MSK - Drugs for Numbness and Weakness

Question 1

Name TWO examples of gabapentinoids

Answer 1

Gabapentin and pregabalin

Question 2

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

Answer 2

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 3

What is the mechanism of action of gabapentin and pregabalin?

Answer 3

They are GABA analogs but act at voltage-gated calcium channels rather than GABA receptors, reducing tonic neural stimulation.

Question 4

What are the primary clinical uses of gabapentin and pregabalin?

Answer 4

Neuropathic pain, chronic pain refractory to other treatments, and as an antiepileptic for partial seizures.

Question 5

What are common side effects of gabapentin and pregabalin?

Answer 5

Somnolence, dizziness, and ataxia; the incidence is higher if not titrated over days to weeks. Renal elimination without metabolites therefore susceptible to drug-drug interactions with drugs altering renal function.

Question 6

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

Answer 6

Selective serotonin-norepinephrine reuptake inhibitors (SNRIs) used for neuropathic pain include duloxetine and venlafaxine

Question 7

What is the mechanism of action of duloxetine?

Answer 7

It is a serotonin and norepinephrine reuptake inhibitor (SNRI), which increases the levels of these neurotransmitters in the synaptic cleft.

Question 8

In what conditions is duloxetine typically used?

Answer 8

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

Question 9

What are severe side effects associated with duloxetine?

Answer 9

Mania, hypomania, bleeding risk, serotonin syndrome, hepatotoxicity, and risk of suicidal ideation (especially in adolescents and children).

Question 10

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

Answer 10

Amitriptyline

Question 11

What is the mechanism of action of amitriptyline?

Answer 11

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

Question 12

What are the common side effects of amitriptyline?

Answer 12

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 13

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

Answer 13

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

Question 14

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

Answer 14

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

Question 15

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

Answer 15

For diabetic neuropathy patients who are refractory to or intolerant of first-line pharmacotherapies. As it is present in many foods, and so is classified as a dietary or nutritional supplement, it is perceived as relatively safe and is still used even though its efficacy remains controversial.

Question 16

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

Answer 16

Adverse Effects:
* Gastrointestinal Disturbances: Nausea, vomiting, and stomach cramps are common.
* Hypoglycaemia: Risk of hypoglycaemia in diabetic patients
* Allergic Reactions: Rare, but may include skin rashes and pruritus.
* Thiamine Deficiency: Long-term use can deplete thiamine levels; supplementation may be necessary, particularly in alcoholics.
* Overdose can cause neurological effects, metabolic acidosis, cardiac effects and hepatotoxicity

Question 17

What is the role of Vitamin B12 in neuropathy?

Answer 17

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

Question 18

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

Answer 18

Mecobalamin: a coenzyme form of Vitamin B12, essential for the normal function of the nervous system and haematopoiesis

Question 19

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

Answer 19

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

Question 20

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

Answer 20

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

Question 21

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

Answer 21

It is used for folate deficiency-related neuropathy and supports DNA synthesis and repair.

Question 22

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

Answer 22

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

Question 23

What is are the adverse effects of Vitamin B9 (Folic acid)

Answer 23

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

Question 24

What are the common side effects of pentoxifylline?

Answer 24

Gastrointestinal discomfort, bleching, bloating, nausea, vomiting, dizziness, flushing

Question 25

Whate are rare but potentially serious side effects of pentoxifylline?

Answer 25

Uncommon and rare side effects include angina, palpitations, bleeding, arrhythmias, anxiety, hallucinations

Question 26

What is the mechanism of action of pentoxifylline in peripheral arterial disease?

Answer 26

It is a nonselective phosphodiesterase inhibitor that improves RBC deformability and reduces blood viscosity thus having a haemorheologic effect (i.e., improving blood flow).

Question 27

What is mucopolysaccharide polysulphate used for in varicose veins?

Answer 27

It is used to treat inflamed and swollen varicose veins due to its antithrombotic and anti-inflammatory properties.

Question 28

What are the mechanisms of action of mucopolysaccharide polysulphate?

Answer 28

Mechanisms of Action:
* Antithrombotic: Inhibits clotting factors by potentiating antithrombin activity
* Anti-inflammatory: Reduces capillary permeability and inflammatory mediators
* Improves Microcirculation: Promotes blood flow and tissue oxygenation
* Fibroblast Modulation: Enhances fibroblast activity and collagen synthesis, supporting wound healing
* Analgesic: Provides mild pain relief by modulating local inflammation.

Question 29

What is the mechanism of action of polidocanol?

Answer 29

It is a non-ionic surfactant that causes localized endothelial damage and induces clot formation leading to sclerosis and obliteration of the vein.

Question 30

What are potential complications of polidocanol when used in sclerotherapy?

Answer 30

Pain, redness, pruritus, hyperpigmentation and/or skin discolouration at the injection site. Thromboembolism, ulceration, or tissue necrosis if extravasation occurs.

Question 31

What is the primary treatment approach for deep vein thrombosis (DVT)?

Answer 31

Use of anticoagulants such as rivaroxaban, apixaban, or low molecular weight heparin followed by warfarin, dabigatran or edoxaban.

Question 32

What are common side effects of anticoagulants used for deep vein thrombosis (DVT)?

Answer 32

Bleeding, bruising, and risk of haemorrhage.