Muscle pain Flashcards
6 Contraindications for NSAIDs
- Severe kidney impairment -> renal excretion
- Severe heart failure
- Active GIT ulcer / bleeding -> COX inhibition
- Bleeding disorders
- Systemic corticosteroids / antiplatelet / anticoagulants being used
- Third trimester of pregnancy
What is the triple whammy?
NSAID:
inhibit COX-1/2 at Kidney -> reduce blood flow to kidney
Diuretics:
By removing fluid from body -> reduce overall serum level -> reduce blood flow to kidney
ACE inhibitors:
Prevent efferent arteriole vasoconstriction -> reduce glomerular pressure -> reduced GFR
Individually they reduce kidney function + increase risk of acute kidney injury. Collectively risk is higher
When is Paracetamol prescribed?
Mild to moderate pain
Benefits of Paracetamol and NSAIDs combination
Alternating NSAIDs and paracetamol -> sustaining antipyretic effect
Take both together -> strong analgesic effect
Name of opioid analgesic
Tramadol
Additional effect of Tramadol
Weak opioid + Serotonin-norepinephrine reuptake inhibitor
When is Tramadol prescribed?
Moderate to severe pain
*in combination with NSAID or paracetamol
Adverse effects of Tramadol
Constipation, nausea and vomiting
Risk of dependence - Addiction
Respiratory depression at very high dose
Hormonal effects
Overdose -> death
Opioid prescription guidelines
- Not first line for pain
- Not anti-inflammatory
- Use lowest effective dose for shortest period of time
80% of long term opioid users will develop at least one of these effects
Risk factors for opioid prescription
Pregnancy
Renal or hepatic dysfunction
Combination with other CNS depressants
history of substance abuse
Already on another opioid
Types of muscle relaxants and their uses
Orphenadrine - Acute muscle pain
Benzodiazepines and GABA analogues - subacute or chronic muscle pain + neuropathic pain
Used in combination with NSAIDs
What is the primary muscle relaxant for acute pain?
Orphenadrine
MOA of Orphenadrine
- Central muscle relaxant with muscarinic receptor antagonism
- Crosses BBB
- H1 antihistamine effects
- Norepinephrine and dopamine reuptake inhibitor
- Sodium channel blocker
Primary implication of Orhpenadrine
Acute muscle pain
2 types of Side effects of Orphenadrine
Muscarinic side effects:
- dry mouth
- dilated pupils
- Nausea and vomiting
- Flushing
At high doses: Tachycardia, nystagmus, drowsiness, visual hallucinations and delirium
Additional effects of Orphenadrine
Antihistamine
Anticholinergics
Antiparkinson -> inhibits dopamine reuptake
Caution when combining with CNS sedatives
Name an example of Benzodiazepine
Diazepam
MOA of Diazepam
- Allosteric modulator of GABA(A) receptors -> increase frequency of opening of chloride channel -> high GABAergic neurotransmission
- suppresses brain reticular activating system -> sedation and amnesia
- Increased inhibitory neurotransmission -> anticonvulsant effects
GABA(B) receptor activating analogue
Baclofen
Clinical application of Diazepam
Anticonvulsant
Antiepileptic
Induction of anasthesia
Muscle relaxant
MOA of Baclofen
GABA anologue that selectively activates GABA(B) receptor in CNS -> reduce tonic neural stimulation to muscles
3 Adverse effects of Diazapam
Drowsiness -> impaired judgement + reduced motor skills
High potential for abuse
DDI with other CNS depressants
Baclofen application
- Multiple sclerosis
- Spinal cord lesions
- Skeletal muscle spasms and/or pain
In combination with NSAIDs
Baclofen guideline
Should be used temporarily
2 Adverse effects of Baclofen
Sedation and weakness
Withdrawal symptoms -> step wise reduction
Hyperthermia, pruritus and increased spasticity
MOA of Gabapentinoids
GABA analogues that work at voltage gated calcium channels -> reduce tonic neural stimulation
Name the Gabapentinoids
Gabapentin and Pregabalin
Clinical application of Gabapentinoids
- Neuropathic pain
- Chronic pain
- Antiepileptic
2 Adverse effects of Gabapentinoids
Ataxia - poor muscle control
Renal clearance -> DDI due to altered renal function
Name the adjuncts used
Topiramate, Duloxetine and Amitriptyline
Adverse effects of topiramate
Fatigue and Ataxia
Clinical application of topiramate
Antiepileptic
Chronic or neuropathic pain
Clinical application of Duloxetine
- Clinical depression
- Chronic or neuropathic pain -> low back and non-radicular neck pain
More effective than tricyclic antidepressants for lower back pain
MOA of Topiramate
- Inhibit excitatory neurotransmission
Block NA+ channels - Induce GABAergic neurotransmission -> reduce tonic neural transmission
MOA of Duloxetine
Seretonin (5-HT) and Norepinephrine (NE) reuptake inhibitor (SNRI) antidepressant
8 Adverse effects of Duloxetine
- Mania
- Bleeding risk
- Hepatotoxicity
4.Fragility fractures - Sexual dysfunction
- Withdrawal syndrome
- Dry mouth and abdominal pain
- Weight loss
MOA of Amitriptyline
Tricyclic antidepressant -> inhibits Seretonin and Norepinephrine
Clinical application of Amitriptyline
- Clinical depression
- Chronic or neuropathic pain
2 Adverse effects of Amitriptyline
- Weight gain
- anticholinergic: Dry mouth, blurred vision, urinary retention and constipation
