Pharmacology of Corticosteroids

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Questions and Answers

What are the main pharmacological actions of glucocorticoids?

Antimicrobial and blood pressure regulation

Hormonal regulation and sodium balance

Anti-inflammatory and immunosuppressive effects (correct)

Pain relief and allergy suppression

Which drugs are classified as anti-inflammatory drugs in the context provided?

Antihistamines, NSAIDs, corticosteroids

Ciclosporin, antibiotics, NSAIDs

Analgesics, corticosteroids, ciclosporin

Corticosteroids, NSAIDs, ciclosporin (correct)

What is one primary mechanism by which corticosteroids exert their anti-inflammatory effects?

Promotion of eicosanoid synthesis

Inhibition of phospholipase A2 (correct)

Increase in leukotriene synthesis

Activation of arachidonic acid metabolism

Which hormone is primarily responsible for regulating the levels of corticosteroids?

Adrenocorticotrophic hormone (ACTH) (B) Signup and view all the answers

What effect do mineralocorticoids primarily have on the body?

Affect sodium balance and influence blood pressure (C) Signup and view all the answers

Which of the following is a common adverse effect associated with prolonged corticosteroid use?

Diabetes mellitus (D) Signup and view all the answers

Which of the following is NOT an anti-inflammatory drug category mentioned?

Antiallergic drugs (D) Signup and view all the answers

What is a therapeutic application of corticosteroids in cancer treatment?

Chemotherapy for acute leukaemia (A) Signup and view all the answers

Which of the following eicosanoids is primarily involved in modulating inflammatory responses?

Prostaglandin E2 (PGE2) (C) Signup and view all the answers

What is a role of ophthalmic corticosteroids?

Treating acute and chronic inflammation (D) Signup and view all the answers

Which ophthalmic corticosteroid is typically indicated for severe inflammation?

Dexamethasone (B) Signup and view all the answers

What factor affects the efficacy of a glucocorticoid preparation besides its strength?

The salt used in the formulation (D) Signup and view all the answers

Which of the following statements about prednisolone acetate is true?

It penetrates the eye better when the cornea is abraded. (B) Signup and view all the answers

In which situation is low strength prednisolone sodium phosphate preferred?

To minimize glucocorticoid side effects. (A) Signup and view all the answers

Which combination of medications is most likely to be used for treating ocular inflammation?

Dexamethasone with antibiotics (B) Signup and view all the answers

What condition is primarily treated with Ozurdex intravitreal implant of dexamethasone?

Macula oedema following retinal venous occlusions (C) Signup and view all the answers

What is an acute adverse reaction associated with the short-term use of corticosteroids?

Increased intraocular pressure (IOP) (D) Signup and view all the answers

What is the primary action of NSAIDs in the inflammatory response?

Inhibiting cyclo-oxygenase (COX) (B) Signup and view all the answers

What is the consequence of prolonged use of ophthalmic corticosteroids?

Development of posterior sub-capsular cataract (B) Signup and view all the answers

Which NSAID is specifically licensed for treating seasonal allergic conjunctivitis?

Diclofenac sodium (B) Signup and view all the answers

What role do eicosanoids play in the body?

Act as mediators of the inflammatory response (D) Signup and view all the answers

Which medication is used as an immunosuppressive for treating severe dry eye disease?

Ciclosporin (A) Signup and view all the answers

What is the effect of vasoconstrictors in ophthalmology?

Constrict conjunctival blood vessels (C) Signup and view all the answers

Which of the following is a mast cell stabilizer used in allergic eye disease?

Sodium cromoglicate (B) Signup and view all the answers

What is an effect of acute allergic conjunctivitis?

Symptoms of redness and itching (C) Signup and view all the answers

Which condition is NOT treated by ophthalmic corticosteroids?

Severe dry eye (D) Signup and view all the answers

How long may mast cell stabilizers take to produce symptomatic relief?

7-14 days (B) Signup and view all the answers

Which drug is an example of a topical antihistamine?

Olopatadine (A) Signup and view all the answers

Which condition is associated with mast cell degranulation?

Vernal keratoconjunctivitis (C) Signup and view all the answers

What is the common response of mast cells in allergic eye disease?

Release of mediators like histamine (D) Signup and view all the answers

Signup and view all the answers

Study Notes

Ophthalmic Drugs 1: Anti-Inflammatory Drugs

Ocular Therapeutic Drugs include anti-inflammatory, anti-infective, dry eye preparations, and anti-glaucoma drugs.
Part 1 of the lecture covers the pharmacology, indications, and side effects of corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), and ciclosporin.
Part 2 of the lecture covers anti-allergy drugs (antihistamines, mast cell stabilisers).

