Prostaglandins and NSAIDS Flashcards
How many standard aspirin tablets are taken every year worldwide?
A. 100 billion
B. 1 billion
C. 100 million
D. 1 million
A. 100 billion
LO Lecture 1 and 2
Lecture 1
- Introduce the cellular and chemical mediators of local immune response to tissue damage/infection highlighting broad role of autacoids.
- Introduce the steroidal approaches used as anti-inflammatory treatments.
- Define Prostaglandins and related eicosanoids as important lipid mediators.
- Explain synthesis and mechanisms of action of the major prostaglandins.
- Highlight physiological actions of prostaglandins and potential therapeutic uses
- Lecture 2
- Describe NSAIDs as broad and selective inhibitors of COX enzymes.
- Show how NSAIDs are used clinically and indicate potential side effects.
- Highlight how aspirin’s unique mode of COX inhibition extends it use to cardiovascular treatment.
- Describe recent experiments that hint at the mode of action for Paracetamol
Tell me about local inflammation through distinct cell types and chemical mediators
What cells are affected by tissue damage/ infection and what chemicals are produced in response?
![](https://s3.amazonaws.com/brainscape-prod/system/cm/342/731/479/a_image_thumb.png?1618392112)
Tell me about chronic inflammation
![](https://s3.amazonaws.com/brainscape-prod/system/cm/342/731/591/a_image_thumb.png?1618392135)
Tell me about inflammatory mediators and how they induce complex molecular and cellular response dependent on changes in gene expression
![](https://s3.amazonaws.com/brainscape-prod/system/cm/342/731/601/a_image_thumb.png?1618392302)
Pharmacological use of physiological steroid hormone pathways has powerful anti-inflammatory effects
Tell me the prime mode of action?
What different chemicals are produced from this process? and provide examples
- Prime mode of action is to bind nuclear receptors to +vely or –vely effect transcription. Additional non-genomic effects
- Physiologically the corticosteroids act widely increase metabolism
- Pharmacologically cortisol and synthetic steroids (e.g., dexamethasone) increase anti-inflammatory gene expression (e.g. annexin -1) and reduce expression of pro-inflammatory gene expression (e.g. COX-2)
Despite the potent anti-inflammatory response. There are limits to steroidal approach. Tell me about some of these limits
- Long term effects are undesirable.
- Suppress the response to infection (act against the immune response),
- Cause widespread metabolic disturbances (impact on steroid production)
- Iatrogenic Cushing’s syndrome (wide systemic dysfunction),
- Growth suppression in children (important function in osteoclasts)
![](https://s3.amazonaws.com/brainscape-prod/system/cm/342/735/088/a_image_thumb.png?1618396426)
What are Eicosanoids?
Eicosanoids are signaling molecules made by the enzymatic or non-enzymatic oxidation of arachidonic acid or other polyunsaturated fatty acids (PUFAs) that are, similar to arachidonic acid, 20 carbon units in length.
![](https://s3.amazonaws.com/brainscape-prod/system/cm/342/735/250/a_image_thumb.png?1618396526)
Tell me the lipid metabolites derived from arachodonic acid or residual after aracidonic acid removal
Tell me some key differences between some of them
- Polar head is hydrophilic and outside of the membrane
- Prostaglandins and leukotrienes key difference between them is that leukotrienes have no rings/ not cyclic and there’s an oxygen group in the ring of PGs but not in leukotrienes
![](https://s3.amazonaws.com/brainscape-prod/system/cm/342/735/351/a_image_thumb.png?1618396664)
Tell me the full sequence of eicosanoid like signalling
![](https://s3.amazonaws.com/brainscape-prod/system/cm/342/735/383/a_image_thumb.png?1618396780)
After eicosanoid like signalling, what is uptake followed by?
Uptake is followed metabolism by “prostaglandin specific enzymes” followed by subsequent catabolism (breakdown) by fatty-acid-oxidizing enzymes.
Tell me the concentrations that eicosanoids work in?
pM-nM
What is antihistamine?
A competitive antagonist to the histamine receptor
When histamine binds to its own receptor, what concentrations does it work in?
µm
Major arachidonic acid and downstream intermediatory metabolism to generate resealable mediators
![](https://s3.amazonaws.com/brainscape-prod/system/cm/342/735/681/a_image_thumb.png?1618397144)
Phospholipid membrane
![](https://s3.amazonaws.com/brainscape-prod/system/cm/342/735/784/a_image_thumb.png?1618397164)
Tell me the role of cyclooxygenase and NSAIDs
![](https://s3.amazonaws.com/brainscape-prod/system/cm/342/735/796/a_image_thumb.png?1618397227)
Potent and controllable (rapid catabolism) of prostaglandin promotes clinical use. Tell me some of these clinical uses
Gynaecological and obstetric.
- Misoprost (Stable PGE) pregnancy termination or induction of labour.
- Carboprost (analogue of PGF2α) to treat postpartum haemorrhage.
Gastrointestinal
- Misoprost to prevent peptic ulcers in patients taking NSAIDs (perhaps ironically).
Cardiovascular
- Presurgical maintenance of arterial ducts prior to surgical correction in congenital
- Heart disease (alprostadil, PGE).
- Inhibit platelet aggregation if preferred route heparin during dialysis also used in
- Pulmonary hypertension.
Ophthalmic.
- Open angle glaucoma (increase in intraocular pressure): latanoprost (PGF2α) eye drops
Blocking the action of prostaglandin may also benefit. Tell me some the associations with the production and synthesis of prostaglandins…
Pain
- Prostaglandins sensitize nociceptors to pain transducers like Bradykinin.
- May also contribute to vasodilatory effects associated with headache.
Fever
- Prostaglandins PGE2 reset to a higher set point the temperature sensing systems of the
- hypothalamus. This central effect of the prostaglandins is pyretic (i.e. leads to fever).
Chronic inflammation
- Prostaglandin lead directly to swelling (vasodilation)
- Indirectly promote oedema (further swelling) sensitizing the effect of other mediators
- cause local pain