AUTACOIDS

(I)
HISTAMINE
AND
ANTI HISTAMINES
Aims and Objectives

The term autacoid is used for a group of

hormone like substances, which
originate from tissues, and produce
effects at the site of release.
Important members of this group are: -
I. Histamine
II. 5 Hydroxytryptamine (5HT)
III. Eicosanoids
1. Prostaglandins
2. Leukotrienes
3. Thromboxanes
I. Kinins
Autacoids play an important role in

the causation of inflammatory

reactions, and a variety of other

clinical disorders.
The agonists and antagonists belonging to this

group of substances are of considerable clinical

importance, and will, therefore, be discussed in

detail.

This lecture deals with Histamine and

Antihistamines.
HISTAMINE
Histamine is derived from amino acid

Histidine. It is found in lungs, skin and GIT.

Present in high concentrations in mast cells.

Also a component of venoms and secretions

from insect stings.

In the mast cells histamine is stored in

granules. The release of histamine from the

granules is responsible for inflammatory

and allergic reactions.

RECEPTORS LOCATION
i. Smooth muscles
H1 ii. Endothelium
iii. Brain
i. Gastric mucosa
ii. Cardiac muscle
H2 iii. Mast cells
iv. Brain
i. Brain
H3 (Presynaptic)
ii. Myenteric Plexus
H 1 and H 2 Receptors
ANTIHISTAMINES
(H1 BLOCKERS)
 FIRST GENERATION

DRUGS ANTICHOLINERGIC COMMENTS

ACTIVITY

ETHANOLAMINES
+++ Slight to moderate
Carbinoxamine
sedation
Dimenhydrinate +++
Marked sedation; anti-
(Dramamine) motion sickness activity
Diphenhydramine +++ Marked sedation; anti-
(Benadryl) motion sickness activity
DRUGS ANTICHOLINERGIC COMMENTS
ACTIVITY

ETHYLAMINE
DIAMINE + Moderate sedation
Tripelennamine
PIPERAZINE
DERIVATIVES
Cyclizine - Slight sedation; anti-
(Marezine) motion sickness
activity
Meclizine - Slight sedation; anti-
motion sickness
activity
DRUGS ANTICHOLINERGIC
COMMENTS
ACTIVITY

ALKYLAMINES
Brompheniramine + Slight sedation
(Dimetane)

Chlorpheniramine + Slight sedation;

DRUGS ANTICHOLINERGIC
ACTIVITY
COMMENTS
PHENOTHIAZINE
DERIVATIVE
Promethazine Marked sedation
(Phenergan) +++
antiemetic; α
block
MISCELLANEOUS
Cyproheptadine + Moderate sedation
(Periactin) Antiserotonin
activity
 SECOND GENERATION
DRUGS ANTICHOLINERGIC COMMENTS
ACTIVITY

PIPERIDINE
Fexofenadine -
MISCELLANEOUS
Longer action
Loratadine
-
Cetrizine (Zyrtec) -
PHARMACOLOGICAL ACTIONS

1. Smooth Muscles
i. Intestine: - Antagonism of Histamine
(competitive antagonism)
ii. Bronchi: - Histamine is blocked
Guinea-pig can tolerate 100 times lethal
dose of Histamine in the presence of a
suitable dose of Antihistamine.
2. Blood Pressure

The initial rapid hypotensive effect is

antagonized by H1 blockers. The hypotensive

effect in the second phase is antagonized by

H2 blockers.

3. HCl secretion: No effect

4. CNS
The first generation induces sedation.
Central excitation is the striking effect of
Poisoning.

5. Anticholinergic actions
Atropine like actions. The second
generation has no such effects.
6. Local anesthetic action
Promethazine
Pyrilamine
However, large doses are required.

7. Blockade of α 1 Adrenergic receptors

Promethazine  Hypotension
8. Other Effects

i. Capillary Permeability and Edema

H1 antagonists strongly block the action

of Histamine, that results in increased
capillary permeability and formation of
edema and wheal.
ii. Flare and Itch:
The flare component of the triple response
and the itching caused by intradermal
injection of histamine are two different
manifestations of the action of histamine on

nerve endings. H1 antagonists suppress

both.
iii. Serotonin (5HT) Blocking Action

Strong blocking effects at serotonin

receptors have been demonstrated for H1

antagonist cyproheptadine. This drug is

promoted as an anti serotonin agent.
THERAPEUTIC USES

I. ALLERGIC DISORDERS

1. Pruritis (Itching)

2. Urticaria

3. Vasomotor Rhinitis

4. Allergic responses to insect bites, chemicals

5. Allergic responses to Drugs

6. Common cold
II. MOTION SICKNESS (Prophylaxis)
Promethazine strongest in the group,
because of anticholinergic effect (See
Scopolamine).
III. NAUSEA & VOMITING
Dimenhydrinate (Drammamine)
Cyclizine HCl (Marezine)
Vestibular Disturbance; Meniere’s Disease
IV. SEDATION (CNS DEPRESSION)

Diphenhydramine (Benadryl)

V. ANAPHYLACTIC SHOCK

1. Edema & Itch  Blocked

2. Hypotension  Controlled to a lesser

extent

3. Bronchospasm  No Effect

Note: - Other substances involved.

SIDE EFFECTS

1. ANTIMUSCARINIC EFFECTS
i) Dryness of mouth
ii) Retention of urine
iii) Dryness of respiratory passages.
These effects are not seen with Second
Generation.
2. CENTRAL ACTIONS (CNS)
i) Sedation (not 2nd generation). May be
useful effect in some cases.
ii) Other central actions.
Dizziness; Tinnitus; Lassitude*; Euphoria;
Tremors; Nervousness
_______________________________________
* Laziness, Sluggishness
3. DIGESTIVE TRACT

Loss of Appetite; Epigastric distress

4. POLYMORPHIC VENTRICULAR
TACHYCARDIA

Terfenadine  Withdrawn

5. OTHER EFFECTS

Mutagenecity; Leukopenia; Agranulocytosis

ACUTE POISONING

• Effects strikingly resemble acute

Atropine poisoning.
• Central excitatory effect
• Dilated pupils
• Flushed face
• Dry mouth
• Sinus tachycardia
• Retention of urine
• Fever
• Finally coma with cardio-respiratory
collapse, and death with in 2-18 hours.
 SIDE
EFFECTS
 SIDE
EFFECTS
QUESTIONS
1. An antihistamine which has comparatively
lower potential to induce drowsiness /
sedation:
a) Loratidine
b) Cetrizine
c) Acrivastine
d) Dimenhydrinate
e) Diphenhydramine
2. A drug which belongs to second
generation of antihistamines:

a) Chlorpheniramine
b) Cyclizine
c) Meclizine
d) Promethazine
e) Acrivastine
3. A second generation antihistamine which
has been withdrawn from the market:

a) Loratidine
b) Cetrizine
c) Terfenadine
d) Promethazine
e) Meclizine
4. Many antihistamines (H1 Blockers) have
additional non-histamine related effects:
These are likely to include which one of
the following?
a) Muscarinic increase in the bladder tone
b) General anesthetic effects if the drug is injected
c) Antimotion sickness effect
d) Increase in total peripheral resistance
e) Insomnia