Battle of two drugs: Who won? – An unusual presentation

Silvera Samson Raj*

MRCEM Resident – 1st year, Department of Emergency Medicine, Kauvery Hospital, Chennai, India

*Correspondence: [email protected]

Abstract

Organo-phosphate/insecticide ingestion is the most common modality of suicide in India, which causes excessive secretions (cholinergic effect) in our body. Anti-histamines are groups of drugs that are used in allergic reactions and are also known to have an effect in decreasing secretions (anti-cholinergic effect] in our body. What if a person consumes both at the same time? Will both drugs compete to nullify the effect or not?

Case Presentation

A 28 years gentleman, with no comorbidity and no known drug allergy, presented to ER at 8 PM on 17/8/2021 with alleged H/O consumption of monocrotophos 36% (OPC) around 30 ml and Tab. Cetirizine 10 mg × 50 nos (total aggregate of 500 mg) at his residence around 10 AM (the same day). He was said to be in depression following demise of his mother recently. He was apparently normal till 4 PM after which he had one episode of vomiting (containing food particles, non-blood stained) and giddiness.

He confessed to his friend that he has consumed the above-mentioned medications. Initially, he was rushed to government general hospital around 5 PM where gastric decontamination was done and activated charcoal was introduced through a nasogastric tube. He was also treated with Inj. Pralidoxime 3 g intravenously. He consumes ethanol occasionally.

On Examination at ER

Airway: Patent, self maintained

Breathing: RR – 20/ min, SpO2 – 99% RA, B/L air entry equal, no added breath sounds, single breath count >10

Circulation

BP – 160/100 mm Hg. HR – 112/ min,

CVS – S1S2 normal, no murmur, JVP – Normal, B/L Peripheral pulses well felt

PA – Soft, non-tender, no organomegaly, bowel sounds heard.

Disability

GCS – E4V5M6 [15/ 15]

B/L pupils pin point, sluggishly reacting to light 1 mm

CBG – 149 mg/dl

 

  R L
Power UL 5/5 5/5
LL 5/5 5/5
DTR + +
Tone N N
Plantar ↓ ↓
Sensory + +

 

Fasciculations noted in B/L Quadriceps femoris muscle, B/L lower eyelid and lips.

 

Exposure

  1. 16 F Ryles tube with activated charcoal in place.
  2. 18 G venflon in dorsum of right hand.

 

ECG

 

ECG

  1. Rate ≃ 115/ min
  2. Sinus rhythm
  3. Normal Axis
  4. S1Q3T3 Pattern
  5. No other specific ST – T Changes

 

ABG (RA)

pH 7.348
PCO2 48.2 mmHg
PO2 71 mmHg
BE 1 mmol/ L
HCO3 26.5 mmol/ L
TCO2 28 mmol/ L
SO2 93%
LAC 2.11 mmol/ L

 

PT-INR – 0.99

 

CHEM – 8

Na+ 141 mmol/L
K+ 3.3 mmol/L
Cl – 106 mmol/L
ica 1.16 mmol/L
GLU 124 mg/dl
BUN 13 mg/dl
CREAT 0.9 mg/dl
HCT 49% PCV
HB 16.7 g/dl

 

Blood Investigations

  17/8/21 18/8/21 19/8/21 26/8/21
Urea 28.6 26.2 31.2 65.3
Creatine 0.83 0.73 0.75 0.70
SGOT 24.6 66.2
SGPT 29.6 201.7
ALP 69.4 95.1
GGT       238.6

 

CBC 17/8/21 18/8/21
HB 16.0 15.3
WBC 26800 19400
Platelet 258000 243000
Neutophil 85.2 92.1
Lymphocyte 8.9 4.4
Monocyte 5.5 3.4
Basophil 0.3 0.1

 

 

 

ABG 18/8/21 19/8/21 22/8/21
PCO2 32 77 34
PO2 491 116 88
SO2 99.6 98.8 98.4
Lac 2.4 0.7 1.0

 

Follow up:

  1. Patient was shifted to ICU and was started on Inj. Atropine infusion in view of bradycardia due to parasympathetic overactivity.
  2. The next day around 4AM, he developed severe respiratory distress due to respiratory muscle weakness secondary to OPC induced excessive acetylcholine at neuromuscular junction. He was intubated and connected to a mechanical ventilator. He was slowly weaned off from supports and patient discharged on 4/9/2021.