Corticosteroids

Corticosteroids are hormones produced by the adrenal cortex.
These include glucocorticoids and mineralocorticoids.
Hormone levels are regulated by ACTH from the pituitary gland.
Glucocorticoids, such as cortisol, maintain blood glucose levels and promote recovery from injury.
Mineralocorticoids, e.g. aldosterone, affect sodium balance, causing sodium reuptake and water retention, thus influencing blood pressure.

Corticosteroids: Actions

Glucocorticoids used therapeutically to treat inflammation.
Glucocorticoids have anti-inflammatory and immunosuppressive effects by reducing the activity of inflammatory mediators (e.g. eicosanoids, platelet-activating factor, and interleukins).
They also have metabolic effects on carbohydrates, proteins, and fats.
The steroid-receptor complex binds to glucocorticoid response elements in chromatin, affecting DNA transcription and the production of inhibitory proteins.

Corticosteroids: Action (cont.)

Corticosteroids inhibit inflammation by impacting inflammatory mediators.
Inflammatory mediators cause effects such as swelling, redness, heat or pain; corticosteroids interfere with this process
This process includes chemotaxis as well as cellular migration.

Corticosteroids: Action (cont.2)

Corticosteroids also inhibit eicosanoid synthesis by preventing the production of eicosanoids such as prostaglandins, thromboxane A2, prostacyclin, leukotrienes, through inhibition of cyclooxygenase and lipoxygenase.

Corticosteroids: Therapeutic Uses (Systemic)

Anti-inflammatory effects (systemic or topical) for conditions such as asthma, eczema, inflammatory bowel disease, and rheumatic disease.
Replacement therapy for adrenal gland diseases.
Chemotherapy for conditions like acute leukaemia and Hodgkin lymphoma.
Immunosuppression, such as post-transplantation.

Corticosteroids: Adverse Effects

Adverse effects are common and can be severe, dependent on dose and treatment duration.
Adverse effects may include impaired glucose tolerance, or diabetes mellitus, osteoporosis, Cushing's syndrome, and immune suppression.

Ophthalmic Corticosteroids: Indications

Used in the treatment of acute and chronic inflammation, such as anterior uveitis and vernal conjunctivitis.
Used after surgery, to help reduce inflammation following procedures.
Intravitreal steroids are used to treat macular oedema and some cases of posterior uveitis.

Ophthalmic Corticosteroids: Indications (cont.)

There's no official potency hierarchy for topical ocular glucocorticoids; efficacy depends on the salt used (prednisolone acetate is more effective than prednisolone sodium phosphate) and corneal integrity.

Ophthalmic Corticosteroids: Indications (cont.2)

Prednisolone acetate and dexamethasone are used for severe inflammation, while milder forms use lower strength topical preparations like prednisolone sodium phosphate or hydrocortisone.
Important to minimise side effects, especially in the presence of viral infections.

Ophthalmic Corticosteroids: Available Preparations

Betamethasone (Betnesol), Dexamethasone (Maxidex), Fluorometholone (FML), Loteprednol Etabonate (Lotemax), Prednisolone(Predsol, Pred Forte) etc.
Combination preparations with antibiotics (e.g., Betnesol N, Maxitrol, Tobradex) sometimes needed.
Intravitreal corticosteroids (e.g., Ozurdex) are used for macular oedema following retinal venous occlusions and non-infectious posterior uveitis.

Ophthalmic Corticosteroids: Adverse Reactions

Prolonged steroid use increases risk of posterior sub-capsular cataract formation.
Cataracts are dose-dependent and account for approx. 4% cases, usually in patients on a high dosage over 1+ years.

Ophthalmic Corticosteroids: Adverse Reactions (cont.)

Raised intraocular pressure (IOP) is a key adverse reaction to short-term use in steroid responsive individuals. This can be caused by topical, inhaled, or systematic use of steroids

Non-steroidal Anti-inflammatory Drugs (NSAIDs)

Topical NSAIDs provide mild to moderate anti-inflammatory action without the side effects of corticosteroids.
NSAIDs prevent the formation of eicosanoids.

Biological Actions of Eicosanoids

Eicosanoids are crucial mediators of the inflammatory response.
Key eicosanoids are prostaglandins and leukotrienes.
Ocular effects include vasodilation, increased IOP, miosis, and macular oedema

Biological Actions of Eicosanoids (cont.)

NSAIDs primarily work by inhibiting cyclo-oxygenase (COX).

