Dinoprostone class
Eicosanoid
Dinoprostone description
PGE2
Dinoprostone mechanism
Autocrine and paracrine signalling Binds GPCR (Gs, Gi, Gq)
Contractile effects on smooth muscle via calcium
Relaxation via cAMP
Carboprost Tromethamine Mechanism
Autocrine and paracrine signalling Binds GPCR (Gs, Gi, Gq)
Contractile effects on smooth muscle via calcium
Relaxation via cAMP
Misoprostol mechanism
Autocrine and paracrine signalling Binds GPCR (Gs, Gi, Gq)
Contractile effects on smooth muscle via calcium
Relaxation via cAMP
Alprostadil mechanism
Autocrine and paracrine signalling Binds GPCR (Gs, Gi, Gq)
Contractile effects on smooth muscle via calcium
Relaxation via cAMP
Epoprostenol mechanism
Autocrine and paracrine signalling Binds GPCR (Gs, Gi, Gq)
Contractile effects on smooth muscle via calcium
Relaxation via cAMP
Latanoprost mechanism
Autocrine and paracrine signalling Binds GPCR (Gs, Gi, Gq)
Contractile effects on smooth muscle via calcium
Relaxation via cAMP
Carboprost Tromethamine class
Eicosanoids
Misoprostol class
Eicosanoids
Alprostadil class
Eicosanoids
Epoprostenol
Eicosanoids
Eicosanoids mechanism
Autocrine and paracrine signalling Binds GPCR (Gs, Gi, Gq)
Contractile effects on smooth muscle via calcium
Relaxation via cAMP
Dinoprostone indication
Ripens cervix @ term
Induces abortion
Carboprost Tromethamine description
15-methyl-PGF2alpha
Carboprost Tromethamine indication
Abortion, post partum hemorrhage
Misoprostil description
PGE1 derivative
Misoprostil indication
Aboriton
used with methotrexate-ripen cervix, post partum hemorrhage
Prevention of PUD in patients with chronic NSAID use
Alprostadil description
PGE1
Alprostadil indication
Maintains patency of ductus arteriousus
Impotence
Epoprostenol description
PGl2
Prostacyclin
Epoprostenol indication
Severe pulmonary HTN
Prevent platelet aggregation on dialysis machine
Latanoprost description
PGF2alpha derivative
Latanoprost adverse
Glaucoma (gold standard)
Zileuton description
leukotriene inhibitor
inhibits 5-lipoxygenase (LOX)
Zileuton indication
Asthma, 2nd line treatment
Zafirlukast, Montelukast description
Leukotriene inhibitor
Inhibits binding of LTD4 to receptor in target tissues
Zafirlukast, Montelukast adverse
Asthma, 2nd line treatment
Eicosanoids info
Glucocorticoids inhibit PLA2 thus blocking the release of AA; they also inhibit the synthesis of COX-2
NSAIDS inhibit both COX’s -> decreased prostaglandins
Serotonin (5-HTs) indication
Anaphylaxis
Sumatriptan drug class
5-HT1D/1B agonist
Metoclopramide and Cisapride mechanism
Prokinetic agent: promote and organize gut motility
Sumatriptan indication
DOC for acute severe migraines
Sumatriptan adverse
Don’t use in patients with coronary heart disease
Metoclopramide, Cisapride drug class
5-HT4 agonist
Metoclopramide, Cisapride description
Prokinetic agent: promote and organize gut motility
Metoclopramide, Cisapride indication
Gstroparesis, emesis
Metoclopramide, Cisapride adverse
Cisapride is no longer in use do to serious cardiac adverse effects
Cyproheptadine drug class
5-HT2 antagonist
Cyproheptadine description
Also blocks H1
Cyproheptadine indication
Allergic/vasomotor rhinitis
Carcinoid (Serotonin) syndrome
Ondansetron, Granisetron class
5-HT3 antagonist
Ondansetron, Granisetron description
Very powerful anti-emetics
Ondansetron, Granisetron indication
Severe nausea and vomiting associated with cancer therapy
Ergotamine, Dihydroergotamine class
5-HT antagonist
Ergotamine, Dihydroergotamine description
Effects on alpha adrenergic, 5-HT, and CNS dopamine receptors
Very non selective
Partial agonists and antagonists
Bromocriptine, Cabergoline description
Effects on alpha adrenergic, 5-HT, and CNS dopamine receptors
Very non selective
Partial agonists and antagonists
Ergonovine, Methylergonovine description
Effects on alpha adrenergic, 5-HT, and CNS dopamine receptors
Very non selective
Partial agonists and antagonists
Ergotamine, Dihydroergotamine indication
migraine
second line after triptans
Bromocriptine, Cabergoline indication
5-HT antagonists
Dopamine agonists used to treat hyperprolactinemia (pituitary tumor)
