Histamine (Ceryak) Flashcards
What are H1 first generation drugs?
Diphenhydramine, doxylamine, chlorpheniramine
What are H1 second gen drugs?
Loratadine, cetirizine, fexofenadine
Describe histamine biosynthesis/metabolism
- biosynthesis: decarboxylation of L-histidine
- metabolism: rapidly broken down to inactive metabolites when released (via enzymes like MAO)
What is it mean that histamine is an autacoid?
released and act locally in periphery
Where is histamine most synthesized and stored?
mast cells and basophils (in granules complexed with heparin/acidic proteins)
Where is histamine distributed?
periphery, CNS (histaminergic neurons)
What is the immunologic release stimuli of histamine?
- allergic rxns (type I hypersensitivity) via IgE:antigen crosslinking
- inflammation: complement system activation at inflammatory site
What drugs block histamine release?
-epinephrine/cromolyn
What are the 2 receptor subtypes and how they differ?
H1 - smooth muscle, endothelium, CNS; Gq path (IP3, cGMP)
H2 - vascular smooth muscle, gastric mucosa, cardiac, CNS; Gs path (cAMP)
Endogenous Histamine: vascular SM
-H1: vasodilation/edema (relaxation of endothelial cell to decrease blood pressure but increase reflex tachycardia)
Endogenous Histamine: non-vascular SM
H1: bronchocontriction
Endogenous Histamine: GI
H2: parietal cell gastric acid release
Endogenous Histamine: PNS (autacoid)
H1: stimulates primary afferent nerve endings (itch, pain)
Endogenous Histamine: CNS (NT)
Mainly H1 (post-synaptic): arousal (wakefulness); appetite, body temp
H1 contracts VSM and relaxes endothelial VSM, while H2 relaxes VSM. What is the net effect?
Relaxation! (w/o endothelial H1 it would be contraction)
Is anaphylaxis caused by histamine?
no!
Are local allergic rxns caused by histamine? (urticaria=hives and allergic rhinitis=hay fever)
yes!
What are 3 classes of pharmacotherapy for allergies?
- subacute and preventative = inhaled steroids (fluticasone)
- mast cell stabilizers (cromolyn sodium to inhibit mast cell degranulation)
- antihistamines
What do antihistamines not work against in the allergic response?
bronchospasm mediated by leukotrienes
First generation H1 antihistamines receptors affected
- cholinergic: dry mouth, urinary retention, sinus tachycardia
- histamine H1: decreased allergic inflam, itching, sneezing, rhinorrhea, but increased sedation and appetite
Diphenhydramine (first gen H1) - duration, anti-ACh, Sed, anti-emetic, other
- 4-6 hours
- +++
- +++
- ++
- anti-motion sickness, OTC sleep aid
Doxylamine (first gen H1) - duration, anti-ACh, Sed, anti-emetic, other
- 6-12 hours
- +++
- ++++
- +++
- OTC sleep aid, anti-emetic (FDA approved for morning sickness)
Chlorpheniramine (first gen H1) - duration, anti-ACh, Sed, anti-emetic, other
- 4-6 hours
- +
- ++
- -
- OTC cold meds
Fexofenadine (second gen H1) - duration, anti-ACh, Sed
- 6-12 hours
- -
- +/-
Loratidine (second gen H1) - duration, anti-ACh, Sed
- 12-24 hours
- -
- +/-
Cetirizine (second gen H1) - duration, anti-ACh, Sed
- 12-24 hours
- +/-
- +
How does second gen compare to first gen H1 antihistamines?
-second gen has less BBB penetration so fewer CNS side effects (no anti-emetic effects); second gen not OTC sleep aid
H1 antihistamines ADME
- rapidly absorbed, lipid soluble, 95% bound to proteins
- first gen penetrate BBB, second gen do not bc second gen ionized at physiological pH (increased affinity for PGP
- second gen longer lasting
- metabolized in liver (except fexofenadine excreted unchanged in bile)
- renal clearance
- crosses placenta but little risk in pregnant women; eliminated in breast milk
H1 antihistamines first gen adverse effects (second gen not much): CNS
impaired alertness, cognition, learning, memory, performance
H1 antihistamines first gen adverse effects (second gen not much): cardiac
dose-related sinus tachycardia, reflex tachycardia
H1 antihistamines first gen adverse effects (second gen not much): glaucoma
contraindicated in persons with glaucoma or prostatic hypertrophy
H1 antihistamines first gen adverse effects (second gen not much): toxicity overdose
respiratory depression (potentially fatal) -adverse CNS effects > adverse cardiac effects
H1 antihistamines first gen adverse effects in elderly
commonly used but cog and mem impairment, falls, incontinence, etc.
H1 antihistamines first gen adverse effects in lactating women
cause drowsiness or irritability in nursing infants
H1 antihistamines first gen adverse effects in infants and young children
adverse effects and occasionally fatalities
Any exceptions to H1 antihistamine sedation?
some children experience CNS excitation
