Autocoids Flashcards
define autacoids
short-lived physiologically active endogenous substances that act locally then undergo rapid inactivation
autacoid types
eicosanoids, histamine, seratonin, kinins
Types of eicosanoids
derived from fatty acids in the body: 1. prostaglandins 2. prostacyclin 3. thromboxanes 4. leukotrienes
leukotrienes (LTB, LTC, LTD, etc) effects
Increase leukocyte chemotaxis and bronchoconstriction
prostaglandins (PGE 1&2) effects
- vasodilation 2. Increase uterine contractions 3. Decrease gastric acid secretion & Increase gastric mucus production (protective)
prostaglandins (PGF2a) effects
- Increase uterine contractions 2. Increase aqueous humor flow
medicinal prostaglandins
Mifepristone (RU 486), Alprostadil (MUSE), Misoprostol (Cytotec), Latanoprost (Xalatan)
Mifepristone (RU 486)
synthetic steroid with antiprogestational effects
Mifepristone (RU 486) uses
abortions, followed 48 hrs later by misoprostol
Alprostadil (MUSE)
naturally occuring form of PGE1
Alprostadil (MUSE) uses
transuretrhal suppository or injection for ED; keep ductus arteriosus open (congenital cardiac abnormalities until the infant can undergo corrective cardiac sx)
Misoprostol (Cytotec)
synthetic analog of PGE1
Misoprostol (Cytotec) uses
protective effects on gastric mucosa (prevention of ulcers)
Latanoprost (Xalatan)
PGF2α-derivative eye drops
Latanoprost (Xalatan) uses
opththalmic tx for glaucoma
Prostaglandin antagonists (NSAIDs)
PGs involved in inflammatory process; NSAIDs prevent synthesis of PGs at inflammation sites
Prostaglandin antagonists (corticosteroids)
Inhibit phospholipase (preventing formation of arachidonic acid & Pgs)and inhibiting inflammation
histamine actions
- involved in allergic & inflammatory rxns (Increase vascular permeability, bronchoconstriction); 2. involved in pain & itching; 3. Increase gastric acid secretion
histamine location
virtually everywhere in body: 1. Increase concentration in respiratory tract, GI tract, skin; 2. high concentrations in mast cells and basophils (stored in granules in mast cells); 3. component of some venoms and insect sting secretions
histamine receptors
H1, H2
H1 receptors
exocrine excretion, bronchial smooth muscle & mucosa, intestinal smooth muscle, sensory n. endings (cause itching & pain)
H2 receptors
in stomach (stimulation of gastric acid secretion)
H1 Receptor Blockers
classic antihistamines that block mediated response in target tissues
Division of H1 Receptor Blockers
1st Generation & 2nd Generation
Use of 1st Gen H1 Receptor Blockers
1st: still widely used due to low cost and effectiveness
Use of 2nd Gen H1 Receptor Blockers
2nd: more specific to H1 receptors and less CNS penetration (less AE)
antihistamine uses
- Tx of allergic rhinitis & urticaria (most effective when used prophylactically) 2. Tx/prevention of motion sickness 3. Treatment of insomnia (not preferred to to Aes)
Why are 1st gen antihistamines used for motion sickness and insomnia?
1) Motion Sickness – Prevent/diminish N/V mediated by chemoreceptor & vestibular pathways, due to blockade of central H1 and muscarinic receptors 2)Insomnia - more sedation with first generation
H1 blockers t 1/2’s
1st gen shorter than 2nd gen; 2nd gen has increase compliance due to fewer pills
H1 blockers (1st gen) AE
low specificity (sedation, dry mouth, blurred vision)
H1 blockers (2nd gen) AE
high specificity for H1 receptors (fewer AE - reduced drowsiness/sedation due to lack of CNS penetration)
H2 blockers uses
GERD & ulcers
H2 blockers MoA
inhibition of H2 receptors in GI tract (inhibit gastric acid secretion)
5HT Receptors
Serotonin receptors
serotonin (5-Hydroxytryptamine) receptors
5HT1, 5HT2, 5HT3, 5HT4
5HT1 actions
vasoconstrictor
5HT1 uses
tx of migraine HA
Headache diagnosis
Migraine without aura (classical, ~75%) or with aura (common)
Potential cause of migraine pain
Possibly due to extracranial and intracranial arterial dilation
General forms of Migraine HA tx
symptomatic, migraine specific (addressing the source of HA), and prophylaxis
migraine specific tx
5HT 1D receptor agonists (triptans & dihydroergotamine)
5HT 1D receptor agonists MoA
believed to cause vasoconstriction or inhibit release of proinflammatory neuropeptides on trigeminal n. innervating cranial blood vessels
5HT 1D receptor agonists types
triptans, dihydroergotamine
triptan tx
individual response varies, may need to try more than one drug
triptan AE
may cause ↑Increase BP & cardiac events
triptan contraindications
cardiac eval needed prior to use if pt has risk factors for CAD
serotonin syndrome
serious drug interaction associated with MAO-inhbitor
dihydroergotamine
given IV, major SE is nausea, most pts prefer triptans
Prophylaxis for Migraines
beta -blockers (propanolol, nadolol), amitriptyline, divalproex, verapamil
