Antihistamines Include: First Generation ( Non-selective )

Ethanolamine- Carbinoxamine. Clemastine, Diphenhydramine. Ethylenediamines- Pyrilamine, Triplennamine Akylamines- Brompheneramine, Chlorpheniramine, Dexchlor pheniramine,Pheniramine,Triprolidine

Phenothiazines- Methidilazine, Promethizine, trimeprazine Piperidines- Azatadine, Cyproheptadine, Phenindamine Miscellaneous- Astemazole, Loratadine, Terfenadine Second Generation ( Peripherally selective ) Phthalazinone - Azelastine Piperazine - Cetrizine

Refer - Chlorpheniramine maleate

Interacting drugs- summary

+ Antihistamines

Azole antifungals/ astemazole/fluconazole/ ketoconazole/miconazole + Terfenadine

 incr Astemazole and tefenadine plasma levels (including metabolite levelsincreased, which lead to serious cardiovascular effects aconazole 

Macrolide antibiotics + tefenadine

incr Astemazole and tefenadine plasma levels (including metabolite levels) increased which lead to serious cardiovascular efects. 

MAO inhibitors

MAOIs prolong and intensify the anticholinergic effects of the antihistamines Use with phenothiazine  cause hypotension and extrapyrimidal reactions.

Dexachlorpheriramine

cause severe hypotension when given with an MAOIs

Antihistamine + alcohol/ CNS depressants

  Additive depress effects may occur. This may be less likely with astemazole,  Lorantidine, Terfenadine

FIXED DOSE COMBINATIONS APPROVED BY DCG(I)

Antihistamines Include: First Generation ( Non-selective )

Ethanolamine- Carbinoxamine. Clemastine, Diphenhydramine. Ethylenediamines- Pyrilamine, Triplennamine Akylamines- Brompheneramine, Chlorpheniramine, Dexchlor pheniramine,Pheniramine,Triprolidine

Phenothiazines- Methidilazine, Promethizine, trimeprazine Piperidines- Azatadine, Cyproheptadine, Phenindamine Miscellaneous- Astemazole, Loratadine, Terfenadine Second Generation ( Peripherally selective ) Phthalazinone - Azelastine Piperazine - Cetrizine

Allergic reactions-

peripheral, angineurotic and laryngeal edema, deremtitis, asthma, lupus erythematous -like-syndrome, urticaria drug rash, anaphylactic shock, photosensitivity.

Cardiovascular- postural hypoternsion, palptations, bradycardia, tachycardia, reflux tachycardia, extrasasystoles, faintness, increases and decreases in blood pressure, vnous thrombosis at injecton site following IV promethazine,cardiac arrest, ECG changes, including blunting if T waves and prolongationof Q-T interval.

CNS- Most frequent- drowsiness ofeten transcient, dsedation, diziness, faintness, disturbed corodination.

Other- fatigue, lassitude, confusion, restlessness, exciration, nervousness, tremor, gal malseizures, headache, irritability, insomnia, euphoria, paresthesias, blurred vision, hallucinations, tongue protrusion (usually in association with IV administration or excessive dosage), disturbing dreams/ nightmares, pseudoschiziphrenia, weakness, diplopia, vertigo. CNS stimulation is possible with phenindamine.

GI- most frequent- epigastric distree(especially ethylene diadiamines)

Other- anorexia, increased appetite and weight gain,nausea, vomiting, diarrhea, constipation, change in bowel habits.

Hematologic- hemolytic anemia, hypoplastic anemia, aplastic anemia, thrombocytopenia, leukopenia, agranulocytosis, pancytopenia.

Respiratory- most frequent- thickening of bronchial secretions.

other- chest tightness, wheezing , nasal stuffiness, dry mouth, nose and throat, sore throat, repiratory depression. Body as a whole- tingling, heaviness and weakness f hands, thrombocytopenic purpura, obstructive jaundice (usually reversible ondiscontinuation) tissue necrosis following SC administration of IV promethazine, erythema, stomatis, high or prolonged glucose tolerance curves.glycosuria, elevated spinal fluid proteins.

Terfenadrine- alopecia, arhythmias, visual distrubances, angioedema, skin eruptins, and itching, broncohospasm, cough, depression, galactorhea, menstrual dosordrs, (eg dysmennorrhea) musculoskeletal pain, nightmares, mild to modeate trnasmaninase elevations,torsades de points.

Tefendine may cause lessdrowsiness than chlorpheniramine maleate , isolated rtepors of jaundice , cholestatic hepatitis and hepatitis have occured.

Loratadine- altered salivatin, asthnia, increasedsweating, altered lacrimation, hypoesthesia, thirst, flushing, conjuntivitis, blurred vision, earcahe, eye pain, back/chest pain, leg cramps, malaise, rogors, fever, aggreavated allergy, upper respiratory infection,hyperkainesia, blepharosapsm, migraine, arthalgia, myalgia, anxiety, depression, agitation, paronia, amnesia, impaired concentration, breast pain, dysmenorrhea, vaginitis, epistaxis.

