MSK - Drugs for Numbness and Weakness Flashcards
Name TWO 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 mechanism of action of gabapentin and pregabalin?
They are GABA analogs but act at voltage-gated calcium channels rather than GABA receptors, reducing tonic neural stimulation.
What are the primary clinical uses of gabapentin and pregabalin?
Neuropathic pain, chronic pain refractory to other treatments, and as an antiepileptic for partial seizures.
What are common side effects of gabapentin and pregabalin?
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.
What is SNRI an abbreviation of? Name TWO examples of SNRI antidepressants used for neuropathic pain
Selective serotonin-norepinephrine reuptake inhibitors (SNRIs) used for neuropathic pain include duloxetine and venlafaxine
What is the mechanism of action of duloxetine?
It is a 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 severe side effects associated with duloxetine?
Mania, hypomania, bleeding risk, serotonin syndrome, hepatotoxicity, and risk of suicidal ideation (especially in adolescents and children).
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
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?
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.
What are the adverse effects of alpha-lipoic acid (ALA)?
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
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: a coenzyme form of Vitamin B12, essential for the normal function of the nervous system and haematopoiesis
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.
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?
It is used for folate deficiency-related neuropathy and 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 is 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.
What are the common side effects of pentoxifylline?
Gastrointestinal discomfort, bleching, bloating, nausea, vomiting, dizziness, flushing
Whate are rare but potentially serious side effects of pentoxifylline?
Uncommon and rare side effects include angina, palpitations, bleeding, arrhythmias, anxiety, hallucinations
What is the mechanism of action of pentoxifylline in peripheral arterial disease?
It is a nonselective phosphodiesterase inhibitor that improves RBC deformability and reduces blood viscosity thus having a haemorheologic effect (i.e., improving blood flow).
What is mucopolysaccharide polysulphate used for in varicose veins?
It is used to treat inflamed and swollen varicose veins due to its antithrombotic and anti-inflammatory properties.
What are the mechanisms of action of mucopolysaccharide polysulphate?
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.
What is the mechanism of action of polidocanol?
It is a non-ionic surfactant that causes localized endothelial damage and induces clot formation leading to sclerosis and obliteration of the vein.
What are potential complications of polidocanol when used in sclerotherapy?
Pain, redness, pruritus, hyperpigmentation and/or skin discolouration at the injection site. Thromboembolism, ulceration, or tissue necrosis if extravasation occurs.
What is the primary treatment approach for deep vein thrombosis (DVT)?
Use of anticoagulants such as rivaroxaban, apixaban, or low molecular weight heparin followed by warfarin, dabigatran or edoxaban.
What are common side effects of anticoagulants used for deep vein thrombosis (DVT)?
Bleeding, bruising, and risk of haemorrhage.