 

Discussion

 

Pathophysiology of OPC Toxicity

 

Organo phosphate

Acetyl choline esterase inhibitors

Increases acetyl choline in synaptic cleft

Overstimulation of ach receptors

Muscarinic

Salivation

Lacrimation

Urination

Defecation

GI cramps

Emesis

Nicotinic

Muscle weakness

Twitching

Fasciculation

Hypertension

Paralysis

Pharmacology of Antihistamines

  1. Blocks HI – Histamine receptors.
  2. Anti-Allergic – Suppression of leukotriene and pro Inflammatory cytokine production.
  3. Anti-inflammatory effect – Decrease in production of granulocytic macrophage factor.

 

Side Effects

  1. Depression of CNS – (Disorders of coordination, fatigue, dizziness, diplopia, tremor, euphoria, nervousness, insomnia).
  2. Disturbance of GI Functions – (increased appetite, nausea, vomiting, constipation of diarrhea).
  3. M-cholino blocking activity – (dryness of mucous membranes, blurred vision, impotence, tachycardia, psychosis).

 

Pharmacokinetics

  1. Action of drug noted within 30–60 min of post-consumption.
  2. Half-life: 8–10 h.
  3. Eliminated by kidneys (apparent total body clearance – 53 ml/min).

 

 

Conclusion

We had received another patient with alleged history of accidental consumption of OPC (chlorpyrifos) of 20 ml at his residence around 8 pm. He was brought to ER at 11 pm the same day. On arrival at the ER he was agitated, with secretions pooling through his oral cavity. Comparing both, there were no secretions noted in our index patient till 18 h of post consumption of OPC which could be due to anti-cholinergic effect of anti- histamines. Hence it is postulated that anti-histamines have a protective role on the airway by delaying onset of respiratory distress due to secretions caused by organophosphates. More studies are required to explore the use of anti-histamines in management of OPC poisoning. In the battle of two drugs, anti-histamines over-powered action of OPC.

 

Acknowledgement

I would like to thank, Drs. Aslesha, Consultant and Clinical lead, Dr. Sridhar, Intensivist, Dr. Vidya, Consultant, Dr. Vetri, Consultant, Dr. Niveanthini, Consultant for helping me to prepare this article.

 

References

  1. Borowy CS, Mukherj P. Antihistamine Toxicity. StatPearls, 2021.
  2. Nurulain SM, Ojha S, Shafiullah M, et al. Protective effects of the antihistamine promethazine aginst acute paraxon-methyl and dicrotophos toxicity in adult rats. Int J Clin Exp Med. 2015;8(10):17891–901.
  3. Simons FE, Simons KJ, Chung M, et al. The comparative pharmacokinetics of H1-receptor antagonists. Ann Allergy. 1987;59(6 Pt 2):20-4.
  4. Paton DM, Webster DR. Clinical pharmacokinetics of H1-receptor antagonists (the antihistamines). Clin Pharmacokinet. 1985;10(6):477-97.
  5. Leysen JE, Gommeren W, Janssen PF, et al. Non-sedative antihistaminics and binding to central and peripheral H1 histamine receptors. Allerg Immunol. 1991 Feb;23(2):51-7.
  6. Simons FE. Recent advances in H1-receptor antagonist treatment. J Allergy Clin Immunol. 1990;86(6 Pt 2):995-9.

 

Dr-Silvera-Samson-Raj

Dr. Silvera Samson Raj

MRCEM Resident

Kauvery Hospital