Where do we find H1 receptors ?

• Endothelium  --> NO
• SMC
• Nerve endings

H1-->G--PLC--↑IP3/DAG-->release Ca++ from SR

Where do we find

H2

Receptors?

• Gastric mucosa:          ↑ HCl secretion
• Cardiac muscle cells:   ↑ HR and contractility
• Some immune cells

H2-->cAMP-->PK

How do H1 and H2 affect

Vasodilation

?

• H1 is FAST and short actin:--> NO
• H2 is SLOWER and longer-acting

H2

increases contractility and HR

Describe

Histamine-induced increase in capillary permeability

• H1 --> histamine-induced edema
  
  • due to increased separation of endothelial cells
    
  • Permits transudation of fluid into perivascular tissue
    
  • --> UTICARIA (hives)

Describe effect of histamine on

EXTRAVASCULAR

smooth muscle

and

effects on SECRETION of gastric acid

• GI tract SMC:  Contraction (H1) 

• Bronchiolar SMC: Bronchoconstriction (H1)

• Stimulates gastric acid production (H2)

Which histamine receptor is responsible for

PAIN

and

ITCH

????

H1

(stimulates sensory nerve endings, especially those for pain and itching)

Aerosol:

Provokes bronchial hyperreactivity

What is the

Physiological antagonist for Histamine

and how does it work?

EPINEPHRINE

has SMC actions opposite histamine

and

WORKS AT DIFFERENT RECEPTORS

Cromolyn

Nedocromil

HISTAMINE RELEASE INHIBITORS

(Note that Beta2 agonists seem to reduce histamine release as well)

DIPHENHYDRAMINE

1st gen H1 receptor locker

(very sedative)

DIMENHYDRINATE

1st gen H1 blocker

Used to Tx motion sickness

DOXYLAMINE

1st gen H1 blocker

Marked sedation

HYDROXYZINE

1st gen H1 blocker

Marked sedation

MECLIZINE

1st gen H1 blocker

Used for motion sickness

PROMETHAZINE

1st gen H1 blocker

Marked sedation

FEXOFENADINE

fex-o-fenadine

2nd gen H1 blocker

Non-sedative

Doesn't get to CNS

LORATADINE

lora-ta-dine

2nd gen H1 blocker

non-sedating

CETIRIZINE

cet-iri-zine

2nd gen H1 blocker

ACRIVASTINE

ac-rivas-tine

TERFENADINE

ter-fen-adine

H1 blocker

(not sure whether 1st or 2nd gen)

They aren't really blockers

They are

INVERSE AGONISTS

Side effects of

First Gen

H1 blockers

• Sedation
  
• Dry mouth

• Increased appetite
• Vertigo
• Urine retention
  
• Trouble remembering drug names and MOAs

CIMETIDINE

cim-et-idine

RANITIDINE

ran-it-idine

FAMOTIDINE

fam-O-tidine

NIZATIDINE

niz-at-idine

Uses of

H2 blockers

• Inhibit secretion of gastric acid

•  
  • Peptic ulcer
  • Acute stress ulcers (remember path!)
  • GERD

Adverse  reactions of

H2 blockers

• Inhibit CYP P450
• Cimetidine binds to ANDROGEN receptors
  
  • gynecomastia
  • reduced sperm count
  • galactorrhea in women

What is the ONLY non-G-protein-based

Serotonin receptor?

5HT3

(ligand-gated ion channel)

Used by the drug

ONDANSETRON

on-dan-set-ron

as an ANTI-EMETIC w/ Cancer Chemo

SUMATRIPTAN

suma-triptan

5-HT 1D/1B

Receptor AGONIST

first line

anti-migrane

METOCLOPRAMIDE

met-O-clo-pram-ide

5-HT 4 RECEPTOR AGONIST

PROKINETIC AGENT

results in coordinated contractions

that enhance transit

CISAPRIDE

cis-a-pride

5-HT 4 RECEPTOR AGONIST

PROKINETIC

DUE TO SERIOUS CARDIO FX,

NO-LONGER AVAILABLE IN USA

CYPROHEPTADINE

cy-pro-hep-tadine

5-HT2 RECEPTOR AGONIST

Also potent H1 blocker

• Allergic rhinitis
• Vasomotor rhinitis
  
• Cold uticaria, dermatographism
• Tx of SMC manifistations of CARCINOID TUMOR
• Treats SERATONIN SYNDROME

ONDANSETRON

on-dan-se-tron

5-HT3 RECEPTOR ANTAGONIST

(remember the good 'ol AREA POSTREMA ????)

anti-emetic

used with chemo

(I think I'm gonna vomit, memorizing all these drug names........)

