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Prostaglandins / Leukotrienes - Coggle Diagram
Prostaglandins / Leukotrienes
Eicosanoids
Autocoid lipid mediators derived from arachidonic acid
Stored not produced in most cells
Role in cardiovascular, inflammation, reproduction, cytoprotection of GI
Implicated in disorders such as RA, IBD, asthma
Arachadonic Acid Pathway
Arachidonic acid held in phospholipid bilayer in membrane
Phospholipase A2
releases AA into cytoplasm
Involved in the
Cyclooxygenase
and
Lipooxygenase
pathways
Cyclooxygenase pathway
Pathway
COX converts AA to Prostaglandin H2 intermediate (PGH2)
COX 1
Maintains renal blood flow :hourglass_flowing_sand:
Platelet function :electric_plug:
Intestinal mucosa protection :shield:
COX-2
Inducible form
Inflammation :fire:
Fever :hotsprings:
Pain :warning:
Ovulation :egg:
Uterine contraction :muscle::skin-tone-2:
Products
Prostaglandins
Thromboxane A2 (TxA2)
Lipoxygenase pathway
Products
Leukotrienes
Lipoxins
5-LOX required accessory activation protein (FLAP)
NSAIDS
Examples
Ibuprofen
Short half life 2 hrs
Moderate selectivity COX-1 over COX-2
Safe in children
Naproxen
Moderate selectivity COX-1 over COX-2
Long half life 15 hrs
Dicolfenac (FIFENE)
Potent, more selective COX-2 inhibitor over COX-1
Short half life 2hr
Indicated RA, OA, back pain and post operative pain and inflammation in orthopaedic, dental and other minor surgery
Indomethacin
Potent, more selective COX-2 inhibitor over COX-1
Short half life 2hr
• Indicated RA, OA, back pain and post operative pain and inflammation in orthopaedic, dental and other minor surgery
Mefenamic acid (Ponstan)
Potent More selective COX-2 inhibitor
Half life - 2 hours
Indicated RA, OA, trauma, headache dental pain, post-op
Piroxicam
Potent slightly more selective for COX-1
Indicated RA and OA not a first line NSAID
Very long half life (30hrs) therefore advantage option admin once daily
MOA
Reversibly bind to Arg120 on COX -1 /2
Prevent cytokine release & peripheral inflammation .....
Use
Analgesics
Anti-inflammatory
Adverse Effects
GI
Dyspepsia
Vomiting :nauseated_face:
Diarrhoea :poop:
Haemorrhage
Reduce effects of anticoagulants
COX-2 Selective Inhibitors
Coxibs
Celecoxib
Effect
Anti-inflammatory :fire:
Analgesic :relaxed:
Antipyretucs :thermometer:
No platelet action :electric_plug:
Maintains Cytoprotective effects
Use / Indications
OA
RA
Actute pain
Adverse effects
GI complications
Cardiovascular complications in elderly
Prostanoid Receptor Mimetic
Misoprostol
MOA
PGE Analogue
Activates E1 Prostaglandin receptor (Gi) to prevent cAMP accumulation, inhibiting parietal cell activation and activating epithelial mucosal productionn
Uses
Pregnancy termination
Induce labour
Treats peptic ulcers
Epoprostenol, Cicaprost, Iloprost
MOA
PGI2 analogues
Prevent Platelet aggregation
Use
Pulmonary hypertension
Latanoprost, Travoprost
MOA
PG F2α analogues
Reduce intraocular pressure
Use
Open angle glaucoma :eye:
Ocular hypertension :eye::arrow_up::tent:
Lipoxygenase inhibitors
Zileuton
MOA
5-LOX inhibitor
Use
Asthma :open_mouth:
Induces bronchodilation
Improves symptoms
Improves pulmonary function tests
Not used for reversal of bronchospasm in acute asthma attacks
Not widely used
Low bioavailability
Low potency
Adverse liver toxicity
Leukotriene Receptor Antagonists
Montelukast
Zafirlukast
MOA
Cysteinyl LT receptor Antagonists
Oral
Use
Prophylactic Treatment of asthma symptoms
Pharmacokinetics
Oral Chewable tablet
Therapeutic effects in a day
Not used as monotherapy
COX Inhibitors
COX-1 Selective Inhibitors
Salicylate
Low dose Aspirin
Non-selective COX Inhibitors
NSAIDS
Ibuprofen
Naproxen
Indomethacin
Dicolfenac / Difene
Ponstan - Fenamate
Piroxicam
Paracetemol
COX-2 Selective Inhibitors
Coxibs
Celecoxib
COX-1 Selective Inhibitors
Low dose Aspirin
MOA
Irreversibly inhibits COX-1 by acetylating serine
Decreases synthesis of TXA2 and PGs
Effects
Intermediate dose
Analgesic :relaxed:
High dose
Anti-inflammatory :forbidden::fire:
Intermediate dose
Antipyretic :forbidden::thermometer:
Low dose
Anti-thrombogenic :forbidden::electric_plug:
Use
Propholaxis management of MI and stroke
Osteoarthritis
Acute pain
RA
Acute Gout
Postop
Muscle skeletal injuries
Adverse Effects
Gastric ulcers
Acute kidney injury
GI bleeding
Ryes Syndrome
Allergic reaction
Intolerance
Paracetamol
Effects
Analgesic
Antipyretic
Weak anti-inflammatory
Use
Headache :face_with_head_bandage:
Cold and flu :cold_sweat:
Menstrual pain :pregnant_woman:
Toothache :lips:
Adverse Effects
Renal and liver damage with long term use
