Anti-Histamine Flashcards
What are various conditions that you can use anti-histamines for?
- Allergic rhinitis
- Eczema
- Urticaria (hives)
- Insomnia
- Motion sickness
- GERD/ Peptic ulcer disease
where is histamine generally found? and what do they do?
- Mast cells, basophils- defend against allergic reactions
- CNS- act as neurotransmitters
- Gut- regulates gastic acid production
Where are H1 receptors located?
Bronchial smooth muscle,
CNS,
Endothelium,
Cardiac muscle
What are the action of histamine binding to H1 receptor?
- Sleep-wake cycle (wakefulness)
- learning/ memory
- stimuate nerve endings (pain)
- bronchocontriction
- vasodilation of blood vessls
- contraction of smooth muscke
Where are the H2 receptors located?
- Parietal cells of the stomach
- Cardiac Tissue
- CNS
What is the action of histamine binding to H2 receptors?
- Gastic acid production
Where are H3 receptor located?
- CNS peripheral tissues
What is the action of histamine binding to H3 receptors?
Modulation of NE release
Where are the H4 receptors located?
- Basophils
- Bone marrow
- Small intestine
- Colon
- Spleen
- Thymus
What is the action of histamine binding to H4 receptors?
Faciliates mast cell chemtaxis
Overall effects of histamine release
- Increased vasular permiabiligy- hypotension
- Bronchocontriction
- Increased bowel peristalsis- diarrhea
- Cardiac effects
- enhances influx of Ca into cardiac myocytes which increases contractility
- Hypotenion secondary to vasodilation
- Tachycardia
What happens when histamine in mast cells during allergic reaction?
- B cell activation which turn into plasma cells that produce IgE.
- IgE primes mast cells and when a person is exposed to allergens the mast cells degranulat and release histamines
Explain how cardiac patients are more susceptible to allgeric reactions?
Patients with cardiomyopathy, arrhythmoa or other structural heart disease
- increase expression in mast cells
- in allergic reaction- will release large quantities of mast cells
What is the role of histamine in immune modulation?
Vasodilation→ capilaries become more permeable → allows for WBC to move into site
- Leads to facial flushing and edema
- speration of endothelial cells → urticaria
- Induces fluid secretion
- gives rise to classic allergy symptoms- Runny nose, water eys, etc.
Explain how histamine works in the parietal cells in the GI tract?
-
Histamine bins to H2 receptors
- increase cAMP
-
Gastin and Ach bind to their receptors (bind first)
- increase Ca+
- Gastrin binding casues release of histamine in the GI tract
- histamine then binds to its receptor
- Increase in cAMP and increase in Ca
- acttivation of proton pump
- H+ is pumped out into the lumen of th stomach
- production of HCL
- K+ is pumped into the parietal cell
- H+ is pumped out into the lumen of th stomach
- acttivation of proton pump
Histamine in CNS
Considered a eurotransmitter (H1, H3 in the brain; some H2)
Modulators
- Ach release → learning& cognition
- Alertless → makes wake-cycle
- Seratonin → mood
- Food intake → supression of appetite
- Emesis center → nausea/ vomitting
What do antihistamine do on H1/H2 receptors?
H1
- Brochodilation
- Constipation (decrease peristalsis)
- Anti-itch, reduction of pain
- Reduce the inflammation/ allergic respone
H2
- Supression of gastric acid/ production
Epinephrine
Histamine Antagonist- works quickly
- Smooth muscle relaxation
- stimulates alpha and beta recptors
Vasodilation and increase BP
Cromolyn
Works over several week
Stabilizes mast cells to prevent degranulation
What do H1 blockers treat?
Treat allergies
insomnia
mottion sickness
Includes first and second generation
What are first generation antihistamines
Treatment- allergic symptoms, motion sickness and insomnia
Poor receptor selectivity- anti-muscarinic, anti-alpha adrenergic, anti-seratonin
- causes constipation, dry mouth, memory impairment, hypotension
Highly lipophilic
- Cross BBB to interfere with histamine transmission- used to treat nausea and vomitting
NOT PREFERED IN ELDERS
Doxylamine
First generation H1 blockers
Anti-cholinergic effect +++ (Hot, dry fast, crazy)
Used for insomnia, allergies
Highly sedating, large doses can cause arrhythmias (QTC prolongation- block K+ receptors), Avoid in elderly
Diphenhydramine
First generation H1 blockers
Anti-cholinergic effect +++ (Hot, dry fast, crazy)
Used for insomnia, allergies
Highly sedating, large doses can cause arrhythmias(QTC prolongation- block K+ receptors), Avoid in elderly
Cyclizine
First generation H1 blockers
Anti-cholinergic effect + (Hot, dry fast, crazy)
Used for motion sickness, vertigo
mildly sedating
Meclizine
First generation H1 blockers
Anti-cholinergic effect + (Hot, dry fast, crazy)
Used for motion sickness, vertigo
mildly sedating
Chlorpheniramine
First generation H1 blockers
Anti-cholinergic effect ++ (Hot, dry fast, crazy)
Used for allergies
moderately sedating, possible prardoxical CNS stimulation
Often combined with cold products
