What Is in a Cortisone Shot? Ingredients Explained

A cortisone shot contains a synthetic corticosteroid as its active ingredient, almost always combined with one or more inactive substances that serve as carriers, preservatives, or pain-numbing agents. The two most commonly used corticosteroids are methylprednisolone acetate (sold as Depo-Medrol) and triamcinolone acetonide (sold as Kenalog), though several others are in regular use depending on where the injection goes and what your doctor is trying to achieve. What surprises many people is that the steroid itself is only part of the syringe’s contents, and those “other” ingredients matter more than most patients realize.

The Active Steroid

The word “cortisone” in everyday language is a catch-all. In practice, doctors almost never inject actual cortisone anymore. Instead, they use one of several synthetic relatives that are far more potent and longer-lasting. A survey of orthopaedic surgeons, rheumatologists, and primary-care physicians found that Depo-Medrol (methylprednisolone acetate) and Kenalog (triamcinolone acetonide) are the most commonly chosen preparations across specialties.¹ Other frequently used options include dexamethasone sodium phosphate (Decadron), betamethasone sodium phosphate and betamethasone acetate (Celestone Soluspan), and hydrocortisone.

These are not interchangeable products that just happen to have different names. They differ in potency, how long they linger at the injection site, and whether they form crystals or dissolve into a clear solution. That last distinction, particulate versus non-particulate, turns out to be clinically significant. Particulate steroids like methylprednisolone and triamcinolone form a crystalline suspension that stays put in the tissue, releasing the drug slowly over days to weeks. Non-particulate steroids like dexamethasone sodium phosphate dissolve into a clear solution and are absorbed faster.² For joint injections, the sustained-release depot effect of a particulate steroid is usually desirable. For epidural injections near the spinal cord, though, those crystals can pose a risk if they migrate into a blood vessel. That is why many pain-medicine specialists prefer dexamethasone for epidural work.

How the Steroid Works Once It Is Injected

The reason any of these drugs relieve pain is that they powerfully suppress inflammation at the molecular level. Once inside a cell, the steroid binds to glucocorticoid receptors, which then travel to the cell nucleus and dial down the activity of genes responsible for producing inflammatory proteins. In effect, the drug reverses the chemical signaling that keeps a joint or tendon swollen and painful.³ At higher concentrations, the steroid also switches on genes that actively produce anti-inflammatory proteins, so it works on both sides of the equation.

This is not a permanent fix. The drug eventually clears the tissue, and if the underlying cause of inflammation is still there, symptoms return. That is why cortisone shots are typically described as buying time: reducing pain and swelling long enough for rehabilitation, healing, or further treatment decisions.

The Local Anesthetic

Most cortisone shots are not pure steroid. Before injecting, the clinician frequently draws up a local anesthetic into the same syringe. Lidocaine (usually at a 1% concentration) and bupivacaine (often at 0.25%) are the standard choices.⁴ The anesthetic serves two purposes. First, it numbs the injection site so the procedure hurts less. Second, it provides immediate but short-lived pain relief, which can help a doctor confirm that the needle actually reached the right spot. If your pain disappears within minutes, the injection likely hit the target; if nothing changes, the anatomy may need to be reassessed.

The ratio of steroid to anesthetic varies with the site and the doctor’s preference. A small finger joint might get a fraction of a milliliter of steroid mixed with a small volume of lidocaine, while a large knee injection might involve a full milliliter of steroid diluted in several milliliters of anesthetic. There is no universal recipe, and practice patterns differ significantly between specialties and even between individual practitioners.

Mixing these drugs in a syringe is not always chemically neutral. Some combinations of local anesthetics and non-particulate steroids can cause unexpected crystal formation. When researchers examined common pairings, they found that mixing ropivacaine or levobupivacaine with betamethasone sodium phosphate produced large crystals exceeding 50 micrometers, while lidocaine combined with the same non-particulate steroids produced no identifiable crystals at all.⁵ The pH differences between the acidic anesthetics and the basic steroid solutions drive this reaction. For routine joint injections this is mostly a concern in theory, but for procedures near blood vessels or nerve roots, unexpected particulates can matter.

