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Flashcards in Histamine Deck (38):
1

Drugs that stimulate histamine release from mast cells without prior sensitization

d-tubocurare, succinylcholine, morphine, codeine, doxorubicin, protamine, Vancomycin

2

Drugs That Block the Release of Histamine from Mast Cells

Cromolyn and Nedocromil (inhaled)

3

What are the two drugs that stabilizes mast cells

Cromolyn and Nedocromil
prevents noncytolytic degranulation.Decreases symptoms of allergic rhinitis.
Prophylactic use to block asthmatic reactions but not useful in managing acute asthmatic attack.

4

Four types of histamine receptors.

H1 receptors – phospholipase C mechanism (respiratory and allergic reactions)
H2 receptors – adenylyl cyclase mechanism parietal cell acid secretion
H3 receptors – on neurons and inhibit the release of histamine (feedback inhibition)
H4 receptors – proinflammatory activity.

5

Histamine phosphate

Assess nasal and bronchial reactivity.
Positive control injection
For allergy skin testing.
Before testing discontinue antihistamines, tricyclic antidepressants, corticosteroids, benzodiazepines.

6

Histamine H1 receptor blockers
1st generation drugs

Widely used, effective and inexpensive. Anticholinergic
CNS sedation
Short acting
diphenhydramine (benadryl), promethazine, hydroxyzine

7

Histamine H1 receptor blockers
2nd generation drugs

loratadine (Claritin, OTC), desloratadine (Clarinex), azelastine (Astelin) , cetirizine (Zyrtec,OTC) fexofenadine (Allegra, OTC ).
Less CNS toxicity or side effects since they do notcross the blood brain barrier or are excluded by p-glycoprotein.
No CNS sedation
Longer acting

8

Cytolytic vs. noncytolytic histamine release from mast cells

Cytolytic release – the plasma membrane is damaged.Not energy dependent, No calcium is requiredLeakage of cytoplasmic contents
Inducers: phenothiazines and narcotic analgesics

Noncytolytic release – no damage to mast cell
Requires energy (ATP) and calcium, and occurs by exocytotic release from granules.
IgE antibodies binding to antigen → histamine release.

9

substances that stimulate release of histamine w/o prior sensitization (no IgE necessary)

Mast cell degranulation protein (from bee venom),
Radiocontrast media
d-tubocurare, succinylcholine, morphine, codeine, doxorubicin, protamine
Vancomycin

10

Red man syndrome

Side effect of vancomycin, when infused too quickly. flushing, pruritus, chest pain, muscle spasm and hypotension during vancomycin infusion.
Pretreatment with intravenous antihistamines attenuates the symptoms of red-man syndrome.

11

H1 receptor

phospholipase C mechanism (respiratory and allergic reactions). increases mucus in nasal cavity and bronchi resulting in respiratory symptoms. (drippy nose). constricts bronchi and intestines (cramps,diarrhea). decreases blood pressure. (vasodilator—explains why pts turn red), also releases nitrous oxide (vasodilator).

12

H2 receptor

adenylyl cyclase mechanism parietal cell acid secretion. stimulates gastric acid secretions. (doesn’t affect nasal).

13

H3 receptor

on neurons and inhibit the release of histamine (feedback inhibition)

14

H4 receptor

proinflammatory activity.

15

Which receptors stimulate heart rate and contractility?

(H1 & H2 )
Histamine directly increases HR and contractility by increasing the influx of calcium.
Histamine indirectly increases HR and contractility by baroreceptor-mediated increase in sympathetic tone in response to histamine induced vasodilation.

16

Which receptors cause dilation and increased capillary permeability?

(H1 & H2)
Histamine causes endothelial cells to contract and expose permeable basement membrane.
Leakage of proteins and fluid into surrounding tissues (swelling) results from the permeable basement membrane.
Gaps between the endothelial cells also permit passage of blood cells that are recruited to the tissue during the mast-cell response. “Bulk Flow”

17

What does an allergic response consist of?

An antigen producing the formation of IgE antibodies which bind to high affinity receptors specific for these IgE antibodies and activate tyrosine kinase.
This leads to an increase in intracellular calcium which triggers exocytosis of the contents of secretory granules in the mast cells. (degranulation)

18

What other mediators of inflammation are released in the allergic response?

activation of phospholipase A2 which produces leukotrienes and prostaglandins.
Leukotrienes contract smooth muscle of the bronchi.

19

What are the drugs that cause IgE-mediated anaphylaxis?

Antibiotics: penicillins, cephalosporins, sulfonamides

20

What are the drugs that cause non-IgE mediated anaphylactoid reactions?

