PHA 520 - L5 Anti-inflammatories and Analgesics

What is the mechanism of action (MOA) of NSAIDs?

NSAIDs inhibit the cyclooxygenase (COX) enzyme, decreasing conversion of arachidonic acid into prostaglandins.

What does cyclooxygenase normally do?

Converts arachidonic acid into prostaglandins such as PGE and PGI.

What are the two cyclooxygenase isoforms?

COX-1 and COX-2.

What is COX-1?

A constitutive enzyme that is constantly produced and is needed for normal regulatory functions.

What are the major functions of COX-1?

Maintains electrolyte balance/kidney function, protects the gastric mucosa, and supports platelet function.

Why is inhibition of COX-1 generally undesirable?

COX-1 performs protective physiologic functions; inhibition can contribute to GI ulceration, prolonged bleeding, and kidney problems.

What is COX-2?

An inducible cyclooxygenase enzyme that is primarily induced at sites of inflammation.

Why is inhibition of COX-2 desirable?

COX-2 inhibition decreases prostaglandin production associated with pain and inflammation, producing the desired anti-inflammatory effect.

COX-1 vs. COX-2

COX-1 = constitutive/protective → inhibition undesirable. COX-2 = inducible during inflammation → inhibition desirable for controlling inflammation.

How do traditional NSAIDs differ from newer-generation NSAIDs?

Traditional NSAIDs are nonselective and inhibit both COX-1 and COX-2; newer-generation NSAIDs are COX-2 selective.

Why can traditional nonselective NSAIDs cause more adverse effects?

They inhibit protective COX-1 in addition to inflammatory COX-2, increasing the risk of ulcers, prolonged bleeding, and kidney problems.

Why are COX-2 selective NSAIDs generally associated with fewer side effects?

They preferentially inhibit inflammatory COX-2 while sparing more of the protective functions of COX-1, particularly reducing GI ulceration.

Examples of traditional/nonselective NSAIDs

Ibuprofen, naproxen, aspirin.

Examples of COX-2 selective NSAIDs

Deracoxib, robenacoxib, firocoxib.

What are the four major pharmacological effects of NSAIDs?

Anti-inflammatory, analgesic (pain relief), antipyretic (lower fever), and antithrombotic (decreased platelet aggregation).

What are the major categories of NSAID adverse reactions?

Gastrointestinal, hematopoietic, reproductive, and renal.

What is the major GI adverse effect of NSAIDs?

Ulcer formation in the stomach or intestine; all NSAIDs are ulcerogenic to some degree and dogs are especially sensitive.

How can NSAIDs affect platelets/blood?

They can inhibit platelet function and prolong bleeding time.

How can NSAIDs affect the kidneys?

They can reduce renal blood flow.

How can NSAIDs affect reproduction?

They can prolong gestation due to inhibition of uterine prostaglandins (PGF and PGE).

Why does NSAID toxicity differ greatly among animal species?

Species differ substantially in drug clearance and metabolism, producing differences in half-life, safety, and toxicity.

What organs should be monitored during extended/chronic NSAID therapy?

Liver and kidneys; NSAIDs are metabolized by the liver and excreted in urine and bile.

Why is aspirin a concern in dogs?

It is highly ulcerogenic in dogs.

How is aspirin use different in cats?

Cats clear aspirin slowly; the PowerPoint states it is administered only twice per week and is most often used as an antithrombotic in heart disease.

What are signs of aspirin toxicity?

GI signs and acid-base disturbances, including hyperventilation.

What species should NEVER receive acetaminophen according to the lecture?

Cats.

Why is acetaminophen highly toxic to cats?

Cats cannot adequately conjugate it, resulting in damage to the liver and red blood cells.

What treatments are listed for acetaminophen toxicity in cats?

Acetylcysteine (Mucomyst), cimetidine (Tagamet), and ascorbic acid (vitamin C).

What species should avoid ibuprofen?

Dogs and cats; ibuprofen is very toxic and can cause severe GI ulceration.

Is naproxen recommended for companion animals?

No. The lecture states that naproxen is not recommended in companion animals.

What is carprofen (Rimadyl) primarily used for?

Relief of pain and inflammation in dogs, especially canine osteoarthritis.

What important contraindication is associated with carprofen?

Contraindicated in dogs with bleeding disorders such as von Willebrand factor disorders.

What species can receive etodolac (Etogesic)?

Dogs only; NOT cats. It is COX-2 preferential.

What species can receive meloxicam (Metacam)?

Dogs and cats; it is COX-2 preferential, with lower doses and decreased frequency used in cats.

