autocoids

Histamine

immed allergic & inflam rxn
Gastirc acid secretion
modest anaphylaxis

histamine - 2

most in mast cells
ECL of stomach
w/ IgE release - CA+2 dept (type 1)
inhib some B and T cell functions

histamine - 3

H1-H4
GPCR

H1

smooth m, endothelium, Brain (postsynaptic)
Ip3 system

h2

gastic mucosa, cardiac m, mast cells, brain
Brain (postsyn)
cAMP production (some ip3)

h3

presyn brain, myenteric plex
inhib camp
Decrease of Histamine

h4

Bone marrow
chemotatic effects on eosionphils

histamine use

test for brncohial hyperreativity
Dont Give to
ASTHMA, ucler disease, GI bleedin

histamine antagonists

Epi + adernergic drugs

histamine release inhibitors

cromolyn, nedocromil, theophylline (asthma)

B2- agnonist
glucocorticoids

h1 - first generation

STRONG sedative (kids may get excited!)
block autonomic receptors
effective 4-6 hrs (cept meclizine)

reversilbe comp inhib (some inverse agonists)
go in CNS readily
active metabolites - degrade by liver

h1- second generation

much less sedating
less complete distrib in CNS

some inhib release from mast/basophils

h1-first gen

Cyproheptadine
Diphenhydramine*
Meclizine
Promethazine

h1-sec gen

Cetirizine*

h1 actions

STRONG INHIB EDEMA & ITCHING
STRONG ANTINAUSEA

h1 actions 2

antipark (due to anti-musc actions)
Diphenhdramine
Supress antipsych drugs sideeffects

urinary rent/blurred vision (atroppine like)

a-recp blocker
cyproheptadine (block serotonine)

potent anestheics (1st gen)

h1 uses

rhiitis (hay fever) & urticaria (B4 exposure)

limited effective angioedema & anaphalx

1st gen - MOTION SICKNESS PREVENTION!! (Diphen & Promethazine)

h1 tox (not second gen)

sleepy, restleness, insomina, tremors, halluc, seizures

GI - dry mouth/const

CVS - hypotension
bluured vision/urinary rention

increased appetite - cyproheptadine

contraindications h1

preg, children, heptaic disease, tacharrythmias

h2

hard to get into CNS, but in all organs

CIMETIDINE Ranitidine, Famotidine

h2 actions

comp inhibitors of parietal cells (gastic a & pepsin)
Stops NOCURTAL
inhib camp

h2 - cimetidine

inhibit cp450

h2 USES

GERD, heartburn (USE B4 MEALS)
PEP ulcers
(do not treat caused by NSAIDS and H. pylori)

Esophagitis

h2 tox

headache, confusion
elevated liver enz
IMPOTENCE
cp450 (clearance of other drugs)

h2 contraindications

renal impairment/disease

SEROTONIN

released from blood clots - induce vasoconstion

90% in EEC cells
after syn - rapidly stored/inactivated (MAO)

mediator in migrane headaches

stored in platelets of blood

mood,sleep, BP, vomit, pain percp

Serotonin Agonists

Buspirone - anxiety
Ergonovine - postpart bleed
Ergotamine - migranes
LSD - hallucinagin
Metoclopramide - GI disorders

Serotonin Ag - 1B/1D

Eletriptan
Naratriptan
Sumatriptan* - nasal
Zolmitriptan - nasal

Serotonin Antag

Butyrophenones
Cyproheptadine
Ketanserin
Ondasetron
Phenothiazines Phenoxybenzamine
Ritanserin

Serotonin Ag - 1B/1D

cerebrl/meng vessels (vasoconstriction)

neurons - presyn inhib receptors

SEVERE ACUTE MIGRANES
Sumatriptan - cluster headaches

serotonin tox

ting, warmth, dizzy, neck pain, myo infarcts

serotonin contraindic

Cereb vasc disease, perip vasc diease, heart disease

serotonin Antag

Butyrophenones - nonselc schzio
Cyproheptadine - sedation
Ketanserin - plate aggrg
Ondasetron - nasuea chemo
Phenothiazines - nonselc schzio
Phenoxybenzamine - inhib 5ht2
Ritanserin - bleeding time & TXH formation

Ergot Alkalods

spon abortions, hallucinations, vasospasm = gangrene

Ergot Use

Migrane pain (first sign of attack)
post part bleeding
hyperprolactiema

ergot tox

TI is narrow
prolonged vasospam
drowsy
hallucinations

Eicosanoids

lipid-derieved
Prostanoids (PG and TA (TXA2)

Leukotines (LT)

To use AA for Eicoansoids

must be relased by Phosopholipase A2 (epi, angioten II bradykinin promote

glucocorticods inhib

COX

Cox 1 - PG all cels - houskeepin
cox 2 - PGH inducible (inflam, fever, cancer) inhib by NSAIDS

AA - PGG2 - PGH2

LOX

AA metabolized by 5, 12, 15 lipgen

=

Hpete - HETE & LT
LTC4 & LTD4 (broncoconstrictors)

Eico

Short 1/2 life
GPCR
misoprotsol - 30-60 mins
others 2-5 mins

eico clincial

inhib syn (cox-2 target)
change diet to change fatty A precursors

Prostagladins

Alprostadil PGE1 DA patency (erectile dysf)
Carboprost Tromethamine- PGF2a - 2nd tri abortion, postpart hemmo -
Dinoprostone - PGE2 mole, abortion, labor induction
Epoprostenol - PGI2 - pulm hyperten, lung/heart transplants
Latanoprost - PGF2a - glaucoma, brown pigments
Misoprostol - PGE1 - abortions, NSAIDS ulcers, (tox = sepsis vag)

Lipid Autacoid Inhibitors

Glucocorticoids - all known pathways
Cromolyn - eicosaniod release
Montelukast & Zafirlukast - LT recp
NSAIDs
Zileuton - LOX

LA inhibtor - uses

Asthma
Bartters syndome - decresed sent to angioten (nml to Low - BP)

cell-med organ rejections!!

delayed closure of DA (PGE2)

painful menstraution (PGE2, PGF2a)

inflamation - arthritis

thrombosis - asprin - irrvs binding