Drugs for Numbness and Weakness 1 (Peripheral Neuropathy) Flashcards
Name the 2 types of numbness and weakness we treat
- peripheral neuropathy
- vascular pathologies
State the 2 types of peripheral neuropathy
- neuropathic pain
- vitamin deficiency associated neuropathy
State the drug classes used to treat neuropathic pain
- gabapentinoids
- anti-depressants (SSNRI, tricyclic antidepressants, nutritional support)
State the drug classes of anti-depressants used in neuropathic pain
- selective serotonin and norepinephrine reuptake inhibitors
- tricyclic antidepressants
- nutritional support
Name 2 examples of gabapentinoids
Gabapentin and pregabalin
What are the key mechanism(s) of action, clinical uses, and side effects of the gabapentinoids?
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.
What is the MOA of Gabapentinoids?
GABA analogues that act at voltage-gated calcium channels instead of GABA-receptors to decrease tonic neural stimulation
What are the primary clinical uses of gabapentin and pregabalin?
- Neuropathic pain
- Chronic pain refractory to other treatments
- Antiepileptic for partial seizures.
What are common side effects of gabapentin and pregabalin?
When should gabapentinoids be used with caution?
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.
What is SSNRI an abbreviation of? Name TWO examples of SNRI antidepressants used for neuropathic pain
Selective serotonin-norepinephrine reuptake inhibitors (SSNRIs)
duloxetine and venlafaxine
What is the mechanism of action of SSNRI?
Serotonin and norepinephrine reuptake inhibitor (SNRI), which increases the levels of these neurotransmitters in the synaptic cleft.
In what conditions is duloxetine typically used?
Clinical depression and chronic or neuropathic pain, usually as an adjunct to NSAIDs or paracetamol.
What are common side effect associated with duloxetine?
- xerostomia
- drowsiness
- abdominal pain
- fatigue
- weight loss
- headaches
What are severe side effects associated with duloxetine?
- Mania
- Hypomania
- Hyponatremia
- Bleeding risk
- Fragility fracture
- Serotonin syndrome
- Hepatotoxicity
- Risk of suicidal ideation (especially in adolescents and children).
- Occular effects
- Withdrawal symptoms
Is duloxetine or amitriptyline more effective in treating neuropathic pain?
duloxetine!
Name an example of a tricyclic antidepressant used to treat neuropathic pain
Amitriptyline
What is the mechanism of action of amitriptyline?
It is a tricyclic antidepressant that inhibits the reuptake of norepinephrine and serotonin.
What are the common side effects of amitriptyline?
Side effects:
* Antihistamine = Sedation, weight gain
* Anticholinergic = Blurred vision, dry mouth, urinary retention, constipation, agitation, tachycardia, seating
* Alpha-1 adrenoceptor blockade = Postural hypotension, tachycardia
State the form of nutritional support administered to treat neuropathic pain
Alpha-lipoic acid (ALA)
State the MOA of ALA.
- Antioxidant –> neutralises free radicals and serves as a cofactor for various enzymes
- Enhances glucose uptake in cells –> effective in diabetic neuropathy
Why might alpha-lipoic acid (ALA) be used in patients with diabetic neuropathy?
It is an antioxidant that neutralizes free radicals and enhances glucose uptake in cells, making it beneficial for diabetic neuropathy.
What is a potential adverse effect of long-term use of alpha-lipoic acid?
It can deplete thiamine levels, requiring supplementation, particularly in alcoholics.
For what patients would alpha-lipoic acid (ALA) be used?
- 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.
What are the adverse effects of alpha-lipoid acid (ALA)
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
What are the 2 vitamins supplemented in vitamin-deficiency associated neuropathy.
State the drug names for each vitamin.
- vitamin B12 (mecobalamin)
- vitamin B9 (folic acid)
State the MOA of mecobalamin
- 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
What is the role of Vitamin B12 in neuropathy
It is essential for the normal function of the nervous system and haematopoiesis, facilitating the synthesis of myelin sheaths.
What form of Vitamin B12 is preferred for the treatment of vitamin deficiency-associated neuropathy?
Mecobalamin
How is Vitamin B12 eliminated? What is the therapeutic implication of the elimination of vitamin B12?
Excess is excreted through the urine thus overdose is not a concern.
How is mecobalamin administered
oral, iv, im
What are the adverse effects of Vitamin B12? Are they common or rare?
Generally well tolerated. Adverse effects are rare but can include hypersensitivity reactions, headache, and nausea.
What is the clinical use of Vitamin B9 (Folic acid) in neuropathy?
- Folate deficiency-related neuropathy
- Supports DNA synthesis and repair.
What is a unique caution when using high doses of folic acid?
High doses can mask Vitamin B12 deficiency, complicating diagnosis and treatment.
What are the adverse effects of Vitamin B9 (folic acid)?
Adverse Effects:
- High doses may mask Vitamin B12 deficiency.
- Nausea, bloating, or sleep disturbances.
- Rare hypersensitivity reactions: Rash or anaphylaxis.
