Pharmacology - NSAIDs vs GCS Flashcards
1
Q
What is the mechanism of NSAID activity?
A
2
Q
Can you administer NSAIDs with systemic GCS?
A
No, never administer NSAIDs with systemic GCS concurrently. They reduce the production and alter the composition of gastric mucous.
3
Q
What is the analesic ladder?
A
- Provides guidance for treating pain
- Mild pain - Mild analgesia, SSRIs
- Moderate pain - non opiod analgesics, NSAIDS or weak opiods
- Severe pain - strong opiods, nerve blocks
4
Q
What is mavacoxib (Trococil)?
A
- NSAID
- Dogs only
- DO NOT give to dogs <12 months or <5kg
- DOSE: 1 tab per month taken with food - less than or equal to seven consecutive doses
5
Q
What adverse effects are seen with NSAIDs?
A
- Gastric ulceration especially when the animal has low blood pressure, hypovolaemic or dehydrated
- Reduction in renal blood flow
- Reduced platelet function – tendency to bleed
- Occasional liver dysfunction
- Occasional idiosyncratic reactions
6
Q
How can gastric ulceration be prevented?
A
- Select your patient wisely (not dehydrated, clinically normal, good liver and kidney function)
- Do not co‐administer with systemic glucocorticosteroids
- Consider the dosage to be used
- Increase stomach pH with a proton pump inhibitor such as omeprazole or a histamine2 (H2) receptor inhibitor e.g. cimetidine
- Or administer a PGE2 analogue such as misoprostol (Cytotec®)
7
Q
How is gastric ulceration treated?
A
- Sucralfate (Carafate) is a drug that is administered orally & covers the ulcer. In the acid environment of the stomach the polymerised product forms a viscous paste. Administered prior to the H2 antagonists or proton pump inhibitors
- Increase stomach pH with a proton pump inhibitor such as omeprazole or a histamine2 (H2) receptor inhibitor e.g. cimetidine
- Supportive treatment: IV fluids, nil by mouth, antibacterial, analgesics
8
Q
What are the contraindications of NSAIDs?
A
- Bleeding disorders or anticoagulation drugs – heparin, glycosaminoglycans, clopidogrel
- Severe kidney dysfunction (current recommendations – can be used with mild / stable chronic kidney disease in
- older cats*)
- Liver disease
- Gastrointestinal ulceration
- Chronic inappetance
- Dehydration
- Prolonged general anaesthesia as can result in hypotension
- Concurrent treatment with systemic glucocorticosteroids
9
Q
Can paracetamol be used in dogs and cats?
A
- Can be used in dogs only, toxic to cats
- Good in head trauma for dogs, particularly when NSAIDs are contraindicated
- We use it at 10 mg/kg q 8h IV (or 15 mg/kg PO) as part of multimodal analgesia.
- If there is any concern about liver dysfunction, we won’t use it.
- Doesnt appear to induce liver toxicity in dogs
10
Q
What is the mechanism of paracetamol in the CNS?
A
- Thought to act through inhibition of a subclass of COX enzyme isoforms in the central nervous system
- May enhance endocannabinoid transmission ‐ may simulate cannabinoid receptors
- Reported to have effects on the descending inhibitory pain pathway. Opioids also stimulate this pathway
- Descending inhibition pathway - thalamus to the dorsal horn and inhibits the pain amplification at the dorsal horn
11
Q
What is the difference in hepatic metabolism between NSAID and paracetamol?
A
- NSAID - undergoes phase I metabolism by CYP2C, +/- a variable degree of phase II metabolism
- Paracetamol - undergoes phase I metabolism by CYP2E. There is also some degree of phase II glucuronidation
12
Q
Is aspirin used in veterinary medicine?
A
- No longer used in veterinary medicine
- Used to be used to inhibit platelet aggregation to minimise thrombo-emboli formation (feline cardiomyopathy and pulmonary endarteritis associated with heartworm disease)
- We now use clopidogrel in place of aspirin.
- May result in severe bleeding in horses
- gastric ulceration
13
Q
What are EP-4 Receptor antagonists and how do they work?
A
- PGE2 binds to one of four receptors (EP1‐EP4)
- EP4 receptors are widely distributed in the body – when activated signal to nerves, heart tissue, blood vessels, bone, gut, renal function, female reproductive function
- Inflammation up‐regulates the EP4 receptors
- Pain, redness and swelling – up‐regulates the EP4 receptors
- In animal models of osteoarthritis (OA) – the EP4 receptors in nerves and bones are upregulated
- Blocking these EP 4 receptors are thought to reduce pain/redness/swelling associated with OA
- They are a new anti-infalmmatory class ‘pripants’
- PRA = Prostaglandin receoptor antagonist
- By blocking this receptor, PG2α constitutive/homeostatic functions are maintained while blocking inflammation and pain at EP‐4 receptor
14
Q
Are EP-4 Receptor antagonists safe?
A
- Safety profile – administered at high doses (35mg/day) for 9 months to dogs and found to have low grade adverse reactions
15
Q
What is an example of an EP-4 receptor antagonist?
A
grapirant (galliprant)
