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DR AAKANKSHA SINGH
What is an antihistamine?
 A drug that reduces or eliminates the effects mediated
by the chemical histamine
 Histamine i...
 Histamine: Histamine was first identified in 1910
and recognized in the 1920s as a major
pathogenic mediator of allergic...
 it is an endogenous substance synthesized
and stored in and released by
(a) mast cells, which are abundant in the
skin, ...
 Allergies are caused by hypersensitivity reaction
involving antibody class IgE (which are located on
mast cells in the t...
Pharmalogical effects of Histamine
1)Histamine promotes( intestinal and Bronchiolar )
smooth muscle contraction which is a...
The different Histamine receptors
LOCATION EFFECT TREATMENT
H1 Throughout the body, specifically in
smooth muscles, on vas...
Clinical Symptoms Associated With
Histamine Release
 mild/cutaneous
 mild to moderate
 severe/anaphylactic
• erythema, ...
CLINICAL CLASSIFICATION OF H1
ANTIHISTAMINICS
DRUG
 1) HIGHLY SEDATIVE
 Diphenhydramine
 Dimenhydrinate
 Promethazine
...
 2)MODERATLEY SEDATIVE
 Pheniramine
 Cinnarizine
 Cyproheptadine
3) MILD SEDATIVE
 Chlorpheniramine
 Cyclizine
First generation H1 antihistamines
 Ethanolamine- Diphenhydramine
 Piperidine- cyproheptidine
 Phenothiazine- promethaz...
 4) SECOND GENERATION ANTIHISTAMINICS
 Terfenadine
 Fexofenadine
 Astemizole
 Loratidine
 Desloratidine
 Cetrizine
...
Hydroxyzine
 Hydroxyzine can be administered orally or via
intramuscular injection. When given orally,
hydroxyzine is rap...
Pheniramine
 is an antihistamine with anticholinergic properties
used to treat allergic conditions such as hay
fever or u...
Cetrizine
 Cetrizine is the carboxylic metabolite of first
generation H1 antihistamine hydroxyzine.
 It is rapidly absor...
Levocetrizine
 It is the most recently introduced second generation
H1 antihistamine.
 More potent in supressing the his...
Terfenadine and fexofenadine
 Terfenadine was an antihistamine formerly used for
the treatment of allergic conditions.
 ...
 Terfenadine, in addition to its antihistamine effects,
also acts as a potassium channel blocker . Since its
active metab...
Loratadine
 It is a piperidine tricyclic selective long acting H1
antihistamine with minimal sedation
 Loratadine is giv...
Systemic and topical doxepin
 Doxepin is tricyclic antidepressent drug with potent
H1 and H2 antihistamine activity.
 It...
 It can also cause allergic contact dermatitis (dermatitis
medicamentosa)
 Topical doxepin should be used for 8 days at ...
Pharmacokinetics
The classical H1 antihistaminics are well absorbed from
oral and parenteral routes,metabolized in liver a...
Drug interactions-H1
antihistamines
Interacting drug group Examples
These drugs may increase serum levels
of
Several H1 an...
Diphenhydramine may increase serum Levels of these drugs
Beta blockers Metoprolol,propanolol,,risk bradycadia
Tolerance(tachyphylaxis and
subsentivity)
 Development of tolerance after continued regular
administration of H1 antihist...
Therapeutic uses
1)Allergic Reactions:
 allergic rhinitis , Atopic dermatitis, hay fever,
urticaria
2)Sedation and hypnot...
USE IN PREGNANCY AND
LACTATION
 Chlorpheniramine, one of the first-generation
antihistamines, is reportedly safe in pregn...
adverse effect
 1)first generation- generally mild,sedation,diminshed
alertness,light headache and tendency to sleep
 2)...
THANK YOU
H2 receptor antangnists
 Cimetidine (Tagamet)
 Ranitidine (Zantac)
 Famotidine (Pepcid)
Clinical uses
 Peptic Ulcer and Duodenal Disease
 Gastric Ulcer: reduce symptoms
promote healing for benign gastric ulce...
Hypersecretory Disease:
 Zollinger-Ellison syndrome:
 acid hypersecretion -- caused by gastrin-secreting
tumor
 Systemi...
adverse effects
 cimetidine --------CNS effects (uncommon): elderly:
confusion states, delirium, slurred speech (most
ass...
Antihistaminics
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Antihistaminics

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Antihistaminics

  1. 1. DR AAKANKSHA SINGH
  2. 2. What is an antihistamine?  A drug that reduces or eliminates the effects mediated by the chemical histamine  Histamine is released by your body during an allergic reaction and acts on specific histamine receptors  The term antihistamine usually refers to H1 receptor antagonists (actually inverse agonists)  Antihistamines compete with histamine for binding sites at the receptors. Antihistamine cannot remove the histamine if it is already bound
  3. 3.  Histamine: Histamine was first identified in 1910 and recognized in the 1920s as a major pathogenic mediator of allergic disorders. Histamine receptor antagonist was introduced in 1937, and from 1942 to 1981, more than 40 compounds have reached the market. Histamine is derived from the decarboxylation of the aminoacid histidine, a reaction catalyzed by the enzyme L-histidine decarboxylase
  4. 4.  it is an endogenous substance synthesized and stored in and released by (a) mast cells, which are abundant in the skin, GI, and the respiratory tract, (b) basophils in the blood
  5. 5.  Allergies are caused by hypersensitivity reaction involving antibody class IgE (which are located on mast cells in the tissues and basophils in the blood)  When an allergen is encountered, it binds to IgE, which activates the mast cells or basophils, leading them to release massive amounts of histamines.
