Autocoids Flashcards
What are autocoids?
List the three types of autocoids
Self-healing substances.
Amine autocoids (histamine, serotonin)
Lipid derived autocoids (prostaglandin, leukotriene, platelet activating factor)
Peptide autocoids (bradykinin, angiotensin)
What is eicosanoids?
Examples?
They are from the lipid derived autocoids, aka eicosanoids= essential fatty acid
Examples : thromboxane, prostaglandins, leukotriene
What are COX 1 & COX 2?
They are enzymes which play a key role in the synthesis of eicosanoids, specifically prostaglandins and thromboxanes.
Difference between COX 1 & COX 2
COX 1 :produce TXA2 which is procoagulatory, prostaglandin to protect stomach from acids
Mostly expressed in tissues
Non-selective COX inhibitor/NSAIDs such as aspirin , ibuprofen
COX 2
Inductively
Present at sites of inflammation and cancer
COX 2 inhibitor such as celecoxib
The four types of histamine receptors are?
Histamine is stored in mast cell.
The four types:
H1- smooth muscles, blood vessel
H2- gastric glands, blood vessels, heart
H3- brain
H4- eosinophils, neutrophils, CD4 T cells/Th
The pharmacological actions of histamine
relate histamine to ALLERGY
exocrine secretion: increased production of nasal & bronchial mucus
bronchial smooth muscle: bronchoconstriction
intestinal smooth muscle: constriction
sensory nerve endings: itching & pain
cardiovascular system: reduce peripheral resistance, decrease in BP, positive chronotropic & inotropic effect
skin: triple response ( RED SPOT, FLUSH, WHEAL)
stomach: increase gastric acid secretion
Classification of antihistamine drugs is divided into
1st gen : chlorpheniramine / chlorphenamine
2nd gen: cetirizine
How 2nd gen histamine blockers/ antihistamine differs from 1st gen?
NON SEDATIVE
DON’T CAUSE ANTICHOLINERGIC ADVERSE EFFECTS like dry mouth
High H1 selectivity
Do not impair psychomotor performance
No increase in appetite/ no weight gain
Mechanism of action of antihistamine
- Block action of histamine at receptor site
- Compete with histamine for binding at receptor
Pharmacokinetic features of antihistamine
Given orally
Metabolise in liver, excrete through urine
1st gen H1 antagonist can cross BBB
Adverse effects of antihistamine
She Did Do The Freaking Bad Calculation Really
Sedation
Dry mouth
Dizziness
Tinnitus
Fatigue
Blurred vision
Constipation
Retention of urine
Example of histamine release inhibitor
disodium cromoglycate
-prevent mast cell degranulation
Uses of antihistaminic drugs
Allergic reactions
Motion sickness
Vertigo
What is serotonin/ 5HT?
A neurotransmitter in CNS.
Can be found in :
GIT enterochromaffin cells
Platelets
Lungs
Bone marrow
Pineal gland
It had 7 receptors & all are GPCR except 5HT 3 which is LIGAND-GATED
The pharmacological effects of serotonin?
Nervous system: vomiting, pain, regulate mood sleep behavior temperature
Respiratory system: bronchoconstriction
CVS: vasoconstriction, increase HR and force of contraction, platelet aggregation
GIT: + gastric peristalsis & secretion
List the uses of serotonin agonist & antagonist
Agonists:
buspirone: anxiety
sumatriptan: migraine
cisapride: gastroesophageal reflux disease (GERD)
Antagonists:
ondansetron: vomiting
clozapine: psychosis
Adverse effects of serotonin agonists & antagonists
Agonists: nausea, vomiting, palpitation, flushing
Antagonists: constipation, drowsiness, arrhythmia
Buspirone is used for
Anxiety
Sumatriptan is used to treat
Migraine
Cisapride is used to treat
GERD
Ondansetron is used to treat
Vomiting
Clozapine is used to treat
Psychosis
Uses of prostaglandins
O&G:
induce labour (dinoprostone)
Terminate pregnancy
Post partum haemorrhage
GIT disorders: prevention of NSAIDs induced ulcers/ peptic ulcers (misoprostol)
Ophthalmic disorders: glaucoma (latanoprost)
List all the prostaglandins & thromboxane
PGE2
PGD2
PGF2a
PGI2/prostacyclin
TXA2
Action of PGE2
Inhibits gastric acid secretion (treat peptic ulcer)
Increase gastric mucus production (treat peptic ulcer)
Lower intraocular P (glaucoma: high IOP)
Bronchodilation
Actions of PGD2
Bronchoconstriction
Inhibits platelet aggregation (treat myocardial infarction)
Actions of PGF2a
Bronchoconstriction
Myometrial contraction (abortion)
Lower IOP
Actions of PGI2 / prostacyclin
Bronchodilatation
Inhibits platelet aggregation (MI)
Actions of TXA2
Vasoconstriction
Stimulates platelet aggregation (MI)
Two main categories of leukotrienes
Leukotrienes are released by WBC
chemoattractant LTB 4 & cysteinyl LTC 4, D4, E4, F4
Function of LTB 4/ chemoattractant & cysteinyl
LTB 4 is for all types of inflammation
Cysteinyl is for asthma & allergic rhinitis
Leukotriene receptors are all GPCRs
Pharmacological actions of leukotrienes
Resp: bronchoconstriction, increase mucus secretion
CVS: fall in BP, constriction of small coronary resistance vessels [IV] ; increase nasal blood flow & local vascular permeability [topically in nose]; wheal & flare [subcut]
Uses of leukotrienes antagonists
Montelukast, Zafirlukast : asthma, allergic rhinitis, allergic conjunctivitis
Zileuton: bronchial asthma
**montelukast blocks leukotrienes receptors
**zileuton inhibits synthesis of leukotrienes
However, it all boils down to treat bronchial asthma, just different MOA
List the autocoid involved and think of suitable agents for the conditions.
1. anaphylactic shock
2. Severe gastritis/peptic ulcers
3. Motion sickness
4. Severe nausea & vomiting
5. Difficulty in giving birth
6. Migraine
- Histamine-adrenaline
- PGE1-misoprostol
- Histamine-hydroxyzine
- serotonin 5HT3-ondansetron
- PGE2-dinoprostone (to induce labour)
- serotonin 5-HT1B/D- sumatriptan
To relieve?
Motion sickness
Hydroxyzine
To relieve?
Allergy
Cetirizine
To relieve?
Anxiety
Buspirone
To relieve?
Migraine
Sumatriptan
To relieve?
Gastroesophageal reflux disease (GERD)
Cisapride
To relieve?
Nausea & vomiting
Ondansetron
To relieve?
Psychosis
Clozapine
To induce labour?
Dinoprostone
To relieve?
Peptic ulcers
Misoprostol (PGE1)
To relieve?
Glaucoma
Latanoprost
To relieve?
Asthma, allergic rhinitis, allergic conjunctivitis
Montelukast
Zafirlukast
To relieve?
Bronchial asthma
Zileuton
