DERM 12: Histamine Flashcards
1
Q
What are the actions of histamine? (2)
A
- immediate hypersensitivity (type I) allergic reactions
- inflames local tissues and increases blood flow
2
Q
Where are H1 receptors located and what is their activity? (5)
A
- CNS: wakefulness and arousal
- bronchial smooth muscles: bronchoconstriction
- intestinal smooth muscles: constriction and cramps
- blood vessels: vasodilation, release of NO (edema)
- sensory nerve endings: itching and pain
3
Q
Where are H2 receptors located and what is their activity? (3)
A
- CVS: increases HR and contractility
- gastric mucosa: stimulates gastric parietal cells to release gastric acid into stomach
- vascular smooth muscle: vasodilation
4
Q
Where are H3 receptors located and what is their activity? (2)
A
- presynaptic nerves in brain (histaminergic nerves): decreases release of neurotransmitters (amine, acetylcholine, peptides)
- presynaptic nerves in airways and GI tract (myenteric plexus): opposes bronchoconstriction and gastric acid release
5
Q
Where are H4 receptors located and what is their activity? (2)
A
- eosinophils, basophils, neutrophils, mast cells, CD4 T cells: chemotaxis and chemokinesis (enhances activity of chemoattractants like chemokines)
- skin nerve endings: itching and pain
6
Q
What is betahistine?
A
- H1 agonist
- H3 antagonist
7
Q
Betahistine
What is the H1 receptor function?
A
stimulate H1 receptors in inner ear
- vasodilation
- decrease vertigo and balance disorders
8
Q
Betahistine
What is the H3 receptor function?
A
antagonize H3 receptors
- increase histamine release from histaminergic nerve endings (direct activity of H1 agonist)
- increase levels of neurotransmitters in brainstem (serotonin) to restore balance (decrease vertigo)
9
Q
Betahistine
What is it used for?
A
anti-vertigo in Meniere’s disease
10
Q
Betahistine
What are the side effects?
A
- CNS: headache
- GI: nausea, vomiting
11
Q
What are H1 receptor blockers?
A
antihistamines
- first-generation
- second-generation
- third-generation
12
Q
How do H1 receptor blockers work?
A
- do not antagonize histamine binding to H1 receptor, but instead bind different sites to produce opposing effect
- more effective in preventing rather than reversing symptoms
- no influence on formation or production of histamine
- no structural relation with histamine
- all have similar action
13
Q
What are some first-generation antihistamines?
A
- diphenhydramine (Benadryl)
- dimenhydrinate (Gravol)
- chlorpheniramine (Chlortripolon)
- doxylamine, meclizine, promethazone, hydroxyzine
14
Q
First-Generation Antihistamines
What are the cons? (3)
A
- sedating, drowsiness, fatigue
- interferes with/decreases REM sleep (next morning effect on attention, memory, motor performance)
- tachyphylaxis
15
Q
First-Generation Antihistamines
What are the side effects?
A
- anticholinergic: dry mouth, blurred vision, urinary retention
- anti-alpha-adrenergic: orthostatic hypotension
16
Q
First-Generation Antihistamines
What are the therapeutic uses? (3)
A
- motion sickness, nausea, vomiting
- sedative
- local anesthetic
17
Q
First-Generation Antihistamines
Use: Motion Sickness, Nausea, Vomiting
A
antiemetic action due to blocking central H1 and M1 receptors
- dimenhydrinate, meclizine, and promethzine: NOT effective if symptoms already present (preventative)
- meclizine: treatment of vertigo in vestibular disorders
- diphenhydramine and doxylamine: safe in pregnancy
18
Q
First-Generation Antihistamines
Use: Sedative
A
partly due to anti-muscarinic effect
- NOT medication of choice
- used for insomnia – OTC
- diphenhydramine and doxylamine: strong sedative
19
Q
First-Generation Antihistamines
Use: Local Anesthetic
A
diphenhydramine
- local effect (potent)
- useful in patient with allergy to local anesthetics
- injectable 1% is inexpensive, safe, and effective for simple dermatological procedures
20
Q
What are some second-generation antihistamines?
A
- loratidine (Claritin)
- cetirizine (Reactine)
- bilastine (Blexten)
- rupatadine (Rupall)
21
Q
What are some third-generation antihistamines?
