Histamine

Addition

Potentiation

Synergism

Antagonism

COMBINED EFFECT OF DRUG

Addition

• “additive effect” combined effect of 2 chemicals is equal to the sum effect of each agent, considering same levels/concentration

Potentiation

• happens when 1 drug is not elicit a response on its own (inactive) but it has a possibility of enhancing the response to another drug

Synergism

• happens when the combined effect of 2 drugs is greater the sum of their effects when given separately

Antagonism

• (opposite of synergism) - less effect 

AUTACOIDS

Aka: local hormones

AUTACOIDS

• Endogenous substance with biological activity

AUTACOIDS

• Not released or stored in glands

• Not circulated in blood

AUTACOIDS

• Are formed at the site of action

• Produce localized action.

BIOLOGICALLY ACTIVE AMINES

• Low molecular weight organic compounds produced in biological system by the process of Decarboxylation of certain amino acids (therefore like Histamine & Serotonin their pre cursor are amino acid)

Decarboxylation of certain amino acids

BIOLOGICALLY ACTIVE AMINES process

Histamine & Serotonin

BIOLOGICALLY ACTIVE AMINES

Histamine

• involved in inflammatory responses and has central fall as a mediator of itchy & allergy

Serotonin

• a key hormone stabilizes our mood, feelings of well-being, and happiness. Mood, sleeping, eating, and digestion

Considered as the Neurotransmitter

• Prostaglandins, Leukotrienes, & Thromboxanes are derived from Arachidonic acid pathway

LIPID DERIVED AUTACOIDS (EICOSANOIDS)

Oxidation of fatty acids

LIPID DERIVED AUTACOIDS (EICOSANOIDS) process

LIPID DERIVED AUTACOIDS (EICOSANOIDS)

• A signaling molecules (hormones) from the Oxidation of fatty acids

Prostaglandins

group of lipids, made a site of tissue damage/infection produce. Involve in dealing injury and illnesses

Prostaglandins

They control processes such as inflammation, blood flow, the formation of blood clots and induction of labour

• arthritis, menstrual cramping

⬆ Prostaglandin

• glaucoma, stomach ulcer (since prostaglandin protects the stomach lining from gastric secretion)

⬇ Prostaglandin

Leukotrienes

• lipid mediator, acute and chronic inflammation and allergic diseases. 

Release by the mast cell during like Asthma attack ~ constricting the bronchioles, since Leukotrienes are Bronchoconstrictor

Leukotrienes release by

• They binds to G-protein coupled receptor (type 2 receptor or metabotropic)

Leukotrienes bind

Thromboxanes

• vasoconstrictor and a potent hypertensive agent, and facilitates platelet aggregation

ERGOT ALKALOIDS

For the management of migraine, headache

Kinins

Angiotensin

Endothelin

Natriuretic peptide

Vasopressin

Substance P

VASOACTIVE POLYPEPTIDES

Substance P

• a peptide mainly secreted by the neurons, involved in many biological processes including the modulation in Intestinal peristalsis (movement of the Intestine), Nociception (or the pain perception) and the inflamation

Vasopressin

aka as the Anti diuretic hormone

Vasopressin

• ⬇ Decreases water excretion by the kidneys by ⬆ increasing water reabsorption in the collecting ducts

Natriuretic peptide

• main physiologic action is to reduced arterial pressure by ⬇ decreasing the blood volume and systemic vascular resistance

Endothelin

• potent vasoconstrictor mainly secreted by endothelial cells

Angiotensin

• causes the blood vessels to become narrower 

Kinins

• proteins in the blood cause inflammation and affect blood pressure primarily to low blood pressure, it also increases the blood flow throughout the body making it for fluid to pass small blood vessels and it can also  stimulates the pain receptor 

Nitric oxide

ENDOTHELIUM DERIVED AUTACOIDS

Nitric oxide

• produce by many cells in the body,  it relaxes vascular smooth muscle

• mast cells and basophils

Histamine stored and found in the highest amounts in

Mast cells

• contribute to the  homeostasis of the immune system. They serve  as  the first line of defense against antigen entering the body

Basophils

• when they encounter allergens they will release histamine. Histamine will ⬆ increase blood flow to the damaged tissues resulting in swelling and then inflammation. A normal physiologic factor under Compensatory mechanism

Energy- and Ca2+ dependent degranulation reaction

Energy- and Ca2+ independent release (displacement)

TWO PROCESSES BY WHICH HISTAMINE IS RELEASED

Energy- and Ca2+ dependent degranulation reaction

• If the mast cell is sensitised by mediators like IgE antibodies the granulate when exposed to specific antigen they will release Histamine

• Histamine release by this mechanism is a mediator of immediate type 1 allergic reaction via Immunologic release

1. Energy- and Ca2+ independent release (displacement)

• The displacement is due to induction of drugs like Morphine, Tubocurarine, Guanethidine, or the amine antibiotics. Causing mast cell damage then the Histamine will release 

• Chemical and mechanical release 

• Occurs following chemical or mechanical injury to mast cells.

• Displacement is induced by drugs such morphine, tubocurarine, guanethidine, and amine antibiotics.

• ❌ Does not require energy