Autocoids agonist and antagonists

Question 1

enterochromaffin-like cell store ?

Answer 1

histamine and

Question 2

Histamine fucntion in GI

Answer 2

An important nonneuronal site of histamine storage and release is the enterochromaffin-like cell of the fundus of the stomach. These cells release histamine, one of the primary acid secretagogues, to activate the acidproducing parietal cells of the muco

Question 3

immunological release of histamine

Answer 3

IMMUNOLOGIC RELEASE

• Mast cells and basophils, if sensitized by IgE antibodies attached to their surface membranes, degranulate when exposed to the appropriate antigen. This type of release requires energy and Ca2+. Degranulation leads to the simultaneous release of histamine, ATP, and other mediators stored together in secretory granules. Histamine released by this mechanism is a mediator in immediate (type I) allergic reactions.

Question 4

Define Chemical release of histamine

Answer 4

Certain amines, including drugs such as morphine and tubocurarine, can displace histamine from the heparin-protein complex within cells. This type of release doesn’t require energy and is not associated with mast cell injury or degranulation.

• Chemical and mechanical mast cell injury causes degranulation and histamine release.

Question 5

classes of histamine

Answer 5

H1, H2, H3 & H4. All belong to the large superfamily of receptors linked to G proteins.

•

Question 6

where is H1 located

Answer 6

H1 receptors are present in endothelium, smooth muscle cells and nerve endings. H1 receptors are coupled to PLC; their activation leads to formation of IP3 and DAG; IP3 causes a rapid release of Ca2+ from the ER.

Question 7

where is h2 located

Answer 7

H2 receptors are present in gastric mucosa, cardiac muscle cells and some immune cells. H2 receptors are linked to the stimulation of adenylyl cyclase and thus to activation of cAMP-dependent protein kinase in the target cell

Question 8

activation of H3 causes

Answer 8

Activation of H3 receptors reduces transmitter release from histaminergic and other neurons.

Question 9

describe H4 receptors

Answer 9

H4 receptors are mainly found on leukocytes in the bone marrow and circulating blood. They appear to have important chemotactic effects on eosinophils and mast cells. They may play an important role in inflammation and allergy.

Question 10

main systems that histamine acts on

Answer 10

Cardiovascular 
extravascular smooth muscle
nervous system 
secretory tissue 
mast cells-->degranulation

Question 11

describe cardiovascular effects of histamine

Answer 11

vasodilation (involves both h1 and h2 –> H1 is fast and fleeting/H2is slow and sustained
H2 receptors are located on vascular smooth muscle cell, and the vasodilation is mediated by cAMP; H1
LD050917 3
receptors reside on endothelial cells and their stimulation leads to formation of NO.

Question 12

describe Histamine effects on heart

Answer 12

Direct cardiac effects of histamine include both increased contractility and increased pacemaker rate
mainly H2
In human atrial muscle, histamine can also decrease contractility: this effect is mediated by H1 receptors. If histamine is given IV, its direct cardiac effects are not prominent and are overshadowed by baroreflexes elicited by the reduced blood pressure.

Question 13

Histamine induced edema due to ?

Answer 13

Histamine-induced edema results from the action of histamine on H1 receptors in the vessels of the microcirculation, especially the postcapillary vessels.

Question 14

triple response

Answer 14

1. A localized red spot, extending a few mm around the site of injection. 2. A brighter red flush, or “flare”, extending about 1cm beyond the red spot and developing more slowly. 3. A wheal, discernible in 1-2 minutes, which occupies the same area as the original red spot.

Question 15

histamine effect on GI smooth muscle

Answer 15

Histamine causes contraction of intestinal smooth muscle (H1 effect) and histamineinduced contraction of guinea pig ileum is a standard bioassay for histamine

Question 16

histamine effect on bronchiolar smooth muscle

Answer 16

Histamine causes bronchoconstriction mediated by H1 receptors. Patients with asthma are very sensitive to histamine.

