Muscle pain

Question 1

6 Contraindications for NSAIDs

Answer 1

1. Severe kidney impairment -> renal excretion
2. Severe heart failure
3. Active GIT ulcer / bleeding -> COX inhibition
4. Bleeding disorders
5. Systemic corticosteroids / antiplatelet / anticoagulants being used
6. Third trimester of pregnancy

Question 2

What is the triple whammy?

Answer 2

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

Question 3

When is Paracetamol prescribed?

Answer 3

Mild to moderate pain

Question 4

Benefits of Paracetamol and NSAIDs combination

Answer 4

Alternating NSAIDs and paracetamol -> sustaining antipyretic effect

Take both together -> strong analgesic effect

Question 5

Name of opioid analgesic

Answer 5

Tramadol

Question 6

Additional effect of Tramadol

Answer 6

Weak opioid + Serotonin-norepinephrine reuptake inhibitor

Question 7

When is Tramadol prescribed?

Answer 7

Moderate to severe pain

*in combination with NSAID or paracetamol

Question 8

Adverse effects of Tramadol

Answer 8

Constipation, nausea and vomiting
Risk of dependence - Addiction
Respiratory depression at very high dose
Hormonal effects
Overdose -> death

Question 9

Opioid prescription guidelines

Answer 9

• 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

Question 10

Risk factors for opioid prescription

Answer 10

Pregnancy
Renal or hepatic dysfunction
Combination with other CNS depressants
history of substance abuse
Already on another opioid

Question 11

Types of muscle relaxants and their uses

Answer 11

Orphenadrine - Acute muscle pain

Benzodiazepines and GABA analogues - subacute or chronic muscle pain + neuropathic pain

Used in combination with NSAIDs

Question 12

What is the primary muscle relaxant for acute pain?

Answer 12

Orphenadrine

Question 13

MOA of Orphenadrine

Answer 13

1. Central muscle relaxant with muscarinic receptor antagonism
2. Crosses BBB
3. H1 antihistamine effects
4. Norepinephrine and dopamine reuptake inhibitor
5. Sodium channel blocker

Question 14

Primary implication of Orhpenadrine

Answer 14

Acute muscle pain

Question 15

2 types of Side effects of Orphenadrine

Answer 15

Muscarinic side effects:
- dry mouth
- dilated pupils
- Nausea and vomiting
- Flushing

At high doses: Tachycardia, nystagmus, drowsiness, visual hallucinations and delirium

Question 16

Additional effects of Orphenadrine

Answer 16

Antihistamine
Anticholinergics
Antiparkinson -> inhibits dopamine reuptake

Caution when combining with CNS sedatives

Question 17

Name an example of Benzodiazepine

Answer 17

Diazepam

Question 18

MOA of Diazepam

Answer 18

1. Allosteric modulator of GABA(A) receptors -> increase frequency of opening of chloride channel -> high GABAergic neurotransmission
2. suppresses brain reticular activating system -> sedation and amnesia
3. Increased inhibitory neurotransmission -> anticonvulsant effects

Question 18

GABA(B) receptor activating analogue

Answer 18

Baclofen

Question 18

Clinical application of Diazepam

Answer 18

Anticonvulsant
Antiepileptic
Induction of anasthesia
Muscle relaxant

Question 19

MOA of Baclofen

Answer 19

GABA anologue that selectively activates GABA(B) receptor in CNS -> reduce tonic neural stimulation to muscles

Question 19

3 Adverse effects of Diazapam

Answer 19

Drowsiness -> impaired judgement + reduced motor skills
High potential for abuse
DDI with other CNS depressants

Question 19

Baclofen application

Answer 19

1. Multiple sclerosis
2. Spinal cord lesions
3. Skeletal muscle spasms and/or pain

In combination with NSAIDs

Question 20

Baclofen guideline

Answer 20

Should be used temporarily

Question 20

2 Adverse effects of Baclofen

Answer 20

Sedation and weakness Withdrawal symptoms -> step wise reduction Hyperthermia, pruritus and increased spasticity

Question 20

MOA of Gabapentinoids

Answer 20

GABA analogues that work at voltage gated calcium channels -> reduce tonic neural stimulation

Question 21

Name the Gabapentinoids

Answer 21

Gabapentin and Pregabalin

Question 22

Clinical application of Gabapentinoids

Answer 22

1. Neuropathic pain 2. Chronic pain 3. Antiepileptic

Question 23

2 Adverse effects of Gabapentinoids

Answer 23

Ataxia - poor muscle control Renal clearance -> DDI due to altered renal function

Question 24

Name the adjuncts used

Answer 24

Topiramate, Duloxetine and Amitriptyline

Question 24

Adverse effects of topiramate

Answer 24

Fatigue and Ataxia

Question 25

Clinical application of topiramate

Answer 25

Antiepileptic Chronic or neuropathic pain

Question 25

Clinical application of Duloxetine

Answer 25

1. Clinical depression 2. Chronic or neuropathic pain -> low back and non-radicular neck pain More effective than tricyclic antidepressants for lower back pain

Question 26

MOA of Topiramate

Answer 26

1. Inhibit excitatory neurotransmission Block NA+ channels 2. Induce GABAergic neurotransmission -> reduce tonic neural transmission

Question 26

MOA of Duloxetine

Answer 26

Seretonin (5-HT) and Norepinephrine (NE) reuptake inhibitor (SNRI) antidepressant

Question 27

8 Adverse effects of Duloxetine

Answer 27

1. Mania 2. Bleeding risk 3. Hepatotoxicity 4.Fragility fractures 5. Sexual dysfunction 6. Withdrawal syndrome 7. Dry mouth and abdominal pain 8. Weight loss

Question 28

MOA of Amitriptyline

Answer 28

Tricyclic antidepressant -> inhibits Seretonin and Norepinephrine

Question 29

Clinical application of Amitriptyline

Answer 29

1. Clinical depression 2. Chronic or neuropathic pain

Question 30

2 Adverse effects of Amitriptyline

Answer 30

1. Weight gain 2. anticholinergic: Dry mouth, blurred vision, urinary retention and constipation