Ergonovine, Methylergonovine indication
5-HT antagonists
Post partum hemorrhage
Ergonovine-> provoke/dx variant angina
Cimetidine, Ranitidine, Famotidine, Nizatidine class
H2 antagonists
Cimetidine, Ranitidine, Famotidine, Nizatidine description
Inhibits gastric acid secretion
Cimetidine, Ranitidine, Famotidine, Nizatidine mechanism
Competitive inhibition of H2 receptors -> decrease gastric acid secretion
Cimetidine, Ranitidine, Famotidine, Nizatidine indication
PUD (promotes healing)
Acute stress ulcers
GERD (prevention and Tx)
Cimetidine, Ranitidine, Famotidine, Nizatidine adverse
Very Safe
Cimetidine inhibits CYP450 and has anti-androgen effects (gynecomastia, galactorrhea, etc)
Fexofenadine, Loratadine, Cetirizine, Astemizole, Terfenadine class
H1 antagonists second generation
Fexofenadine, Loratadine, Cetirizine, Astemizole, Terfenadine description
Less sedating -> decrease lipid solubility and actively pumped out of brain by P-glycoprotein
Fexofenadine, Loratadine, Cetirizine, Astemizole, Terfenadine mechanism
Inverse agonist -> decrease constitutive activity
Fexofenadine, Loratadine, Cetirizine, Astemizole, Terfenadine indication
DOC for allergic rhinitis and urticaria (not used in asthma… many other mediators)
Motion sickness and nausea
Somnifacient: Tx of insomnia (less likely in second gen)
Fexofenadine, Loratadine, Cetirizine, Astemizole, Terfenadine adverse
Astemizole and Terfenadine cause ventricular arrhythmia when used in combination with CYP3A4 inhibitors (block cardiac K+ channels responsible for repolarization)
Chlorpheniramine, Dimenhydrinate, Diphenhydramine, Hydroxyzine, Promethazine class
H1 antagonists 1st gen
Chlorpheniramine, Dimenhydrinate, Diphenhydramine, Hydroxyzine, Promethazine description
Crosses BBB -> more likely to block autonomic receptors -> sedation
Chlorpheniramine, Dimenhydrinate, Diphenhydramine, Hydroxyzine, Promethazine mechanism
Inverse agonist -> decrease constitutive activity
1st gen also block cholinergic, alpha adrenergic, serotonin and local anesthetic receptors (sodium channels)
Chlorpheniramine, Dimenhydrinate, Diphenhydramine, Hydroxyzine, Promethazine indication
DOC for allergic rhinitis and urticaria (not used in asthma … many other mediators)
Motion sickness and nausea
Somnifacient: Tx of insomnia
Chlorpheniramine, Dimenhydrinate, Diphenhydramine, Hydroxyzine, Promethazine adverse
Dry mouth (anti cholinergic effect) Sedation
Histamine receptor/mechanism
G protein linked
Constitutive activity -> active even in the absence of histamine
Some antihistamines are actually inverse agonist
H1 mechanism
Gq -> PLC -> IP3/DAG and calcium
Present on endothelium, smooth muscle and nerve endings
H2 mechanism
Gs -> Adenylyl cyclase -> increase cAMP
Gastric mucosa, cardiac muscle cells and some immune cells
H3 mechanism
Reduces NT release from histaminergic and other neurons
H4 mechanism
Chemotactic for EOS and mast cells; found on leukocytes in BM and blood
Inflammation and allergies
Histamine indications/effect
CVS:
- Vasodilation via H1 and H2,
- increase contractility and HR via H2,
- increase capillary permeability -> edema via H1 especially at the post capillary venules
Triple response: intradermal injection causes a localized red spot, flare and wehal
GIT: H1 mediated contraction
Bronchiolar: H1 mediated bronchoconstriciton (esp. in asthmatics)
Nervous: stimualtes nerve endings causing pain and itching (H1)
Secretory tissue: H2 mediated gastric acid secretion
Clinical use: Pulmonary function testing -> aerosol used to test nonspecific bronchial hyperreactivity
Histamine adverse
Anaphylaxis
Dose related toxicity: flushing, hypotension, tachycardia, HA, wehals, bronchoconstriction, GI upset
DO NOT give to asthmatics or patients with peptic ulcer disease/GI bleed
Histamine storage and release
Immunologic (Type 1 HS):
Ag binds IgE on surface of mast cells and basophils -> calcium mediated degranulation -> release of histamine, ATP and other mediators
Chemical and mechanical:
Amines (morphine and tubocurarine displace bound histamine from heparin complex in nrg independent fashion)