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Autos:  self y akos : relief“A chemical substance produced by one type of cell that affects 

the function of different types of cells in the same region ”.

1. Eicosanoids: Prostaglandins (PG)Tromboxanes (TX)Leucotrienes (LT)

2. Nitric oxide (NO) and platelet activating factor (PAF)

3. Polipeptides: Angiotensine and Bradykinin.

4. Amines: Histamine and serotonin

AUTACOIDS

Generated

“de novo” 

stored

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HISTAMINE

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DISTRIBUTION OF HISTAMINE

Mast cells: Mucosa of the lungsDigestive track

SkinMouth, conjuntiva and nose

BasophilsNeurons (CNS)Platelets

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NN

CH2 -CH2 -NH2

CH3

1-METHYLHISTAMINE

NN

CH2-COOH

ACIDO 5-IMIDAZOLACETIC

Biosynthesis and metabolism

Histamine

Decarboxilase

diaminooxidase N-methyltransferase

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Mast cellHistamine

Symptoms

Allergen induced histamine release

B cell (plasma)

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Histamine releasing agents

- Neuromuscular blockers (tubocurarine).

- Morphine

- Antibiotics (vancomicyn, polimixine B)

- Substance P, bradikinine.

- Others: Radiation, bacterial toxins...

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Histamine receptors

Types H1 H2

Transducc Gq/11

PLC↑Ca++

NO↑GMPc

Gs

AC↑AMPc

H3

Gi/o

AC↓cAMP

Distribution • Lungs• endotelial cells• heart• gi tract• sensitive nerves

• stomach

parietal cells• Vessels• Heart

CNS

(presynaptic)

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Pharmacological actions of histamine

Histamine

H1 endotelial cells

Nitric oxide formation

Vasodilation

H2 smooth muscle

↑ cAMP

Persistent dilation

Blood pressure decrease

Cardiovascular (H1 and H2)

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Pharmacological actions of histamine

Stomach (H2 )

Increases secretion of HCl

Sensitive nerve terminals (H1 )

Itching, pain

Respiratory (H1)

Contraction of smooth muscle in the lungs (H1).

InflammationInduce IL-10 secretion

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1 3

2

Pharmacological actions of histamine

Triple response (Sir Thomas Lewis)(Intradermic injection triggers triphasic skin reaction )

Red spot: due to capillary dilation

Flare: redness in the surrounding area due to arteriolar dilatationmediated by axon reflex.

Wheal: due to exudation of fluid from capillaries and venules

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Antihistaminic drugs H1

First generation Second generation

DiphenhydramineClorpheniramineMepyramineDoxylamine

MeclizinePrometacineDimenhydrinate

CetirizineEbastineLoratadineTerphenadine

-Pass the blood brain barrier

-Less specific (5-HT,cholinergic, adrenergic…)

-Don´t pass the blood brainbarrier

-More specific

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Clinical use of antihistaminics H1

First and second generation

1) AllergiesRhinitis/ Allergic conjunctivitisUrticaria/ dermatitis

First generation

2) Kinetosis, dizzyness, emesis, vertigo (Dimenhydrate)

3) Sedation

4) Local anaesthetic (prometazina)

Second generation

5) Inflamation (Cetiricine, inhibit production of LTB4)

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Adverse effects of antihistaminics

First generation- Sedation (if cross blood brain barrier). (Tolerance)

- Antimuscarinic effect; dry mouth, anorexia, nausea…

-Gastrointestinal alterations: nausea

- 5-HT effects: increase of appetite

Second generation

-Arrithmia (terphenadine and asthemizol ).

- Sedation (only Cetiricine)

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H2 antagonist drugs

Ranitidine Cimetidine

Therapeutic use: peptic ulcer, gastic mucosal acidosis

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Allergie inhibition

Histamine

Respiratory tract

stomach wall

alergies

HCl secretion

Discovery of H1 and H2 receptor subtypes (~70s Sir James Black)

Cimetidine

~1976

Characterizationof H2 receptors

Difenhydramine

H1?

H2?

HCl secretionpersist

HCl secretioninhibition

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PG

G

H2

PG

K+

MOCO

HCO3-

Célula parietal

Célula epitelial

LUZ

PGE2

PGI 2

Histamina

Gastrina

Célula paracrina

G

M1 ACh

N. vagoATPasaH+ / K+ AMPc

Histamina

H+

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Cimetidina

Cimetidina

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(I) Histamine

Mepiramina Difenhidramina

NedocromileCromoglicate sodium

Histamina

Inhibitors of Histamine release

Pharmacological action: prophylaxis of the brocoespasmo

induced by histamine

Therapeutic use: Allergic bronchial asthma and

induced by exercise