What the heck do we use

ERGOT ALKALOIDS

for ???

Migraine relief

Variant angina

Hyperprolactenemia

Postpartum hemmorhage

ERGOTAMINE

er-got-amine

DIHYDROERGOTAMINE

di-hydro-ergot-amine

MIGRAINE RELIEF

highly-specific

triptans are preferred, but

ergotamine and dihydroergotamine are less $$

BROMOCRIPTINE

bromo-crip-tine

CABERGOLINE

cab-er-go-line

PROLACTIN REDUCER

from pituitary tumor

remember, infant suckling -->

↑ prolactin-->

milk PRODUCTION (not let-down)

OXYTOCIN

oxy-toe-cin

Preferred agent

POSTPARTUM HEMORAGE CONTROL

If doesn't work, give

ERGONOVINE or METHYLERGOVINE IM

ERGOVINE

er-go-vine

IV

Used to DIAGNOSE

VARIANT ANGINA

(provokes coronary artery spasm)

Where do

EICOSANOIDS

come from ?

Mommy and Daddy Eicosanoids ??

Nope,

ARACHIADONIC ACID

20 carbons, 2 double bonds

Name the

TWO

major

EICOSONOID PATHWAYS

1. CYCLO-OXYGENASE
   1. Prostaglandins
   2. Prostacyclins
   3. thromboxanes

1. LIPOXYGENASE
   1. leukotrienes

so,

Tell me about

COX 1 and COX 2

• COX-1
  • found in most cells as CONSTITUTIVIVE
  • Used in normal homeostasis
• COX-2
  • COX-1's inflammatory brother
  • Found in INFLAMMATORY CELLS
  • induced by INFLAMMATORY STIMULI

WHAT ARE

LEUKOTRIENES

ASSOCIATED WITH?

• ASTHMA
• ANAPHYLACTIC SHOCK
• CARDIOVASCULAR DISEASE

LTC4 and LTD4

Potent bronchoconstrictors

secreted in asthma and anaphylaxix

How do

EICOSONOIDS

work?

(They are sooo confused !)

• autocrine and paracrine
• Bind to receptors-->couple to G protein
  
  • some activate AC
  • some inhibit Adenylyl Cyclase
  • Some activate PPL C

--> ↑ Ca++ --> CONTRACT SMC

or relax SMC via cAMP

DINOPROSTONE

dino-pros-tone

Prostaglandin

OBSTETRICS

ripen the cervix before

inducing labor with oxytocin

CARBOPROST TROMETHAMINE

carb-O-prost   tro-meth-amine

Induce uterine contractions

control postpartum bleeding

(use with caution in asthmatics)

MISOPROSTOL

mis-O-prostal

derivative of PGE1

Used in combo with antiprogestin

MIFERISTONE or METHOTREXATE

abortifacient

also used for prevention of peptic ulcers in NSAID users

ALPROSTADIL   (PGE1)

al-prost-a-dil

MAINTAINS PATENCY OF THE

DUCTUS ARTERIOSUS

PROSTACYCLIN (PGI2)

prost-a-cyclin

severe pulmonary hypertention

prevent platlet aggregatioin

LATANOPROST

lat-tan-o-prost

PGF2 alpha derivative

GLAUCOMA

VIMATOPROST

TRAVOPROST

UNOPROSTONE

Newer than LATANOPROST

ANTI-GLAUCOMA

ZILEUTON

zil-u-ton

INHIBITS  5-lipooxygenase

so no leukotrienes !

ZAFIRLUKAST

za-fir-lu-kast

MONTELUKAST

mon-te-lu-kast

So, tell me what

corticosteroids

do with respect to prostaglandins and leukotrienes

• Inhibit production of ARACHIADONIC ACID by PPL in cell membranes (so no leukotrienes or prostaglandins)
• Inhibit synthesis of COX-2

How do NSAIDS work?

Inhibit COX-2

so reduce inflammation

(As I recall, they also inhibit COX-1)