IPS2: Pharmacology - Part 6.1 - Autacoids - Introduction, Histamine

Autacoids

I. Localized Hormones

II. Site of release is near the site of action

III. Elicits their physiological action in the body on the area that they were released

IV. Does not need to be incorporated, circulated, distributed in the body

V. Produced by virtually all cells

a. I, II, III

b. III, IV, V

c. I, II, III, IV

d. II, III, IV, V

e. I, II, III, IV, V

e. I, II, III, IV, V

Endocrine hormones compared to autacoids.

a. Act systemically

b. They need to be incorporated in the blood

c. Produced by specific cells

d. a and b

e. b and c

f. All

f. All

Example of endocrine hormones is insulin which is essential in every cell of the body for efficient glucose utilization but is only produced by beta cell of the pancreas.

a. True

b. False

a. True

Major types of autacoids

I. Bradykinin

II. Eicosanoids

III. Serotonin

IV. Histamine

V. Dopamine

a. I, II, III, IV, V

b. I, II, III, IV

c. II, III, IV, V

d. I, II, III,

e. IV, V

b. I, II, III, IV

Histamine locations.

I. Mast cells

II. Basophils

III. Stomach parietal cells

IV. CNS

a. I, II, III, IV

b. I, II

c. III, IV

d. I

e. II

a. I, II, III, IV

Location wherein huge amount of histamine is usually stored and high sequestered in areas with potential tissue injury thus are effectors during allergic reaction.

I. Mast cells

II. Basophils

III. Stomach

IV. CNS

a. I, II, III, IV

b. I, II

c. III, IV

d. I

e. II

b. I, II

Histamine.

a. Histamine being found in parietal cells is also a mediator of hydrochloric acid release in the stomach

b. Huge amount is usually stored in mast cells and basophils

c. Found in the brain

d. a and b

e. b and c

f. All

f. All

Precursor for the biosynthesis of histamine.

a. Tryptophan

b. Tyrosine

c. Histidine

d. Arachidonic acid

e. Methacholine

c. Histidine

Histidine will undergo ________, through the enzyme ________ to be converted to histamine.

a. Hydroxylation; Prolyl hydroxylase

b. Methylation; Aldolase

c. Decarboxylation; L-histidine decarboxylase

d. Hydrolysis; Phospholipase A2

c. Decarboxylation; L-histidine decarboxylase

Histamine mechanism of release

a. Stored via vesicle

b. Ca2+ dependent degranulation

c. Ca2+ independent degranulation

d. a and b

e. a and c

f. All

f. All

Histamine release through Ca2+ dependent degranulation.

I. Induced by immunoglobulin E (IgE) fixation to mast cells

II. IgE Medicated

III. Increase Histamine level available for action

IV. Lead to fixation of IgE to mast cells which causes Anaphylaxis

a. I, II, III, IV

b. I, II

c. III, IV

d. I

e. II

a. I, II, III, IV

Histamine release through Ca2+ independent degranulation.

I. Induced by drugs

II. Drugs inducers include Morphine, Guanethidine, Tubocurarine, Amine Antibiotics

III. Enhance release of histamine via exocytosis: increasing histamine level, available for action

IV. Histamine increased effects are referred to as Anaphylactoid Reaction

a. I, II, III, IV

b. I, II

c. III, IV

d. I

e. II

a. I, II, III, IV

Drugs that can induce release of Ca2+-independent degranulation release of histamine.

I. Morphine

II. Guanethidine

III. Tubocurarine

IV. Amine Antibiotics

a. I, II, III, IV

b. I, II, III

c. II, III, IV

d. I, II

e. III, IV

a. I, II, III, IV

Types of histaminic receptors.

I. Histaminic-1 (H1)

II. Histaminic-2 (H2)

III. Histaminic-3 (H3)

IV. Histaminic-4 (H4)

a. I, II, III, IV

b. I, II, III

c. II, III, IV

d. I, II

e. III, IV

a. I, II, III, IV

Histaminic-1 (H1) locations except:

a. Vascular smooth muscles

b. Extravascular smooth muscles

c. Sensory nerve endings

d. Endothelial cells

e. Stomach parietal cells

f. None

e. Stomach parietal cells - this is location of H2 receptors

Histaminic-1 (H1) activation effects.

I. Relaxation or vasodilation → Reduction of Blood Pressure → (Excessive ↑Histamine) Anaphylactic Shock

II. Bronchoconstriction or spasm → Difficulty of breathing or shortness of breath

III. Pain, itchiness

IV. Contraction of endothelial cells → cell shrinkage → fluid leakage → localized edema causing hives known as wheals.

V. Wakefulness

a. I, II, III

b. III, IV, V

c. I, II, III, IV

d. II, III, IV, V

e. I, II, III, IV, V

e. I, II, III, IV, V

Activation of this histamine receptor type lead to localized edema causing hives known as wheals.

a. Histaminic-1 (H1)

b. Histaminic-2 (H2)

c. Histaminic-3 (H3)

d. Histaminic-4 (H4)

a. Histaminic-1 (H1)

Histaminic-2 (H2) locations.

