Pharmacology of inflammation Flashcards
What drugs are included in the pharmacology of inflammation?
Aspirin and other NSAIDs
Steroids
Anti-inflammatory histamine antagonists (H1 blockers)
What do NSAIDs do?
act by irreversibly inhibiting COX enzymes (COX-1 and COX-2), leading to reduced prostanoid
synthesis, which has a number of anti-inflammatory effects:
1. Reduced vasodilation in response to prostaglandins PGE 2 and PGI 2 (prostacyclin) – as a result, there
is less oedema and swelling (probably main effect in headache)
2. Reduced sensitisation of nociceptive nerve endings to 5-HT and bradykinin
3. Reduced fever
What is aspirin?
A non-specific COX inhibitor
Adverse effects of aspirin
Major side effects of NSAIDs is gastric-bleeding due to a dual assault on the GI tract:
- Direct irritation of gastric mucosa by acidic molecules
- Loss of the protective effect of prostaglandins in the stomach due to COX-1 inhibition, resulting in
increased gastric acid secretion, reduced gastric blood flow and reduced mucus secretion
Is paracetamol an NSAID?
Its an analgesic but not an anti-inflammatory
Inhibits a specific COX and has analgesic and antipyretic effects on
What is the effect of steroids?
anti-inflammatory effect, primarily through inhibition of
transcription of the gene for IL-2 required for cloning of Th2 cells crucial to the inflammatory response
- In addition, they inhibit transcription of other inflammatory cytokines, including TNFa, IL-1, and IFN-gamma, as well as the expression of inducible inflammatory enzymes, such as phospholipase A2 (and
consequently leukotrienes, prostaglandins and platelet-activating factor, PAF), COX-2 , and inducible
nitric oxide synthase (iNOS)
Example of steroid
Dexamethasone
What are steroids used in?
Allergic conditons, including asthma
Adverse effects of steroids
- Immune depression, increasing susceptibility to viral infection
- Hypertension via effects on fluid and electrolyte balance
- Bone resorption, diabetes, peptic ulcers, effects on the skin
What is ca2+-mediated histamine release from mast cells partly responsible for?
The first two elements of the so-called ‘triple response’ to a mild insult to the skin:
- the reddening due to arteriolar vasodilation
- the wheal due to increased permeability of venules
- (the ‘flare’ in surrounding tissue is due to release of vasodilators such as CGRP from nerve ending of sensory nerves in the vicinity of the insult)
Example of antihistamine
Chlorpheniramine
Downsides of antihistamines
non-specific effects, through inhibition of muscarinic, 5-HT, and -
adrenoreceptors – these effect contribute to drowsiness (but may be prescribed for motion sickness of
sedation)
What does treatment for RA typically involve?
Generally involves multiple anti-inflammatory and immunosuppressive drug therapy, combined with
analgesia to help with pain associated:
Aspirin and other NSAIDs – reduce both pain and stiffness; but no effect on long-term disease
Corticosteroids can be used – can be used short-term for flare-ups, while waiting for slow-onset
drugs to take effect; can be directly injected into joint (but long-term = osteoporosis)
What are DMARDS?
Disease modifying anti-rheumatic drugs - the primary treatment of RA
What do DMARDs do?
Depress the immune system over time (full effect takes over several months)
