History

Fact Explanation
Drowsiness Occurs due to brain H1-receptor blockage. This is the most common presentation[1][2][3][5]
Dizziness Is a presentation due to brain H1-receptor blockage[1][2][3]
Somnolence Occurs due to brain H1-receptor blockage[3][4]
Inability to concentrate Occurs also due to brain H1-receptor blockage[2][3][5]
Agitation Occurs due to brain H1-receptor blockage and /or anticholinergic/antimuscarinic effect seen in some antihistamine drugs[1][2][3]
Incoordination Is a presentation in some patients with antihistamine poisoning[1][2]
Dry mouth Occurs due to the anticholinergic/antimuscarinic effect of antihistamines[1][2][3][5]
Blurred vision Occurs due to the anticholinergic/antimuscarinic effect[1][2][3][5]
Difficulty passing urine Occurs due to the peripheral anticholinergic/antimuscarinic effect[1][2][3][5]
Nervousness Occurs also due to brain H1-receptor blockage[2][3]
Hallucinations Is present in some patients with antihistamine poisoning. These occur mainly due to anticholinergic actions at muscarinic receptors [1][3][5]
Insomnia Somnolence caused by first generation antihistamines interfere with the natural circadian sleep-wake cycle leading to insomnia in some patients[3]
Tremor Is present in some patients. This occurs due to antimuscarinic effect on the central nervous system of some antihistamines[1][2]
Convulsions/seizures Occurs also due to brain H1-receptor blockage and anticholinergic actions at muscarinic receptors[1][2][3][5]
Constipation Occurs due to the anticholinergic/antimuscarinic effect seen in some antihistamine drugs, but some patients may develop diarrhea[3]
Difficulty swallowing Occurs due to antimuscarinic blockage[1]
Difficulty breathing Respiratory depression is seen in severe antihistamine poisoning[2][3]
Dystonic reactions These are extrapyramidal side effects that result due to antidopaminergic action of some antihistamines. These include oculogyric crisis (i.e.deviation of eyes in all directions), involuntary protrusion of tongue,trismus, difficulty in speaking, facial grimacing, torticollis etc. that result from involuntary contraction of muscles[3][6]
References
  1. SCHARMAN JE, ERDMAN AR, WAX PM, CHYKA PA, CARAVATI EM, NELSON LS, MANOGUERRA AS, CHRISTIANSON G, OLSON KR, WOOLF AD, KEYES DC, BOOZE LL, TROUTMAN WG. Diphenhydramine and Dimenhydrinate Poisoning: an Evidence-Based Consensus Guideline for Out-of-Hospital Management.Clinical Toxicology [online] 44:205–223, 2006. [viewed on 3 June 2014] Available from: http://www.researchgate.net/publication/7032484_Diphenhydramine_and_dimenhydrinate_poisoning_an_evidence-based_consensus_guideline_for_out-of-hospital_management/file/d912f50adba47b9e1f.pdf
  2. FERNANDO R. Management of poisoning. Fourth edition. The Medical Defence Organization, Sri Lanka. 2011
  3. CANTISANI C, RICCI S, GRIECO T, PAOLINO G, FAINA V, SILVESTRI E, CALVIERI S. Topical Promethazine Side Effects: Our Experience and Review of the Literature Biomed Res Int [online] 2013:151509 [viewed 04 June 2014] Available from: doi:10.1155/2013/151509
  4. CHURCH MK, CHURCH DS. Pharmacology of Antihistamines Indian J Dermatol [online] 2013, 58(3):219-224 [viewed 04 June 2014] Available from: doi:10.4103/0019-5154.110832
  5. VEARRIER D, CURTIS JA. Case Files of the Medical Toxicology Fellowship at Drexel University: Rhabdomyolysis and Compartment Syndrome Following Acute Diphenhydramine Overdose J Med Toxicol [online] 2011 Sep, 7(3):213-219 [viewed 04 June 2014] Available from: doi:10.1007/s13181-011-0157-3
  6. OYEWOLE A, ADELUFOSI A, ABAYOMI O. Acute Dystonic Reaction as Medical Emergency: A Report of Two Cases Ann Med Health Sci Res [online] 2013, 3(3):453-455 [viewed 04 June 2014] Available from: doi:10.4103/2141-9248.117932

