Toxiccology of anti-histamines

Introduction :

Anti-histamines are H1 receptor antagonists that provide symptomatic relief of allergic signs caused by histamine release, including pruritis and anaphylactic reactions . They are also used as sedatives and antiemetic.

         First generation may cause adverse reactions because of their cholinergic activity and ability to cross the blood-brain barrier . Second generation antihistamines are more lipophobic than first generation and lack CNS and cholinergic effect at therapeutic doses.

Sources:

1. Vitamin C ( citrus fruit, kiwi, strawberry, cauliflower, tomatoes)
2. Butterbur (plant extract of shrubs)
3. Core and juice of pineapple (bromelain)
4. Probiotics (containing lactobacillus)
5. Quercetin ( antioxidant flavonoid present in apple, berry, green tea, peppers, red onions)
6. Alternatives( medications)

Antihistamines are divided into two types:

1. First generation :
2. Chlorpheniramine dose for cat and dog (1-2 mg/kg) and large animals (7-8mg/kg)
3. Cyclizine

iii.Diphenhydramine (2-4 mg/kg)

1. Promethazine (1mg/kg)
2. Second generation :
3. Cetrizine (1mg/kg)
4. Levocetrizine

Mode of transmission :

1. a) Grazing of animals on pasture rich in Vit. C
2. b) Too much intake of probiotics rich in lactobacillus
3. c) Oral ingestion of overdose of antihistamines ➔ Which later on show anticholinergic effect
4. d) Feeding of peel of fruits (rind) : apple, berries, etc.

Mode of action:

 The binding of H1 blockers to the histamine receptors prevents the adverse consequences of histamine stimulation

 – vasodilation

 – increase gastrointestinal and respiratory secretions

 – stimulate sensory nerve ending

– show anticholinergic effect

-Cetrizine decrease  histamine release from basophils.

Clinical Signs:

 i)Chlorpheniramine toxicity: Ataxia , tremor, depression, hyperactivity, hyperthemia, Seizures ii)Diphenhydramine toxicity: Hyperactivity or depression , Hypersalivation , Trachypnea, Trachycardia iii)Promethazine toxicity: CNS depression and excitation .

Common signs of all antihistamine toxicity:

1. a) Increase drowsiness
2. b) Blurred vision/ Dry mouth
3. c) Nausea d) Vomiting
4. e) Increase heart rate
5. f) Confusion / nervousness
6. g) Loss of balance
7. h) Difficulty in passing urine and constipation ( Due to anti-cholinetgic and anti-muscarinic effect)
8. i) Increase in body temperature (hyperpyrexia)
9. j) Flushed skin
10. k) Arrythmia ( secondary to anticholinergic reactions at muscarinic receptors)

 Diagnosis:

1. Based on history and clinical findings
2. History of intake of feed and grazing
3. History of dosages of antihistamine medications
4. Toxicology screen for :
5. Sample of blood and antihistamines
6. Urine test for presence of antihistamines
7. Complete blood count : to detect leucopenia and agranulocytosis
8. Blood culture: to exclude systemic infection presenting with pyrexia and delirium
9. Sodium creatinine kinase level: to rule rhabdomyolysis
10. ECG: to detect arrhythmia
11. Liver function test : as antihiatmine can cause hepatotoxicity.

 Treatment :

Treatment of antihistamine toxicosis is primarily symptomatic and supportive:

1. Activated charcoal : 1-2 gm per kg body weight mixed with 10-20 ml of water drench orally This prevents absorption of toxins from GI tract.
2. . Diazepam to control seizures : 1-4 mg/ kg body weight TID/QID

•  Physostigmine is recommended to counteract the CNS anticholinergic effects of antihistamine overdoses. Dose of (0.5 -0.6 mg/ Kg body weight)

 Differential Diagnosis :

1. TCA ( Tricyclic antidepressant) overdose
2. Acetaminophen overdose

• Hypoglycemia

1. Serotonin syndrome