  6. 6. Pharmalogical effects of Histamine 1)Histamine promotes( intestinal and Bronchiolar ) smooth muscle contraction which is an H1 receptor mediated effect 2)Histamine significantly increases gastric acid and gastric pepsin secretion which is an H2 receptor mediated effect 3) Vasodilation of arterioles and precapillary sphincters which is an H1and H2 receptor mediated effect
  7. 7. The different Histamine receptors LOCATION EFFECT TREATMENT H1 Throughout the body, specifically in smooth muscles, on vascular endothelial cells, in the heart and the CNS Mediate an increase in vascular permeability at sites of inflammation induced by histamine Allergies, nausea, sleep disorders H2 In more specific locations in the body mainly in gastric parietal cells, a low level can be found in vascular smooth muscle, neutrophils, CNS, heart, uterus Increases the release of gastric acid Stomach ulcers H3 Found mostly in the CNS, with a high level in the thalamus, caudate nucleus and cortex, also a low level detected in small intestine, testis and prostate. Neural presynaptic receptor, may function to release histamine Unknown H4 They were recently discovered in 2000. They are widely expressed in components of the immune system such as the spleen, thymus and leukocytes. unkonwn In addition to benefiting allergic conditions, research in the h4 receptor may lead to the treatment of autoimmune diseases. (rheumatoid arthritis)
  8. 8. Clinical Symptoms Associated With Histamine Release  mild/cutaneous  mild to moderate  severe/anaphylactic • erythema, urticaria, and/or itching • skin reactions, tachycardia, dysrhythmias, moderate hypotension, mild respiratory distress • severe hypotension, ventricular fibrillations, cardiac arrest, bronchospasm, respiratory arrest
  9. 9. CLINICAL CLASSIFICATION OF H1 ANTIHISTAMINICS DRUG  1) HIGHLY SEDATIVE  Diphenhydramine  Dimenhydrinate  Promethazine  Hydroxyzine
  10. 10.  2)MODERATLEY SEDATIVE  Pheniramine  Cinnarizine  Cyproheptadine 3) MILD SEDATIVE  Chlorpheniramine  Cyclizine
  11. 11. First generation H1 antihistamines  Ethanolamine- Diphenhydramine  Piperidine- cyproheptidine  Phenothiazine- promethazine  Alkylamine- chlorpheniramine  Piperazine- hydroxyzine
  12. 12.  4) SECOND GENERATION ANTIHISTAMINICS  Terfenadine  Fexofenadine  Astemizole  Loratidine  Desloratidine  Cetrizine  5)NEW SECOND GENERATION- Levocetrizine
  13. 13. Hydroxyzine  Hydroxyzine can be administered orally or via intramuscular injection. When given orally, hydroxyzine is rapidly absorbed from the gastro- intestinal tract. The effect of hydroxyzine is notable in 30 minutes  hydroxyzine is rapidly absorbed and distributed in oral and intramuscular administration, and is metabolized in the liver; the main metabolite (45%) is formed is cetirizine
  14. 14. Pheniramine  is an antihistamine with anticholinergic properties used to treat allergic conditions such as hay fever or urticaria. It has relatively strong sedative effects, Pheniramine may cause drowsiness, bradycardia and sleep disorders. Overdose may lead to seizures, especially in combination with alcohol.
  15. 15. Cetrizine  Cetrizine is the carboxylic metabolite of first generation H1 antihistamine hydroxyzine.  It is rapidly absorbed after oral administration.  A single 10 mg oral dose causes significant histamine wheal suppression in 20-60 minutes and lasts for 24 hours.  Indication – urticaria  It is formulated as 1o mg tablets and a 1mg/ml syrup.
  16. 16. Levocetrizine  It is the most recently introduced second generation H1 antihistamine.  More potent in supressing the histamine wheal in healthy volunteers with low sedation.  It is licensed for patients over 6 years of age in dosage of 5 mg daily for the indication of urticaria.
  17. 17. Terfenadine and fexofenadine  Terfenadine was an antihistamine formerly used for the treatment of allergic conditions.  Terfenadine is a prodrug, generally completely metabolized to the active form fexofenadine in the liver . Due to its near complete metabolism by the liver immediately after leaving the gut, terfenadine normally is not measurable in the plasma. Terfenadine itself is cardiotoxic(specifically cardiac arrhythmia caused by QT interval prolongation). at higher doses, while its major active metabolite is not.
