Immunology Block: Pharmacology 8 - Histamine And Anti-Histamine

Front 1

what are some of the basic functions of histamine?

Back 1

mediate type I hypersensitivity (allergic reactions),

brain neurotransmitter.

make stomach secrete acid

systemic inflammation.

Front 2

what makes histamine and where is it stored?

Back 2

histadine turns into histamine with the enzyme L-histadine decarboxylase.

it's stored in mast cells and basophils.

also lots in the lungs and mucous membranes, GI, skin. Nerves.

Front 3

what causes histamine to be released?

Back 3

endogenous factors include IgE for immediate hypersensitivity.

also, remember the anaphalotoxins, which include complements C3a, C4a, C5a, and substance P.

also basic amino acids like argenine and lysine.

conditions include trauma, different drugs (morphine and other antibiotics), and allergic reactions.

Front 4

how do you inacavtivate histamine?

Back 4

INMT (imidazol n methyl transferase) followed by MAO (mono amine oxidase).

minor pathway uses DAO.

makes methyl histamine, followed by methyl imidazol acetic acid.

Front 5

what perceives histamine?

Back 5

receptors: H1 and H2.

H1 are more likely to be on endothelium of vessels and smooth muscles, causes vasodilation

H2 are on gastric mucosa, cardiac muscle, some immune cells - likely causes increase in the secretion of acids.

activation of the receptors causes influx of Ca++ and Na++, then activates G-proteins.

Front 6

what's anaphylaxis?

Back 6

sudden allergic reaction that's sytemic. involves skin, respiratory tract, GI, and cardiovascular system.

Front 7

what's the response of lewis?

Back 7

triple response of lewis:

Flush Flare, and wheal.

Flush and Flare think it's H1 and H2. Wheal is H1.

Flush = reddness, from vasodilation

Flare = irregular outline, slower to develop.

wheal = edema.

Front 8

what are some physiological antagonists of histamine's action?

Back 8

epinephrine - doesn't mess with histamine, but it does massively vasoconstrict and bronchodilate, which fights both actions of histamine.

Albuterol is a Beta-2 Agonist, which should bronchodilate and vasoconstrict as well.

Front 9

big differences between H1 and H2 in terms of location and function

Back 9

H1 is in endothelium and smooth muscle, works through IP3/DAG to increase Ca++.

H2 is in the gastric mucosa, cardiac muscle, brain. It works through cAMP.

cardiovascular: H1 vasodilates, H2 ups heart rate and contraction.

Respiratory: H1 is a bronchoconstrictor in asthma patients. they have increased response to histamine in the lungs.

remember that H2 on parietal cells ups the secretion of stomach acid.

Front 10

what are the basic targets of drugs to stop histamines?

Back 10

physiological antagonists like epinephrine.

stop release of histamine by stopping degranulation (membrane -supporters).

Receptor antagonists.

Front 11

okay, how can we stop degranulation? What drugs and what aren't they good for?

Back 11

Cromolyn sodium (nasalcrom)
Nedocrom (tildade)

ineffective on acute attack, as the horse is already out of the barn.

good on alallergic rhinitis and atopic diseases of the eye.

Front 12

what are the classes of receptor antagonists?

Back 12

H1 and H2.


note that H1 is divided into first generation and second generation histamine 1 blockers.

Front 13

what are the general kinds of diseases treated wit H1 receptor antagonists?

Back 13

Allergies, including urticaria.

common colds - good for drying out mucous membranes.

pre-anesthetic sedation

motion sickness

antiemetics

migraines.

Front 14

what are the first generation H1 blockers and what's wrong with them?

Back 14

they're all sedatives.

Bromopheniramine
Chloropheniramine
Diphenydramine
Hydroxyzine

the ethanolamines include diphenylhyramine (benadryl) and dimenhydrate ) dramamaine)

Front 15

second generation?

Back 15

second generation h1 blockers include loratadine (claratin) and feoxfenadine (allegra)

don't cause sleepy or dry mouth seen in first generations.

pipiradines include allegra and loratadine.
piparizines include zyrtec (good against hives!).

note that if asked, desloratadine is the best one of them all.

Front 16

what are our H2 antagonists? advandages/disadvantages?

Back 16

Famotadine = pepcid

Cimetadine = tagamet

ranitidine = zantac

nizatadine is AXID.

note that CIMEATINE is not great because it's a potent inhibitor of P450.

only possible downdie is that they can all compete with other drugs for being kicked out by P-glyco protein, so that's another route that other drugs can be made more potent.