Ophthalmic NSAIDs: Indications

Reduction of intra-operative and post-operative inflammation.
Use in some centers for post-operative pain management.
Reduction of pain after corneal trauma—diclofenac sodium is used in some cases.
Allergic conjunctivitis—diclofenac sodium and others are used in some cases.
Episcleritis—occasionally used, but is off-license.

Available Topical NSAIDs

Diclofenac sodium (Voltarol).
Flurbiprofen (Ocufen).
Ketorolac trometamol (Acular).
Nepafenac (Nevanac).
Bromfenac (Yellox).
Diclofenac sodium has a licence for post-corneal trauma pain and sometimes also for seasonal allergic conjunctivitis (SAC)(See indications above)

Ciclosporin

Ciclosporin inhibits cytokine release from T-lymphocytes, thus suppressing the cell-mediated immune response.
It is licensed for severe keratitis in dry eye disease (usually when other treatments haven't worked).
Licensed for severe vernal keratoconjunctivitis.

Summary (Ophthalmic Drugs 1 Part 1)

In the UK, ophthalmic corticosteroids are usually reserved for managing moderate-to-severe inflammation by qualified ophthalmologists and can also be prescribed by independent optometrists.
Topical NSAIDs are mainly licensed to reduce post-operative inflammation; however, diclofenac is used for seasonal allergic conjunctivitis and pain.
Ciclosporin is an immunosuppressant, primarily used for severe cases of dry eye and vernal keratoconjunctivitis.

The Ocular Allergic Response

Eyes are a common site for allergic inflammation.
The majority of allergic eye conditions affect the conjunctiva.
Mast cells play a key role in allergic responses.
Degranulation of mast cells releases substances like histamine.
Released mediators cause signs and symptoms of ocular allergy.

Allergic Eye Diseases

Acute allergic conjunctivitis.
Seasonal/perennial allergic conjunctivitis.
Giant papillary conjunctivitis.
Atopic keratoconjunctivitis.
Vernal keratoconjunctivitis.

Role of Mast Cells in Ocular Allergy

Mast cells are involved in processing and presenting antigens, producing IgE, and activating inflammation.
Mast cell degranulation occurs when inflammatory mediators are released.
Mast cell stabilization involves stopping degranulation, which can be done using mast cell stabilisers.

Anti-allergy Drugs

Antihistamines, mast cell stabilisers, corticosteroids, NSAIDs, and vasoconstrictors are used to treat allergic eye conditions.

Antihistamines

Available in topical and systemic forms (many OTC preparations).
Systemic antihistamines are often used for hay fever and other conditions. The common example of a topical antihistamine is cetirizine. (examples: diphenhydramine and cetirizine).
Topical antihistamines are a very common treatment for seasonal and perennial allergic conjunctivitis.
Newer antihistamines also have mast cell stabilizing properties.

Available Anti-allergy Preparations (Topical Antihistamines)

Antazoline, Azelastine, Epinastine (POM), Ketotifen, and Olopatadine.

Topical Mast Cell Stabilizers

Block calcium influx to mast cells, preventing degranulation, decreasing the symptoms and signs of allergic reactions.
Symptom relief takes 7-14 days.
Effective for moderate to severe allergic eye conditions.

Available Anti-allergy Preparations(Mast Cell Stabilizers)

Sodium cromoglicate, Lodoxamide, and Nedocromil sodium.

NSAIDs (for allergic conditions)

Diclofenac sodium (POM) is a licensed, well-tolerated NSAID for allergic eye conditions, particularly SAC, and provides symptomatic relief within 30 minutes of administration.

Vasoconstrictors

Vasoconstrictors are sympathomimetic drugs, stimulating alpha adrenoceptors to cause constriction of conjunctival blood vessels. Reducing redness and inflammation.
Vasoconstrictors reduce conjunctival hyperemia and oedema. Examples include: Xylometazoline and Naphazoline.

Summary (Ophthalmic Drugs 1 Part 2)

Several topical drugs treat allergic eye conditions, including antihistamines, mast cell stabilisers, dual-acting drugs (some over-the-counter), topical NSAIDs and vasoconstrictors.
Newer antihistamines also have mast cell stabilizing properties.
Some drugs are available over the counter.
Topical NSAIDs and vasoconstrictors have a limited role in treating allergic eye conditions.

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Description

This quiz examines the pharmacological actions of glucocorticoids and their role as anti-inflammatory agents. Participants will explore therapeutic applications in various contexts, including cancer treatment and ocular conditions. Test your knowledge on corticosteroid mechanisms and adverse effects.