Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

PDA Block 2 > Histamines > Flashcards

Histamines Flashcards

1
Q

Describe the synthesis and metabolism of Histamine

A

Histidine → Histamine → Imidazole → Imidazole acetate

Histidine → Histamine → N1 methylhistamine → N1-methylimidazole acetate

Enzyme from histidine to histamine: Histidine decarboxylase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Alterations in ______ ______ _______ can account for histamine intolerance (1% population)

A

Histamine degrading enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Histamine Functions

A
  • Mediator of immediate allergic and inflammatory reactions
  • Role in gastric acid secretion
  • Neurotransmitter and neuromodulator
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Localization of Histamine

A

Ubiquitous

  • Highest amounts in lung, skin, GI tract
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Characteristics of histamine in tissues (mast cells) and in blood (basophils)

A
  • Synthesized and stored in secretory granules in an inactive form
  • Bound to a proteoglycan
    • Heparin sulfate and ATP: mast cells
    • Chondroitin-sulfate: basophils
  • Slow turnover
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Characteristics of histamine from non-mast cells

A
  • No granules, continuously synthesized and released, rapid turnover
  • Histidine decarboxylase levels correlate with activity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Effects of histamine release (within seconds? minutes?)

A
  • Within seconds
    • Burning, itching
    • Intense warmth
    • Skin reddens
    • BP ↓
    • HR ↑
  • Within Minutes
    • BP recovers
    • Hives
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Explain the release of mast cell histamine

A
  • Antigen-antibody reaction
    • IgE mediated sensitivity to drugs and other allergens
    • Response of IgE sensitized cells to subsequent exposure to allergens
  • Ca2+ dependent
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Drugs, Venoms, and peptides can promote the release of histamine - what are some examples of each?

A

Drugs: Succinylcholine, morphine…

Peptides: Bradykinin, complement, substance P

Venoms: Wasps

* mechanism of release is through an increase in intracellular calcium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Red-Man Syndrome

A
  • Caused by vancomycin interaction w/ gram-positive bacteria
  • Due to mast cell degranulation
  • Rash in face, neck, upper torso
  • Following rapid IV infusion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Other stimuli that release histamine

A
  • Cold Urticaria
  • Cholinergic Urticaria
  • Solar Urticaria

* Urticaria = hives

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Cromolyn sodium

Administration:

Mechanism:

Side Effects:

A

Administration: Inhalation (oral, nasal, opthalmic possible)

Mechanism: Stabilizes mast cell membrane to prevent release of histamine - exact cellular mechanism is unclear

Side Effects: Safe drug/ few side effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Cromolyn sodium therapeutic uses

A
  • Chronic control of asthma
  • Prophylaxis of bronchospasm (NOT A RESCUE MED)
  • Nasal formulation for allergies
  • Opthalmic for conjuctivitis
  • Oral for systemic mastocycosis
  • Off label use for food allergy and IBS (irritable bowel)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Omalizumab (Monoclonal antibody)

Administration:

Mechanism of Action:

A

Administration: Subcutaneous

Mechanism of Action:

  • Decrease amount of IgE that normally binds to mast cells
  • An IgG antibody for which antigen is Fc region of IgE
  • Binds tightly to free IgE in circulation to form complex
  • No affinity for FcRI
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

G Protein Coupling and Distribution of Histamine Receptors

H1:

H2:

H3:

H4:

A

H1:

  • G Protein: Gq (Ca2+, ↑ NO and ↑ cGMP)
  • Dist: Smooth muscle, endothelial cells, CNS

H2:

  • G Protein: Gs (↑ cAMP)
  • Dist: Gastric parietal cells, cardiac muscle, mast cells, CNS

H3:

  • G Protein: Gi ( ↓ cAMP; ↑ MAP)
  • Dist: CNS: presynaptic

H4:

  • G Protein: Gi ( ↓ cAMP; ↑ Ca2+)
  • Dist: Cells of hematopoietic origin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Representative antagonists for H1 and H2

A

H1: Chlorpheniramine

H2: Ranitidine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Histamine receptors that induce vasodilation

A

H1 (endothelial cells) - ↑NO = vasodilation

H2 (vascular smooth muscle cells) - increase cAMP so decrease intracellular calcium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Histamine Receptors and Vasoconstriction of large vessels

A

H1 receptors located on vascular smooth muscle cells

  • Increase intracellular calcium
19
Q

Histamine Receptors and Blood Pressure

A

Both H1 and H2 receptors

  • In general histamine dilates resistance vessels and causes an overall fall in BP
20
Q

Histamine Receptors and Increased vascular permeability

A
  • H1 receptors located on post-capillary venules- endothelial cells
    • Increase in Ca2+ causes endothelial cells to contract and expose basement membrane
21
Q

Histamine Receptors and Effects on Heart

A

Predominantly H2 receptors

  • Contractlity increased
  • Increase electrical conduction
22
Q

Histamine Receptors and Bronchioles

A

H1: contraction

H2: relaxation (minor)

23
Q

Histamine Receptor activation of Intestinal Smooth muscle, Exocrine Glands and Peripheral nerve endings

