Histamine Is a protein substance manufactured & found in human tissues Its also a component of some venoms & secretions of stinging insects Storage of histamine In tissue mast cells (mainly) In basophils Enterochromaffin-like (ECL) cells of fundus of the stomach Histamine release from mast cells; Its released in response to; 1.Direct chemical /physical trauma to tissue mast cells 2. Drugs like morphine which displace histamine from their storage sites 3. Immunologic reactions esp the type 1allergic reactions coz degranulation of mast cells Mechanism of action of histamine Actions of histamine are mediated via histamines receptors found on cell membranes of different tissues Types of histamine receptors; H1 receptors H₂ receptors H₃ receptors H₄ receptors

1. Dr. NDAYISABA CORNEILLE
CEO of CHG
MBChB,DCM,BCSIT,CCNA
Supported BY
HISTAMINE
ANTAGONISTS

2. Histamine
 Is a protein substance manufactured & found in
human tissues
 Its also a component of some venoms &
secretions of stinging insects
Storage of histamine
 In tissue mast cells (mainly)
 In basophils
 Enterochromaffin-like (ECL) cells of fundus of
the stomach

3.  Within tissues mast cells are found at sites likely to
be damaged like;
 Nose & respiratory mucosa
 Mouth
 Feet
 Internal body surfaces
 Blood vessels
NB; No mast cells are found in brain

4. Histamine release from mast cells;
 Its released in response to;
1.Direct chemical /physical trauma to tissue mast
cells
2. Drugs like morphine which displace histamine
from their storage sites
3. Immunologic reactions esp the type 1allergic
reactions coz degranulation of mast cells

5. Mechanism of action of histamine
 Actions of histamine are mediated via histamines
receptors found on cell membranes of different
tissues
Types of histamine receptors;
1. H1 receptors
2. H₂ receptors
3. H₃ receptors
4. H₄ receptors

6. Location of the various histamine receptors
1. H1 receptors
 Smooth muscle cells
 Endothelium
 Brain
2. H₂ receptors
 Gastric mucosa cells
 Cardiac muscle
 Mast cells
 Brain

7. 3. H₃ receptors
 Presynaptic: brain, myenteric plexus, other neurons
4. H₄ receptors
 Eosinophils
 Neutrophils
 CD4 T cells

8. Physiological effects of histamine
1. Acts as a neurotransmitter in brain with resultant;
 Neuroendocrine control
 Cardiovascular regulation
 Thermal & body weight regulation
 Control of arousal

9. 2. It promotes HCl production after it binds to
H-2 receptors on parietal cells of the gastric
mucosa
3. It mediates inflammation by binding to H-1
receptors on blood vessels, nerve cells,
leading to sneezing, vasodilatation, swelling
,pruritus, nasal discharge etc

10. Histamine antagonists

11. Definition
 Are drugs that inhibit the actions of histamine
by blocking histamine receptors
Types /classification of histamine antagonists
1. H1-receptor antagonists
2. H2 receptor antagonists
3. H3- & H4-receptor antagonists

12. 1. H1-receptor antagonists
 Are drugs commonly referred to antihistamines
 Thus a term antihistamines refers only to H1
receptor antagonists
 Are drugs which block H1-receptors located on
vessel smooth muscle cells, brain ,heart etc
 Clinically
 H1 antagonists are used mainly to treat
allergic reactions

13. Mechanism of action
Bind & block H-1 receptors thus relieving Sxs of
inflammation like swelling, nasal discharge
pruritus, sneezing etc
Drugs bind to & block H1 receptors found on ;
a. Smooth muscle cells of blood vessels
b. Brain
c. Nerves
d. Glandular cells
e. Endothelium & mast cells

14.  This inhibits histamine-induced wheal
(swelling) & vasodilation (flare)
response
 Itching & sneezing are suppressed by
antihistamine blockage of H1-receptors
on nasal sensory nerves

15. Pharmacokinetic aspects H1-receptor antagonists
 Most anti-histamines;
 Are given orally & are well absorbed from gut
 Reach their peak effect in 1-2 hours
 Are effective for 3-6 hours
 Are widely distributed thru out the body
 Some do not penetrate BBB e.g non-sedative anti-
histamines
 Are metabolised in liver & excreted in urine

16. Types of H-1 anti-histamines
Sedating H1 antihistamines And Non sedating
antihistamines
1. Sedating H1 antihistamines
 Are also known as;
 1st generation antihistamines
 Older antihistamines
 They coz sedation
 This sedating activity is some times used to manage
pruritus associated with some allergies

17. Examples
 Promethazine (phenergan)
 Chlorphenamine (piriton)
 Cyclizine
 Alimemazine
NB; Little evidence occurs some sedating
antihistamines are superior to the other