Examination

Fact Explanation
Dilated pupil Is due to the anticholinergic effect[1][2][4][6]
Tachycardia Occurs due to the anticholinergic/antimuscarinic effect seen in some antihistamine drugs[1][2][3][4][6]
Muscle weakness Is seen in some with patients antihistamine toxicity and may indicate presence of rhabdomyolysis, in which case patient may have additional symptoms such as myalgia and dark color urine[1][2][4][7]
Incoordination Have been reported in some instances, secondary to anticholinergic actions at muscarinic receptors[1][2][4]
Increased body temperature (hyperpyrexia) Is seen in patients with antihistamine poisoning[1][2][6]
Reduced respiratory rate Respiratory depression is seen in some patients with antihistamine poisoning[1][4]
Arrythmia Occurs due to blockage of fast sodium channels. Arrhythmia may also arise secondary to anticholinergic actions at muscarinic receptors[1][2][4][5][6]
Flushed skin Is seen in some patients with antihitamine poisoning[1]
Reduced bowel sounds Occurs mainly due to anticholinergic actions at muscarinic receptors[1][6]
Changes in blood pressure Hypertension or hypotension can result from cardiac toxicity caused in antihistamine overdose[4]
References
  1. SCHARMAN JE, ERDMAN AR, WAX PM, CHYKA PA, CARAVATI EM, NELSON LS, MANOGUERRA AS, CHRISTIANSON G, OLSON KR, WOOLF AD, KEYES DC, BOOZE LL, TROUTMAN WG. Diphenhydramine and Dimenhydrinate Poisoning: an Evidence-Based Consensus Guideline for Out-of-Hospital Management.Clinical Toxicology [online] 44:205–223, 2006. [viewed on 3 June 2014] Available from: http://www.researchgate.net/publication/7032484_Diphenhydramine_and_dimenhydrinate_poisoning_an_evidence-based_consensus_guideline_for_out-of-hospital_management/file/d912f50adba47b9e1f.pdf
  2. FERNANDO R. Management of poisoning. Fourth edition. The Medical Defence Organization, Sri Lanka. 2011
  3. PAGE CB, DUFFULL SB, WHYTE IM, ISBISTER GK. Promethazine overdose: clinical effects, predicting delirium and the effect of charcoal. QJM [online] 2009 Feb, 102(2):123-31 [viewed 04 June 2014] Available from: doi:10.1093/qjmed/hcn153
  4. CANTISANI C, RICCI S, GRIECO T, PAOLINO G, FAINA V, SILVESTRI E, CALVIERI S. Topical Promethazine Side Effects: Our Experience and Review of the Literature Biomed Res Int [online] 2013:151509 [viewed 04 June 2014] Available from: doi:10.1155/2013/151509
  5. CHURCH MK, CHURCH DS. Pharmacology of Antihistamines Indian J Dermatol [online] 2013, 58(3):219-224 [viewed 04 June 2014] Available from: doi:10.4103/0019-5154.110832
  6. VEARRIER D, CURTIS JA. Case Files of the Medical Toxicology Fellowship at Drexel University: Rhabdomyolysis and Compartment Syndrome Following Acute Diphenhydramine Overdose J Med Toxicol [online] 2011 Sep, 7(3):213-219 [viewed 04 June 2014] Available from: doi:10.1007/s13181-011-0157-3
  7. KELTZ E, KHAN FY, MANN G. Rhabdomyolysis. The role of diagnostic and prognostic factors Muscles Ligaments Tendons J [online] , 3(4):303-312 [viewed 05 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940504

Differential Diagnoses

Fact Explanation
Anticholinergic drug overdose Anticholinergic poisoning can produce similar clinical presentation to antihistamine poisoning[1][2]
Delirium Delirium is an important differential diagnosis. It can result from antihistamine poisoning[3]
Hallucinogen abuse Some patients may present with hallucinations which arises the suspicion of hallucinogen usage[1][2]
Seizure disorders This is an important differential diagnosis when a patient presents with seizures[1][2]
Systemic infections Can present with pyrexia, delirium, hypotension etc. which are also seen in antihistamine poisoning[2][3]
References
  1. FERNANDO R. Management of poisoning. Fourth edition. The Medical Defence Organization, Sri Lanka. 2011
  2. CANTISANI C, RICCI S, GRIECO T, PAOLINO G, FAINA V, SILVESTRI E, CALVIERI S. Topical Promethazine Side Effects: Our Experience and Review of the Literature Biomed Res Int [online] 2013:151509 [viewed 04 June 2014] Available from: doi:10.1155/2013/151509
  3. PAGE CB, DUFFULL SB, WHYTE IM, ISBISTER GK. Promethazine overdose: clinical effects, predicting delirium and the effect of charcoal. QJM [online] 2009 Feb, 102(2):123-31 [viewed 04 June 2014] Available from: doi:10.1093/qjmed/hcn153

