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MSK > Drugs for Numbness / Weakness > Flashcards

Drugs for Numbness / Weakness Flashcards

This deck tests your knowledge of drugs for numbness / weakness.

1
Q

What are gabapentinoids?

A

GABA analogues, which act on VGCCs in the CNS neurons

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2
Q

What are the two gabapentinoids?

A
  1. Gabapentin
  2. Pregabalin
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3
Q

What are gabapentinoids used for?

A
  • For neuropathic pain (peripheral neuropathy)
  • Decreases tonic stimulation of CNS neurons
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4
Q

How do gabapentinoids work?

A
  1. By binding to VGCCs, gabapentinoids decrease influx of calcium into the neurons
  2. This suppresses excitatory NT release in the CNS, and prevents abnormal pain signals from being transmitted
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5
Q

How are gabapentinoids cleared?

A

Renally excreted unchanged

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6
Q

What are the adverse effects of gabapentinoids?

A
  • Drowsiness, sedation, dizziness, ataxia
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7
Q

What is the main DDI for gabapentinoids?

A
  • No mixing with drugs that affect renal function
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8
Q

What are the two antidepressant classes?

A
  1. SNRIs
  2. Tricyclic antidepressants
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9
Q

What are SNRIs?

A
  • Serotonin and NE reuptake inhibitors, which increase the availability of S/N in the CNS
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10
Q

What are the two SNRIs?

A
  1. Duloxetine
  2. Venlafaxine
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11
Q

What are SNRIs used for?

A
  • Mainly depression
  • Neuropathic pain, together with NSAID
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12
Q

How do SNRIs work?

A
  • Serotonin improves mood regulation
  • NA improves mood and pain regulation
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13
Q

There are many adverse effects for SNRIs. Can you broadly categorise them into three sections?

A
  1. NA-related adverse effects
  2. Serotonin-related adverse effects
  3. Miscellaneous
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14
Q

What are the two NA-related adverse effects of SNRIs?

A
  1. Anti-adrenergic effects (hypertension, miosis, nausea, abdominal pain, constipation)
    - nausea and abdominal pain can lead to weight loss
  2. Excess NA affects sleep regulation (dizziness, confusion, insomnia)
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15
Q

What are the five serotonin-related adverse effects of SNRIs?

A
  1. Bleeding risk
  2. Sexual dysfunction
  3. Fragility fractures
  4. Serotonin syndrome
  5. Suicidal ideation
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16
Q

What are the four miscellaneous effects of SNRIs?

A
  1. Mania / Hypomania
  2. Hepatotoxicity
  3. Hyponatremia - Duloxetine can induce SIADH
  4. Withdrawal syndrome (dizziness, nausea, irritability, headaches, life-threatening)
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17
Q

What is a tricyclic antidepressant?

A
  • SNRIs that also block function of M, H1, and A1-adrenoceptors
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18
Q

What is a tricyclic antidepressant used for?

A
  1. Depression
  2. Neuropathic pain, together with NSAID
19
Q

What is the main tricyclic antidepressant?

A

Amitriptyline

20
Q

How does a tricyclic antidepressant work?

A
  1. Serotonin improves mood regulation
  2. NA improves mood and pain regulation
  3. H, M, and A1-adrenoceptors are all inhibited, thus reducing transmission of excitatory pain signsl
21
Q

What are the adverse effects of a tricyclic antidepressant?

A
  1. Anti-muscarinic (xerostomia, tachycardia, constipation, miosis, sweating, urinary retention)
  2. Anti-adrenergic (postural hypotension, tachycardia)
  3. Anti-histamine (sedation, weight loss)
22
Q

What is alpha-lipoic acid?

A

A dietary supplement that has questionable efficacy for diabetic neuropathy

23
Q

How does alpha-lipoic acid work?

A
  1. ALA is an antioxidant that neutralises inflammatory free radicals
  2. ALA is a coenzyme for various mitochondrial enzymes
  3. ALA activates the AMPK pathway, thus leading to improved glucose uptake and reduced insulin resistance
24
Q

What are the adverse effects of alpha-lipoic acid?

A
  1. GIT disturbances
  2. Hypoglycemia
  3. Allergic reactions
  4. Thiamine deficiency (LT, esp. in alcoholics)
  5. Overdose (metabolic acidosis, cardiac and neurological effects, hepatotoxicity)
25
Q

How does vitamin B-induced neuropathy occur?

