Anti-inflammatories (year 2) Flashcards
name the drugs that can be used as anti-inflammtories
NSAIDs glucocorticoids anticytokines immunosuppressants antihistamine
what is the mode of action of NSAIDs?
inhibit COX enzyme
what does the COX enzyme do?
forms prostanoids from arachidonic acid
what does the prostanoid group contain?
prostaglandins and thromboxanes
what three effects do NSAIDs have?
anti-inflammatory
analgesic
antipyretic
what prostaglandin do NSAIDs reduce that reduces inflammation?
prostaglandin E2 and prostacyclin
what does a decrease in prostaglandin E2 and prostacyclin causes?
reduced vasodilation and oedema
how does a decrease in prostaglandins result in analgesia?
decrease in sensitisation of nociceptive nerve endings to inflammatory mediators
why do NSAIDs have a lot of adverse effects?
prostaglandins are important in normal homeostatic function
what are some of the normal functions prostaglandins?
gastric protection - mucus production and proton pump inhibitor
platelet aggregation
renal blood flow autoregulation
which of the COX enzymes is a constitutive enzyme and which is an induced enzyme?
constitutive - 1
induced - 2
what is a constitutive enzyme?
one found in most tissues with a role in homeostasis
which COX is mainly responsible for the mediators of inflammation?
COX-2
inhibition of which COX enzyme are most of the side effects of NSAIDs due to?
1
describe the absorption of NSAIDs
weak acids that are readily absorbed from the GI tract
how are NSAIDs transported in blood?
bound to albumin
why is the fact NSAIDs are distributed bound to albumin important?
changes in protein alters the transport and efficacy of the drug
if given with another drug that is bound to albumin then they compete
how are NSAIDs eliminated from the body?
hepatic phase I and II metabolism
excreted in urine/faeces
what species should NSAIDs be given sparingly and why?
cats - insufficient cytochrome P450 and glucoronidation conjugation
what species should you not give paracetamol?
cats
when might NSAIDs be used?
infectious disease
pain
osteoarthritis
what is the main side effects of reduced prostaglandins?
GI ulceration and erosion leading to gastric bleeding
other than GI ulceration what are other side effects of NSAIDs?
vomiting, diarrhoea, renal toxicity, hepatotoxicity, CNS depression, circulatory disturbance
when should NSAIDs not be used?
with other NSAIDs or glucocorticoids
pregnancy
with renal, liver or cardiac impairment
what are some examples of NSAIDs?
phenylbutazone, meloxicam, firocoxib, paracetamol, aspirin,
what are the advantages of phenylbutazone?
long duration of action (intense protein binding)
cheap
what animals is phenylbutazone not licensed in?
food producing animals
what is the therapeutic use of meloxicam?
acute/chronic pain and inflammation
which COX enzyme does meloxicam preferentially bind to?
2 - meaning less side effects
where does paracetamol act in the body?
specific effect in CNS so has poor local inflammatory action - don’t get peripheral adverse effects
what animals is paracetamol licensed in?
pigs and dogs
where is paracetamol metabolised?
liver - highly toxic to cats
which COX enzyme does aspirin inhibit?
1 - significant side effects
aspirin inhibits platelet aggregation, what does this mean it can be used as?
an anti clotting agent
what effects do glucocorticoids have on neutrophils?
reduce extravasation and activation
what effects do glucocorticoids have on fibroblasts?
reduce the function so reduce collagen production and hence reduce wound healing
what chemical mediators do glucocorticoids reduce the production of?
prostanoids, cytokines, IgG, complement components, nitric oxide
what chemical mediators do glucocorticoids increase the synthesis of?
anti-inflammatory mediators such as IL1
what do large doses of glucocorticoids for extended periods of time cause?
iatrogenic cushings
what are the adverse effects of glucocorticoids?
GI ulceration, decrease wound healing, myopathy, osteoporosis, oedema, thrombosis, abortion, diabetes, laminitis
what are cytokines?
soluble protein or polypeptides released from a cell
cytokines are important in the control of what system?
immune
what are the 4 main classes of cytokines?
chemokine
interferons
interleukins
colony stimulating factors
what is colchicine?
an anti fibrotic drug
what is colchicine used for?
treat liver fibrosis
