Medchem

Front 1

Histamine Structure

Back 1

.
.
.
.
.
.
.
.
.

Front 2

Histamine-in general

Back 2

autocoid and neurotransmitter

Front 3

HA-peripheral effects

Back 3

synthesized and stored in mast cells and chromaffin cells
MAST: IgE-related allergic response
GI: gastric acid secretion

Front 4

HA-neurotransmitter

Back 4

overall alertness, general psychiatric functions (emotions, appetite) BLOCK=sedation

Front 5

H1 Receptors

Back 5

Where? periphery and CNS
Modulated? G-alpha-Q => PLC, IP, DAG, ^ Ca release

Front 6

H1 Mediates?

Back 6

typical allergic response-immediate, primary
ALSO: contraction of smooth muscles, asthma, diarrhea
**epithelial contraction= redness, swelling, edema

Front 7

H2 Receptor

Back 7

where? periphery and CNS
Mediated? G-alpha-S =>Aden cyclase, cAMP, PKA

Front 8

H2 Receptor effects

Back 8

GI: acid secretion (parietal cells)
vasodilation
CNS-unknown

Front 9

H3 Receptor

Back 9

where? CNS only
mediated? G-alpha-I=> decreases AC, cAMP, PKA
**negatively regulates NT release

Front 10

H4 Receptor

Back 10

where? CNS and periphery
mediated? G-alpha-S, AC, cAMP
**leukocytes and bone marrow = immune response

Front 11

HA chemistry

Back 11

lone pairs on nitrogen, fairly basic

Front 12

Histadine Structure

Back 12

.
.
.
.
.
.
.
.
.

Front 13

HA Metabolism-
Histadine + ...

Back 13

histadine decarboxylase

Front 14

Histamine-
Breakdown (1st)

Back 14

histamine methyl transferase--adds methyl where?

Front 15

HA-
Breakdown (2nd)

Back 15

diamine oxidases (and others)

Front 16

end product of HA metabolism

Back 16

1-methylimidazole acetic acid
**diagnostic urine metab--for allergic rxns

Front 17

HA storage

Back 17

in storage granules: + form ionic bonds with - acidic groups
**heparin & chondroitin (-)

Front 18

HA activation-in general

Back 18

positively charged drugs displace HA and goes on to activate receptors
**esp. alkaloid drugs like morphine, piperidines, amine, ammonium

Front 19

HA activation step 1

Back 19

IgE on mast cells are receptors for allergens

Front 20

HA activation step 2

Back 20

IgE receptor is activated by allergen
**DAG & IP3 -release Ca, HA released

Front 21

HA activation step 3

Back 21

Release Ca from ER-facilitates degranulation, HA released
***can be blocked by antihistamines

Front 22

HA block (1)

Back 22

-block increase in IP3--cromolyn sodium

Front 23

cromolyn sodium structure

Back 23

.
.
.
.
.
.
.
.
.
.

Front 24

HA block (2)

Back 24

-increase in cAMP=relax the secretory response of mast cells
EX: beta agonists-relax smooth muscle

Front 25

PDE inhibitors

Back 25

block conversion of cAMP to AMP--imp for asthma tx

Front 26

immediate release from mast cells

Back 26

HA, heparin, chondroitin, TNF

Front 27

5 minutes-released from mast cells

Back 27

prostaglandins, leukotrienes, PAF

Front 28

1 hour-released from mast cells

Back 28

cytokines (interleukins)

Front 29

DRUGS

Back 29

.
.
.

Front 30

H1 Receptor 1st generation antagonists

Back 30

diphenhydramine, chlorpheniramine, cyclizine

Front 31

H1 Receptor 2nd generation antagonists

Back 31

meclizine, terfenadine, fexofenadine, loratadine

Front 32

H1 Receptor 3rd generation antagonists

Back 32

desloratadine, hydroxyzine, cetirizine

Front 33

H2 Receptor antagonists

Back 33

cimetidine, ranitidine, famotidine, nizatidine

Front 34

Diphenhydramine structure

Back 34

.
.
.
.
.
.
.
.
.
.

Front 35

Dimenhydrinate structure-chlorotheophylline salt of benadryl

Back 35

.
.
.
.
.
.
.
.
.
.

Front 36

all 1st gen HA antagonists

Back 36

1. non-selective: also block ACh muscarinic, alpha adren (dec. BP), 5HT
2. dec. gi contract
3. other CNS mech and dec. nausea/vomiting (** X BBB)

Front 37

chlorpheniramine structure

Back 37

.
.
.
.
.
.
.
.
.
.
**S (+) =ACTIVE
R (-) =INACTIVE, contributes to SE's, chlor-trimeton=racemate

Front 38

cyclizine structure

Back 38

.
.
.
.
.
.
.
.
.
.

Front 39

meclizine structure

Back 39

.
.
.
.
.
.
.
.
.
.

Front 40

Meclizine in general

Back 40

add'l Ph ring, binds to albumin, retained in blood
-hydrophobic aromatic & H-bonding
LESS: X BBB, sedation
INCREASED: t1/2
stablized mast cell HA granules

Front 41

terfinadine structure

Back 41

.
.
.
.
.
.
.
.
.
.
** racemic & is prodrug

Front 42

fexofenadine structure

Back 42

.
.
.
.
.
.
.
.
.
.
*active metabolite

Front 43

Terfinadine problems

Back 43

Block metab by P450?
= cardiac arrhythmias
(macrolide ABX, antifungals, grapefruit juice)

Front 44

loratadine structure
-comp to chlorpheniramine

Back 44

.
.
.
.
.
.
.
.
.
.

Front 45

desloratidine structure

Back 45

.
.
.
.
.
.
.
.
.
.

Front 46

hydroxyzine structure

Back 46

.
.
.
.
.
.
.
.
.
.

Front 47

cetirizine structure

Back 47

.
.
.
.
.
.
.
.
.
.
*active metabolite of hydroxyzine

Front 48

general structure of H2 receptor antagonists

Back 48

.
.
.
.
.
.
.
.
.
.
**x,Y= N, S, O

Front 49

H2 recep. antagonists

Back 49

1. decrease gi acid secretion
2. receptors in blood vessels
3. many interactions with cimetidine and ranitidine