.  A key diagnostic sign is the patientís heart rate, with tachycardia pointing to dehydration or vasodilating drugs and relative bradycardia increasing the suspicion for sympatholytic agents or agents causing conduction blockade.

4)                Intravenous fluid administration should be initiated, followed by vasopressors or chronotropes/inotropes if needed.  If the involvement of a particular toxin or medication is suspected or known, its specific antidote should be considered. 


Consultation assistance

Consultation with a specialist in poison information or with a medical toxicologist can be obtained free of charge by calling the California Poison Control System at 1-800-411-8080.

This issue of CALL US... was written by Lisa Wu, M.D., Medical Toxicology Fellow, Department of Clinical Pharmacology & Experimental Therapeutics, University of California San Francisco, San Francisco, CA.

CALL US... is published by the California Poison Control System. Editorial Board: Executive Director, Stuart E. Heard, PharmD; CPCS Medical Directors Timothy E. Albertson, MD, Richard F. Clark, MD, Richard Geller, MD, Kent R. Olson, MD; CPCS Managing Directors Judith Alsop, PharmD, Thomas E. Kearney, PharmD, Lee Cantrell, PharmD. Managing Editor: Richard F. Clark, MD.

The California Poison Control System is operated by the School of Pharmacy, University of California, San Francisco.


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