Drugs for Muscle Pain Flashcards
What are the 3 kinds of drugs used in treating muscle pain?
- analgesics
- muscle relaxants
- adjuncts
Compare and contrast the clinical actions of aspirin and ibuprofen
Both aspirin and ibuprofen are:
(1) Anti-inflammatory
(2) Analgesic
(3) Antipyretic
Aspirin but NOT ibuprofen is an irreversible cyclo-oxygenase (COX) inhibitor and so a potent:
(4) Anti-platelet
What would be the usual analgesic choice for a child with mild to moderate pain?
Paracetamol would usually be the preferred first choice. Ibuprofen may be considered if greater anti-inflammatory action and analgesia is required.
Why does indometacin have a stronger anti-inflammatory profile than other nonselective NSAIDs?
Besides being a non-selective inhibitor of cyclo-oxygenase (COX), indometacin also inhibits phospholipase A2. Thus, indometacin reduces the production of leukotrienes, in addition to prostanoids, and so has a broader spectrum anti-inflammatory effect.
Which form of cyclo-oxygenase is expressed in inflammatory cells at sites of acute inflammation.
Inducible cyclo-oxygenase-2 (COX-2)
Why should etoricoxib be used with caution in a patient with active peptic ulcers?
Etoricoxib will impair wound healing and so pre-existing peptic ulcers are likely to persist.
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What is the MOST common adverse effect of paracetamol at clinical analgesic doses?
Nausea
Which NSAID has the greatest risk of precipitating an asthma attack in a patient with NSAID exacerbated respiratory disease (NERD)?
Aspirin because it is an irreversible inhibitor of cyclo-oxygenase (COX)
Which NSAIDs has the strongest anti-platelet effect?
Aspirin because it is an irreversible inhibitor of cyclo-oxygenase (COX)
What is the normal function of prostaglandins in the stomach?
Protective effects:
(1) Increase bicarbonate secretion
(2) Increase mucus secretion
(3) Increase blood flow to mucosa
(4) Decrease acid secretion
For what severity of pain are NSAIDs useful as analgesics?
NSAIDs are only useful for analgesics for mild to moderate pain. NSAIDs have an analgesic ceiling as they work as analgesics by preventing prostaglandin-mediated sensitisation of nociceptive fibres.
Explain why diclofenac is useful for the management of joint pain and inflammation.
Diclofenac accumulates in synovial fluid enabling a prolonged analgesic and anti-inflammatory at the joints while it has a relatively short plasma half-life and so fewer gastrointestinal adverse effects than other non-selective COX inhibitors.
Why are ALL NSAIDs contraindicated in late pregnancy?
All NSAIDs inhibit cyclo-oxygenase-2 (COX-2) at analgesic and anti-inflammatory doses. Inhibition of COX-2 risks premature closure of the ductus arteriosus. All NSAIDs are therefore contraindicated in the third trimester.
Which form of cyclo-oxygenase (COX) do platelets predominantly express?
Platelets express cyclo-oxygenase-1 (COX-1) which makes thromboxane-2 (TXA-2)
In general, COX-1 is constitutive and COX-2 is inducible but EXCEPTIONS include…
Expression of COX-2 in the kidney, synovial joints, CNS and female reproductive system.
The renal adverse effects of NSAIDs are due to inhibition of…
Both COX-1 and COX-2
Hepatoxicity of paracetamol (acetaminophen) overdose can be treated with…
N-acetyl-cysteine helps to treat paracetamol toxicity by replenishing glutathione, which detoxifies the toxic metabolites of paracetamol to nontoxic metabolites
The coxibs are markedly safer than non-selective NSAIDs for patients…
At risk of stomach ulcers
List at least THREE adverse effects of COX-1 inhibition
Increased risk of nausea and vomiting, gastro-oesophageal reflux, stomach ulcers, bruising/bleeding, renal adverse effects contributing to hypertension and fluid retention. (Note that COX-2 inhibition also contributes to renal adverse effects).
Name an NSAID available in a patch formulation suitable for lower back pain
Ketoprofen or diclofenac
Name TWO NSAIDs available in topical gel or cream formulations
Piroxicam, diclofenac, ketoprofen
State the mechanism of action of NSAIDs.