18. Clinical indications of Chlorphenamine (piriton)
1.Symptomatic relief of allergies like;
 Hay fever/allergic rhinitis
 Rashes due to drug hypersensitivity
 Urticaria
2.Used in combination with adrenaline in emergency
tx of anaphylactic reactions
3. Symptomatic relief of pruritus due to chicken pox

19. Contraindications & cautions of PIRITON
 This drugs are contraindicated or used with caution in;
1. Pregnancy
2. Breast feeding
3. Pylorodeudenal obstruction
4. Benign prostatic hypertrophy
5. Urine retention
6. Angle closure glaucoma
7. Pts with epilepsy

20. Indications of Promethazine (phenergan)
1. Symptomatic relief of allergies like;
 Hay fever
 Urticaria
2. Emergency tx of anaphylactic shock
3. Treatment of nausea & vomiting (anti-emetic)
4. Induction of sedation

21. Contraindications & cautions of prometazine
 These drugs are contraindicated or used with
caution in ;
1. Children < 2 years
2. Severe coronary artery disease
3. Pregnancy
4. Breast feeding
5. Pylorodeudenal obstruction

22. 6. Benign prostatic hypertrophy
7. Urine retention
8. Angle closure glaucoma
9. Pts with epilepsy

23. 2. Non sedating antihistamines
 These are also known as;
 2nd generation antihistamines
 Newer anti-histamine
 They coz less; sedation & psychomotor impairment
bcoz they poorly penetrate the BBB

24.  Examples
 Cetrizine
 Levocetrizine
 Loratadine
 Desloratadine
 Fexofenadine
 Mizolastine
 Etc

25. Clinical indications of Cetrizine
1. Symptomatic relief of allergies like
 Hay fever
 Chronic idiopathic urticaria
 Angioedema
 Atopic dermatitis in which drug reduces
awareness of itching
2. In UTRI due to rhinovirus infection to reduce
inflammation

26. Clinical indications of H-1 antihistamines
1. Treatment & prevention of allergic conditions like;
 Seasonal allergic rhinitis (hay fever)
 Pruritus
 Drug hypersensitivity reactions
 Insect & bee stings
 Urticaria rashes
2.Emergency Tx of angioedema & anaphylactic shock in
combination with adrenaline
3. Treatment of occasional insomnia

27. 1. Drowsiness –very common
2. Headaches
3. Psychomotor impairment
4. Anti-muscarinic (blockage of Parasympathetic NS) S/Es
like
 Urine retention
 Dry mouth
 Constipation
 Blurring of vision
 Palpitations
Common unwanted effects of older anti-histamines

28. Other rare S/Es of all anti-histamines
1. CNS
 Extra pyramidal S/Es
 Dizziness
 Confusion
 Restlessness
 Depression
 Tremors
 Seizures

29. 2. CVS
 Palpitations
 Cardiac arrhythmias
 Hypotension
3.GIT
 Liver disorders

30. 4. Hypersensitivity reactions like
 Bronchospasms
 Angioedema
 Anaphylactic shock
 Rash
 Photosensitivity reactions
NB; What is defined as 'unwanted' will depend to a
certain extent on what the drugs are used for

31. Contraindications & cautions
 These drugs are contraindicated or used with caution
in pts with conditions like;
1. Benign prostatic hypertrophy
2. Urine retention
3. Angle closure glaucoma
4. Pylorodeudenal obstruction
5. Pts with epilepsy
6. Liver disease
7. Acute porphyria

32. 8.Pregnancy
9.Breast feeding
10.Renal failure
Dr Ndayisaba Corneille

33. 2. H2 receptor antagonists;
 Drugs that bind to & block histamine-2 receptors
located on parietal cells of gastric mucosa
Mechanism of action
 Blockage of histamine-2 receptors located on
parietal cells of stomach mucosa leading to ↓
HCl production

34. Indications
 Tx of acid reflux disease (heart burn)
 Tx of gastric ulcers
Examples
 Cimetidine ,Ranitidine
 Nizatidine, Famotidine
 Lafutidine
 Roxatidine

35. 3. H3 & H4-receptor antagonists
 Drugs that block H3- & H4-receptors
 These are still experimental drugs
 These do not yet have a defined clinical use

36. END
BY
DR NDAYISABA CORNEILLE
MBChB,DCM,BCSIT,CCNA,Cyber Security
contact: amentalhealths@gmail.com ,
ndayicoll@gmail.com
whatsaps :+256772497591 /+250788958241
THANKS FOR LISTENING
Dr Ndayisaba Corneille