NSAIDs and Corticosteroids: Pharmacology and Safe Use

Introduction

Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are the two big families of anti-inflammatory drugs in veterinary practice. Technicians dispense them, draw the baseline blood work, teach owners which side effects to watch for and take the phone call when a dog on carprofen starts to vomit.

This guide explains where each family acts in the inflammation pathway, why that predicts its side effects, why the two families are not given together, and how glucocorticoid doses and tapering work. It ends with the species warnings, above all for cats, that the VTNE likes to test.

Key facts

How the VTNE tests this

• Recognize drug classes, their mechanisms and clinically relevant side effects (Domain 1 Task F).¹
• Classify a named drug as an NSAID, a coxib, a glucocorticoid or a mineralocorticoid (K8, drug classification).¹
• Match a drug to its contraindications, side effects and interactions, such as the NSAID plus steroid combination (K12).¹
• Expect scenarios: an owner reporting black stool, a cat prescribed repeat meloxicam, a dog on prednisone for months whose owner wants to stop it.
• Expect a dose or volume calculation for an oral suspension or an injectable steroid.

Core concepts

The arachidonic acid cascade

When a cell membrane is injured, the enzyme phospholipase A2 releases arachidonic acid from membrane phospholipids. COX enzymes turn arachidonic acid into prostaglandins and thromboxane. A second enzyme, lipoxygenase, turns it into leukotrienes. Glucocorticoids act upstream: they induce lipocortin, a protein that inhibits phospholipase A2 and so blocks the synthesis of prostaglandins, leukotrienes and platelet-activating factor.³ NSAIDs act one step lower, mainly by inhibiting COX.² That is why steroids affect many more pathways, and why their side effects are broader.

COX-1 and COX-2

COX-1 is found in almost every tissue and makes constitutive prostaglandins. These keep up blood flow to the gastric mucosa, stimulate bicarbonate and mucus, protect the kidney when blood pressure falls and let platelets form thromboxane A2 (TXA2), a strong aggregating agent.² COX-2 is activated in damaged tissue and drives inflammation, fever and pain. Blocking COX-2 gives the useful effects. Blocking COX-1 at the same time causes many of the adverse effects, including gastric ulceration and kidney toxicity.²

"COX-2 selective" or "COX-1 sparing" NSAIDs inhibit COX-2 at lower concentrations than COX-1. In dogs, favorable ratios have been reported for carprofen, meloxicam, deracoxib, firocoxib and robenacoxib, and unfavorable ratios for aspirin, phenylbutazone and vedaprofen.² Selective does not mean safe. COX-2 selective drugs still cause gastritis and ulcers, and they are not safer for the kidney, because COX-2 prostaglandins also protect renal blood flow during hypotension.²

Grapiprant is a newer drug in a different class: it blocks the EP4 receptor for PGE2 and is not a COX inhibitor.²

NSAID adverse effects by body system

• Gastrointestinal. Vomiting is the most common sign. Bleeding may be hidden, leading to iron-deficiency anemia, or obvious as hematemesis (vomited blood) and melena (black, tarry stool). Low albumin, ulceration and perforation can follow.²
• Renal. Patients with kidney disease can decompensate. Keep patients hydrated and renal perfusion up, especially during anesthesia and surgery.²
• Hepatic. Usually mild liver enzyme increases. Rare idiosyncratic liver failure has been reported in dogs with carprofen and etodolac.² About one-fourth of hepatic reports for carprofen were in Labrador Retrievers.⁵
• Platelets. Aspirin binds platelet COX-1 irreversibly and prolongs bleeding. COX-2 selective NSAIDs do not appear to delay clotting much in dogs.²

Source: Merck Veterinary Manual, Nonsteroidal Anti-inflammatory Drugs in Animals; Rimadyl and Metacam labels on DailyMed.²⁵⁶

Corticosteroids: glucocorticoids and mineralocorticoids

The adrenal cortex makes two classes of steroid hormone. Mineralocorticoids, mainly aldosterone, keep electrolytes in balance by holding sodium and excreting potassium. Glucocorticoids, mainly cortisol, affect metabolism, inflammation and immunity.³ Synthetic drugs differ in how much of each activity they have and how long they last.

Source: Merck Veterinary Manual, Relative Potencies of Commonly Used Corticosteroids.⁴

Prednisone is a prodrug: the liver converts it to prednisolone. In horses, prednisone is poorly absorbed and rarely converted, so prednisolone is recommended.³

Physiologic, anti-inflammatory and immunosuppressive doses

The same drug does different jobs at different doses, because its physiologic and pharmacologic effects work through the same receptor.³

• Physiologic (replacement). Low doses replace missing cortisol, as in hypoadrenocorticism (Addison disease). Dogs in stable condition receive DOCP (desoxycorticosterone pivalate) for mineralocorticoid replacement plus prednisone for glucocorticoid replacement, or fludrocortisone alone.⁷
• Anti-inflammatory. For acute atopic or flea allergy dermatitis, prednisolone at 0.5 to 1 mg/kg per day controls itching.³
• Immunosuppressive. Higher doses suppress the immune system. The ACVIM consensus for immune-mediated hemolytic anemia (IMHA) in dogs recommends prednisone or prednisolone at 2 to 3 mg/kg/day to start, or 50 to 60 mg/m2/day for dogs over 25 kg.⁸