Inhibit COX1 and COX2 to prevent conversion of arachidonic acid to prostanoids (PGI2, PGE2, TXA2)
PGI2 - vasodilation, inhibit platelet aggregation, anti-coagulant
PGE2 - pain, vascular permeability
TXA2 - vasoconstriction, platelet aggregation, coagulant
State the selective and non-selective NSAIDs.
paiKIA NID CPE
Ketoprofen
Indomethacin
Aspirin
Naproxen
Ibuprofen
Diclofenac (avoid in liver disease)
COX2 only
Celecoxib
Parecoxib
Etoricoxib
State the common adverse effects of non-selective NSAIDS
- renal failure
- dyspepsia (GI)
- asthma
State the common adverse effects of COX selective NSAIDs
- nephrotoxicity
- impaired wound healing
- thrombosis
State the common contraindications for NSAIDs
- renal failure (eGFR <30ml/min)
- severe HF
- GI bleeding or ulcer
- bleeding disorders
- third trimester of pregnancy
- use of systemic corticosteroids/antiplatelet agents/anticoagulants
In the event of a risk of renal toxicity, how should treat patient?
- avoid NSAIDs in renal disease
- look out for acute kidney injury
- avoid concurrent nephrotoxci medications (ACE-I, aminoglycoside antibiotics)
- maintain hydration to avoid hypovolaemia
In the event of a risk of CV toxicity, how should we treat patient?
- avoid diclofenac and COX-2 selective NSAIDs other than celecoxib
- use celecoxib or ibuprofen limited to =< 5 days
- consider paracetamol alone
In the event of a risk of GI toxicity, how should we treat patient?
- avoid non-selective NSAIDs
- use COX-2 selective NSAIDs with caution
- consider co-prescribing GI protectant (PPI)
In the event of a risk of NSAID-related bronchospasm and or pseudoallergic reaction, how should we treat patient?
- avoid non-selective NSAIDs
- use cox-2 selective NSAID with caution
State the 3 drugs included in the triple whammy.
State what occurs in the triple whammy.
- NSAIDs
- ACE-I
- diuretics
triple whammy = significantly increase risk of acute kidney injury by decreasing blood flow to kidneys
State the 3 common presentations of the triple whammy
- fluid retention
- decrease urine output
- increase CK serum levels
State the common risk factors of acute kidney injury
- increasing age, with chronic HTN and atherosclerosis
- pre-existing glomerular diseases or renal insufficiency
- volume depletion
- use of ACE-I or ARB
- use of triple whammy
How does
1. increasing age, with chronic HTN and atherosclerosis
2. pre-existing glomerular diseases or renal insufficiency
3. volume depletion
4. use of ACE-I or ARB
5. use of triple whammy
lead to acute kidney injury>
- narrows renal arterioles which may reduce their capacity for renal afferent dilation
- renal afferent dilation likely required to maintain GFR
- Lowers afferent glomerular arteriolar pressure and stimulates the secretion of angiotensin II
- ACE inhibitors and ARBs prevent efferent arteriole vasoconstriction which is also important in maintenance of GFR
- Diuretic may cause volume depletion.
Paracetamol has ____ and ____ action with low incidence of adverse effects.
It is not _______ at clinical doses.
Paracetamol has ANALGESIC and ANTIPYRETIC action with low incidence of adverse effects.
It is not ANTI-INFLAMMATORY at clinical doses.
State the contraindications of paracetamol.
- hepatic dysfunction
- alcohol abuse
State when dose reduction of paracetamol is necessary
- patient is underweight
- significant liver disease
- cachetic or frail
Overdose of paracetamol leads to ______.
Overdose of paracetamol leads to LIVER DAMAGE.
State the drugs used to produce a stronger for longer analgesic effect. (1 NSAID, 1 non-NSAID)
paracetamol + ibuprofen!
State why alcohol cannot be consumed with paracetamol
Minor pathway enzyme CYP450 2E1 converts paracetamol to toxic metabolites. Alcohol depletes glutathione which converts toxic metabolites to non-toxic metabolites.
State the common opioid analgesic used for muscle pain
tramadol.
State the mechanism of action of tramadol.
Tramadol is (1) a weak opioid analgesic with (2) additional norepinephrine and serotonin (5-HT) re-uptake inhibition
Is tramadol a first-line drug for pain
NO as not anti-inflammatory
State the clinical use of tramadol.
Moderate to severe pain in combination with paracetamol or NSAID
State the adverse effects of tramadol
- respiratory depression at high doses
2, risk of dependence - GI
- depression and hormonal effects
- overdose and death
- falls and fractures
- sedation and drowsiness
- opioid-induced hyperalgesia
If opioid analgesics are deemed appropriate, use _____ effective dose of _____ effective opioid for _______ period of time.