Investigations - for Diagnosis

Fact Explanation
Toxicology screen for antihistamines Samples of blood and urine can be tested for presence of antihistamines[1]
References
  1. CANTISANI C, RICCI S, GRIECO T, PAOLINO G, FAINA V, SILVESTRI E, CALVIERI S. Topical Promethazine Side Effects: Our Experience and Review of the Literature Biomed Res Int [online] 2013:151509 [viewed 04 June 2014] Available from: doi:10.1155/2013/151509

Investigations - Fitness for Management

Fact Explanation
Complete blood count Done to detect leucopenia and agranulocytosis, that can occur rarely[2]
Blood culture Done to exclude systemic infections in patients presenting with pyrexia, delirium etc.[5]
Serum electrolytes Should be done in patients with cardiac toxicity or delirium to exclude the presence of electrolyte imbalance[4][5]
Serum creatinine kinase level Done to rule our rhabdomyolysis, as some patients with antihistamine toxicity may develop rhabdomyolysis[2][3][6]
Electrocardiogram(ECG) It is important to take a 12-lead ECG to detect arrhythmia that can result from antihistamine toxicity[1][2]
Liver function tests Done because some antihistamines can cause hepatotoxicity[2]
References
  1. SCHARMAN JE, ERDMAN AR, WAX PM, CHYKA PA, CARAVATI EM, NELSON LS, MANOGUERRA AS, CHRISTIANSON G, OLSON KR, WOOLF AD, KEYES DC, BOOZE LL, TROUTMAN WG. Diphenhydramine and Dimenhydrinate Poisoning: an Evidence-Based Consensus Guideline for Out-of-Hospital Management.Clinical Toxicology [online] 44:205–223, 2006. [viewed on 3 June 2014] Available from: http://www.researchgate.net/publication/7032484_Diphenhydramine_and_dimenhydrinate_poisoning_an_evidence-based_consensus_guideline_for_out-of-hospital_management/file/d912f50adba47b9e1f.pdf
  2. CANTISANI C, RICCI S, GRIECO T, PAOLINO G, FAINA V, SILVESTRI E, CALVIERI S. Topical Promethazine Side Effects: Our Experience and Review of the Literature Biomed Res Int [online] 2013:151509 [viewed 04 June 2014] Available from: doi:10.1155/2013/151509
  3. PAGE CB, DUFFULL SB, WHYTE IM, ISBISTER GK. Promethazine overdose: clinical effects, predicting delirium and the effect of charcoal. QJM [online] 2009 Feb, 102(2):123-31 [viewed 04 June 2014] Available from: doi:10.1093/qjmed/hcn153
  4. VEARRIER D, CURTIS JA. Case Files of the Medical Toxicology Fellowship at Drexel University: Rhabdomyolysis and Compartment Syndrome Following Acute Diphenhydramine Overdose J Med Toxicol [online] 2011 Sep, 7(3):213-219 [viewed 04 June 2014] Available from: doi:10.1007/s13181-011-0157-3
  5. ILLINGWORTH RN, GRAHAM CA, HOGG K. Oxford Handbook of Emergency Medicine. Oxford University Press, 2012
  6. KELTZ E, KHAN FY, MANN G. Rhabdomyolysis. The role of diagnostic and prognostic factors Muscles Ligaments Tendons J [online] , 3(4):303-312 [viewed 05 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940504