A
  1. Impaired DNA synthesis due to no B9 = impaired neuronal function
  2. Megaloblastic anaemia due to no B9 = tissue hypoxia to nerves
  3. Hyperhomocystinemia due to no B9 and B12, which normally convert homocysteine to methionine = vascular damage and tissue hypoxia to nerves
  4. Demyelination due to no B12
26
Q

What happens to excess folate (B9) and mecobalamin (B12), and why is this important?

A
  • Renally cleared unchanged
  • Will never overdose
27
Q

What are the five adverse effects of folate (B9)?

A
  1. GIT discomfort
  2. Bloating
  3. Allergic reactions
  4. Sleep disturbances, due to increased serotonin and dopamine production
  5. Correcting anaemia may mask B12 demyelination issues
28
Q

What are the two adverse effects of mecobalamin (B12)?

A
  1. GIT discomfort
  2. Allergic reactions
29
Q

How does varicose vein-induced neuropathy occur?

A

Varicose veins compress on nerves

30
Q

What is mucosaccaride polysulphate used for?

A

Treat inflamed (swollen) varicose veins

31
Q

How does mucopolysaccharide polysulphate work?

A
  1. Enhances GAG function = stimulates fibroblast and endothelial cell migration = tissue repair
  2. Anti-inflammatory (inhibits production of inflammatory mediators; inhibits leukocyte adhesion and chemotaxis)
  3. Anticoagulant (similar to heparin)
  4. Tissue regeneration (promotes fibroblast proliferation and angiogenesis)
32
Q

How is mucopolysaccharide polysulphate administered?

A

Topical

33
Q

What are the three adverse effects of mucopolysaccharide polysulphate?

A
  1. Local skin irritation / Contact dermatitis (LT)
  2. Allergic reactions
  3. Systemic anticoagulation (if applied to large area of body)
34
Q

What is polidocanol?

A

A sclerosing agent used to treat varicose veins

35
Q

How does polidocanol work?

A
  1. Disrupts endothelial cell membranes, causing endothelium of the varicose veins to undergo cell lysis and necrosis
  2. Exposes the subendothelial layer, triggering thrombus formation
  3. Thrombus narrows vein lumen, forcing blood elsewhere
  4. In the LT, vein is hardened, obliterated, and reabsorbed by the body
36
Q

What are the five adverse effects of polidocanol?

A
  1. Local injection site reactions (irritation, discolouration)
  2. Allergic reactions
  3. Thromboembolism
  4. Tissue necrosis / ulceration
  5. Nausea, headache
37
Q

What does pentoxifylline do?

A

Improves blood flow, thus reducing symptoms of peripheral arterial disease

38
Q

How does pentoxifylline work?

A
  1. Increases RBC deformability
  2. Decreases blood viscosity (by preventing platelet and RBC aggregation)
  3. Inhibits phosphodiesterase = increases cellular cAMP = vasodilation, inhibited inflammatory cytokine production, inhibited platelet aggregation
  4. Antagonises adenosine A2 receptors = vasodilation, inhibited pro-inflammatory signalling
39
Q

What are the five adverse effects of pentoxifylline?

A
  1. GIT disturbances
  2. CNS disturbances
  3. CVS disturbances (vasodilation causes reflex tachycardia; cAMP causes cardiac arrythmias)
  4. Bleeding risk
  5. Skin effects
40
Q

What is the main vitamin K antagonist?

A

Warfarin, whose effects can be reversed by vitamin K

41
Q

How does warfarin work?

A
  1. Warfarin inhibits Vitamin K reductase complex 1 (VKORC1), which is necessary for the recycling of vitamin K
  2. Vitamin K oxidation is coupled to carboxylation of glutamic acid residues on coagulation factors (to activate them)
42
Q

What are the three adverse effects of warfarin?

A
  1. Haemorrhage (poor wound healing, heavy menstrual bleeding, blood in stool / urine, excessive bruising, petechiae)
  2. Cutaneous necrosis (due to infarction of buttocks, breasts, and extremities)
  3. Hepatitis
43
Q

What are the contraindications for warfarin?

A
  1. Pregnancy / Breastfeeding
  2. Bleeding / severe hypertension / surgery
  3. Hypersensitivity
  4. Hepatorenal dysfunction
  5. Pericardial / Endocardial damage

MSK (6 decks)

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