Anesthesia: NMJ blocking agents, opioids, plasma expanders.
Antbiotics: vancomycin (red man syndrome)
Others: Protamine

21

What is the difference between an Allergic Reaction vs Anaphylactic Response?

differences are due to location of the sites from which mediators are released and the rates of release of the mediators.
Response remains localized if histamine release is in a specific area, for example nasal cavity, & is slowly absorbed and metabolize.
Anaphylactic reaction if histamine is released rapidly and diffuses via the blood then the response may be full-blown.

22

True anaphylaxis must be treated with what?

Epinephrine

23

Histamine phosphate uses

Assess nasal and bronchial reactivity.
Positive control injection
For allergy skin testing.
Before testing discontinue antihistamines, tricyclic antidepressants, corticosteroids, benzodiazepines.

24

Whats the difference between 1st vs. 2nd generation H1 blockers?

1st generation: Anticholinergic, CNS sedation. Short acting
2nd generation: No anticholinergic (none of theses sd effects), No CNS sedation, Longer acting

25

Which H1 antihistamine is used in the prevention of motion sickness?

Promethazine- most effective of antihistamines used. Others: diphenhydramine, cyclizine, meclizine
Action probably relates to anticholinergic effects.
Administered 1 hr before the anticipated motion. Dosing after the onset of sickness is rarely beneficial.
None are as effective as the selective anticholinergic scopolamine which is the most effective drug used to prevent motion sickness. (no antihistamine action)

26

Which H1 antihistamine is used in the prevention of nausea/vomiting?

Phenothiazine class: promethazine, timeprazine.
Blockade of dopamine D2 receptors

27

Which H1 antihistamine is used as sleep medication for its' strong sedative properties?

OTC treatment of hyposomnia; diphenhydramine
(Nytol, Benadryl, Tylenol PM, Nytol, Sominex, Tylenol Simply Sleep) & doxylamine (Aldex AN, Nighttime Sleep Aid and Unisom) are FDA approved. [Doxepin(Silenor) ® FDA approved].
Tolerance - limit to 10 consecutive nights.

28

Which H1 antihistamine is used for its' antiparkinsonism effects?

Antimuscarinic actions - Diphenhydramine.

29

Which H1 antihistamine is used for its local anesthetic effects?

Block sodium channels
Sunburn preparations – promethazine (removes pain and inflammation)
Magic Mouthwash: Formulated from prescription. Used to treat oral ulcers, infections, inflammation, pain (have diphenhydramine)

30

Whats the difference between 1st vs. 2nd generation H1 blockers?

1st generation: Anticholinergic, CNS sedation. Short acting
2nd generation: No anticholinergic (none of theses sd effects), No CNS sedation, Longer acting

31

Which H1 antihistamine is used in the prevention of motion sickness?

Promethazine- most effective of antihistamines used. Others: diphenhydramine, cyclizine, meclizine
Action probably relates to anticholinergic effects.
Administered 1 hr before the anticipated motion. Dosing after the onset of sickness is rarely beneficial.
None are as effective as the selective anticholinergic scopolamine which is the most effective drug used to prevent motion sickness. (no antihistamine action)

32

Which H1 antihistamine is used in the prevention of nausea/vomiting?

Phenothiazine class: promethazine, timeprazine.
Blockade of dopamine D2 receptors

33

Which H1 antihistamine is used as sleep medication for its' strong sedative properties?

OTC treatment of hyposomnia; diphenhydramine
(Nytol, Benadryl, Tylenol PM, Nytol, Sominex, Tylenol Simply Sleep) & doxylamine (Aldex AN, Nighttime Sleep Aid and Unisom) are FDA approved. [Doxepin(Silenor) ® FDA approved].
Tolerance - limit to 10 consecutive nights.

34

Which H1 antihistamine is used for its' antiparkinsonism effects?

Antimuscarinic actions - Diphenhydramine.

35

Which H1 antihistamine is used for its local anesthetic effects?

Block sodium channels
Sunburn preparations – promethazine (removes pain and inflammation)
Magic Mouthwash: Formulated from prescription. Used to treat oral ulcers, infections, inflammation, pain (have diphenhydramine)

36

What's the most frequent side effect of 1st generation antihistamines?

sedation

37

What are the anticholinergic effects of antihistamines?

Dry mouth and nasal passages, constipation, blurred vision, and urinary retention.
2nd generation antihistamines- less antimuscarinic effects

38

overdoses with H1 antagonists are rare but acute poisoning is relatively common, especially in children. the effects are:

initial excitement
ataxia and convulsions
coma and cardiorespiratory collapse.