Numbness & Weakness Pharm Flashcards
What are 3 general drug classes used to treat peripheral neuropathy?
1) Gabapentinoids
- Gabapentin, Pregabalin
2) Antidepressants
a) SSRIs, NERIs:
- Duloxetine, Venlafaxine
b) TCAs:
- Amitriptyline
3) Nutritional support for diabetic neuropathy
- α-lipoic acid
What is the moa of gabapentinoids used in the treatment of peripheral neuropathies?
GABA analogues → act at voltage-gated Ca channels rather than GABAR
→ ↓tonic neural stimulation managing neuropathic pain
What are 3 indications for Gabapentinoids?
1) Neuropathic pain
2) Chronic pain refractory to other treatments
3) Antiepileptic for partial seizures
What are 3 AEs of Gabapentinoids?
1) Somnolence
2) Dizziness
3) Ataxia (esp if not titrated over days/weeks)
What is the main DDI for Gabapentinoids?
Drugs altering renal f(x)
- Gabapentinoids undergo renal elimination w/o metabolites → propensity for toxic accumulation
What are 2 examples of Gabapentinoids?
1) Gabapentin
2) Pregabalin
What is the moa of Duloxetine?
Serotonin (5-HT) and Norepinephrine (NE) reuptake inhibitor (SNRI) antidepressant
What are 2 clinical indications for Duloxetine?
1) Clinical depression
2) Chronic/Neuropathic pain (usually adjunct w NSAID/paracetamol)
What are 5 AEs of Duloxetine?
Common:
1) Xerostomia
2) Abdo pain
3) Drowsiness
4) Fatigue
5) Headache
6) Weight loss
Severe:
7) Mania/Hypomania
8) Easy bleeding
9) Fragility fractures
10) Hepatotoxicity
11) HypoNa
12) Ocular effects
13) Serotonin syndrome
14) Sexual dysfunction
15) Suicidal ideation
16) Withdrawal syndrome
What is the moa of Amitriptyline?
Tricyclic antidepressant inhibits reuptake of NE and Serotonin
What are 2 clinical indications for amitriptyline?
1) Clinical depression
2) Chronic/neuropathic pain (adjunct to NSAID/paracetamol)
What are 5 AEs of amitriptyline?
Antihistaminergic:
1) Sedation
2) Weight gain
Anticholinergic:
3) Blurred vision
4) Xerostomia
5) Urinary retention
6) Constipation
7) Agitation
8) Tachycardia
9) Sweating
α1-receptor blockade:
10) Postural hypotension
11) Tachycardia
What is the main indication for α-lipoic acid?
Diabetic neuropathy px who are refractory/intolerant to first-line pharmacotherapies
What is the moa of α-lipoic acid in treating peripheral neuropathies?
1) Antioxidant
- neutralise free radicals
- serve as co-factor to several enzymes
2) ↑ glucose uptake in cells
What are 5 AEs of α-lipoic acid?
1) Hypogly in diabetic px
2) N&V
3) Abdo pains
4) Allergic rxn
5) Thiamine deficiency (esp in alcoholics)
Overdose:
6) Neurological effects
7) Metabolic acidosis
8) Cardiac effects
9) Hepatotoxicity
In which patients taking α-lipoic acid, would thiamine supplementation be needed?
Alcoholics
What are 2 forms of vitamin related deficiency-related neuropathy?
1) B12
2) Folate (B9)
What is the moa of Mecobalamin in treating vitamin deficiency-related neuropathy?
Coenzyme form of B12
- facilitates synthesis of methionine from homocysteine → myelin sheath formation
What are 3 AEs of Mecobalamin?
Rare:
1) HS rxns
2) Headache
3) Nausea
True or false:
Mecobalamin overdose is not a concern in all patients.
False.
Excess is excreted through urine
How is mecobalamin adminstered?
1) Oral
2) IV
3) IM
What is the moa of Folic acid in treating vitamin deficiency-related neuropathy?
1) precursor needed for DNA synthesis and repair.
2) involved in the conversion of homocysteine to methionine, similar to Vitamin B12, and is crucial for the production of red blood cells and neuroprotection
What are 3 AEs of Folic acid?
1) Nausea
2) Bloating
3) Sleep disturbances
4) High doses may mask B12 deficiency
5) HS rxns (Rare)
How is folic acid administered?
Oral
What are 4 drugs used to treat peripheral artery disease?
Anti-hypertensives:
1) ACEi (eg. captopril)
2) ARBs (eg. candesartan)
Anti-lipid therapy:
3) Statins (eg. Atorvastatin)
Anti-platelet therapy:
4) ADP P2Y21 receptor inhibitor (eg. clopidogrel)
Xanthine derivatives:
5) Pentoxifylline
What is the moa of pentoxifylline in treating peripheral artery disease?
1) Non-selective PDE inhibitor
2) Adenosine 2 receptor antagonist
3) Haemorheologic mechanisms not clear
- ↑deformability of RBC
- ↓ blood viscocity
- ↓ platelet aggregation
What are 4 AEs of pentoxifylline?
Common:
1) Belching
2) Bloating
3) Abdo pain
4) N&V
5) Indigestion
6) Dizziness
7) Flushing
Rare:
8) Angina
9) Palpitations
10) Bleeding
11) Arrhythnmias
12) Anxiety
13) Hallucinations
What are 2 pharmacological treatments for varicose veins?
1) Mucopolysaccharide polysulphate
- inflamed & swollen varicose veins
2) Polidocanol
- sclerotherapy to narrow lumen of varicose veins and force blood flow elsewhere
What is the moa of mucopolysaccharide polysulphate in treating varicose veins?
1) Antithrombotic:
- Inhibits clotting factors by potentiating antithrombin activity
2) Anti-inflammatory:
- ↓ capillary permeability and inflammatory mediators
3) ↑ Microcirculation:
- ↑ blood flow and tissue oxygenation
4) Fibroblast Modulation:
- ↑ fibroblast activity and collagen synthesis,
supporting wound healing
5) Analgesic:
- Provides mild pain relief by modulating local inflammation
What are 4 AEs of mucopolysaccharide polysulphate?
Local:
1) Mild skin irritation (erythema, pruritus)
2) Contact derm (prolonged use)
Systemic: (Rare)
3) HS rxn
4) Systemic anticoagulation
How is Polidocanol administered?
IV foam
What are 4 drug options for deep vein thrombosis?
1) Rivaroxaban/Apixaban monotherapy
2) LMW Heparin + Warfarin
3) LMW Heparin then Dabigatran & Edoxaban
What is the moa of polidocanol in treating varicose veins?
1) Surface-active agent:
- acts as non-ionic surfactant
2) Endothelial damage:
- localised endothelial cell destruction → inflammation & fibrosis
3) Vessel occlusion
- induces thrombus formation within vein → sclerosis → obliteration of vessel
4) Minimal pain perception
- mild anaesthetic
What are 5 AEs of polidocanol?
Local:
1) Inflammation/skin rxn @ injection site
2) Skin discoloration
Systemic:
3) Allergic rxn/anaphylaxis
4) Nausea
5) Headache
6) Thromboembolism
7) Ulceration/tissue necrosis (if extravasation occurs)