Inactive Ingredients and Preservatives

Beyond the steroid and the anesthetic, the vial contains a small cast of supporting characters. These inactive ingredients, called excipients, keep the drug stable, maintain the right pH, and prevent bacterial growth. The exact list depends on the product, but common excipients in injectable corticosteroid formulations include polyethylene glycol (PEG), carboxymethylcellulose, benzyl alcohol (a preservative), sodium chloride for isotonicity, and sometimes propylene glycol.

Most patients never think about these additives. But for the small number of people who react badly to a cortisone shot despite tolerating oral steroids just fine, an excipient is often the culprit. In a study evaluating patients referred for suspected steroid allergy, the majority of those with confirmed positive reactions turned out to be allergic not to the corticosteroid itself but to excipients, specifically carboxymethylcellulose and polyethylene glycol.⁶ A broader review of drug hypersensitivity confirmed that corticosteroid preparations are among the drug classes where excipient reactions are particularly well documented, with gelatin, carboxymethylcellulose, and polyethylene glycols implicated in immediate reactions and propylene glycol linked to delayed skin reactions.⁷

If you have had an unexplained reaction to a cortisone injection in the past, this is worth bringing up with an allergist. The problem may not be the steroid at all, and switching to a formulation with different excipients can sometimes solve it entirely.

What the Ingredients Do to Cartilage and Tendons

One of the most persistent worries about cortisone shots is whether the drug damages the joint it is supposed to help. The evidence here is nuanced. A systematic review of basic science and clinical studies found that methylprednisolone, dexamethasone, triamcinolone, and other corticosteroids all displayed dose-dependent harmful effects on cartilage cells in both lab and animal models. At low doses, some steroids actually promoted cell growth and recovery. But at higher doses, significant cartilage damage and cell death occurred.⁸ The key takeaway is that the dose and the number of repeat injections matter enormously. A single moderate-dose shot into a knee is a very different proposition from repeated high-dose injections over months.

The local anesthetic in the syringe adds its own layer of concern. Lab and animal studies have found that combinations of local anesthetic and corticosteroid can reduce the viability of both cartilage cells and the cells lining the joint. In one animal study, cartilage exposed to a lidocaine-methylprednisolone combination showed significantly lower cell density after seven days compared to controls.⁹ Whether this translates to meaningful joint damage in a person receiving occasional injections remains an open question, but it does feed the clinical instinct to space injections out rather than giving them frequently.

Tendons are also vulnerable. A systematic review of basic science studies found that corticosteroids suppress inflammation but induce cell death in tendon tissue, reduce collagen quality, and lower the mechanical strength of tendons including their load to failure.¹⁰ Laboratory testing of isolated collagen fascicles showed that both high and low concentrations of corticosteroids cut tensile strength roughly in half or worse within a week.¹¹ These effects appear to be transient and dose-dependent, which is why doctors generally limit injections around tendons and advise against heavy loading for a period after a shot.

Skin and Fat Changes at the Injection Site

Some patients notice a pale, sunken patch of skin near where the needle went in. This happens when steroid crystals deposit in the skin or fat layer instead of staying deep in the target tissue, or when a small amount of the injected fluid tracks backward along the needle path. The steroid inhibits the cells that produce collagen and activates enzymes that break it down, while also suppressing the cells responsible for skin pigmentation. The result is a divot of thin, pale skin that can take months to fill back in, if it does at all.¹² This is more common with superficial injections and with particulate steroid preparations, since the crystals linger in tissue longer. Injecting deeper and applying pressure after withdrawing the needle helps reduce the risk.

Blood Sugar Spikes After a Shot

Even though a cortisone shot is delivered locally, some of the steroid always makes it into the bloodstream. For most people, this causes no noticeable problem. For anyone with diabetes, it can raise blood sugar meaningfully for a day or two. In a study of diabetic patients who received methylprednisolone injections into the hand or wrist, fasting blood glucose jumped significantly on the first day after the shot and remained elevated on day two, then returned to baseline by day four.¹³ Patients with type 1 diabetes and those already using insulin saw the largest spikes.