Avoid in elderly
Brompheniramine
First generation H1 blockers
Anti-cholinergic effect ++ (Hot, dry fast, crazy)
Used for allergies
moderately sedating, possible prardoxical CNS stimulation
Often combined with cold products
Avoid in elderly
Hydroxyzine HCl
First generation H1 blockers
Anti-cholinergic effect + (Hot, dry fast, crazy)
Used for allergies, urticaria
Mid-moderate sedation
Hydroxyzine PAMoate
First generation H1 blockers
Anti-cholinergic effect ++ (Hot, dry fast, crazy)
Used for insomnia, anxiety- cross BBB
Mid-moderate sedation
Promethazine
First generation H1 blockers
Anti-cholinergic effect +++ (Hot, dry fast, crazy)
Used for anti-emetic, highly sedating, alpha blockade→ hypotension, D2 blockade→ dystonic reactions, akathisia
Potent anti-muscarinic effects
Avoid in elderly
Cyproheptadine
First generation H1 blockers
Anti-cholinergic effect + (Hot, dry fast, crazy)
Weight gain due to 5-HT2 bloackade
used to treat seratonin syndrome and in cachexia
DDI with first generation H1 blockers
Metabolized via 2D6 and 3A4
Avoid with
- alcohol (synergestic sedative effects)
- Other hypnotics and/ or benzos
- TCA
- Acetylcholinesterase inhibitors
Second generation H1 antihistamines
Used to treat allergic symptoms only
highly selective for H1 receptors with no other receptors wffecrs
Limited penetration to BBB- minimally or non- sedating
Preferred in elderly
Rapid onset
Longer duration of action
Azelastine
Second generation H1 blocker
Nasal spray
MOA- Mast cell stabilizer + H1 blocker
Nasal spray→ less systemic side effects
Local irritation can occur- nasal irritation, nosebleeds, bitter taste/ smell
Avoid use if any preexisitng damage to the nasal pasage
Olopatidine
Second generation H1 blocker
Nasal spray
MOA- Mast cell stabilizer + H1 blocker
Nasal spray→less systemic side effects
Local irritation can occur- nasal irritation, nosebleeds, bitter taste/ smell
Avoid use if any preexisitng damage to the nasal pasage
Fexofenadine
Second generation H1 blocker
Highest safety profile, NO CYP 450 metabolism, excreted in feces
NO RENAL DOSE ADJUSTMENT
Cetirizine
Second generation H1 blocker
MOst somnolence of second generation- gets into BBB
Active metabolite of hydroxyzine (first generation H1 blocker)
Levocetirizine
Second generation H1 blocker
Active metabolite of cetirizine
Loratidine
Second generation H1 blocker
Metabolized via 3A4, 2D6→ check 3A4 inhibitors
Desloratidine
Second generation H1 blocker
Least likely to cause somnolence
Active metabolite of loratadine
Potencies of second generation
Potency: Desloratidine> levocetirizine> fexofenadine
sits on receptor with higher affinity does not mean its more effective
- if someone is one a lower potenty drug like fexofenadine and it doesn’t work switch to a higher potency drug like levocetirizine or desloratidine
ADR of second generation antihistamine
Somnolence
- at high doses
- highest with cetirizine and levocetirizine
Constipation
Headache
No signifcant cardiac effect
DDI with second generation H1 blocker
- Fexofenadine
- Loratidine
- desloratidine
- ceterizine
- levocetirizine
- Fexofenadine
- avoid grapefruit, orange and apple juice (compund that impairs absorption)
- must seperate by at least 4 hours
- avoid grapefruit, orange and apple juice (compund that impairs absorption)
- Loratidine, desloratidine
- metabolized via 3A4 and 2C6
- erythromycin, ketoconazole, clarithromycin, cimetidine and grapefruit juice
- Avoid with alcohol and benzo
- metabolized via 3A4 and 2C6
- ceterizine, levocetirizine
- PgP substrates→ DDI with grapefruit jucie and colchicine
- Avoid other sedative drugs→ additive effect
H2 receptor antagonist
Reversibly decreases fasting and food stimulated acid secretion by inhibiting histamine on the histamine 2 receptor of the parietal cell
Used for episodic heartburn
Good for on-demand, meal provoked symptoms
Onset- 30-45 min
Duration- 4-10 hours
all equally efficacious
OTC 1/2 the perscription dose
Absorption may be delayed by administration of antacids but not by food
- bioavailability of cimetidine and ranitidine reduced with simultaneous hgih dose antacids
Rantidine
H2 receptor antagonist
used for episodic heartburn
Cimetidine
H2 receptor antagonist
used for episodic heartburn
Nizatidine
H2 receptor antagonist
used for episodic heartburn
Famotidine
H2 receptor antagonist
used for episodic heartburn
ADR associated with h2 blcokers
well tolerated
ADR are mostly CNS related (H2 recptors in the CNS)
Headache, dizziness, fatigue,confusion (incidence increased in elderly and renal impairment)
Dose related gynecomastia with cimetidine
Tolerance reported with porlonged use (use PRN)
H2 blockers DDI
Drugs depend on acid for proper absorption
- ketoconazole, itraconazole, protease inhibitors (atazanivir), calcium carbonate, iron salts
Cimetidinne inhibits CYP450 enzymes (3A4, 2D6, 1A2, 2C9)
- substrates- cyclosprine, amiodarone, theophylline, phenytonin, antidepressants, warfarin