a. Parietal cells of the stomach

b. Mast cells

c. Basophils

d. a and b

e. b and c

f. All

f. All

Histaminic-2 (H2) activation effects.

a. Gastric acid production and release

b. Enhanced granulation of histamine

c. Increase histamine level available for action

d. a and b

e. b and c

f. All

f. All

Histamine receptor type that is inhibitory promoting autoregulation wherein further release of histamine from the vesicles would be inhibited thus decreasing histamine levels.

a. Histaminic-1 (H1)

b. Histaminic-2 (H2)

c. Histaminic-3 (H3)

d. Histaminic-4 (H4)

c. Histaminic-3 (H3)

Histamine receptor type that causes chemotaxis.

a. Histaminic-1 (H1)

b. Histaminic-2 (H2)

c. Histaminic-3 (H3)

d. Histaminic-4 (H4)

d. Histaminic-4 (H4)

Chemotaxis.

a. Enhanced movement of inflammatory cells like neutrophils and also monocytes at the site of injury

b. Enhanced levels of these inflammatory cells at the site of injury means there is induction of inflammation

c. Both

d. None

c. Both

Histamine agonist.

a. Exogenous Histamine

b. Betahistine

c. Impromidine

d. a and b

e. b and c

f. All

f. All

1) No longer clinically useful, but historically used to diagnose patients with suspected bronchial asthma

2) Also used for test of gastric secretory function as it can activate histaminic-2 receptors

a. Exogenous Histamine

b. Betahistine

c. Impromidine

d. a and b

e. b and c

f. All

a. Exogenous Histamine

Cholinomimetic drug that replace histamine and now used for Pulmonary Challenge Test.

a. Edrophonium

b. Bethanechol

c. Methacholine

d. Pilocarpine

c. Methacholine

Betahistine.

a. H1 agonist and an H3 receptor antagonist

b. Used in management of Endolymph associated with Vertigo which is observed in patients with Meniere's Disease (Vertigo)

c. Anti-vertigo

d. a and b

e. b and c

f. All

f. All

Investigational histamine agonists.

a. Exogenous Histamine

b. Betahistine

c. Impromidine

d. a and b

e. b and c

c. Impromidine

Histamine antagonist.

a. Facilitate antagonisms by 2 groups

b. Can be functional antagonist

c. Can be pharmacologic antagonist

d. a and b

e. b and c

f. All

f. All

Opppose the effects of histamine by interacting to different targets or different receptors.

a. Functional antagonist

b. Pharmacologic antagonist

a. Functional antagonist

A functional histamine antagonist as it interact with adrenergic receptors causing vasoconstriction (alpha1) and bronchodilation (beta2) opposing the vasodilation and bronchoconstriction effect of histamine.

a. Cimetidine

b. Doxylamine

c. Tripelennamine

d. Epinephrine

e. Dopamine

d. Epinephrine

Competitively block binding of histamine to its receptors or direct competition on which a ligand will bind on histaminic receptors and these antagonists, have greater affinity in binding to histaminic receptors.

a. Functional antagonist

b. Pharmacologic antagonist

b. Pharmacologic antagonist

H1 Antihistamines.

a. Inhibit binding of histamine to H1 receptors

b. Anti-allergy agents

c. Has 1st and 2nd gen

d. a and b

e. b and c

f. All

f. All

First Generation H1 Antihistamines

a. Has lipophilic chemical property

b. Anticholinergic agents

c. Sedating antihistamines

d. a and b

e. b and c

f. All

f. All

First Generation H1 Antihistamines.

I. Ethanolamines

II. Ethylenediamines

III. Piperazines

IV. Alkylamines

V. Phenothiazine

VI. Piperidines

a. I, II, III, IV,

b. III, IV, V, VI

c. I, II, III, IV, VI

d. I, II, III, V, VI

e. I, II, III, IV, V, VI

e. I, II, III, IV, V, VI

Most sedating and most efficacious First Generation H1 Antihistamines.

a. Ethanolamines

b. Ethylenediamines

c. Piperazines

d. Alkylamines

e. Phenothiazine

f. Piperidines

a. Ethanolamines

Ethanolamines except:

a. Diphenhydramine

b. Dimenhydrinate

c. Carbinoxamine

d. Doxylamine

e. Pyrilamine

f. None

e. Pyrilamine - this is Ethylenediamines.

Salt form of Diphenhydramine

a. Diphenhydramine

b. Dimenhydrinate

c. Carbinoxamine

d. Doxylamine

b. Dimenhydrinate

DOC for Acute Dystonic Crisis.

a. Diphenhydramine

b. Dimenhydrinate

c. Carbinoxamine

d. Doxylamine

a. Diphenhydramine

Sleeping aid with the brand Unisom.

a. Diphenhydramine

b. Dimenhydrinate

c. Carbinoxamine

d. Doxylamine

d. Doxylamine

First Generation H1 Antihistamines that can cause moderate sedation and GI upset.

a. Ethanolamines

b. Ethylenediamines

c. Piperazines

d. Alkylamines

e. Phenothiazine

f. Piperidines

b. Ethylenediamines

Ethylenediamines.

a. Pyrilamine

b. Tripelennamine

c. Doxylamine

d. a and b

e. b and c

f. All

d. a and b

Doxylamine is ethanolamine.

