Pain / MSK Drugs Flashcards
NSAIDs examples
Naproxen, Ibuprofen, Diclofenac, Etoricoxib, Diclofenac
NSAIDs indications
- PRN treatment of mild - moderate pain
2. Regular treatment of pain related to inflammation, particularly MSK
NSAIDs MOA
Inhibits COX-enzymes
- COX-1: Stimulates prostaglandin synthesis essential to preserve gastric mucosa, maintain renal perfusion and inhibit thrombus formation at vascular endothelium. COX-1 inhibition produces adverse effects.
- COX-2: expressed in response to inflammatory stimuli, producing prostaglandins that cause inflammation and pain. COX-2 inhibition produces therapeutic benefit.
NSAIDs administration
Oral
Topical
Suppositories
Injectable
NSAIDs contraindications
Absolute Contraindications:
- sever renal impairment
- heart failure
- liver failure
Caution in:
- peptic ulcer disease
- GI bleed
- CV disease
- renal impairment
- asthma
NSAIDs side effects
- GI toxicity
- Renal impairment
- Cardiovascular events: MI and stroke
- Hypersensitivity reactions: bronchospasm and angioedma
- Fluid retention
NSAIDs interactions
- GI ulceration: aspirin, corticosteroids
- GI bleed: anti-coagulants, SSRIs, venflaxine
- Renal impairment: ACEi, diuretics
- Bleeding: Warfarin
- Reduce therapeutic effects of anti-hypertensives and diuretics
NSAIDs patient info
Take with food to minimise GI upset
Strong opioids examples
Morphine, oxycodone
Strong opioids indications
- Rapid relief of acute severe pain inc. post-op and MI pain
- Relief of chronic pain, when paracetamol / NSAIDs / weak opiates are insufficient
- Relief of breathlessness in end-of-life care
- Relief of breathlessness and anxiety in acute pulmonary oedema
Strong opioids MOA
- opioids = naturally occurring opiates + synthetic analogues
- activate opioid mu-receptors in CNS
- activation reduces neuronal excitability and pain transmission
- in medulla, blunt the respiratory response to hypoxia / hypercapnoea - reduces respiratory drive and breathlessness
- reduce sympathetic nervous system activity
Strong opioids administration
Acute: IV
Chronic: oral
Strong opioids contraindiations
- caution in hepatic / renal impairment / elderly as eliminated by liver and kidneys
- avoid in biliary colic as can cause spasm of the sphincter of oddi
Strong opioids side effects
- Respiratory depression by reducing respiratory drive
- Euphoria and detachment, neurological depression in high doses
- Nausea and vomiting as can activate chemoreceptor trigger zone
- Pupillary constriction due to activation on Edinger-Westphal nucleus
- Activation of mu-receptors in large intestine increases smooth muscle tone + decreases motility = constipation
- Histamine in skin = itching, urticarial vasodilation and sweating
- Tolerance in continued use
Strong opioids interactions
Interact with other sedating drugs e.g. antipsychotics, benzodiazepines, tricyclic antidepressants
Strong opioids patient information
- Advise may feel drowsy
- Good hydration to avoid constipation
Weak opioids examples
Tramadol, codeine, dihydrocodeine
Weak opioids indications
PRN for mild / moderate pain when simple analgesics are insufficient
Weak opioids MOA
- Metabolised in liver to form small amounts of morphine / dihydromorphine
- Metabolites are mu-receptor agonists
Weak opioids administration
Oral
IM during operations
Weak opioids contraindications
- Caution in renal / hepatic impairment / elderly as eliminated by liver and kidneys
- Tramadol lowers seizure threshold - avoid in epilepsy and contraindicated if severe epilepsy
Weak opioids side effects
- Nausea
- Constipation
- Dizziness and drowsiness
- Can cause neurological and respiratory depression when taken in overdose
- Codeine / dihydrocodeine must never be given IV as can cause anaphylactic - type reactions
Weak opioids interactions
- Other sedating drugs: antipsychotics, benzodiazepines, tricyclics
- Tramadol should not be used with other drugs that lower the seizure threshold e.g. SSRuIs, tricyclics
Weak opioids patient info
- Most effective if taken at regular intervals
- Advise may feel drowsy
Paracetamol indications
- First-line analgesic for acute and chronic pain
2. Anti-pyretic to reduce fever and associated symptoms
Paracetamol MOA
Weak inhibitor of COX:
- increases pain threshold
- reduces prostaglandin concentrations in thermoregulatory region of hypothalamus, controlling fever
- specific to COX-2 however weak anti-inflammatory as actions are inhibited by presence of peroxides
Paracetamol administration
Oral
IV or rectal if NBM
Paracetamol contraindications
Dose reduction in people at increased risk of liver toxicity:
- Increased NAPQI production e.g. chronic alcohol use
- Reduced glutathione stores e.g. malnutrition, low body weight, severe hepatic impairment
Paracetamol side effects
- None at treatment doses
- At overdose: liver failure. Metabolised by p450 enzymes to toxic metabolite NAPQI, which is conjugated with glutathione before elimination. After overdose, this pathway is saturated, and NAPQI accumulation causes hepatocellular necrosis.
- OD treatment: glutathione precursor, acetlycysteine
Paracetamol interactions
-Cytochrome P450 inducers increase rate of NAPQI production and risk liver toxicity after overdose
Xanthine Oxidase Inhibitors example
Allopurinol
Xanthine Oxidase Inhibitors indications
- Acute gout attacks
- Prevent uric acid and calcium oxalate renal stones
- Prevent hyperuricaemia and tumour lysis syndrome associated with chemotherapy
Xanthine Oxidase Inhibitors MOA
- Xanthine oxidase metabolises xanthine (produced from purine) into uric acid
- Inhibition lowers plasma uric acid concentrations and reduces precipitation of uric acid in joints and kidneys
Xanthine Oxidase Inhibitors administartion
oral
Xanthine Oxidase Inhibitors contraindications
- During acute gout attack as causes sudden fluctuations in uric acid levels
- If hypersensitivity / severe recurrent skin rash occurs
- Metabolised in liver / kidney, dose reduction needed in impairment
Xanthine Oxidase Inhibitors side effects
- Most common is skin rash - an also indicate serious hypersensitivity e.g. Stevens Johnson syndrome or toxic epidermal necrolysis
- Drug hypersensitivity syndrome: life-threatening reaction to allopurinol which includes fever, eosinophilia, lymphadenopathy and multi-organ involvement
- Starting allopurinol can trigger / worsen acute gout attack
Xanthine Oxidase Inhibitors interactions
- Mercaptopurine and azathioprine (mercaptopurine pro-drug): require xanthine oxidase for metabolism, may lead to toxicity
- Amoxicillin: increased risk of skin rash
- ACEi / thiazides: increased risk of hypersensitivity
Xanthine Oxidase Inhibitors patient info
Take after meals
Good hydration: 2-3 litres water per day