What are the veterinary COX-2 specific NSAIDs emphasized in the lecture?

Deracoxib (Deramaxx), firocoxib (Previcox), and robenacoxib (Onsior).

Deracoxib (Deramaxx): species, route, and use

Dogs; PO chewable tablets; post-operative pain and inflammation control.

Firocoxib (Previcox): species and route

Dogs; PO.

Robenacoxib (Onsior): species and routes

Dogs AND cats; SQ injection or PO tablets.

What is grapiprant (Galliprant)?

A piprant and PGE2 EP4 receptor antagonist that selectively blocks the EP4 receptor rather than inhibiting COX.

What is Galliprant used for?

Long-term control of inflammation and pain associated with osteoarthritis/degenerative joint disease in dogs.

What is analgesia?

Relief from pain or absence/deadening of the sense of pain without loss of consciousness.

What are analgesics?

Drugs that relieve pain.

What are the two major types of analgesics described in the lecture?

Non-narcotic analgesics for mild pain (including NSAIDs) and narcotic/opioid analgesics for severe pain.

Where are mu opioid receptors primarily located?

In pain-regulating areas of the brain.

What are the common effects/side effects of opioids?

Analgesia plus CNS depression/sedation, respiratory depression, bradycardia, decreased GI motility, and constipation.

What unusual opioid response can occur in horses, cattle, swine, and cats?

They may exhibit contradictory effects such as excitement and defecation.

Is addiction/dependency typically seen with opioids in companion animals?

No dependency or addiction is typically seen, but tolerance can be an issue with chronic use.

What is the treatment of choice for opioid overdose?

Naloxone, an injectable opioid antagonist.

When would naloxone be indicated?

Opioid overdose causing profound respiratory and/or CNS depression.

What are the major opioid examples from the lecture?

Morphine, oxymorphone, hydromorphone, codeine, hydrocodone, fentanyl, buprenorphine, tramadol, and butorphanol.

Morphine: routes of administration

Injectable IM, IV, or SQ; oral tablets/solution; may also be administered epidurally or by CRI.

Oxymorphone: routes of administration

IV, IM, or SQ; used for orthopedic pain and as a pre-anesthetic.

Hydromorphone (Dilaudid): routes of administration

IV, IM, or SQ; may be given as a CRI or used as a pre-anesthetic.

Codeine: major uses

Antitussive and analgesic.

What is an important warning for codeine combination products in cats?

Do NOT use products combined with acetaminophen because acetaminophen is toxic to cats.

Hydrocodone: major uses and formulations

Antitussive and analgesic; available as tablets and syrup.

What is an important warning for hydrocodone combination products in cats?

Do NOT use products combined with acetaminophen because acetaminophen is toxic to cats.

Fentanyl: routes/methods of delivery

Transdermal patch (listed as discontinued in the lecture), IV, CRI, and epidural.

How potent is fentanyl compared with morphine?

Approximately 50–100 times more potent than morphine.

How long did a fentanyl transdermal patch require before providing analgesia?

Approximately 12–24 hours.

Buprenorphine (Buprenex): routes of administration

IM, IV, SQ, and transmucosal/buccal administration in cats.

Why is buprenorphine especially useful in cats?

It can be absorbed transmucosally; buccal administration is well tolerated and effective in cats.

What is Simbadol?

A buprenorphine product given SQ once daily for 24-hour surgical pain control in cats.

What is Zorbium?

A transdermal buprenorphine formulation for cats that provides post-operative pain relief for approximately 4 days.

Tramadol (Ultram): route and use

Tablets; used for chronic and surgical pain in dogs, sometimes with an NSAID.

Why has tramadol fallen out of favor in dogs?

Pain control may be less effective/reliable than previously believed because of low bioavailability; it has largely been replaced by gabapentin.

What important drug interaction is associated with tramadol?

Avoid with SSRIs such as fluoxetine or MAOIs such as selegiline.

Butorphanol (Torbugesic): opioid activity

Partial opioid agonist/antagonist.

Butorphanol: routes of administration

PO, IM, SQ, or IV.

What is butorphanol used for?

Antitussive, pre-anesthetic/premedication, and short-acting analgesia.

Why is butorphanol not ideal for significant pain?

It is not a good choice for moderate-to-severe pain and its analgesia is poor/unpredictable in cats.

Which patients require extra caution when receiving opioids?

Geriatric or severely debilitated patients; patients with head injuries/increased intracranial pressure, acute abdominal conditions, hypothyroidism, Addison's disease, pre-existing respiratory problems, or severe renal insufficiency.