A

Intestinal Smooth Muscle: H1 - contraction

Exocrine Glands (Parietal Cell): H2 - gastric acid secretion

Peripheral Nerve Endings: H1 - pain and itching

24
Q

Neuroendocrine Effects of Histamine Receptors

Increasing Arousal/wakefullness:

A

H1 (in the brain)

25
H1 receptor blockers ## Footnote First Generation: Second Generation:
First Generation: * Diphenhydramine * Dimenhydrinate * Chlorpheniramine * Promethazine Second Generation * Fexofenadine * Loratadine * Cetirizine * Desloratidine
26
Histamine Receptor drugs are considered _____ \_\_\_\_\_\_\_ because they reduce constitutive activity at receptors and compete with histamine
Inverse agonists
27
Major pharmacologic Effect of H1 antagonists
By blocking histamine receptors on vascular tissue, reduce the symptoms associated with allergic responses/inflammation * Inhibition of vascular permeability * Suppress itching * No effect on BP or bronchoconstriction
28
Major pharmacologic effects of H1 Antagonists ## Footnote CNS: Peripheral and central anticholinergic effect: Local Anisthetic Effect:
CNS: 1st generation * Sedation (most common) * Stimulation (children) * Motion sickness (anticholinergic effect) Peripheral and central anticholinergic effect: 1st generation * Dry mucus membranes * Urinary retention Local Anisthetic Effect: block nerve conduction
29
H1 receptor Drugs ## Footnote Administration: Distribution: Metabolism:
Administration: Oral (topical, nasal possible) - rapid absorption Distribution: widely distributed - **2nd generation less likely to enter brain** Metabolism: Liver * 2nd generation metabolized by P450 enzymes * Terfenadine → **fexofenadine** * **Loratadine** → **Desloratadine** * Hydroxyzine → **Cetirizine**
30
Sedation is most common with __________ drugs due to inhibition of central H1 effect AND central cholinergic effect 2nd generation with most sedative effect is \_\_\_\_\_\_
1st generation Cetirizine
31
Give 2 reasons that 1st generation antihistamines have a sedative effect
1. Enter CNS and block H1 receptors that mediate arousal 2. Non-specific and also have structures that allow them to block cholinergic receptors in CNS
32
GI side effects of drugs
Loss of appetite, nausea, vomiting
33
Major Cardiovascular Toxicity due to _________ drugs \_\_\_\_\_\_\_\_ is metabolized by P450 and has never shown adverse effects on QT interval; no cardiac toxicity
2nd generation Loratadine
34
Drugs used to treat allergies First genaration: Second Genearation: \_\_\_\_\_\_\* is the first generation with most sedative effect
First Gen: * Diphenhydramine\* * Chlorpheniramine Second Gen: * Fexofenadine * Loratadine * Desloratadine * Cetirizine
35
Motion sickness Definition: Drugs:
Definition: A temporary condition that involves dizziness, nausea, and vomiting Drugs: Anti cholinergic effect: * Dimenhydrinate * Promethazine * Diphenhydramine * (Scopolamine)
36
Drugs for... ## Footnote Non-prescription sleeping tablets: Vestibular disturbances: Chemotherapy-induced nausea and vomiting: Early stage Parkinson's disease:
Non-prescription sleeping tablets: Diphenhydramine Vestibular disturbances: Dimenhydrinate Chemotherapy-induced nausea and vomiting: Promethazine Early stage Parkinson's disease: Diphenhydramine
37
Function of H2 receptor antagonists
* Relief from symptoms of peptic ulcer disease * Gastroesophageal reflux disease * Peptic ulcer secondary to *Helicobacter pylori* infection * Gastric injury caused by nonsteroidal anti-inflammatory drugs
38
Physiology of Gastric Acid secretion (H2 receptors)
* Histamine released from mast cells and enterochromaffin-like cells (vagus stimulation) * Stimulation of H2 receptors on parietal cells increase cAMP and PKA * Cause increase in Acid (H+) \* ACH and gastrin also have direct effect on parietal cells to release acid
39
Pharmacological Profile of H2 Antagonists
* Reversible competitive inhibitors * Act as inverse agonists * Specific for H2 receptors on basolateral membrane of parietal cells * Inhibit basal (fasting) gastric acid secretion * Inhibit nocturnal gastric acid secretion * Reduce volume of gastric acid and H+ concentration
40
H2 Antagonists ## Footnote Administration: Metabolism: Excretion:
Administration: Oral administration - rapid Metabolism: Small amounts undergo liver metabolism Excretion: Kidney
41
H2 Antagonists Adverse Effects
* Incidence relatively low - except for cimetidine * More common minor side effects - diarrhea, headaches, drowsiness * Less common * CNS effects of confusion, delirium, slurred speech * Happens with IV administration or in elderly patients
42
Adverse effects of Cimetidine
Inhibits P450 metabolism * Prolongs half-life of other drugs Long term use: * Decreased testosterone binding * Inhibition of CYP enzme that hydroxylates estradiol
43
Major Use of H2 Antagonists
Uncomplicated Gastro-Esophageal Reflux Disease (GERD) * Promote healing of ulcers * Prevent occurence of ulcers
44
H2 Antagonist Potency
Famotidine \> Nizatidine = Ranitidine \> Cimetidine

PDA Block 2 (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions