Antihistamines Flashcards
Antihistamines
Histamine H1 receptor antagonists
1st gen antihistamines
Chlorpheniramine Diphenhydramine Meclizine Promethazine Doxylamine
2nd gen antihistamines
Cetirizine
Fexofenadine
When is histamine released?
Allergic/inflammatory reactions
Functional histamine antagonists
Epinephrine
Cromolyn sodium
Cells that release histamine
Mast cells
Basophils
Enterochromaffine like cells (G cells)
Histaminergic neurons
Histamine is what type of hormone?
Autocoid (local)
Mast cells
- For pathogen defense
- in most tissue, near blood vessels
- enriched at body interfaces (ears, eyes, nose, throat, gut)
Histamine release triggers
- immunologic
- chemical
- tissue damage
Enterochromaffin-like cells
- ## release histamine that act on H2 receptors on parietal cells
Which histamine receptor is therapeutically most relevant?
H1
Which histamine receptors are involved in allergic reaction?
H1, also H2 and H3
Histamine actions in allergic reactions
- VSM dilation
- increased vascular permeability
- peripheral sensory nerve excitation
- nasal congestion
- bronchial smooth muscle contraction
- intestinal smooth muscle contraction
VSM dilation in allergic reaction
Flushing
Fall in systemic BP
Reflex tachycardia
Small reaction —> H1 stimulated
Large —> H2
Where is H1 receptor?
Endothelium (NO)
Where is H2 located?
Smooth muscle cells (cAMP)
VSM dilation can cause what?
Histamine shock in systemic anaphylaxis
H receptors are what type of receptors?
GPCR
Increased vascular permeability in allergic reaction
Endothelial cell retraction
Edema/wheal formation (plasma and protein leaking)
H1 recpetor
Peripheral sensory nerve excitation in allergic response
Pain and itching
H1 and H3 receptors
Triple response of allergic reaction
- rapid reddening
- swelling (edema)
- flare
Rapid reddening in allergic reaction is due to what?
Dilation of small vessels
Swelling (edema) in allergic reaction is due to what?
Increased vascular permeability
Flare in allergic reaction is due to what?
Neural activated vasodilation
Triple response is used for what?
Quantify allergic response of an individual
Nasal congestion is from what H receptor?
H1
Bronchial smooth muscle contraction in allergic reaction
H1
Bronchial hyperactivity to histamine in asthmatics
Involves neural response
Other histamine receptor actions
- H2 on gastric parietel cells
- H2 on cardiac muscle
- CNS (wakefullness, analgesic)
- H4 modulate cytokine production
- anaphylactic shock
Anaphylactic shock
- bronchospasms
- severe hypotension
- angioedema
- mucous membrane congestion
- CNS: confusion, anxiety
- N/V
- palpitations
What should you give in anaphylactic shock?
Epinephrine
H1 blockers not effective
Physiological antagonist of histamine
- occurs when chemicals counterbalance each other by producing opposite effects on same physiological function
- Epi
Epi and histamine reaction
A1: NE activation, vasoconstriction (increase BP0
B2: NE activation, bronchodilation
Histamine release inhibitor
Cromolyn sodium
Cromolyn sodium and histamine
- inhibit lung mast cell histamine release
- prophylactic use in asthma, hay fever
First gen antihistamine overview
- enter CNS
- sedation
- anti-cholinergic effects
- GI problems
2nd gen antihistamine overview
- mostly do not enter CNS
- less sedating
- less muscarinic action
- more metabolized by CYP3A4 —> drug interactions
1st generation antihistamine metabolism
CYP450 most 2D6
- don’t have to worry about interfering with other drugs
Antihistamine excreteion
Urine
Feces (fexofenadine)
Antihistamine pharmacodynamics
- inhibit vasodilation and bronchial contraction
- inhibit increased capillary permeability and edema/wheal formation (does not reverse)
- anti allergic, anti inflammatory
Antihistamine use general information
- best to take before needed
- symptom relief may be incomplete
- tolerance usually does not develop
- less effective with chronic/high antigen exposure
T/f tolerance usually develops in antihistamines
False
Usually does not
Antihistamine PK
Most 4-6 hours
2nd gen are 12-24 hour
Antihistamine uses
- Seasonal allergic rhinitis and conjunctivitis (hay fever)
- hives
- anaphylaxis
- atopic dermatitis (eczema)
- CNS and vestibular disorders
For seasonal allergic rhinitis what are antihistamines combined with?
Pseudoephedrine
Phenylephrine
Antihistamines and anaphylaxis
- NOT to replace epinephrine
- only to reduce flushing, itching, urticaria, rhinorrhea
Antihistamines for motion sickness
- diphenhydramine
- promethazine
- meclizine
Antihistamines for antiemetic
Promethazine
Doxylamine
Antihistamines for insomnia
Diphenhydramine
Promethazine
Sedation from antihistamines can be enhanced by what?
EtOH and CNS depressants
CNS adverse effects of antihistamines
- sedation
- dizziness, HA
- stimulation in children
T/F there are fewer adverse effects with 2nd gen antihistamines
True
GI adverse effects of antihistamines
- due to muscarinic, adrenergic, serotonin receptor block
- constipation/diarrhea
- loss of appetite
- N/V/ epigastric distress
Anti-muscarinic effects of antihistamines
- dry mouth and sinuses
- urinary retention
Antihistamines CI
Narrow angle glaucoma
Dysuria
Allergic reactions from antihistamines
- dermatitis
- drug fever
- some photosensitization
Antihistamine overdose
Tachycardia
Dry mouth
Dilated pupils
Hallucinations
T/F caution in pregnancy with antihistamines
True
T/F generally avoid 2nd gen antihistamines in children and elderly
False
1st gen
Diphenhydramine uses
- allergic rhinitis
- dermatologic pain and itching
- insomnia
- motion sickness
Adverse effects of diphenhydramine
- sedation
- excitation in children
- reduce lactation
- enter breast milk
- avoid in narrow angle glaucoma
Chlorpheniramine use
- allergic rhinitis
- dermatologic pain and itching
- OTC cold (>2-4 yo)
Adverse effects of chlorpheniramine
- sedation, but less than benadryl
- less muscarinic effects
- still glaucoma concern
Promethazine use
- antiemetic
- sedative
Adverse effects of promethazine
- similar to other 1st gen
- photosensitivity
BBW promethazine
- respiratory depression (<2yo)
- severe tissue injury with injection
Meclizine use
- vertigo
- prevent motion sickness
Adverse effects of meclizine
Sedation (less than other 1st gens)
Diclegis
Doxylamine + pyridoxine (vitamin B6)
Diclegis use
Morning sickness
Sedative
T/F 2nd gen antihistamines have increased 1st pass effect
True
Cetirizine use
- allergic rhinitis
- dermatologic pain and itch
Adverse effects of cetirizine
- very well tolerated
- some sedation
- weak anti-muscarinic effects
- metabolized by CYP3A4
Fexofenadine use
- allergic rhinitis (oral only)
- dermatologic pain and itching (better prophylactically)
Adverse effects of fexofenadine
- usually well tolerated
- not sedating
- dysmenorrhea
- enters breast milk
Which antihistamine should you NOT take with fruit juice?
Fexofenadine (reduces absorptioN)
- OATP transport for absorption, not a CYP3A4
Decongestant general use
- relief from nasal congestion and pressure
