Anti-inflammatory and immunosuppressant drugs Flashcards
What classes of Anti-inflammatory drugs are there
- Steroidal anti-inflammatory drugs
- Non-steroidal anti-inflammatory drugs (NSAIDs)
- Traditional or “non-selective” NSAIDS
- COX-2 inhibitors
Give an example of steroidal anti-inflammatory drugs
Corticosteroids - prednisolone
Give an example of NSAIDs
Acetyl salicylic acid - aspirin
Give an example of Traditional or “non-selective” NSAIDs
- Ibuprofen
- Naproxen
- Diclofenac
Give an example of COX-2 inhibitors
- Celecoxib
What is the general mechanism of NSAIDs
They inhibit the production of Prostaglandins from arachidonic acid by COX enzymes
What effects does aspirin have
Analgesic, anti-inflammatory and anti-thrombotic effects
Where is aspirin metabolised and excreted
Metabolised in Liver
Excreted in Kidneys
In which patients should you avoid using aspirin
In patients with severe liver disease and on dialysis
What does aspirin act on
Permanently affects platelet cohesiveness for the entire life span of the platelets
Affects primary homeostasis ~ prolonged bleeding time
What is aspirin’s effect on platelet count, PT/INR and APTT
Nothing
What general effects do traditional/non-selective NSAIDs have
Analgesic, anti-inflammatory and antipyretic actions
What do traditional/non-selective NSAIDs inhibit
COX-1 and COX-2
What does the inhibition of COX-1 and COX-2 result in
- Inhibition of COX-1 = accounts for NSAIDs side effects and toxicity
- Inhibition of COX-2 = accounts for anti-inflammatory actions
What are the side effects of traditional/non-selective NSAIDs
- Gastric irritability
- Platelet dysfunction ~ temporarily affect platelet cohsiveness
- Acute renal failure ~ short term, low dose use does not cause this effect
- Leukotriene overproduction ~ bronchoconstriction ~ avoid in asthmatic patients
What general effects do selective NSAIDs or COX-2 inhibitors have
- Analgesic
- Anti-inflammatory
- Anti-pyretic
Give examples of selective NSAIDs or COX-2 inhibitors
Celecoxib
Etoricoxib
What do selective NSAIDs or COX-2 inhibitors affect
Promotes platelet aggregation - avoid use in patients with significant history of atherosclerosis
Where are selective NSAIDs or COX-2 inhibitors metabolised and excreted
Metabolised in the liver
Excreted in the kidneys
Name some types of anti-inflammatory/immunosuppressive drugs
Antimitotic agents
Calcineurin inhibitors
Biological response modifiers
Name some kinds of anti-inflammatory drugs
Corticosteroids
Name some kinds of anti-mitotic agents
- Azathioprine
- Cyclophoshphamide
- Chlorambucil
Name some types of calcineurin inhibitors
- Ciclosporin
- Tacrolimus
Name some types of biological response modifiers
- Adalimumab
- Infliximab
- Etanercept
What actions do corticosteroids carry out in order to reduce inflammatory reaction
- Limiting capillary dilation and permeability of the vascular structures
- Restricts accumulation of polymorphonuclear leukocytes and macrophages and reduces the release of vasoactive kinins
What are the indications for use of corticosteroids
- Primary and secondary arden-cortical insufficiency
- Psoriatic arthritis
- Rheumatoid arthritis
- Ankylosing spondylitis
- Bursitis
- Acute gouty arthritis
- Systemic lupus erythematosus
- Leukaemias, lymphomas, thrombocytopenia purpura and autoimmune haemolytic anaemia
- Coeliac, UC and liver disorders
What are the potential endocrine side effects of corticosteroid use
Adrenal insufficiency
weight gain
diabetes mellitus
What are the potential gastrointestinal side effects of corticosteroid use
Peptic ulceration with perforation and haemorrhage
Dyspepsia
Abdominal distension
Oesophageal ulceration
What are the potential psychiatric side effects of corticosteroid use
Confusion
Irritability
Delusions and suicidal thoughts
What are the potential musculoskeletal side effects of corticosteroid use
Osteoporosis
Proximal myopathy
What are the potential ophthalmic side effects of corticosteroid use
Glaucoma
Cataract
Blurred vision
What are the potential skin related side effects of corticosteroid use
Thinning of the skin
Easy bruising
Delayed wound healing
