Histamine

Question 0

Modifiers of Histamine: Epi, Ephedrine, selective B2 agonists, Albuterol, Salmeterol

Answer 0

Beta 2 agonists, antagonize all causes of smooth m contraction –> reverse bronchoconstriction
Tox: skeletal m tremor, cardiac palpitations, Epi can cause CNS excitement and HTN

Question 1

Histamine : H1 receptor

Answer 1

MOA1: Gq, IP3, Ca++–> GI smooth muscle: contracts, Sensory Nerves: Pain, itching, Bronchioles: Bronchoconstriction.
Tox: Proinflammatory response to insect stings: pain, redness and swelling. Urticaria. Bronchospasm in asthma
MOA2: NO –> Arterioles, Venules Dilation, leakage causing edema
Tox: Hypotension in shock syndromes. Edema. Flushing, hypotension, tachycardia, headache

Question 2

Modifiers of Histamine: Cromolyn Na, Nedocromil

Answer 2

Unknown MOA
Stabilize mast cells a/g IgE-sen release of histamine
Very safe, inhaled not absorbed

Question 3

Histamine acts via 4 receptor types

Answer 3

H1 – smooth muscle, endothelium and brain (Gq, IP3, DAG)
H2 — Gastric mucosa, mast cells (Gs, increase cAMP)
H3 — Presynaptic neuronal, Brain (Gi, decrease cAMP)
H4 — Eosinophils, neutrophils, CD4 T Cells (Gi, decrease cAMP)

Question 4

Triple Response

Answer 4

red spot, edema, flare response:
Red spot is local vasodilation.
Edema is microcirculation leaking in a wheal.
Flare is redness surrounding the wheal, and is caused by a axonal reflex

Question 5

Histamine: H2 receptor

Answer 5

Gs, cAMP
Gastric Parietal Cell Acid release
Tox: Erosion, Ulcers

Question 6

Dimenhydrinate (Dramamine), Diphenhydramine (Benadryl), Promethazine (Phenergan)

Answer 6

Competitive H1 antagonists First Generation: Strong Anti- cholinergic action
ALL: anti- motion sickness actions, antiemetic, strongly sedating Sedation may be good for control of symptoms of seasonal allergy, Hay Fever, dermatitis.
Tox: Strong sedation. Can be dangerous in daytime (workplace, driving, etc.) and is disruptive for mental function at work, school. Blurred vision, urinary retention

Question 7

Cimetidine Ranitidine Nizatidine Famotidine

Answer 7

H2 Antagonists : Block the histamine action which stimulates acid (proton) release at the parietal cell of the gastric fundus
Tox: Safe drugs. Diarrhea, headache, fatigue, myalgias, constipation. Cimetidine (enzyme inhibitor), gynecomastia

Question 8

Fexofenadine (Allegra) Loratadine (Claritin) Cetirizine (Zyrtec)

Answer 8

H1 Antagonists Second Generation
No Anti- cholinergic action
Non-sedating. A major advantage for daytime treatment of allergies, urticaria, Hay Fever, etc
Tox: No antiemetic effect. No benefit against motion sickness