A separate study looking at shoulder injections in people with type 2 diabetes confirmed the same pattern. Mean glucose rose from about 136 mg/dL before injection to 159 mg/dL on day one, then gradually settled back to baseline by day three or four. The time spent with dangerously high glucose (above 250 mg/dL) roughly doubled on the first post-injection day, though no patients in the study needed emergency care for their blood sugar.¹⁴ Another study found that patients with higher baseline HbA1c levels (a marker of longer-term blood sugar control) experienced larger glucose spikes after injection.¹⁵

The practical advice here is straightforward. If you have diabetes, let the doctor giving the injection know. You should monitor your blood sugar more closely for about 48 hours afterward, and your insulin or medication dose may need a temporary adjustment. The spike is real but predictable and short-lived.

Sterility and Multi-Dose Vials

Most cortisone shots come from either a single-use vial or a multi-dose vial, and the distinction is more than administrative. Multi-dose vials contain a preservative (commonly benzyl alcohol) that allows the vial to be punctured repeatedly without bacteria taking hold. In a study comparing the two formats, about 5.5% of multi-dose vials showed bacterial contamination after repeated use, while none of the single-dose vials were contaminated.¹⁶ Outbreaks of serious joint and soft-tissue infections have been traced to contaminated multi-dose vials, underscoring the importance of strict aseptic technique and proper storage.¹⁷ Single-dose vials, while safer from a contamination standpoint, lack preservatives entirely, meaning they must be used immediately after opening. In reputable clinical settings, the infection risk from either format is very low, but it is one more reason to avoid cut-rate injection clinics with questionable sterile practices.

How Cortisone Shots Differ From Other Joint Injections

You may hear about hyaluronic acid injections as an alternative, particularly for knee osteoarthritis. Hyaluronic acid is not a steroid. It is a gel-like substance that mimics the natural lubricant already in your joint fluid. The two injectables work on different timelines. Corticosteroid injections tend to provide stronger short-term pain relief, especially in the first few weeks, while hyaluronic acid injections tend to show better results further out, though the benefit at six months is only moderate.¹⁸ Hyaluronic acid injections do not carry the same concerns about cartilage damage or blood sugar spikes, which is part of their appeal for patients who need repeated treatment.

Platelet-rich plasma (PRP) is another alternative that has gained popularity, though its evidence base is more mixed and it is not covered by most insurance plans. None of these options contain the same ingredients as a cortisone shot; they represent fundamentally different approaches to managing joint pain.

How These Drugs Came to Exist

The story begins in 1948, when the first patient with rheumatoid arthritis received an injection of cortisone at the Mayo Clinic. The results were dramatic, and oral and intra-articular cortisone use began by 1950-51.¹⁹ But natural cortisone had significant side effects, including fluid retention and metabolic disruption, and producing it was difficult and expensive. Chemists spent the next decade systematically modifying the steroid skeleton to see what each tweak did. They discovered that adding a fluorine atom at one position dramatically increased anti-inflammatory power but also worsened fluid retention. Introducing a double bond in another part of the molecule created prednisone and prednisolone, which were more effective with fewer side effects. Combining multiple chemical modifications eventually yielded dexamethasone, which became the most potent non-salt-retaining anti-inflammatory steroid of its era.²⁰

The products used in today’s cortisone shots are direct descendants of that mid-century chemical tinkering. Each one represents a different balance of potency, duration, solubility, and side-effect profile. Methylprednisolone emphasizes a moderate depot effect with good local potency. Triamcinolone is a workhorse for larger joints. Dexamethasone is reserved for situations where a non-particulate, fast-acting steroid is preferred. The diversity of options is the legacy of decades of very deliberate molecular engineering, and it is why “a cortisone shot” is actually many different products depending on what your doctor reaches for.