Phenothiazine antihistamines- infrequently cause typical phenothiazine adverse effects

Hypersens, Pregnancy, Neonates. Special precautions:

Elderly, pyloric obstruction, BHP, bladder neck obstruction. Hypotension.

Hematologic- use promathazine with caution in bone marrow deprssion , Leukopenia and granulocytosis have been reported., usually when used with other toxic agents.

Anticholinergic effects- antihistamines have varying degrees of atropine-like actions, use with caution in patients with a predispostion to urinary retention, history of bronchialasthma, increased intraocular pressure, hyperthyroidism, cardiovacular disease or hypertension.

Phenothiazines- use phenothiazines with caution in patients with cardiovascular disease , liver dysfunction,or ulcer diseases. Phenithiazine has been associated with cholestatic jaundice. Discontinue phenothiazine at least 24 hours post procedure. Do not use phenothiazine to control nausea and vomiting before or after myelography. Parentral use- do not give promethizine intra-arterially because of possible severe arteriospasm and resultant gangrene.

Hazardous tasks- may cause drowsiness and reduce mental alertness , patients should not drive or perform tasks requiring alertness, cordination or physical dexterity. Astemazole.lorantidine and terfemadine appear to cause less sedation. supervise children who are taking antihistatmines when they angage in potentially hazardous activities (eg bicyle riding)

Photosentivity- photosentisizatin may occur, therfore caution patientsto take protective measures (ie sunscreen, protective clothing)

Drug/Lab interactions- diagnostic pregnancy tests based on imunological reactions between HCG and anti-HCG may result in false negative or false-positive interpretationsin patients on phenothiazine antihistamines, promethazine, trimeprazine and methodilazine

Warnings

Cardiovasculr effects- be aware of conditions that may inhibit the metabolism of terfenadine such as impaired metabolic function or certain drug interactions

Respiratory disease- in general antihistamines are not recommended to treat lower resipratory tract symptoms including asthma, as their anticholinergic (drying ) effects maycause thickening of secretions and impair expectoration.

Promethazine- may lower seizure threshold. Take this into consideration when administering to persons with known seizure disorders.

Sedatives/ CNS depressants- avoid sedatives and CNS depresants in patients with sleep apnea.

Hepatic function impairment- use with cautin in patients with cirrhosis or other liver diseases.

Elderly- antihistamines are more likely to cause dizziness, excessive sedation, syncope, toxic confusional states and hypertension in elderly patients.

Pregnancy- do not use during the third trimester ,newborn and premature infants may have severe reactions (eg convulsions)

Lactation- antihistamine therapy is contraindicated in nursing mothers.

Children- antihistamines may diminish mental aletness. In young child they may produce paradoxical excitation.

Dosage-

Adults and children over 12- 4mg every 4 to 6 hours. Do not exceed 24mg in 24 hourrs. Children (6 to 12 years) 2mg every 4 to 6 hours. Do not exceed 12mg in 24 hours (2 to 6 years ) 1 mgevey 4 hours. Do not exceed 4mg in 24 hours. Administratin with food delays absorption, but does not affect bioavailability.

Overdosage-

Symptoms Effects may vary from mild CNS depressin (sedation, apnea, diminished mental alertness) and cardiovascular collapse to stimulation (insomnia,hallucination,tremors, or convulsions) especially in children and geriatric patients. Profound hypotension, respiratory depression, unconsciousness, coma and death may occur, particularly in infants and children. Convulsions rarely occur. The convulsant dose lies near the lethal dose. Convulsions indicate poor prognosis. Treatment

1. Induce emesis even emesis has occured spontaneously using syrup of ipecac, except with phenothiazine

2. Following emesis, administer activated charcoal as a slurry with water and a cathartic to minimse absorption ,

3. Oral sodium or magnesiun sulfate may be given,saline cathartics (eg milk of magnesia) draw water into the bowel by osmosis and threfore are valuable for their action in rapid dilution of bowel content.

4. Corect acidosis and electroltyte imbalances.

5. Do not induce emesis innunconscious patients

6. If vomiting is unsuccessful,gastric lavage is indicated within 3 hours after ingestion and even later if large amounts of milk or cream were given.

7. Early gastric lavage may be beneficial if promethazine has ben taken orally.

8. Isotonic orisotonicsaline is the lavage of choice,particularly inchildren.

9. In adults tap water can be used

10. Continue therapy directed at reversing the side effects of time-released medication and at supporting the patient for as long as as symptoms remain.

11. Treatment includes usual supportive measures

12. Hypotension is an early sign of impending cardiovascular collapse. Treat it vigourously using general supportive measures or specific treatment with vassopressor (inorephinephrine,phenylephrine, dopamine)

13. Avoid epinephrine because it may wprsen hypotension.

14. Propranol, can be used for refractory ventricular arrhythmias

15.Use only short acting depressants eg diazepam to treat convulsions.

