Histamine & antihistaminics

Histamine And

H1-Antihistaminics

Dr. Mushtaq AhmedAssociate Professor, Pharmacology

PIMS, Medical College, Jalandhar, Punjab

Autacoids

These are diverse substances produced by wide variety of cells,

having intense biological activity, but act locally at the site of

synthesis and release

Types of autacoids:

• Amine autacoids

- Histamine, 5-HT (Serotonin)

• Peptide autacoids

- Plasma kinins (Bradykinin, Kallidin), Angiotensinogen

• Lipid autacoids

- Prostaglandins, Leucotrienes, PAF

Storage And Release

• Storage

- Mast cells and Basophils

- Non – mast cell histamine

* Stomach (ELC)

* Brain

• Release

- Immunological

- Chemical & mechanical

Drugs and Chemicals

Drugs and chemicals causing release of Histamine

Morphine

D-tc, Aminoglycosides etc

Inactivation Pathway of Histamine

Histamine Receptors

• H1 :-

Location: Smooth muscle, exocrine glands, vascular endothelium,

brain; coupled to phospholipase C, leading to IP3 and

diacylglycerol (DAG) production

• H2 :-

Location: Parietal cells, heart, vascular smooth muscle, mast

cells, brain; coupled to cAMP production

• H3 :-

Location: Brain, myenteric plexus (no therapeutic applications,

yet)

MOA of Histamine

• Activation of H1 → ↑ phosphoinositol hydrolysis and ↑ in

intracellular calcium → SM contraction, ↑ in vascular

permeability and mucus secretion

• Activation of H2 → ↑ intracellular CAMP → ↑ gastric acid

secretion

• Activation of H3 → ↓ transmitter release from histaminergic

and other neurons

Pharmacological actions of Histamine

• CNS

- No BBB penetration

- On Intracerebrovascular injection:

* ↑ in BP, cardiac stimulation

* Vomiting, ADH release

• Heart

- Insitu heart – No prominent action

- Isolated heart - ↑ in rate & FOC

Pharmacological actions of Histamine Contd.

• Blood Vessels

- Dilation of smaller Bl. Vessels

- S.C. injection- heat, flushing, ↑ in HR & CO

- Rapid IV injection- ↓ BP

- Intradermal Injection: (Triple Response)

* Red Spot – Capillary dilatation

* Wheal – Exudation of fluid from capillaries and venules

* Flare – Arteriolar dilation

• Viceral Smooth Muscles

- Bronchoconstriction

- Abd. Cramps & colic

• Glands

- ↑ in gastric secretion

• Sensory nerve endings

- IV – itching , Pain

• Autonomic ganglia & Adrenal medulla

- Release of Adrenaline → secondary ↑ in BP

Pharmacological actions (contd.)

Effect of IV histamine on blood pressure

Mediated by H1 receptors on endothelium

Mediated by H2 receptors on vascular smooth muscle

Pathophysiological roles

• Gastric Secretion

• Allergic Phenomena

• As transmitter

• Inflammation

• Tissue growth and repair

SUMMARY OF EFFECTS OF HISTAMINE

Uses Of Histamine

No Therapeutic Use• Diagnostic Uses:

* Secreting (Acid) capacity of stomach

* Pheocromocytoma

* Bronchial hyper-reactivity in Asthamatics

H1 Selective Histamine Analogue:

Betahistine (used to control vertigo in Meniere’s disease)

Antagonists of Histamine

Physiological antagonists :

Adrenaline – effects are opposite to effects of histamine

Histamine release Inhibitors →

Mast cell stabilizers : Cromoglycate

Histamine receptor blockers :

H1 blockers and H2 blockers

Antihistaminics (H1- Antagonists)• Classification:• Highly Sedative:

- Diphenhydramine - Dimenhydrinate- Promethazine - Hydroxyzine

• Moderately sedative:- Antazoline - Cyproheptadine- Buclizine - Pheniramine Melate

• Mild Sedative:- Chlorphenramine - Cyclizine- Dimethindine - Methidilazine

• Non Sedative:- Astemizole - Cetrizine, levocetrizine- Terfenadine - Loratadine- Cinnarizine - Fexofenadine- Mizolastine - Rupatadine

• CNS- Variable degree of CNS depression

• BP- IV inj. – cause ↓ BP

• Antagonism of Histamine- Effectively block:

* Bronchoconstriction* Contraction of sm. Mus.* Triple response

• Anti-allergic action- Type- I reactions are suppressed

Pharmacological actions of H1-Antihistamines

PK & SE

• PK- A – Well absorbed- D - Wide distribution- M- Metabolized in liver- E - Excreted through urine

D. O. A : 4-6 hrs 2nd Gen: 12-24 hrs

• SE- 1st Gen;

- Sedation, Light headedness, Diminished alertness &concentration, motor in-cordination & fatigue

- 2nd Gen;- Dryness of mouth, Alteration of bowl movements,

Urinary hesitancy

Therapeutic Uses of H1- Antagonists

• Allergic Disorders

• Pruritus

• Common Cold

• Motion sickness

• Vertigo

• Preanesthetic medication

• Cough

• Parkinsonism

• Acute muscle dystonia

• As sedative, hypnotic and anxiolytic

HISTAIME

↓

Anaphylactic Shock

Anaphylaxis

A medical emergency needs immediatetreatment of:

- Hypotension

- Bronchospasm

- Laryngeal Edema

Treatment of Anaphylactic Shock• Lay the patient flat & raise the legs• Attend to the airway

• Inj. Adrenaline - 0.5 ml (1:1000) IM or 3-5 ml (1:10,000) Slow IV = adult- 0.01 ml (1:1000) IM or 0.1 ml (1:10,000) Slow IV = children

• Inj. Salbutamol- For Pts on non-selective β- blockers

• IV Fluids- To correct hypotension

• Inj. Hydrocortisone Hemisuccinate 100mg - IV• Antihistaminics

- Do not counter hypotension & bronchospasm

• Inj. Aminophylline IV or Nabulized Salbutamol• Supportive Measures

- Oxygen & assisted ventilation

Why Adrenaline is DOC for Anaphylactic Shock ?

Epinephrine is a physiological antagonist ofhistamine, not a pharmacological antagonist

α-1 = Vasoconstriction

ß-1 = Increased HR

ß-2 = Bronchodilatation

Thank You

Histamine