Question 17

nervous system effect of histamine

Answer 17

Histamine is a powerful stimulant of sensory nerve endings, especially those mediating pain and itching. This H1-mediated effect is an important component of urticarial response and reactions to insect and nettle stings

Question 18

secretory tissue effect of histamine

Answer 18

Histamine is a powerful stimulant of gastric acid secretion and to a lesser extent of gastric pepsin and intrinsic factor production. The effect is caused by activation of H2 receptors in gastric parietal cells, and is associated with increased adenylyl cyclase activity, cAMP concentration and intracellular Ca2+ concentration. Histamine also stimulates secretion in the small and large intestine

Question 19

clinical use of hitamine

Answer 19

Pulmonary Function Testing In pulmonary function laboratories, histamine aerosol is sometimes used as a provocative test of nonspecific bronchial hyperactivity.

Question 20

Ae of histamine

Answer 20

Adverse effects are dose-related. Flushing, hypotension, tachycardia, headache, wheals, bronchoconstriction, GI upset.

• Histamine should not be given to asthmatics or to patients with active ulcer disease or GI bleeding

Question 21

drugs that reduce degranualtion of histamine

Answer 21

Cromolyn and nedocromi and b2 agonists

Question 22

1st generation H1 receptor antagonist

Answer 22

• Chlorpheniramine • Cyclizine • Dimenhydrinate • Diphenhydramine
• Hydroxyzine • Meclizine • Promethazine

Has a large sedating effect –> highly lipophilic

Question 23

2nd generation h1 receptor antagonist

Answer 23

Second-generation:

• Fexofenadine • Loratadine
• Cetirizine

less sedating effects –> metabolised by p-glycoprotein

Question 24

h1 receptor antagonist actions

Answer 24

Historically, H1-antihistamines were considered to be H1 receptor antagonists. Recently, however, they have been shown to be inverse agonists.

• Histamine-induced contraction of bronchiolar and GI muscle can be completely blocked by these agents.
• H2 receptor-mediated actions such as increase in gastric acid secretion are unaffected.
• The first-generation H1 antagonists have additional effects unrelated to their blocking of H1 receptors. These effects reflect binding of the H1 antagonists to cholinergic, adrenergic, serotonin and local anesthetic receptor sites.

Question 25

vomiting reflex centers

Answer 25

H1, M1, D2, 5-HT3, and NK1.

Question 26

H1 antagonist uses

Answer 26

allergic conditions
motion sickness
somanifacients

Question 27

H1 antagonist sue in allergic sickness

Answer 27

H1 blockers are useful in treating allergies caused by antigens acting on IgE-antibody sensitized mast cells. Antihistamines are the drugs of choice in controlling symptoms of allergic rhinitis and urticaria because histamine is the principal mediator. • H1 blockers are ineffective in treating bronchial asthma because histamine is only one of several mediators. • Epinephrine is the drug of choice in treating systemic anaphylaxis and other conditions that involve massive release of histamine.

Question 28

H1 receptor antagonist for Motion sickness

Answer 28

Five neurotransmitter receptors are of primary imporance in the vomiting reflex: H1, M1, D2, 5-HT3, and NK1. The two most commonly used classes of drugs for motion sickness are the antihistaminics and the antimuscarinics. First-generation H1 receptor blockers bind to central H1 and M1 receptors and evoke an antiemetic effect that is the result of central inhibition of these receptors. They are effective agents for prevention of symptoms of motion sickness. Second generation H1 antagonists are ineffective antiemetics because they lack central actions.

Question 29

H1 receptor blocker antagonist uses in somnifacients

Answer 29

Some first-generation H1 blockers, such as diphenhydramine, have strong sedative properties and are used in the treatment of insomnia. The use of H1 antihistaminics is contraindicated in individuals working in jobs where wakefulness is critical.

Question 30

H1 antagonist AE

Answer 30

ADVERSE

• Sedation: less common with second generation agents. • Dry mouth: due to anticholinergic effects