T1 L14: Pharmacological aspects of immunology Flashcards
What are some examples of NSAIDS?
- Aspirin
- Propionic acid derivatives: ibuprofen, naproxen
- Arylalkonic acids: indometacin, diclofenac
- Oxicams: piroxicam
- Fenamic acids: mefanamic acid
- Butazones: phenylbutazon
What is the mechanism behind NSAIDS?
They antagonise cyclo-oxygenase (COX) to prevent the production of prostaglandins
What does COX-1 do?
It’s expressed in all tissues
Its inhibition causes anti-platelet activity
What does COX-2 do?
It’s induced during inflammation (IL-1)
Its inhibition causes analgesia and anti-inflammatory actions
What does COX-3 do?
May be relevant to paracetamol
What is Reye’s syndrome?
Swelling of the brain and liver most often in children caused by viral infection or aspirin
What is fulminant hepatic failure in children?
In children, fulminant hepatic failure is a rare multisystem disorder in which severe impairment of liver function, with or without encephalopathy, occurs in association with hepatocellular necrosis in a patient with no recognized underlying chronic liver disease
(Reye’s syndrome)
What is aspirin used for?
Pain, inflammation, primary and secondary prevention of stroke and MI, treatment for acute MI and stroke
Limited by GI toxicity and tinnitus
What is tinnitus?
Hearing ringing that comes from inside the ear
What are the risk factors for GI bleeding due to NSAIDS?
Previous GI bleeding
Increasing age
Chronic disease Eg. rheumatoid arthritis
Steroids
How do NSAIDS cause nephrotoxicity?
They change glomerular blood flow
-They decrease GFR, cause sodium retention, hyperkalaemia, papillary necrosis
Why do asthmatics experience bronchospasm when using NSAIDS?
The inhibited prostaglandins prevent the production of leukotrienes which cause vasodilation
What is acetaminophen?
Paracetamol
How can paracetamol metabolism lead to liver necrosis?
In high does of paracetamol, the phase 1 reaction happens and produces NAPQI which causes hepatic necrosis
Which drug is used in paracetamol overdose?
N-acetylcysteine (glutathione precursor) which prevents the metabolism of NAPQI
What are coxibs?
COX-2 inhibitors used as anti-inflammatory and analgesic drugs
But the efficacy is not superior to non-selective NSAIDS. Only recommended in high risk patients and those who have had a cardiovascular assessment because the drugs seem to increase risk of MI
What is mechanism of action of steroids?
They reduce immune activation by altering gene expression in certain cells
What is hydrocortisone used for?
It has a low potency but high lipid solubility
Systemic use: replacement therapy
Topical use: skin, joints
What is Prednisolone used for?
It has a medium potency and good lipid solubility
Systemic use: anti-inflammatory
Topical use: enemas
What are enemas?
They’re injected into the GI tract to clear the tract to allow examination or to relieve constipation
What is Beclomethasone used for?
It has medium potency and poor lipid solubility
Topical use: Asthma, Crohn’s
What is Dexamethasone used for?
It has high potency and good lipid solubility
Systemic use: cerebral oedema
What is Triaminiclone used for?
It’s a steroid
It has a high potency and poor lipid solubility
Topical use: skin, joints
What are some early and later side-effects if using steroids?
Early
- Weight gain
- Glucose intolerance
- Mood change (depression, anxiety, psychosis)
- suppression of ACTH release
Later
- Proximal muscle weakness
- Osteoporosis
- Skin changes
- Body shape changes
- Hypertension
- Cataracts
- Adrenal suppression
What does DMARD’s stand for?
Disease-modifying anti-rheumatic drugs
How does Methotrexate work?
A DMARD. It’s a competitive inhibitor of dihydrofolate reductase (DHR), so it has anti-folate action
-folate is needed for purine synthesis in DNA so this reduced T-cell activity and tumour synthesis
Indications: Rheumatoid arthritis, psoriasis, Crohn’s disease
Main toxicities: Hepatotoxicity, leukopenia, pulmonary fibrosis, teratogenic
How does Azathioprine work?
A DMARD. It inhibits thiopurine S methyltransferase (TPMT), so it inhibits purine synthesis
Very similar to methotrexate in terms of indications and side-effects
How does Ciclosporin work?
A DMARD. It inhibits calcineurin, which reduces T-cell activity
Used more in dermatology and transplantation
Main toxicities: nephrotoxic, hepatotoxic, gum hyperplasia, hirsutism
