autocoid definition
-hormone like substance produced close to where they have an effect
5 examples of autocoids
- leukotrienes
- prostaglandins
- histamines
- kinins
- serotonin
leukotrienes
- synthesis
- target
- involved in
- therapeutic target
- synthesis from arachadonic acid via lipooxygenase
- binds to receptors in the respiratory tract
- involved in inflammation conditions such as asthma
- receptor agonists are used to treat asthma (as well as targetting LOX)
thromboxanes
- synthesis
- function
- equal in amount with
- made by COX1 using arachadonic acid
- promote platelet aggregation and vasoconstriction
- equal in concentration to PGI2 during health
PGE
- synthesis
- location of action
- function
- from arachadonic acid, catalyzed by COX1
- located in the GI
- production of the mucosal barrier
function of prostaglandins in the kidney -what are they made by
- increased blood flow
- COX1 and COX2 are located in the kidney
prostacyclins (PGI2)
- synthesis
- function
- inhibition of synthesis may lead to
- from arachadonic acid via COX2
- inhibits platelet aggregation and is a vasodilator
- may lead to clot formation and possibly MI/thrombotic stroke
prostaglandins involved in pain, fever, and inflammation are made by
COX2
NSAIDs
- function
- mode of action
- side effects, why
- reduce pain, inflammation, fever by blocking COX
- primary target is COX2 but will also block COX1 (this is what leads to the side effects of bleeding and GI ulcerations)
adverse kidney side effects with NSAIDs in the kidney
- always a risk because the kidney has both COX1 and 2
- inhibits healthy blood flow to the kidney
COX2 inhibitors may shift the balance
- of prostacylcins and thromboxanes
- this may lead to the risk of thrombosis since thromboxanes are at a higher concentration
selective COX1 inhibitors
-how does aspirin work
- aspirin can be used in relatively small doses as a blood thinning agent via blocking thromboxane production
- in order to treat pain and inflammation, a patient must take higher doses to overcome COX1 selectivity
H1 receptor
- involved in
- target for
- involved in allergic reactions
- target of antihistamine drugs such as diphenhydramine (benadryl) or loratidine (claratin)
diphenhydramine vs loratidine
-diphenhydramine is sedating because it can cross the blood brain barrier
H1 antagonists have a propensity to antagonize
-muscarinic Ach receptors leading to anti-muscarinic effects
H2 receptors
- found where
- function
- stomach
- when stimulated, cause gastric acid secretion
H2 receptor antagonists
- inhibit parietal cells
- available over the counter for dyspepsia or acid reflux
bradykinins
-degraded by what
-degraded by ACE into kinins
ACE does what
-facilitates the conversion of angiotensin 1 into the active form, angiotensin 2 which is a potent vasoconstrictor
inhibiting ACE leads to
- less conversion of bradykinins into kinins
- vasodilation
ACE inhibitors end in
-pril
an accumulation of bradykinins tends to
-irritate and inflame tissues leading to the cough associated with ACE inhibitors
serotonins role in the GI tract
-serotonin antagonists in the GI
- when stimulated, people experience nausea and vomiting
- antagonists used to reduce those symptoms
- ondansterone is the serotonin antiemetic prototype
serotonins role in migraine
-a spike produces cerebral vasoconstriction which is followed by a rebound vasodilation effect causing a throbbing headache