  18. 18.  Terfenadine, in addition to its antihistamine effects, also acts as a potassium channel blocker . Since its active metabolite is not a potassium channel blocker, there is no cardiotoxicity associated with fexofenadine.  Fexofenadine is absorbed by oral route with peak plasma levels being achieved at 1 to 3 hours after administration.  After a single dose 80% is recovered unchanged in the faeces and 12% excreted in urine.  dose of fexofenadine 30,60,180mg
  19. 19. Loratadine  It is a piperidine tricyclic selective long acting H1 antihistamine with minimal sedation  Loratadine is given orally, is well absorbed from the gastrointestinal tract, and has rapid first-pass hepatic metabolism  Its metabolite desloratadine, which is largely responsible for the antihistaminergic effects.  Indication – is administered as 10 mg capsules and syrup(1mg/ml) for the treatment of chronic urticaria
  20. 20. Systemic and topical doxepin  Doxepin is tricyclic antidepressent drug with potent H1 and H2 antihistamine activity.  It has proved useful when given systemically in the treatment of severe urticaria.  Doxepin has also been formulated as a 5% cream with indication of pruritus in eczematous dermatitis.  Although effective,5% doxepin cream may cause significant drowsiness because of percutaneous absorption
  21. 21.  It can also cause allergic contact dermatitis (dermatitis medicamentosa)  Topical doxepin should be used for 8 days at the most.
  22. 22. Pharmacokinetics The classical H1 antihistaminics are well absorbed from oral and parenteral routes,metabolized in liver and excreted in urine except fexofenadine which is excreted in faeces Duration of action of most agents is 4-6 hours,except newer antihistamines which act for 12-24 hours or more.
  23. 23. Drug interactions-H1 antihistamines Interacting drug group Examples These drugs may increase serum levels of Several H1 antihistamines Antibacterial Erythromycin,clarithromycin Azole antifungal agents Fluconazole at doses 300 mg daily or higher H2 antihistamines cimetidine These drugs may decrease serum levels of Several H1 antihistamines Antibacterial Rifamycin,rifabutin (risk with fexofenadine,loratidine) anticonvulsants Carbamazepine,phenytoin
  24. 24. Diphenhydramine may increase serum Levels of these drugs Beta blockers Metoprolol,propanolol,,risk bradycadia
  25. 25. Tolerance(tachyphylaxis and subsentivity)  Development of tolerance after continued regular administration of H1 antihistamines is frequently perceived as a problem.  In a comparison of several antihistamines administered daily for 3 weeks ,hydroxyzine(75mg daily) proved to be the most effective in suppressing intracutaneously injected histamine wheel.  Hydroxyzine showed greatest degree of tolerance in contrast chlorpheniramine showed little or no tendency to produce subsentivity.
  26. 26. Therapeutic uses 1)Allergic Reactions:  allergic rhinitis , Atopic dermatitis, hay fever, urticaria 2)Sedation and hypnotics. :  these agents to be used has sleep-aids, i.e. hypnotics.  The newer H1 antagonists, by contrast, cause minimal or no sedation.
  27. 27. USE IN PREGNANCY AND LACTATION  Chlorpheniramine, one of the first-generation antihistamines, is reportedly safe in pregnancy. There is little information on the use of the new antihistamines during pregnancy although cetirizine,levocetrizine,hydroxyzine,fexofenadine and loratadine are considered relatively safe for use during pregnancy(FDA category B).H1antihistamines are excreted in small amounts in breast milk (<0.1% of a maternal dose). Breast-fed infants whose mothers have ingested first-generation antihistamines may experience irritability, drowsiness or respiratory depression;no symptoms have been attributed to second-generation antihistamines to date.
  28. 28. adverse effect  1)first generation- generally mild,sedation,diminshed alertness,light headache and tendency to sleep  2)dryness of mouth,alteration of bowel movements,urinary hesitancy and blurring of vision  3)epigastric distress  4)local application can cause contact dermatitis  Acute overdose produces central excitation,tremors,convulsions,flushing, hypotension.  Death is due to respiratory and cardiovascular failure
  29. 29. THANK YOU
  30. 30. H2 receptor antangnists  Cimetidine (Tagamet)  Ranitidine (Zantac)  Famotidine (Pepcid)
  31. 31. Clinical uses  Peptic Ulcer and Duodenal Disease  Gastric Ulcer: reduce symptoms promote healing for benign gastric ulcers  Gastroesophageal Reflux Disorder (erosive esophagitis)
  32. 32. Hypersecretory Disease:  Zollinger-Ellison syndrome:  acid hypersecretion -- caused by gastrin-secreting tumor  Systemic mastocytosis and multiple endocrine adenomas:
  33. 33. adverse effects  cimetidine --------CNS effects (uncommon): elderly: confusion states, delirium, slurred speech (most associated with cimetadine)  ---------antiandrogenic effects  ---------Blood Dyscrasias (granulocytopenia , thrombocytopenia , neutropenia , aplastic anemia)

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