Triamcinolone acetonide

Description

Triamcinolone acetonide is a synthetic corticosteroid. It decreases cytokine levels, the firing rate of sensory neurons, and mechanical hypersensitivity in a rat spinal nerve ligation model when used at a dose of 1.5 mg/kg prior to and following surgery for three days. Triamcinolone acetonide also decreases outflow facility in a mouse model of steroid-induced glaucoma when 20 μl of a 40 mg/ml suspension is administered subconjunctivally. Formulations containing triamcinolone acetonide are used in the treatment of diabetic macular edema.

Chemical properties

White Solid

Originator

Kenalog,Squibb,US,1958

The Uses of Triamcinolone acetonide

Triamcinolone acetonide is a topical and systemic corticosteroid belonging to the group-B (triamcinolone acetonide) type of steroids.

definition

ChEBI: A synthetic glucocorticoid that is the 16,17-acetonide of triamcinolone. Used to treat various skin infections.

Indications

Triamcinolone acetonide (Aristocort, Kenalog) is a synthetic fluorinated corticosteroid.

Manufacturing Process

A solution of 250 mg of 9α-fluoro-11β,16α,17α,21-tetrahydroxy-1,4- pregnadiene-3,20-dione in 70 ml of hot acetone and 7 drops of concentrated hydrochloric acid is boiled for 3 minutes. After standing at room temperature for 17 hours, the reaction mixture is poured into dilute sodium bicarbonate and extracted with ethyl acetate. The extract is washed with saturated saline solution, dried and evaporated to a colorless glass. The residue is crystallized from acetone-petroleum ether to afford 166 mg of the acetonide, MP 270° to 274°C, decomposition, (with previous softening and browning). Three recrystallizations from acetone-petroleum ether give 113 mg of 9α-fluoro- 11β,21-dihydroxy-16α,17α-isopropylidenedioxy-1,4-pregnadiene-3,20-dione, MP 274° to 279°C, decomposition, (with previous softening and browning).

brand name

Triamcinolone acetonide was sold under the brand name Kenalog among others.

Therapeutic Function

Glucocorticoid

Mechanism of action

Triamcinolone acetonide is a corticosteroid. It is specifically a glucocorticoid, or an agonist of the glucocorticoid receptor, that is about five times as potent as cortisol. It has very little mineralocorticoid effects.The affinities of triamcinolone acetonide for the androgen and estrogen receptors are both <0.1% (relative to testosterone and estradiol).

General Description

The three main metabolitesof triamcinolone acetonide (Azmacort, Nasacort) are 6β-hydroxytriamcinolone acetonide, 21-carboxytriamcinoloneacetonide, and 6β-hydroxy-21-carboxytriamcinolone acetonide.All are much less active than the parent compound.The 6β-hydroxyl group and the 21-carboxy group are bothstructural features that greatly reduce GC action. The increasedwater solubility of these metabolites also facilitatesmore rapid excretion.

General Description

Triamcinolone acetonide is approximately 8 times morepotent than prednisone in animal inflammation models.Topically applied triamcinolone acetonide is a potent antiinflammatoryagent, about 10 times more sothan triamcinolone. The plasma half-life is approximately 90minutes, although the plasma half-life and biological halflivesfor GCs do not correlate well. The hexacetonide isslowly converted to the acetonide in vivo and is given onlyby intra-articular injection. Only triamcinolone and the diacetateare given orally. The acetonide and diacetate may begiven by intra-articular or intrasynovial injection. In addition,the acetonide may be given by intrabursal or, sometimes,IM or subcutaneous injection. A single IM dose of thediacetate or acetonide may last up to 3 or 4 weeks. Plasmalevels with IM doses of the acetonide are significantly higherthan with triamcinolone itself. The acetonide is also used totreat asthma and allergic rhinitis.

Clinical Use

Triamcinolone acetonide used topically to treat various skin conditions, to relieve the discomfort of mouth sores, and by injection into joints to treat various joint conditions.Triamcinolone acetonide frequently is used by inhalation for the treatment of lung diseases (e.g., asthma).