16. Avoid analeptics because they may cause convulsions

17. Any depressants effects of promethazine are not reversed by naloxone.

18. Ice packs and cooling sponge baths, not alcohol can aid in reducing fever comonly seen in children.

19. Hemoperfusion may be used in sevee cases.

20. Astemizole and loratadine do not appar to be dialyzable. It is not known if terfanadine is dialyzable

Missed dose-

1. If you miss a dose of this medicine, take it as soon as possible.

2. However, if it is almost time for next dose, skip the missed dose and go back to your regular dosing schedule.

3. Do not double doses.

For Availability/supplies 

Classification: Antihistamines Patent position:

Major brands: COREX PFIZER DRISTAN WYETH TUXYNE FRANCO-INDIA Raw materials:

1.Chloropyridine **

2.Chlorobenzyl cyanide **

3.Dimetanolamine **

4.Chloropheramine base **

5.Chlorobenzyl pyridine **

6.Dimethylaminoethyl chloride hydrochloride **

7.Dimethylaminoethyl p- chlorophenone pyridyl lithium

8.Chloraniline ** concessional duty Manufacturers: 1.Jehovah Labs Pvt Ltd.- 24T

Antihistamines Include: First Generation ( Non-selective )

Ethanolamine- Carbinoxamine. Clemastine, Diphenhydramine. Ethylenediamines- Pyrilamine, Triplennamine Akylamines- Brompheneramine, Chlorpheniramine, Dexchlor pheniramine,Pheniramine,Triprolidine

Phenothiazines- Methidilazine, Promethizine, trimeprazine Piperidines- Azatadine, Cyproheptadine, Phenindamine Miscellaneous- Astemazole, Loratadine, Terfenadine Second Generation ( Peripherally selective ) Phthalazinone - Azelastine Piperazine - Cetrizine Refer - Chlorpheniramine maleate

1. Inform physician about any history of glaucoma, peptic ulcer, urinary retention, or pregnancy before starting antihistamine therapy

2. May cause nervousness, insomnia, and dry mouth

3. May cause drowsiness, or dizziness(except astemazole,loratadine, and tefenadine)

4. Patients should observe caution while driving or performing other tasks requiring alertness, coordination or physical dexterity.

5. Avoid alcohol and other CNS depressants (eg,. sedatives, hypnotics, tranquilizers)

6. May cause GI upset, take with food. Take Astemazole on an empty stomach, at least 2 hours after or 1 hour before a meal. Take Lorantidine on an empty stomach.

7. Avoid prolonged exposure to sunlight, may cause photosentivity.

8. Do not crush or chew sustained releae preparations

9.Astemazole/ Terfenadine: Patients should not take these agents if they have hepatic dysfunction or if they are also receiving ketoconazole, itraconazole or erythromycin

10. Phenothiazines- Patients should report any involuntary muscle movements or unusual sensitivity to sunlight.

11. Allergies- Tell your doctor if you have ever had any unusual or allergic reaction to antihistamines. Also tell your doctor if you are allergic to any other substances such as foods, or drinks.

12. Diet- Make sure that your doctor knows that you are on a low sodium .ow sugar or other special diet. Most medicines contain more than their active ingredient and liquid medicines contain alcohol.

13.Pregnancy- Studies have shown that antihistamines cause birth defects in animals. Cetrizine and hydroxyzine are not recommended for use in the first months of pregnancy.

14.Breast feeding- small amounts of antihistamines pass into the breast milk. Use is not recommended since babies are more suseptible to the side efects of antihistamines such as unusual excitement or irritability

15. Children- serious side effects suchas convulsions (seizures) are more likely to occur in younger patients and would be of greater risk to infants than to older children or adults.

16. Elderly- elderly patients are more sensitive to the efects of antihistamine. Confusion, difficult or painful urination, dizziness, drowsiness, feeling faint or dryness of mouth, nose, or throat may be more likely to occur in elderly patients

17. Other medicines- When you taking antihistamines, it is important that your doctor knows if you are taking any other  medicines- Anticholinergics- or Clarithromycin or Erythromycin or Itraconazole or Ketoconazole or use of these medicine with astemizole or terfenadine may cause herat problems such as irregular heartbeat. Use of these medicines should not be used together.

 .

18. Other medical problems- Tell your doctor if you have any other medical problems- Enlarged prostrate or Urinary tract blockage or difficult urination - antihistamines may make urinary problems worse Glaucoma - these medicines cause slight increase in eye pressure that may make the condition worse.

 19 Missed dose- If you are taking the medicine regularly and you miss a dose, take it as soon as possible. Khowever ifis time for the next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Pharmacology-

Antihistamines competitively antagonize histamine H1eceptor site, but do not bind with histamine to inactivate it.

Pharmacokinetics-

Pharmacokinetics have not been extensively studied .These agents are well absorbed following oral administration use, have an onset of action of 15 to 30 minutes, are maximal within 1 to 2 hours and have a duratin of action of about 4 to 6 hours, although some are longer acting.

Administration with food delays absorption, but does not affect bioavailability.
Take with food or without food

Pregnancy-

Do not use during the third trimester ,newborn and premature infants may have severe reactions (eg convulsions) Lactation- Antihistamine therapy is contraindicated in nursing mothers.

Children-

Antihistamines may diminish mental aletness. In young child they may produce paradoxical excitation.