What recommendation are there for minimise the side effects of corticosteroids
- Prescribe low effective dose for the minimum time possible
- Take corticosteroids in the morning and on alternate days
- Provide a steroid treatment card
- Prescribe a proton pump inhibitor for GI protection in patients with high risk of GI bleed
- Withdrawal from long-term treatment, must be gradual
- Be alert to signs and symptoms of adrenal insufficiency and prescribe steroid cover if needed
What are some withdrawal strategies for corticosteroids
- Short courses can be stopped abruptly
Gradual withdrawal for people: - whose disease is unlikely to relapse and who have received more than 3 weeks of corticosteroid treatment
- history of previous long term therapy
- other possible causes of adrenal suppression, alcohol, stress
- Had more than 40mg of prednisolone daily or equivalent for more than a week
What kind of drug is azathioprine
Immunosuppressive and antimetabolite drug
What is azathioprine converted into in the body
6-mercaptopurine
Describe the basic mechanism of azathioprine
Inhibits purine and DNA synthesis needed for the proliferation of cells, especially leukocytes and lymphocytes
What disease is azathioprine used to manage
- Rheumatoid arthritis
- Preventing renal transplant rejection
- Crohn’s disease
- Recurrent oral ulceration
- Behcet’s disease
- Colitis
What are the side effects of azathioprine
- Myelosuppression
- Hepatotoxicity
- Leukopenia
- Thrombocytopenia
- Infections
- Lymphoproliferative disorders
- Teratogenicity
What are the clinical signs of toxicity
- Rash
- Oral ulceration
- Abnormal bruising
- Severe sore throat
What kind of drug is cyclosporin and what does it act on
- Immunosuppressant with specific action on T-lymphocytes
Describe the mechanism of cyclosporin
- Binds to immunophilins, inhibits calcineurin that is normally responsible for activating transcription of IL-2
- Inhibits lymphokine production and interleukin release and preferentially inhibits t-helper and killer t-cells
Where is cyclosporin metabolised
Liver
When is cyclosporin used
Used in immunosuppression for prophylactic treatment of:
- organ transplant
- rheumatoid arthritis
- severe psoriasis
What are the potential side effects of ciclosporin
- Hypertension
- Nephrotoxicity
- Neurotoxicity
- Gingival hypertrophy/hyperplasia
- Lymphoproliferative disorders
- Malignancies
- Teratogenicity
What possible drug interactions are there for ciclosporin
- Antibiotics: Macrolides increases toxicity
- Antifungal: Fluconazole, Miconazole increase toxicity
- Analgesic: avoid use of NSAIDs with ciclosporin because they promote nephrotoxicity
What kind of drug is mycophenolate mofetil
Antibiotic substance
Immunosuppressive agent
Describe the basic mechanism of mycophenolate mofetil
- Blocks de novo biosynthesis of purine nucleotides by inhibiting inosine monophosphate dehydrogenase
- Prevents the proliferation of T cells, lymphocytes and the formation of antibodies from B cells
How is mycophenolate mofetil usually used
Prophylaxis of organ rejection, often used in combination with ciclosporin and prednisolone
What are the potential side effects of mycophenolate mofetil
- Fever
- Chills
- Hyperglycaemia
- Hypertension
- Easy bruising/bleeding
- Skin reactions
- Abdominal pain; nausea and vomiting; dyspepsia; diarrhoea; oesophagitis; gastritis; GI bleed
- Increased risk of infection
- Leukopenia, thrombocytopenia
- Depression
What do biological response modifiers
- Block inflammation and immune responses
- Act directly to neutralise specific target immune components
- Less immunosuppressive compared to conventional therapy that broadly cause immunosuppression
What are biological response modifiers used for in the treatment of
- Rheumatoid arthritis
- Ankylosing spondylitis
- Psoriasis
- Crohn’s disease
- Ulcerative colitis
- Malignancies
- Vesciulo-bullous disease
- Lichen planus
- Behcets disease
How are biological response modifiers administered
Injection or infusion
What are the most commonly used biologics and give examples
TNF-alpha inhibitors
Adalimumab, Infliximab, Etanercept
