Histamine/Anti-Histamines

histamine is formed by the decarboxylation of the amino acid _______ via what enzyme?

histidine; histidine decarboxylase

chemically, histamine is classified as an?

amine

while histamine can be derived from _____ _____ or _______ in the GI, it is mostly formed from ______ ______

dietary sources; bacteria; amino acids

histamine is highly concentrated where?

lung, intestinal mucosa, skin

what cell type stores histamine

mast cells, leukocytes, enterochromaffin cells, neurons

what is it called when histamine is released from mast cells

degranulation (or exocytosis)

histamine is stored in a vesicle/complex with ______ or ______ ______ within the mast cell

heparin; chondroitin sulfate

what antibody is often found on mast cells

IgE

When an allergen binds with _____ antibodies on mast cells, this results in release of chemical mediators, called:

IgE; degranulation

what are the main causes to histamine release

tissue injury, allergic rxns, drugs or foreign substances

if a tissue injury occurs, the initial histamine release causes?

increase in vascular permeability

what are the two generalized phases of histamine response? which stage do antihistamines work best on/in?

initial sharp phase, sustained response; initial phase

if an individual is already in anaphylaxis, will antihistamines still work?

no; they are now in the sustained phase and will need epi

can drugs induce a histamine response with prior sensitization?

no

what are common drugs that induce a histamine response

morphine, dextran, antimalarial drugs, abx

what are common foreign compounds that induce histamine repsonses

dyes, chemicals, toxins/venoms

what are the pharmacological effects of histamine on the arterioles, mj capillaries, venules

vasodilation, systemic hypotension, increased permeability (edema)

what are the pharmacological effects of histamine on the terminal vasculature

triple effect

what is the triple effect? what is an example

reddening at the side of vasodilation; ex. hives

drugs that inhibit the _____ receptor inhibit the triple effect

H1

what are the pharmacological effects of histamine on the smooth muscle of bronchioles

contraction of non-vascular smooth muscle (bronchoconstriction)

what are the pharmacological effects of histamine on the exocrine glands

increase secretions

what are the pharmacological effects of histamine on the peripheral ns

itching, pain

what type of receptors are Histamine receptors

GPCR

how many histamine receptors are there

4 (H1-4)

H1 receptor is responsible for ______ condition

allergic

what does the H1 receptor stimulate in response?

bronchoconstriction, vasodilation, separation of endothelial cells (edema), pain/itching, allergic rhinitis, motion sickness

where is the H1 receptor located

smooth muscle, endothelium, CNS, heart

location of H2 receptor

gastric parietal cells, vascular smooth muscle, neutrophils, CNS, heart, uterus

what does H2 receptor do in response to stimulation

regulate gastric acid secretion, vasodilation

location of H3 receptor

mainly CNS

anti-histamines competitively/noncompetitively block histamine

competitively

first generation H1 can/cannot cross the BBB

can

first generation H1 can be used for?

sedation

what is the major difference between H1/H2

second generation is designed to not cross the BBB with significantly decreased sedation

anti-histamines can potentiate ____ _____

CNS depressants

examples of CNS depressants that anti-histamines can potentiate

opioids, sedatives, narcotic analgesics, alcohol, anti-muscarinics

what histamine do we need to know for this lecture?? what is its general name

diphenhydramine; benadryl

what anti-histamine class does diphenhydramine belong to

ethanolamine

does diphenhydramine have sedative effects?

yes

what OTC drug is it often found in combination with?

Tylenol PM

diphenhydramine can also be used in what motion sickness drug?

dramamine

in taking dramamine, diphenhydramine blocks the _____ receptor in the brain which is responsible for ______ _______

H1; motion sickness

H2 receptor anti-histamines are commonly used for _____ ______

acid reflux

H2 receptor antagonists can actually (increase or decrease) the bioavailability of _______

increase; ethanol

(lowers alcohol tolerance)

new drugs targeting H3 receptors are likely to target?

neuronal diseases

new drugs targeting H4 receptors are likely to target?

immunomodulation