diabetic neuropathy defeated 1st preview- sokhna cycle meeting

TegretolDIABETIC NEUROPATHY DEFEATED

Neuropathy… what is it?

Pain arising from injury or abnormal nervous system activity.

It might be central, peripheral, or both.

It might occur without physical or chemical stimuli.

Classification of neuropathy

Mononeuropathy - involvement of a single nerve. Like:

carpal tunnel syndrome.

Multiple mononeuropathy - two or more nerves individually

affected.

Polyneuropathy - generalized involvement of peripheral nerves.

Like: diabetic neuropathy.

Diabetic neuropathy

Diabetic neuropathiy is a neuropathic disorder that’s associated with diabetes mellitus. These conditions are thought to result from diabetic microvascular injury involving small blood vessels that supply nerves (vasa nervorum) in addition to macrovascular conditions.

It affects all peripheral neuropathy including motor neurons and autonomic nervous system. therefore can affect all organs and systems.

The most common of all the late complications of diabetes mellitus

Risk factors

Poor glycaemic control

Long duration

Age

Height

Excessive alcohol

Smoking

Duration of diabetes

Hypertension

STAGING

1. No-no symptoms or signs of neuropathy

2. N1-asymptomatic,signs of neuropathy

3. N2-symptomatic neuropathy

4. N3-disabling polyneuropathy

Symptoms

Numbness or feeling of walking in cotton

Sharp shooting or stabbing pain

Tingling pins & needles

Hot or cold sensation

Allodynia

Cramps

Treatment

Prevention is the best form of treatment.

Pain control

Treatment of secondary depression

Good diabetic control

SYMPTOMATIC TREATMENT

• Proper footwear• Foot care• Nocturnal splint• physiotherapy

• NSAIDS• Antidepressants• Anticonvulsants

• PHYSICAL APPROACH • PHARMACOLOGICAL

ANTICONVULSANTS

Carbamezipine , Gabapentin , pregabaline are often used.

Used alone or as add on therapy to tricyclics.

Well tolerated.

Carbamezipine: 200-600 mg/day

Gabapentin: 900-3600 mg/day

Pregabaline: 75-300 mg/day

Tegretol (Carbamazepine) (CBZ)

Carbamazepine was discovered by chemist Walter Schindler at J.R. Geigy AG (now part of Novartis) in Basel, Switzerland, in 1953. Schindler then synthesized the drug in 1960, before its anti-epileptic properties had been discovered.

Carbamazepine was first marketed as a drug to treat trigeminal neuralgia (formerly known as tic douloureux) in 1962. It has been used as an anticonvulsant and antiepileptic in the UK since 1965, and has been approved in the U.S. since 1974.

It was first used to control mania at 1971.

Indications It’s used primarily in the treatment of epilepsy and bipolar disorder, as well as

trigeminal neuralgia.

It is also used off-label for a variety of indications, including Attention-deficit hyperactivity disorder (ADHD),

Schizophrenia, phantom limb syndrome,

Complex regional pain syndrome,

Paroxysmal extreme pain disorder,

Neuromyotonia,

intermittent explosive disorder,

borderline personality disorder,

post-traumatic stress disorder.

PharmacokineticsBioavailability 80 % (CR tab is less by 15% than other forms)

Protein binding 76 %

MetabolismHepatic by CYP3A4 to active epoxide from (10,11 epoxide)

Half-life (25-65) hours

Excretion72 % in urine (2-3) % unchanged 28 % in feces

Therapeutic range (17-50) ngm/ml

Saliva conc.(Compared with plasma conc.)

(20-30) %

Breast milk conc.(Compared with plasma conc.)

(25-60) %

Placental barriers Cross

PPCReached after

Syrup 2 hours

Conv. tab 12 hours

CR tab 24 hours (CR is less by 25% than conv. tabs).

T1/2

Single dose 36 hours

Multiple doses 16-24 hours

Mechanism of action

The mechanism of action of carbamazepine and its derivatives is relatively well understood. Carbamazepine stabilizes the inactivated state of Voltage-gated sodium channels, making fewer of these channels available to subsequently open. This leaves the affected cells less excitable until the drug dissociates. Carbamazepine has also been shown to potentiate GABA receptors made up of alpha1, beta2, gamma2 subunits

Tegretol interactions

Forms & Concentrations