Drugs for Numbness / Weakness

Question 1

What are gabapentinoids?

Answer 1

GABA analogues, which act on VGCCs in the CNS neurons

Question 2

What are the two gabapentinoids?

Answer 2

1. Gabapentin
2. Pregabalin

Question 3

What are gabapentinoids used for?

Answer 3

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

Question 4

How do gabapentinoids work?

Answer 4

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

Question 5

How are gabapentinoids cleared?

Answer 5

Renally excreted unchanged

Question 6

What are the adverse effects of gabapentinoids?

Answer 6

• Drowsiness, sedation, dizziness, ataxia

Question 7

What is the main DDI for gabapentinoids?

Answer 7

• No mixing with drugs that affect renal function

Question 8

What are the two antidepressant classes?

Answer 8

1. SNRIs
2. Tricyclic antidepressants

Question 9

What are SNRIs?

Answer 9

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

Question 10

What are the two SNRIs?

Answer 10

1. Duloxetine
2. Venlafaxine

Question 11

What are SNRIs used for?

Answer 11

• Mainly depression
• Neuropathic pain, together with NSAID

Question 12

How do SNRIs work?

Answer 12

• Serotonin improves mood regulation
• NA improves mood and pain regulation

Question 13

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

Answer 13

1. NA-related adverse effects
2. Serotonin-related adverse effects
3. Miscellaneous

Question 14

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

Answer 14

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)

Question 15

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

Answer 15

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

Question 16

What are the four miscellaneous effects of SNRIs?

Answer 16

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

Question 17

What is a tricyclic antidepressant?

Answer 17

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

Question 18

What is a tricyclic antidepressant used for?

Answer 18

1. Depression
2. Neuropathic pain, together with NSAID

Question 19

What is the main tricyclic antidepressant?

Answer 19

Amitriptyline

Question 20

How does a tricyclic antidepressant work?

Answer 20

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

Question 21

What are the adverse effects of a tricyclic antidepressant?

Answer 21

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

Question 22

What is alpha-lipoic acid?

Answer 22

A dietary supplement that has questionable efficacy for diabetic neuropathy

Question 23

How does alpha-lipoic acid work?

Answer 23

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

Question 24

What are the adverse effects of alpha-lipoic acid?

Answer 24

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

Question 25

How does vitamin B-induced neuropathy occur?

Answer 25

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

Question 26

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

Answer 26

- Renally cleared unchanged - Will never overdose

Question 27

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

Answer 27

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

Question 28

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

Answer 28

1. GIT discomfort 2. Allergic reactions

Question 29

How does varicose vein-induced neuropathy occur?

Answer 29

Varicose veins compress on nerves

Question 30

What is mucosaccaride polysulphate used for?

Answer 30

Treat inflamed (swollen) varicose veins

Question 31

How does mucopolysaccharide polysulphate work?

Answer 31

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)

Question 32

How is mucopolysaccharide polysulphate administered?

Answer 32

Topical

Question 33

What are the three adverse effects of mucopolysaccharide polysulphate?

Answer 33

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

Question 34

What is polidocanol?

Answer 34

A sclerosing agent used to treat varicose veins

Question 35

How does polidocanol work?

Answer 35

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

Question 36

What are the five adverse effects of polidocanol?

Answer 36

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

Question 37

What does pentoxifylline do?

Answer 37

Improves blood flow, thus reducing symptoms of peripheral arterial disease

Question 38

How does pentoxifylline work?

Answer 38

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

Question 39

What are the five adverse effects of pentoxifylline?

Answer 39

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

Question 40

What is the main vitamin K antagonist?

Answer 40

Warfarin, whose effects can be reversed by vitamin K

Question 41

How does warfarin work?

Answer 41

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)

Question 42

What are the three adverse effects of warfarin?

Answer 42

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

Question 43

What are the contraindications for warfarin?

Answer 43

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