A
- fexofenadine (Allegra) – metabolite of terfenadine
- desloratidine (Aerius) – metabolite of loratadine
- levocetirizine – enantiomer of cetirizine
22
Q
Second and Third-Generation Antihistamines
What are the pros? (2)
A
- highly selective for H1 receptors
- little or no sedation – does not cross BBB (polar, carboxyl groups)
23
Q
Second and Third-Generation Antihistamines
What are the cons? (3)
A
- headache – most common
- tachyphylaxis
- levocetirizine: may cause drowsiness
24
Q
Second and Third-Generation Antihistamines
What are the therapeutic uses? (3)
A
- chronic urticaria
- allergic rhinitis
- atopic dermatitis – adjunct
25
What causes urticaria (hives)
histamine release due to IgE or non-IgE-mediated mast cell activation
26
What is acute urticaria (hives)?
< 6 weeks
- type I hypersensitivity reactions
- resolves within hours but may recur
- trigger – drug (NSAID, aspirin), food, infection, insect bite/sting, emotional/physical stimuli
27
What is chronic urticaria (hives)?
> 6 weeks, months to years, recurrent
- signs and symptoms many days
- resolves without findings cause
- causes – idiopathic, autoimmune disorders (SLE or thyroid), drugs, emotional/physical stimuli
28
What is the pharmacological treatment for urticaria (hives)?
take H1 receptor blockers regularly instead of PRN
- note: topical corticosteroids/antihistamine are not beneficial
29
What is the pharmacological treatment for acute urticaria (hives)?
older antihistamines (hydroxyzine, diphenhydramine)
- sedating
- inexpensive
- sometimes effective (faster onset)
30
What is the pharmacological treatment for chronic urticaria (hives)?
- first-line: 2nd and 3rd generations once daily (less sedating)
- oral corticosteroids (not long-term)
31
What are some H2 receptor antagonists?
- famotidine (Pepcid)
- ranitidine (Zantac)
32
H2 Receptor Antagonists
How do they work?
- competitively block histamine binding to H2 receptors on parietal cells
- reduce gastric acid secretion
- fully reversible and selective
33
H2 Receptor Antagonists
What are the therapeutic uses? (2)
- peptic and duodenal ulcers (previously) – decreased use with introduction of PPIs
- OTC products for dyspepsia (indigestion), heartburn, GERD (short-term)
34
H2 Receptor Antagonists
What are the side effects?
- generally well-tolerated
- mild: headache, drowsiness, fatigue, abdominal pain, constipation, diarrhea
- CNS: delirium, confusion, hallucination, slurred speech in renal/hepatic impairment, elderly, ICU patient
35
H2 Receptor Antagonists
How are they used for treatment of urticaria?
used in combination with H1 receptor blockers
- low level evidence for efficacy
- mechanism: interaction between H1 antihistamine and H2 receptor antagonist at level of hepatic metabolism (CYP3A4 inhibition), ↑ in plasma concentration of both drugs rather than true synergy
36
What are some H3 receptor antagonists?
pitolisant (Wakix)
- selective anatgonist/inverse agonist at H3 receptors – enhance histamine release from histaminergic neurons)
37
H3 Receptor Antagonists
What are the side effects?
insomnia, headache, dizziness, nausea, vomiting, and itching if applied locally
38
H3 Receptor Antagonists
What are the contraindications? (4)
- severe liver impairment
- breastfeeding
- not recommended in end-stage renal disease
- no established safety and efficacy for < 18 years old
39
H4 Receptor Antagonists
- no drugs
- targets for medicines in inflammatory bowel disease, rheumatic arthritis, asthma
40
What are the major neuronal pathways of itching/pruritus? (2)
- histaminergic (acute itch)
- non-histaminergic (chronic itch)
41
Describe the transmission of itching/pruritus.
from skin to spinal cord through unmyelinated C fibres
- mechanically insensitive unmyelinated C fibres (CMi) – histamine-induced (rash and allergy)
- cutaneous polymodal C fibres – non-histaminergic itch (thermal, chemical, mechanical stimuli)
42
What is the treatment for itching/pruritus?
- H1 receptor blockers effective in acute, but not chronic itch (atopic dermatitis)
- H4 receptor blockers show promising efficacy
- combined H1-H4 blockade is novel therapeutic avenue for histamine-induced itch
43
Summary of Histamine Receptors
- H1: allergy, inflammation
- H2: gastric acid secretion
- H3: neuro-inflammatory diseases, sleep-wake cycle
- H4: allergy, inflammation
