3 classes of autacoids
Histamine, Serotonin, Eicosanoids
nitrogenous compound involved in:
immune responses, inflammatory response, gut regulation, neurotransmitter, released by mast cells
Histamine
Receptor in smooth muscle, endothelium, brain
H1
Gq, increase IP3, DAG
H1
Allergic reactions (dermatitis, rhinitis, conjunctivitis) proinflammatory
H1
Gastric mucosa, cardiac muscle, mast cells, brain
H2
Gs, increase cAMP
H2
presynaptic: brain, histaminergic neurons
H3
Gi, decrease cAMP
H3
inhibits histamine release and synthesis
H3
eosinophils, neutrophils, CD4 T cells
H4
stimulates chemotaxis of eosinophils and mast cells, potential target in allergic rhinitis and asthma
H4
reduce or block the actions of histamine by reversible competitive binding to the H1 receptor
H1 receptor anatagonist
negligible potency at H2 and H3 receptors
H1 receptor anatagonist
all have sedative effects, can treat N/V, some anticholinergic side effects (urinary retention, blurred vision), some are local anesthetics (procaine, lidocaine, promethazine)
First generation anti-histamines
Promethazine (Phenergan)
first generation anti-histamine
Diphenhydramine (Benadryl)
first generation anti-histamine
Chlorpheniramine (Chlor-trimeton)
first generation anti-histamine
Clemastine (Travist)
first generation anti-histamine
Dimenhydrinate (Dramamine)
first generation anti-histamine
hydroxyzine (atarax)
first generation anti-histamine
meclizine (antivert)
firs generation anti-histamine
Do not have anti-emetic properties
2nd generation anti-histamine
mainly used to trx allergies (allergic rhinitis and chronic uticaria)
2nd generation anti-histamine
do not produce significant sedation
2nd generation anti-histamine
fewer anti-cholinergic side effects
2nd generation anti-histamine
Fexofenadine (allegra)
2nd generation anti-histamine
Loratadine (claritin)
2nd generation anti-histamine
Desloratadine (clarinex)
2nd generation anti-histamine
cetirizine (zyrtec)
2nd generation anti-histamine
azelastine (astelin)
2nd generation anti-histamine
(nasal spray)
olopatadine (patanase)
2nd generation anti-histamine
(nasal spray)
autacoid, NT produced by platelets, gut cells, neurons
Serotonin
metabolized by MAO
serotonin
many 5-HT receptors identified
serotonin
present in nervous system, respiratory system, cardiovascular system, GI, skeletal muscles
serotonin
stimulant of pain and itch
serotonin
triggers vomiting
serotonin
contraction of smooth muscles (GI)
serotonin
vasoconstrictor
serotonin
bradycardia and hypotension (vagal nerve)
serotonin
neuroendocrine control (sleep, temp, appetite)
serotonin
Bind to and activate 5-HT receptors, like serotonin
5-HT agonist
Sumatriptian (Imitrex)
5-HT agonist (migraines)
Eletriptan (Relpax)
5-HT agonist (migraines)
Buspirone (Buspar)
5-HT agonist (anxiolytic)
Tegaserod (Zelnorm)
5-HT agonist (IBS- limited use)
Clozapine (Clozaril)
5-HT antagonist (anti-psychotic)
Ondansetron (Zofran)
5-HT antagonist (anti-emetic)
Derived from arachidonic acid
eicosanoids
2 main categories of eicosanoids
Prostaglandins and Leukotrienes
Alprostadil (Caveriect, Muse)
synthetic PGE1
maintain patency of ductus arteriosus in neonates
tx erectile dysfunction
Misoprostol (Cytotec)
synthetic PGE1
prevents peptic ulcer
termination of pregnancy (in combo with RU-486)
Dinoprostone (Cervidil)
synthetic PGE2 and PGF2
produce cervical ripening
Carboprost (Hemabate)
synthetic PGE2 and PGF2
control post-partum bleeding
Epoprostenol (Flolan)
Prostaglandin I2 (Prostacyclin)
treat pulmonary arterial hypertension
produced by leukocytes
leukotrienes
