Combination Pharmacotherapy for Painful Diabetic Neuropathy

Introduction

Diabetes is one of the chronic disorders that does occur if and when the pancreas is no longer able to generate insulin. This may even be possible if the body is not able to make any positive use of the insulin that it produces. Insulin is a hormone of the body that is made by the pancreas. This behaves like a key ingredient in letting glucose from the food eaten by the individual pass from within the bloodstream directly into the cells of the body in order to produce the required energy. All the carbohydrates in the foods are completely broken down into much-needed glucose in the blood. Insulin thus aids glucose in getting into the cells. When an individual is not able to generate insulin or is not able to use it efficiently, it leads to an elevated glucose level in the bloodstream, and this is known as hyperglycemia. Over the long-term high glucose levels are linked with damage to the body's organs as well as the failure of several organs and tissues.

What Is Painful Diabetic Neuropathy?

Painful diabetic neuropathy is nerve damage that may occur in individuals suffering from diabetes. Multiple kinds of nerve damage lead to different signs and symptoms. Clinical manifestations may range from a small amount of pain and numbness in the patient’s feet to issues with the functions of internal organs, such as the heart and urinary bladder. Over time, a high blood glucose level called blood sugar, as well as high levels of fats, like triglycerides, in the blood due to diabetes, has the potential to damage the nerves of the patient. An early diagnosis of painful diabetic neuropathy allows the patient a valid chance for effective treatment. Since not all limbic pain leads to painful diabetic neuropathy, an accurate diagnosis is crucial in order to ensure apt treatment. The diagnosis of painful diabetic neuropathies is based on thorough case history, clinical evaluation, and investigatory laboratory tests.

There are numerous antidepressants that are available for the rehabilitation of painful diabetic neuropathy. The most common ones are Amitriptyline and Desipramine. Clinical studies have established that a few antidepressants may be effective for certain patients who are suffering from painful diabetic neuropathy. The dose of the respective antidepressant is used in such a way that they treat painful diabetic neuropathy. The dose is generally much lower than what is prescribed for the treatment of depression. There are a few side effects of such drugs, namely dizziness, confusion, lethargy, and swelling in the lower limbs, as well as sudden weight gain. It is possible to become an addict to such drugs, and thus any alterations in the doses must be carefully monitored.

What Causes Painful Diabetic Neuropathy?

Diabetes is called a silent killer since it is one of the leading causes of painful neuropathy. Approximately 50 percent of the diagnosed diabetic patients have the potential to develop painful neuropathy within 25 years. Painful diabetic neuropathy has several features, such as a burning sensation in the joints, excruciating discomfort in the toes, stabbing type of pain in the limbs, and several presentations of tingling sensations. The pathophysiology of this condition is predominantly because of several metabolic as well as vascular factors. A poor glycemic index is a huge risk factor for the development of painful diabetic neuropathy. A direct link is found between the duration of a poor glycaemic index as well as painful diabetic neuropathy. It is observed that approximately 50 percent of diabetic patients do develop painful peripheral neuropathy even post the early diagnosis of diabetes mellitus.

What Are the Symptoms of Painful Diabetic Neuropathy?

Patients who are suffering from painful diabetic neuropathy present themselves with uncontrolled tingling sensations, limb numbness, burning sensation in the joints, excruciating kind of stabbing pain in the lower limbs, and at times paraesthesia with hyperesthesia along with deep aches in the feet and hands. Mentioned below are a few of the signs and symptoms of painful diabetic neuropathy.

• Sensory loss.

• Pain involvement in the upper limbs.

• Pain in the trunk.

• Discomfort in the vertex of the head.

• Disturbance with a light touch sensation.

• Sensitivity to pressure.

• Intolerance of vibration.

• Joint pain.

• Difficulty with mobility.

• Loss of self-esteem.

• Depression.

What Is Combination Pharmacotherapy?

Combination pharmacotherapy is the use of two or more medications to treat a medical condition. This approach is often used when monotherapy (treatment with a single medication) is not effective or when the patient experiences side effects from a single medication. Combination pharmacotherapy is often employed if it has proven to be more effective than monotherapy or in order to reduce the side effects to optiimize treatment outcome.

How to Treat Painful Diabetic Neuropathy With Combination Pharmacotherapy?

There are a few established ways to treat painful diabetic neuropathy. One of the main causes of the treatment of this condition is the optimal control of increased blood sugar, called hyperglycemia. This can be achieved by intensive therapy in those suffering from type 1 diabetes mellitus. This does have the potential to drastically reduce painful diabetic neuropathy by around 60 percent over a span of five years. Mentioned below are a few of the treatment modalities for painful diabetic neuropathy with combination pharmacotherapy.

• Adequate glycaemic control by oral hypoglycemic.

• Combination of euglycaemic agents and insulin therapy.

• Antidepressants.

• Anticonvulsants.

• Opioids.

• NMDA or N-Methyl-D-Asparate receptor antagonists.

• Antiarrhythmics.

• Topical agents.

• Aldose reductase inhibitors such as Alrestatin, Sorbinil, Tolrestat, and Zepolrestat.

• Non-steroidal anti-inflammatory drugs or NSAIDs.

• Protein kinase C inhibitors.

• Gamma-linolenic acid.

• Nerve growth factor.

• Recombinant human nerve growth factor.

• Insulin-like growth factor-1.

• Vascular endothelial growth factors.

• Immune therapy.

• Acupuncture.

• Hyperbaric oxygen.

• Physical therapy.

• Amitriptyline.

• Imipramine.

• Nortriptyline.

• Desipramine.

• Duloxetine.

• SSRIs or selective serotonin reuptake inhibitors.

• Venlafaxine.

• Citalopram.

• Paroxetine.

• Fluoxetine for diabetic neuropathy.

What Are the Combination Therapies Used to Treat Painful Diabetic Neuropathy?

There are several different medications that can be used in combination pharmacotherapy for PDN. Some of the most common combinations include:

• Pregabalin and Amitriptyline: Pregabalin is an anticonvulsant medication that works by blocking the transmission of pain signals. Amitriptyline is a tricyclic antidepressant that also works by blocking the transmission of pain signals.

• Pregabalin and Duloxetine: Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI) that works by increasing the levels of serotonin and norepinephrine in the brain. These neurotransmitters are involved in pain modulation.

• Gabapentin and Nortriptyline: Gabapentin is another anticonvulsant medication that works by blocking the transmission of pain signals. Amitriptyline is a tricyclic antidepressant that also works by blocking the transmission of pain signals.

Conclusion

Diabetes mellitus is one of the leading causes of painful diabetic neuropathy. The result of these conditions is numerous, such as significant morbidity, patient mortality as well as deterioration in the patient’s quality of life. Eventually, they will pose a difficult and enormous financial burden for both the patient as well as the caregivers of the patient. Painful diabetic neuropathy is an extremely broad as well as heterogeneous term that encompasses numerous underlying factors and clinical manifestations that may be difficult to diagnose at an earlier stage.