Adverse reactions

Significant: Adrenal suppression, immunosuppression (e.g. secondary infections, superinfections); kaposi sarcoma, myopathy, psychiatric disturbances including insomnia and depression (parenteral); local topical, nasal or ocular effects (e.g. sensitization, visual disturbances such as increased intraocular pressure, endophthalmitis).

Eye disorders: Cataract (ocular).

Gastrointestinal disorders: Dyspepsia, tooth disorder (nasal).

Injury, poisoning and procedural complications: Injection site reactions (e.g. blurring of vision for ocular, discomfort, pain, erythema, swelling, necrosis, abscess).

Investigations: Elevated blood pressure, weight gain (parenteral).

Metabolism and nutrition disorders: Increased appetite, fluid retention, glucose tolerance alteration (parenteral).

Musculoskeletal and connective tissue disorders: Arthralgia (parenteral).

Nervous system disorders: Headache.

Respiratory, thoracic and mediastinal disorders: Epistaxis (nasal).

Potentially Fatal: Rarely, anaphylaxis.

Side Effects

The side effects of using Triamcinolone acetonide include:Skin dryness, flaking, crusting, burning, or blistering; Skin irritation; Skin soreness, itching, swelling, scaling, or severe redness; Scaling or redness near mouth; Skin thinning or bruising, especially in skin folds (like between the finger) or on the face (when directed to use it there); New or worsening pimples or acne; Skin burning and itching with tiny red blisters; Skin softening; Itching, pain, or burning sensation in hairy areas, or pus at the root of the hair; Increased hair growth on the legs, arms, back, or forehead; Lightening of skin tone; Red or purple lines on the arms, face, legs, groin, or trunk.

Safety Profile

Poison by subcutaneous and intraperitoneal routes. An experimental teratogen. Other experimental reproductive effects. Human mutation data reported. When heated to decomposition it emits acrid smoke and toxic fumes of F-.

Veterinary Drugs and Treatments

The systemic veterinary labeled product (Vetalog? Injection) is labeled as “indicated for the treatment of inflammation and related disorders in dogs, cats, and horses. It is also indicated for use in dogs and cats for the management and treatment of acute arthritis, allergic and dermatologic disorders.”
Glucocorticoids have been used in an attempt to treat practically every malady that afflicts man or animal, but there are three broad uses and dosage ranges for use of these agents. 1) Replacement of glucocorticoid activity in patients with adrenal insufficiency, 2) as an antiinflammatory agent, and 3) as an immunosuppressive. Among some of the uses for glucocorticoids include treatment of: endocrine conditions (e.g., adrenal insufficiency), rheumatic diseases (e.g., rheumatoid arthritis), collagen diseases (e.g., systemic lupus), allergic states, respiratory diseases (e.g., asthma), dermatologic diseases (e.g., pemphigus, allergic dermatoses), hematologic disorders (e.g., thrombocytopenias, autoimmune hemolytic anemias), neoplasias, nervous system disorders (increased CSF pressure), GI diseases (e.g., ulcerative colitis exacerbations), and renal diseases (e.g., nephrotic syndrome). Some glucocorticoids are used topically in the eye and skin for various conditions or are injected intra-articularly or intra-lesionally. The above listing is certainly not complete.

Metabolism

Triamcinolone acetonide frequently is used by inhalation for the treatment of lung diseases (e.g., asthma). After inhalation, triamcinolone acetonide can become systemically available when the inhaled formulation is swallowed and absorbed unchanged from the GI tract, causing undesirable systemic effects. Triamcinolone acetonide that is swallowed is metabolized to 6β-hydroxytriamcinolone acetonide, 21-carboxytriamcinolone acetonide, and 21-carboxy-6β-hydroxytriamcinolone acetonide, all of which are more hydrophilic than their parent drug. Only approximately 1% of the dose was recovered from the urine as triamcinolone acetonide. Triamcinolone is not a major metabolite of triamcinolone acetonide in humans, suggesting that acetonide is resistant to hydrolytic cleavage. Triamcinolone acetonide is approximately eight times more potent than prednisolone.