pathway associated with asthma, anaphylactic shock, cardiovascular disease
leukotrienes
Leukotriene D4 causes: 3 respones
bronchoconstriction, mucosal edema, mucus hypersecretion
Drugs that inhibit leukotrienes:
LTD4 receptor blockers
LOX inhibitors (lipooxygenase)
LTD4 receptor blockers: 2
Zafirlukast (accolate)
montelukast (singulair)
LOX inhibitors: 1
Ziluton (Zyflo)
potential liver toxicity
sustained release tablet 2/day
must be careful; inhibits CYP450 enzymes. Be careful with STATINS
Ziluton (Zyflo)
chronic inflammatory disease of the airways
asthma
hyperresponsiveness
asthma
stabilizes mast cells
cromolyn, nedocromil,
IgE Abs- Omalizumab
only valuable for prophylactic use to tx asthma
cromolyn, nedocromil
(sprays or eye drops as well for rhinoconjunctivitis)
don't effect airway smooth muscle tone
cromolyn, nedocromil
inhaled fine powder
cromolyn
metered dose inhaler
nedocromil
Anti IgE antibody
Omalizumab (xolair)
giving in addition to existing long term inhaled steroid to tx asthma
Omalizumab (xolair)
major toxicity- hypersensitivity and anaphylaxis
omalizumab (xolair)
observe for at least 2 hrs and carry epinephrine
block release of inflammatory mediators
glucocorticoids) prednisone, methylprednisone
LIs- Montelukast, Zafirlukast
block production of cytokines
glucocorticoids) prednisone, methylprednisone
Block mast cell migration
glucocorticoids) prednisone, methylprednisone
Do NOT directly relax bronchial muscle but DO reduce bronchial reactivity
glucocorticoids) prednisone, methylprednisone
Improve pulmonary function
Long-term treatment to prevent asthma attacks
glucocorticoids) prednisone, methylprednisone
inhaled glucocorticoids (5)
FLUTICASONE (FLOVENT�)
BECLOMETHASONE (VANCERIL�)
TRIAMCINOLONE (AZMACORT�)
FUNISOLIDE (AEROBID�)
BUDESONIDE (PULMICORT�)
increase lipolysis, redistribution of fat
glucocorticoids
water retention
glucocorticoids
decrease Ca absorption from gut
glucocorticoids
stimulate gastric acid production
glucocorticoids
mood changes
glucocorticoids
promote bronchodilation
methylxanthines- theophylline
SABA- albuterol, Epi, terbutaline
LABA- salmeterol, Formoterol
Anticholinergics- Ipratropium bromide
Inhibits phosphodiesterase - enzyme that degrades cAMP (??cAMP levels)
methylxanthene- theophylline (Elixophyllin)
Aminophylline
main use COPD
narrow therapeutic window, N/V, half-life varies, metabolized in liver (DDI), 2nd line drugs from chronic asthma
Bronchodilators
methylxanthene- theophylline (Elixophyllin)
Aminophylline
have potential for tremor, tachycardia, nausea
SABA
Epinephrine
Albuterol (Proventil�)
Terbutaline (Brethine�)
LABAs with ICS
Budesonide/formoterol (Symbicort�)
Fluticasone/salmeterol (Advair Diskus�, Advair HFA�)
Mometasone/formoterol (Dulera�)
Anticholinergics
Acts as a bronchodilator
Aclidinium bromide (Tudorza Pressair �)
Ipratropium (Atrovent �)
Tiotropium (Spirvia �)
Increase goblet cells, decrease in ciliated epithelial cells, decrease in ME clearance
COPD
Blocks constricting effects of parasympathetic nerve stimulation
Mainly used for COPD
Bronchodilators: Muscarinic Receptor Antagonists
IPRATROPIUM (ATROVENT�)
Inhaled agent
Few side effects, poor absorption
Mist complexed with SOY (cautious with peanut allergies)
TIOTROPIUM (SPIRIVA�)
No issue with soy or peanut allergy
Increase in stroke
Mainly due to activation of H1 receptors causing vasodilation, congestion, edema and inflammation
Allergic Rhinitis (Allergies)
tx with:
Antihistamines
Inhaled steroid preps
Bronchodilators
ANTI-TUSSIVES - suppress cough
DEXTROMETHORPHAN
CODEINE
BENZONATE (TESSALON�)
EXPECTORANTS - aids in expelling mucus
GUAIFENESIN