Management - General Measures

Fact Explanation
Emergency management Assess and secure the airway, breathing and circulation in any patient in an acute debilitated state. Once there is no acute threat to life take a relevant brief history and do relevant examination to recognize the potential cause for the patient's presentation[3]
Oxygen therapy and assissted ventilation Is given to patients with impaired respiration[2][3]
Physostigmine This drug is given via intravenous route to patients presenting with severe agitated delirium, to calm the patient[1][2]
Management of seizures Benzodiazepines such as diazepam is given via intravenous route if patient develops seizures in order to control seizures[1][2]
Sodium bicarbonte Is given via intravenous route to manage the cardiac toxicity caused by antihistamine poisoning, if ECG shows QRS complex widening[1]
Temporary cardiac pacing Should be tried in patients developing atrio-ventricular block following severe toxicity[2]
Magnesium sulphate Can be given to control torsades de pointes type of ventricular arrythmia if patient develops them[2]
Psychiatric referral Should be done if the patient committed deliberate self harm/had suicide intent or if he/she is a known patient with a psychiatric disorder[3]
Management of rhabdomyolysis The aim of treatment is to prevent myoglobinuric acute kidney injury which occurs because of renal vasoconstriction and myoglobin precipitation resulting in renal tubule obstruction and injury. This is augmented by intravascular volume depletion that results from sequestration of fluid in damaged myocytes. The treatment for rhabdomyolysis is aggressive intravenous hydration to correct the intravascular volume depletion and renal vasoconstriction[4][7]
Management of dystonic reactions To manage dystonic reactions, oxygen is given by face mask and an anticholinergic agent such as intramuscular biperiden lactate 1 mg stat should be given[5]
Management of hyperthermia Controlling hypothermia is done by removal of all unnecessary clothing, placing patient under a fan (place with increased air circulation), tepid sponging etc. If the patient is severely agitated and has a very high temperature may even require neuromuscular paralysis to control hyperthermia[6]
References
  1. SCHARMAN JE, ERDMAN AR, WAX PM, CHYKA PA, CARAVATI EM, NELSON LS, MANOGUERRA AS, CHRISTIANSON G, OLSON KR, WOOLF AD, KEYES DC, BOOZE LL, TROUTMAN WG. Diphenhydramine and Dimenhydrinate Poisoning: an Evidence-Based Consensus Guideline for Out-of-Hospital Management.Clinical Toxicology [online] 44:205–223, 2006. [viewed on 3 June 2014] Available from: http://www.researchgate.net/publication/7032484_Diphenhydramine_and_dimenhydrinate_poisoning_an_evidence-based_consensus_guideline_for_out-of-hospital_management/file/d912f50adba47b9e1f.pdf
  2. FERNANDO R. Management of poisoning. Fourth edition. The Medical Defence Organization, Sri Lanka. 2011
  3. ILLINGWORTH RN, GRAHAM CA, HOGG K. Oxford Handbook of Emergency Medicine. Oxford University Press, 2012
  4. VEARRIER D, CURTIS JA. Case Files of the Medical Toxicology Fellowship at Drexel University: Rhabdomyolysis and Compartment Syndrome Following Acute Diphenhydramine Overdose J Med Toxicol [online] 2011 Sep, 7(3):213-219 [viewed 04 June 2014] Available from: doi:10.1007/s13181-011-0157-3
  5. OYEWOLE A, ADELUFOSI A, ABAYOMI O. Acute Dystonic Reaction as Medical Emergency: A Report of Two Cases Ann Med Health Sci Res [online] 2013, 3(3):453-455 [viewed 04 June 2014] Available from: doi:10.4103/2141-9248.117932
  6. Emergency treatment of poisoning. British National Formulary. 64 September 2012. BMJ group and RPS publishing. London; 2012.
  7. KELTZ E, KHAN FY, MANN G. Rhabdomyolysis. The role of diagnostic and prognostic factors Muscles Ligaments Tendons J [online] , 3(4):303-312 [viewed 05 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940504

Management - Specific Treatments

Fact Explanation
Activated charcoal Activate charcoal 50-100 g in 200 mL of water is given orally. This reduces absorption of the ingested antihistamines in to the circulation through the gut[1][2][3][4]
Gastric aspiration and lavage Is not routinely done for all patients. Useful if only done within 1-2 hours from a life threatening ingestion. Done in the presence of a doctor and in a patient with a protected airway.Should not be done if the patient develops seizures, uncooperative or clinically unstable[2][4]
References
  1. SCHARMAN JE, ERDMAN AR, WAX PM, CHYKA PA, CARAVATI EM, NELSON LS, MANOGUERRA AS, CHRISTIANSON G, OLSON KR, WOOLF AD, KEYES DC, BOOZE LL, TROUTMAN WG. Diphenhydramine and Dimenhydrinate Poisoning: an Evidence-Based Consensus Guideline for Out-of-Hospital Management.Clinical Toxicology [online] 44:205–223, 2006. [viewed on 3 June 2014] Available from: http://www.researchgate.net/publication/7032484_Diphenhydramine_and_dimenhydrinate_poisoning_an_evidence-based_consensus_guideline_for_out-of-hospital_management/file/d912f50adba47b9e1f.pdf
  2. FERNANDO R. Management of poisoning. Fourth edition. The Medical Defence Organization, Sri Lanka. 2011
  3. PAGE CB, DUFFULL SB, WHYTE IM, ISBISTER GK. Promethazine overdose: clinical effects, predicting delirium and the effect of charcoal. QJM [online] 2009 Feb, 102(2):123-31 [viewed 04 June 2014] Available from: doi:10.1093/qjmed/hcn153
  4. ILLINGWORTH RN, GRAHAM CA, HOGG K. Oxford Handbook of Emergency Medicine. Oxford University Press, 2012