Piperazines.

a. Meclizine

b. Cyclizine

c. Hydroxyzine

d. a and b

e. b and c

f. All

f. All

Used in the treatment of motion sickness.

a. Meclizine

b. Cyclizine

c. Hydroxyzine

d. a and b

e. b and c

f. All

f. All

Prodrug of Cetirizine.

a. Meclizine

b. Cyclizine

c. Hydroxyzine

d. a and b

e. b and c

f. All

c. Hydroxyzine

Alkylamines

a. Chlorpheniramine

b. Brompheniramine

c. Tripelennamine

d. a and b

e. b and c

f. All

d. a and b

Tripelennamine is ethylenediamines.

Often included in cold medications that's why they serve as components of cold medications.

a. Chlorpheniramine

b. Brompheniramine

c. Both

d. None

c. Both

Phenothiazine

a. Promethazine

b. Fenergon

c. Both

d. None

c. Both - Fenergon is brand of Promethazine

Promethazine.

a. Used as an adjunct for anaesthesia because it can produce marked sedation

b. Has anti-emetic property

c. Has application in inducing preoperative sedation

d. a and b

e. b and c

f. All

f. All

Used in inducing preoperative sedation.

a. Chlorpheniramine

b. Brompheniramine

c. Tripelennamine

d. Promethazine

e. Cyproheptadine

d. Promethazine

Cyproheptadine.

a. Ethanolamines

b. Ethylenediamines

c. Piperazines

d. Alkylamines

e. Phenothiazine

f. Piperidines

f. Piperidines

Cyproheptadine.

a. Also possesses anti-serotonergic and anticholinergic properties

b. Used in the management of a hyperthermic disorder that is serotonin syndrome

c. Both

d. None

c. Both

Used in the management of a hyperthermic disorder that is serotonin syndrome.

a. Chlorpheniramine

b. Brompheniramine

c. Tripelennamine

d. Promethazine

e. Cyproheptadine

e. Cyproheptadine

Second generation H1 Antihistamines.

a. Less lipophilic

b. Less sedating

c. Both

d. None

c. Both

Second generation H1 Antihistamines.

I. Cetirizine

II. Levocetirizine

III. Loratadine

IV. Desloratadine

V. Fexofenadine

a. I, II, III, IV, V

b. I, II, III, IV

c. I, II, IV, V

d. I, II

e. III, IV, V

a. I, II, III, IV, V

Less sedating Piperazine

Second generation H1 Antihistamines.

I. Cetirizine

II. Levocetirizine

III. Loratadine

IV. Desloratadine

V. Fexofenadine

a. I, II, III, IV, V

b. I, II, III, IV

c. I, II, IV, V

d. I, II

e. III, IV, V

d. I, II

True Non-sedating Piperidines

Second generation H1 Antihistamines.

I. Cetirizine

II. Levocetirizine

III. Loratadine

IV. Desloratadine

V. Fexofenadine

a. I, II, III, IV, V

b. I, II, III, IV

c. I, II, IV, V

d. I, II

e. III, IV, V

e. III, IV, V

Most applicable drugs to patients with allergy that has jobs or activities requiring mental alertness.

I. Cetirizine

II. Levocetirizine

III. Loratadine

IV. Desloratadine

V. Fexofenadine

a. I, II, III, IV, V

b. I, II, III, IV

c. I, II, IV, V

d. I, II

e. III, IV, V

f. I

e. III, IV, V

True non-sedating piperidines are the most applicable drugs to patients with allergy that has jobs or activities requiring mental alertness.

H2 Antihistamines

I. Given to promote healing of gastric and duodenal ulcers due to inhibition of hydrochloric acid

II. Can also be used in the treatment of hypersecretory states just like in patients with Zollinger-Ellison Syndrome

III. Given as adjuncts in management of allergic reactions

a. I, II, III

b. I, II

c. II, III

d. I, III

a. I, II, III

H2 Antihistamines

I. Cimetidine

II. Famotidine

III. Ranitidine

IV. Nizatidine

V. Loratadine

a. I, II, III, IV, V

b. I, II, III, IV

c. I, II, IV, V

d. I, II

e. III, IV, V

f. I

b. I, II, III, IV

Loratadine is 2nd gen H1 antihistamine.

1st ever commercially available H2 blocker (Prototype).

a. Cimetidine

b. Famotidine

c. Ranitidine

d. Nizatidine

a. Cimetidine

Least potent H2 blocker.

a. Cimetidine

b. Famotidine

c. Ranitidine

d. Nizatidine

a. Cimetidine

Cimetidine actions.

a. Enzyme inhibitor

b. Antiandrogenic

c. Both

d. None

c. Both

Cimetidine effects as antiandrogenic.

a. Gynecomastia

b. Loss of libido

c. Infertility

d. a and b

e. a and c.

f. All

f. All

Most potent H2 antihistamine.

a. Cimetidine

b. Famotidine

c. Ranitidine

d. Nizatidine

b. Famotidine