Presentation on drugs used in the treatment of Neuropathic Pain.

1. ANTIDEPRESANTS
USED IN THE
TREATmENT OF
NEUROPATHIc PAIN
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2. OBJEcTIVES
• Back Ground Information On Depression
• Synopsis of Pain
• Types And Classification Of Pain
• Neuropathic Pain
• Pain and depression
• Antidepressants used to treat pain
• Tricyclic antidepressants used to treat pain
• MOA of Tricyclic Antidepressants
• Side effects Of TCAs
• Pharmacology Of TCAs
• Contraindications/ Precautions Of TCAs
• SNRI- serotonin-norepinephrine reuptake inhibitors used to treat pain
• Pharmacology Of Duloxetine
• Side Effects Of Duloxetine
• Pharmacology Of Venlafaxine
• Adverse effects and Contraindicated of Venlafaxine
• References
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3. Back Ground Information On
Depression
According to Rang et al., 2012 Depression is the
most common form of affective disorders.
This affective disorder of the mood, thought or
cognition is considered a heterogeneous disorder
with individuals presenting with one or more
symptoms.
It is characterized by lethargy, sadness, and a
loss of interest or pleasure in normal activities.
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4. Synopsis of Pain
Pain is an unpleasant sensory or emotional
experience associated with actual or potential
tissue damage.
Pain originates in the primary sensory neurons
and terminates in the dorsal horn of the spinal
cord; at the dorsal horn pain signals activate
many brain structures through the ascending
pathways.
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5. Types And Classification Of Pain
Acute pain is short-lasting and can be described, as
it is usually the result of an injury, surgery or illness. It
last lesser than six months.
Chronic pain is a constant or intermittent pain that
persists beyond the expected healing time and
seldom attributed to a specific cause or injury. It lasts
longer than six months. Eg cancer pain
Nociceptive pain: stimuli from somatic (skin and
deep tissue) and visceral (internal organs) structures.
Neuropathic pain: stimuli abnormally processed by
the nervous system
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6. NEUROPATHIC PAIN
Neuropathic pain is caused by a problem with one
or more nerves. The function of the nerve is
affected in a way that it sends pain messages to
the brain. Neuropathic pain is often described as
burning, stabbing, shooting, aching, or like an
electric shock.
Some common causes of neuropathic pain
include: Alcoholism, Amputation, Chemotherapy,
Diabetes, HIV infection or AIDS, Multiple
sclerosis, Shingles and Spine surgery.
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7. Pain and depression
There are link between
depression and pain
biologically, where there is a
dysfunction of the
neurotransmitters serotonin
hydroxytryptamine (5HT),
Norepinephrine (NE) and
dopamine. Thus causing a
dysfunctional pathway.
Persons with chronic pain
are prone to depression
because of the continuous
disease burden impose by
the pain.
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8. Antidepressants Used To Treat Pain
 Tricyclic antidepressants
– Analgesic effects separate from anti-depressant effects.
– Amitriptyline: most studied, but has most side effects
– Nortriptyline & desipramine: better tolerated, less well
studied.
 Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs
– inhibit both norepinephrine and serotonin reuptake
– efficacy in neuropathic pain syndromes or pain associated
with depression (duloxetine [Cymbalta®], venlafaxine
[Effexor®])
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9. Tricyclic antidepressants used to treat
pain
 Tricyclic antidepressants particularly
Amitriptyline, Nortriptyline and Desipramine
are widely used in the treatment of neuropathic
pain. These drugs act centrally by inhibiting
noradrenaline reuptake and are highly effective in
relieving neuropathic pain in some cases, but not
all, cases. Their action is however, independent
of the antidepressant effects.
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10. MOA Of Tricyclic Antidepressants
 The MOA of TCA’s is to block the uptake of amines on nerve
terminals, by competition for the binding site of the amine
transporter. Most TCAs inhibit noradrenaline and 5-HT uptake
but have much less effect on dopamine uptake. It has been
suggested that the improvement of emotional symptoms
reflects mainly an enhancement of 5-HT mediated
transmission, whereas relief of biological symptoms results
from noradrenergic transmission.
 In addition to their effects on amine uptake, most TCAs
affects other receptors, include muscarinic acetylcholine
receptors, histamine receptors and 5-HT receptors.
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11. Side Effects Of TCAs
Sedation. (30% amitriptyline/2% nortriptyine)
 postural hypotension .This is due to blockade of H2
and musacarinc receptors
Anticholoinergic effects includes: (dry mouth: 30%
amitriptyline/10% nortriptyline), constipation, urinary
retention, blurred vision, tachycardia, cognitive
impairment)
Cardiac arrhythmias ( especially in overdose)
Weight gain 11

12. Pharmacology Of TCAs
Dose: start with 10 mg at bedtime with
Gradual escalation every three days in 10
mg increments.
( Analgesic response typically seen with 10
– 75 mg daily)
Given Orally
Half life 10-20 hrs
90-95% PPB
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13. Contraindications/ Precautions Of
TCAs
Should not administered to persons with
cardiovascular disease and low blood pressure
 Should not be given to elderly people as they
consist of many side effects.
Precautions:
Benign prostatic hypertrophy, closed angle
glaucoma, CV disease
Screening EKG for cardiac conduction
abnormalities if > 40 yo
Risk of suicide by overdose (> 750 mg or 15 - 20
mg per kg)
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14. SNRI- Serotonin-norepinephrine
Reuptake Inhibitors Used To Treat Pain
Duloxetine is primarily used to treat major
depression. It is also used to treat pain and
tingling caused by diabetic neuropathy (damage
to the nerves) and fibromyalgia. Its also used to
treat on going bone or muscle pain such as lower
back pain or osteoarthritis.
MOA of SNRI : increase levels of norepinephrine
( and serotonin) to stimulate the descending pain
pathway
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15. Pharmacology Of Duloxetine
Duloxetine (Cymbalta ®)
Start at 15 mg once daily and titrate slowly up to 60
mg daily
Dosage adjustment not necessary in renal
dysfunction; caution with hepatic insufficiency
It is given orally
Half life: 12 hours (range 8-17 hours)
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16. Side Effects Of Duloxetine
 Signs of an allergic reaction: skin rash or
hives; difficulty breathing; swelling of your face,
lips, tongue, or throat.
Agitation, hallucinations, fever, fast heart rate.
Headache, trouble concentrating, memory
problems
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17. Pharmacology Of Venlafaxine
Start at 15 mg once daily and titrate slowly up to 60
mg daily
It is given orally
Half life: 5 hours
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18. Adverse Effects And Contraindicated Of
Venlafaxine
SE: nausea, headaches, sedation, sweating,
increased blood pressure
Minimal anticholinergic side effects
Contraindicated in alcohol and St.John's Wort.
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19. References
 Rang H.P., Dale M.M., Ritter J.M., Flower R.J., Henderson G. (2012).
Rang and Dale’s Pharmacology. The Nervous System Pages 506 &
521
 Rang H.P., Dale M.M., Ritter J.M., Flower R.J., Henderson G. (2012).
Rang and Dale’s Pharmacology. Antidepressant drugs Page 564
 Tricyclic Antidepressants and Tetracyclic Antidepressants . Retrieved
on September 19, 2014 from
http://www.mayoclinic.org/diseases-conditions/depression/in-depth/antidepressants/ Skapinakis, P.(2008).Tricyclic Antidepressants - Effects and
Contraindications. Retrieved on September 19, 2014 from
http://web4health.info/en/answers/bipolar-depr-med-tcas-effect.htm
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20. THAT MOMENT JUST BEFORE PAIN
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