Glucocorticoid adverse effects

Most adverse effects come from long-term supraphysiologic doses.³ Iatrogenic (drug-caused) Cushing syndrome shows polyuria, polydipsia, bilaterally symmetric alopecia, more infections, muscle wasting and fat redistribution. Glucocorticoids can bring on or worsen diabetes mellitus, slow enterocyte turnover and add to GI ulcer risk, and they potentiate the ulcer effect of NSAIDs. High doses can induce laminitis in horses. Dexamethasone and flumethasone can induce parturition in cattle after 255 days of gestation.³

Tapering and the adrenal axis

Synthetic glucocorticoids suppress the hypothalamic-pituitary-adrenal axis (HPAA). With long-term use the adrenal glands atrophy, causing iatrogenic secondary hypoadrenocorticism. If the drug is then stopped abruptly, the animal can develop an Addisonian-like crisis with lethargy, weakness, vomiting and diarrhea, and in severe cases shock and death.³ This is why long courses are tapered. After inflammation is controlled with daily intermediate-acting prednisone or prednisolone, the dose can be moved gradually to alternate days, which reduces adverse effects of treatment longer than 2 weeks.³

Procedure or technique

Starting a patient on a long-term NSAID or glucocorticoid. The veterinarian prescribes; the technician carries out and teaches.

1. Check the record for current drugs. Flag any other NSAID, aspirin or corticosteroid, including a recent long-acting injection, to the veterinarian so a washout can be planned.⁵
2. Collect baseline blood work as ordered. The carprofen label advises hematology and serum chemistry before and periodically during any NSAID.⁵
3. Confirm species and label. Never dispense a dog oral meloxicam suspension for a cat.⁶
4. Measure the dose with the syringe or tablet strength dispensed, and write the dose in mg and in mL or tablets on the label.
5. Give the client information sheet and teach the warning signs: decreased appetite, vomiting, diarrhea, black or tarry stool, more drinking or urination, pale or yellow gums, lethargy or behavior change.⁵
6. Tell the owner to stop the NSAID and call the clinic at once if any sign appears.⁵
7. For a glucocorticoid course, write the taper schedule out day by day and tell the owner not to stop the tablets suddenly.³
8. Book the recheck and repeat blood work.

Flowchart

Species differences

• Dogs. Most US NSAID labels are for dogs. Breed can change drug handling, as with some coxibs in Beagles, so doses cannot be safely extrapolated between species.²
• Cats. Cats are deficient in glucuronyl transferase, so acetaminophen is contraindicated: it causes methemoglobinemia, Heinz body anemia and liver necrosis.² In the US, meloxicam is not approved for cats beyond a single injection, and the label warns not to give additional injectable or oral meloxicam.²⁶ Robenacoxib is approved for cats for up to 6 days.² Outside the US, low-dose meloxicam is used long term in some cats under close supervision.²
• Horses. Phenylbutazone and flunixin are common. Phenylbutazone is more ulcerogenic than flunixin and ketoprofen. Firocoxib is approved for equine osteoarthritis for up to 14 days.² High-dose glucocorticoids carry a laminitis risk.³
• Cattle. Some corticosteroids can induce parturition late in pregnancy, often with retained placenta.³

Calculation

Safety, legal and client education

• Dogs that react to one NSAID may react to another. Owners should not give aspirin, ibuprofen or leftover pills at home.⁵ Ibuprofen is not recommended for dogs or cats.²
• If more pain relief is needed on top of an NSAID, the meloxicam label points to a non-NSAID, non-corticosteroid analgesic.⁶
• Explain washout: when switching from one NSAID to another, or from a corticosteroid to an NSAID, the veterinarian sets a drug-free gap.⁵
• Explain that a steroid course must be tapered as written, and that more thirst, urination and appetite are expected effects to report, not reasons to stop suddenly.³
• Glucocorticoids raise infection risk and can wake up latent infections. Report new coughs, skin infections or urinary signs.³

Common mistakes and exam traps

Quick review

1. NSAIDs inhibit COX; glucocorticoids inhibit phospholipase A2 through lipocortin.
2. COX-1 protects the gut, the kidney and platelet function; COX-2 drives pain, fever and inflammation.
3. Vomiting is the most common NSAID side effect; GI ulceration is the most dangerous.
4. Melena and hematemesis mean possible bleeding ulcer: stop the drug and call.
5. Never combine NSAIDs with each other or with steroids; use a washout when switching.
6. Baseline and periodic CBC and chemistry for long-term NSAIDs.
7. US meloxicam: repeat dosing in cats is under a boxed warning.
8. Acetaminophen is contraindicated in cats.
9. Prednisolone potency 5, dexamethasone 25, fludrocortisone mineralocorticoid 125.
10. Long-term steroids: iatrogenic Cushing signs, diabetes risk, infection risk.
11. Taper long courses to avoid an Addisonian-like crisis.