If opioid analgesics are deemed appropriate, use LOWEST effective dose of WEAKEST effective opioid for SHORTEST period of time.
State some risk factors of opioid analgesics
- dosage in combination with other CNS depressants
- renal or hepatic insufficiency in elderly
- pregnancy
- personal or family history of substance use disorder
- already prescribed opioids
State the 3 types of muscle relaxants
- central muscle relaxant - orphenadrine
- benzodiazepines - diazepam
- GABA derivatives - baclofen
State which muscle relaxant should be used for
- acute muscle pain
- subacute/chronic muscle pain
Acute - central muscle relaxant (orphenadrine)
Subacute/chronic - benzodiazepines (diazapem), GABA derivatives (baclofen)
Briefly describe the mechanism(s) of action of orphenadrine
Orphenadrine is a central muscle relaxant blocking muscarinic receptors in the basal ganglia in the brain. Additionally, it has H1 antihistamine, NMDA receptor antagonism, norepinephrine and dopamine re-uptake inhibitor and sodium channel blocker actions that may contribute to adjunct analgesic and muscle relaxant actions.
List THREE common adverse effects of orphenadrine
Nausea and vomiting, flushing, dilated pupils, dry mouth
List THREE adverse effects of orphenadrine seen only at higher doses
Tachycardia, ataxia, nystagmus, drowsiness, delirium, agitation, visual hallucinations
Name an analgesic available in a combined formulation with orphenadrine
Paracetamol, mefenaminc acid. Note that paracetamol alone is usually insufficient for acute lower back pain but in combination with orphenadrine may be effective.
Name a muscle relaxant used for acute (< 4 weeks) pain
Orphenadrine
Briefly describe the mechanism(s) of action of diazepam
Allosteric modulator of GABA-A receptors increasing the frequency of opening of chloride channels and hence the potency of endogenous GABAergic neurotransmission
Suppresses brain reticular activating system: sedation, amnesia, loss of consciousness
Increased inhibitory neurotransmission also has anticonvulsant and muscle relaxant effect
List THREE significant adverse effects of benzodiazepines
Drowsiness, impaired judgement, reduced motor skills, tolerance and high potential for dependence.
Briefly describe the mechanism(s) of action of baclofen
GABA analogue that selectively activates GABA-B receptors in CNS
? Reduces tonic neural stimulation to muscles
What is the risk associated with discontinuation of baclofen?
Abrupt cessation causes withdrawal syndrome:
- Potentially life-threatening withdrawal syndrome.
- Common effects are hyperthermia, pruritus, and increased spasticity.
Name TWO adverse effects of baclofen
Sedation, weakness, and other CNS effects. Additionally, abrupt cessation causes a potentially life-threatening withdrawal syndrome.
Name a gabapentinoid
Gabapentin, pregabalin
Briefly describe the mechanism(s) of action of gabapentionoids
GABA analogues but act at voltage-gated calcium channels rather than GABA receptors.
? Reduces tonic neural stimulation to muscles.
List TWO side effects of gabapentinoids
Somnolence, dizziness, ataxia (greater incidence if not titrated over days to weeks)
Which antidepressant commonly used as an adjunct for chronic pain has LEAST risk of adverse effects?
While all antidepressants have a risk of adverse effects, duloxetine is a more selective serotonin (5-HT) and norepinephrine (NE) reuptake inhibitor (SNRI) than the tricyclic antidepressants (e.g., amitriptyline), which have antihistamine, anticholinergic and alpha-1 antiadrenergic adverse effects.
Which antidepressant commonly prescribed as an adjunct for chronic pain is MORE EFFECTIVE for lower back pain?
Duloxetine is usually more effective than tricyclic antidepressants (e.g., amitriptyline) for chronic lower back pain.
List THREE major mechanisms of adverse effects of amitriptyline and at least ONE example of an adverse effect caused by each mechanism
Antihistamine: Sedation, weight gain
Anticholinergic: Blurred vision, dry mouth, urinary retention, constipation, agitation, tachycardia, heating (due to block of sweating)
Alpha-1 adrenoceptor blockade: Postural hypotension, tachycardia
Briefly describe the mechanisms of action of topiramate
Inhibits excitatory neurotransmission:
- Blockade of AMPA subtype glutamate receptors
- Blockade of voltage-sensitive Na+ channels
May also potentiate inhibitory GABAergic neurotransmission
Together the above mechansims ? reduced tonic neural stimulation to muscles
List THREE adverse effects of topiramate
Dizziness, fatigue, ataxia, confusion (although note that the adverse effects are usually mild)
