Histamine (Ceryak)

Question 1

What are H1 first generation drugs?

Answer 1

Diphenhydramine, doxylamine, chlorpheniramine

Question 2

What are H1 second gen drugs?

Answer 2

Loratadine, cetirizine, fexofenadine

Question 3

Describe histamine biosynthesis/metabolism

Answer 3

• biosynthesis: decarboxylation of L-histidine

- metabolism: rapidly broken down to inactive metabolites when released (via enzymes like MAO)

Question 4

What is it mean that histamine is an autacoid?

Answer 4

released and act locally in periphery

Question 5

Where is histamine most synthesized and stored?

Answer 5

mast cells and basophils (in granules complexed with heparin/acidic proteins)

Question 6

Where is histamine distributed?

Answer 6

periphery, CNS (histaminergic neurons)

Question 7

What is the immunologic release stimuli of histamine?

Answer 7

• allergic rxns (type I hypersensitivity) via IgE:antigen crosslinking
• inflammation: complement system activation at inflammatory site

Question 8

What drugs block histamine release?

Answer 8

-epinephrine/cromolyn

Question 9

What are the 2 receptor subtypes and how they differ?

Answer 9

H1 - smooth muscle, endothelium, CNS; Gq path (IP3, cGMP)

H2 - vascular smooth muscle, gastric mucosa, cardiac, CNS; Gs path (cAMP)

Question 10

Endogenous Histamine: vascular SM

Answer 10

-H1: vasodilation/edema (relaxation of endothelial cell to decrease blood pressure but increase reflex tachycardia)

Question 11

Endogenous Histamine: non-vascular SM

Answer 11

H1: bronchocontriction

Question 12

Endogenous Histamine: GI

Answer 12

H2: parietal cell gastric acid release

Question 13

Endogenous Histamine: PNS (autacoid)

Answer 13

H1: stimulates primary afferent nerve endings (itch, pain)

Question 14

Endogenous Histamine: CNS (NT)

Answer 14

Mainly H1 (post-synaptic): arousal (wakefulness); appetite, body temp

Question 15

H1 contracts VSM and relaxes endothelial VSM, while H2 relaxes VSM. What is the net effect?

Answer 15

Relaxation! (w/o endothelial H1 it would be contraction)

Question 16

Is anaphylaxis caused by histamine?

Answer 16

no!

Question 17

Are local allergic rxns caused by histamine? (urticaria=hives and allergic rhinitis=hay fever)

Answer 17

yes!

Question 18

What are 3 classes of pharmacotherapy for allergies?

Answer 18

• subacute and preventative = inhaled steroids (fluticasone)
• mast cell stabilizers (cromolyn sodium to inhibit mast cell degranulation)
• antihistamines

Question 19

What do antihistamines not work against in the allergic response?

Answer 19

bronchospasm mediated by leukotrienes

Question 20

First generation H1 antihistamines receptors affected

Answer 20

• cholinergic: dry mouth, urinary retention, sinus tachycardia
• histamine H1: decreased allergic inflam, itching, sneezing, rhinorrhea, but increased sedation and appetite

Question 21

Diphenhydramine (first gen H1) - duration, anti-ACh, Sed, anti-emetic, other

Answer 21

• 4-6 hours
• +++
• +++
• ++
• anti-motion sickness, OTC sleep aid

Question 22

Doxylamine (first gen H1) - duration, anti-ACh, Sed, anti-emetic, other

Answer 22

• 6-12 hours
• +++
• ++++
• +++
• OTC sleep aid, anti-emetic (FDA approved for morning sickness)

Question 23

Chlorpheniramine (first gen H1) - duration, anti-ACh, Sed, anti-emetic, other

Answer 23

• 4-6 hours
• +
• ++
• -
• OTC cold meds

Question 24

Fexofenadine (second gen H1) - duration, anti-ACh, Sed

Answer 24

• 6-12 hours
• -
• +/-

Question 25

Loratidine (second gen H1) - duration, anti-ACh, Sed

Answer 25

- 12-24 hours - - - +/-

Question 26

Cetirizine (second gen H1) - duration, anti-ACh, Sed

Answer 26

- 12-24 hours - +/- - +

Question 27

How does second gen compare to first gen H1 antihistamines?

Answer 27

-second gen has less BBB penetration so fewer CNS side effects (no anti-emetic effects); second gen not OTC sleep aid

Question 28

H1 antihistamines ADME

Answer 28

- 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

Question 29

H1 antihistamines first gen adverse effects (second gen not much): CNS

Answer 29

impaired alertness, cognition, learning, memory, performance

Question 30

H1 antihistamines first gen adverse effects (second gen not much): cardiac

Answer 30

dose-related sinus tachycardia, reflex tachycardia

Question 31

H1 antihistamines first gen adverse effects (second gen not much): glaucoma

Answer 31

contraindicated in persons with glaucoma or prostatic hypertrophy

Question 32

H1 antihistamines first gen adverse effects (second gen not much): toxicity overdose

Answer 32

``` respiratory depression (potentially fatal) -adverse CNS effects > adverse cardiac effects ```

Question 33

H1 antihistamines first gen adverse effects in elderly

Answer 33

commonly used but cog and mem impairment, falls, incontinence, etc.

Question 34

H1 antihistamines first gen adverse effects in lactating women

Answer 34

cause drowsiness or irritability in nursing infants

Question 35

H1 antihistamines first gen adverse effects in infants and young children

Answer 35

adverse effects and occasionally fatalities

Question 36

Any exceptions to H1 antihistamine sedation?

Answer 36

some children experience CNS excitation