Drugs for Numbness and Weakness 1 (Peripheral Neuropathy)

Question 1

Name the 2 types of numbness and weakness we treat

Answer 1

1. peripheral neuropathy
2. vascular pathologies

Question 2

State the 2 types of peripheral neuropathy

Answer 2

1. neuropathic pain
2. vitamin deficiency associated neuropathy

Question 3

State the drug classes used to treat neuropathic pain

Answer 3

1. gabapentinoids
2. anti-depressants (SSNRI, tricyclic antidepressants, nutritional support)

Question 4

State the drug classes of anti-depressants used in neuropathic pain

Answer 4

1. selective serotonin and norepinephrine reuptake inhibitors
2. tricyclic antidepressants
3. nutritional support

Question 5

Name 2 examples of gabapentinoids

Answer 5

Gabapentin and pregabalin

Question 6

What are the key mechanism(s) of action, clinical uses, and side effects of the gabapentinoids?

Answer 6

Mechanism: GABA analogues but act at voltage-gated calcium channels, reducing tonic neural stimulation.

Clinical Uses: Neuropathic pain, chronic pain, antiepileptic for partial seizures.

Side Effects: Somnolence, dizziness, ataxia; renal elimination without metabolites therefore susceptible to drug-drug interactions with drugs altering renal function.

Question 7

What is the MOA of Gabapentinoids?

Answer 7

GABA analogues that act at voltage-gated calcium channels instead of GABA-receptors to decrease tonic neural stimulation

Question 8

What are the primary clinical uses of gabapentin and pregabalin?

Answer 8

• Neuropathic pain
• Chronic pain refractory to other treatments
• Antiepileptic for partial seizures.

Question 9

What are common side effects of gabapentin and pregabalin?

When should gabapentinoids be used with caution?

Answer 9

Somnolence, dizziness, and ataxia; the incidence is higher if not titrated over days to weeks.

Use in caution for patients with renal dysfunction. Renal elimination without metabolites therefore susceptible to drug-drug interactions with drugs altering renal function.

Question 10

What is SSNRI an abbreviation of? Name TWO examples of SNRI antidepressants used for neuropathic pain

Answer 10

Selective serotonin-norepinephrine reuptake inhibitors (SSNRIs)

duloxetine and venlafaxine

Question 11

What is the mechanism of action of SSNRI?

Answer 11

Serotonin and norepinephrine reuptake inhibitor (SNRI), which increases the levels of these neurotransmitters in the synaptic cleft.

Question 12

In what conditions is duloxetine typically used?

Answer 12

Clinical depression and chronic or neuropathic pain, usually as an adjunct to NSAIDs or paracetamol.

Question 13

What are common side effect associated with duloxetine?

Answer 13

• xerostomia
• drowsiness
• abdominal pain
• fatigue
• weight loss
• headaches

Question 14

What are severe side effects associated with duloxetine?

Answer 14

• Mania
• Hypomania
• Hyponatremia
• Bleeding risk
• Fragility fracture
• Serotonin syndrome
• Hepatotoxicity
• Risk of suicidal ideation (especially in adolescents and children).
• Occular effects
• Withdrawal symptoms

Question 15

Is duloxetine or amitriptyline more effective in treating neuropathic pain?

Answer 15

duloxetine!

Question 16

Name an example of a tricyclic antidepressant used to treat neuropathic pain

Answer 16

Amitriptyline

Question 17

What is the mechanism of action of amitriptyline?

Answer 17

It is a tricyclic antidepressant that inhibits the reuptake of norepinephrine and serotonin.

Question 18

What are the common side effects of amitriptyline?

Answer 18

Side effects:
* Antihistamine = Sedation, weight gain
* Anticholinergic = Blurred vision, dry mouth, urinary retention, constipation, agitation, tachycardia, seating
* Alpha-1 adrenoceptor blockade = Postural hypotension, tachycardia

Question 19

State the form of nutritional support administered to treat neuropathic pain

Answer 19

Alpha-lipoic acid (ALA)

Question 20

State the MOA of ALA.

Answer 20

• Antioxidant –> neutralises free radicals and serves as a cofactor for various enzymes
• Enhances glucose uptake in cells –> effective in diabetic neuropathy

Question 21

Why might alpha-lipoic acid (ALA) be used in patients with diabetic neuropathy?

Answer 21

It is an antioxidant that neutralizes free radicals and enhances glucose uptake in cells, making it beneficial for diabetic neuropathy.

Question 22

What is a potential adverse effect of long-term use of alpha-lipoic acid?

Answer 22

It can deplete thiamine levels, requiring supplementation, particularly in alcoholics.

Question 23

For what patients would alpha-lipoic acid (ALA) be used?

Answer 23

• Diabetic neuropathy patients who are refractory to or intolerant of first-line pharmacotherapies
• A dietary or nutritional supplement, it is perceived as relatively safe and is still used even though its efficacy remains controversial.

Question 24

What are the adverse effects of alpha-lipoid acid (ALA)

Answer 24

Adverse Effects:
- GI: Nausea, vomiting, and stomach cramps are common.
- Hypoglycaemia (esp diabetics)
- Allergic Reaction (Rare) = skin rashes and pruritus.
- Thiamine Deficiency
- Overdose = neurological effects, metabolic acidosis, cardiac effects and hepatotoxicity

Question 25

What are the 2 vitamins supplemented in vitamin-deficiency associated neuropathy. State the drug names for each vitamin.

Answer 25

1. vitamin B12 (mecobalamin) 2. vitamin B9 (folic acid)

Question 26

State the MOA of mecobalamin

Answer 26

- coenzyme form of vitamin B12 which is essential for normal function of nervous system and hematopoiesis - facilitates synthesis of methionin from homocysteine which is crucial for formation of myelin sheaths

Question 27

What is the role of Vitamin B12 in neuropathy

Answer 27

It is essential for the normal function of the nervous system and haematopoiesis, facilitating the synthesis of myelin sheaths.

Question 28

What form of Vitamin B12 is preferred for the treatment of vitamin deficiency-associated neuropathy?

Answer 28

Mecobalamin

Question 29

How is Vitamin B12 eliminated? What is the therapeutic implication of the elimination of vitamin B12?

Answer 29

Excess is excreted through the urine thus overdose is not a concern.

Question 30

How is mecobalamin administered

Answer 30

oral, iv, im

Question 31

What are the adverse effects of Vitamin B12? Are they common or rare?

Answer 31

Generally well tolerated. Adverse effects are rare but can include hypersensitivity reactions, headache, and nausea.

Question 32

What is the clinical use of Vitamin B9 (Folic acid) in neuropathy?

Answer 32

- Folate deficiency-related neuropathy - Supports DNA synthesis and repair.

Question 33

What is a unique caution when using high doses of folic acid?

Answer 33

High doses can mask Vitamin B12 deficiency, complicating diagnosis and treatment.

Question 34

What are the adverse effects of Vitamin B9 (folic acid)?

Answer 34

Adverse Effects: - High doses may mask Vitamin B12 deficiency. - Nausea, bloating, or sleep disturbances. - Rare hypersensitivity reactions: Rash or anaphylaxis.