Month: January 2023

Gabapentin Pharmacology

Gabapentin is structurally related to GABA. However, it does not bind to GABAA or GABAB receptors, and it does not appear to influence synthesis or uptake of GABA.

Gabapentin is a medication that belongs to the class of drugs known as anticonvulsants or antiepileptics. It is primarily used to treat seizures and neuropathic pain, but it is also used off-label for various other conditions such as anxiety, insomnia, and restless leg syndrome.

Gabapentin works by binding to a specific type of voltage-gated calcium channel (the alpha-2-delta subunit) in the brain and spinal cord. This reduces the release of various neurotransmitters, including glutamate, substance P, and noradrenaline, which are involved in pain perception and seizures.

Gabapentin is rapidly absorbed after oral administration, and its bioavailability is not affected by food. The peak plasma concentration is reached within 2-3 hours after administration. Gabapentin is not metabolized in the liver and is primarily eliminated by renal excretion.

The half-life of gabapentin is approximately 5-7 hours, and it is typically administered three times a day to maintain therapeutic levels in the blood. The dosage of gabapentin may need to be adjusted in patients with renal impairment, and it should be used with caution in patients with a history of substance abuse or suicidal ideation.

Overall, gabapentin is a well-tolerated medication, but common side effects may include dizziness, drowsiness, fatigue, and ataxia. Gabapentin may also increase the risk of suicidal thoughts or behaviors, particularly in younger patients. Therefore, close monitoring is recommended during treatment with gabapentin.

High affinity gabapentin binding sites have been located throughout the brain; these sites correspond to the presence of voltage-gated calcium channels specifically possessing the alpha-2-delta-1 subunit.

Gabapentin 800mg
Gabapentin 800mg

This channel appears to be located presynaptically, and may modulate the release of excitatory neurotransmitters which participate in epileptogenesis and nociception.

Absorption

Variable, from proximal small bowel by L-amino transport system; saturable process; dose-dependent

Vd: 58 ± 6 L; CSF concentrations are ~20% of plasma concentrations

Metabolism

Not metabolized

Excretion

Proportional to renal function; urine (as unchanged drug)

Clearance: Apparent oral clearance is directly proportional to CrCl: Clearance in infants is highly variable; oral clearance (per kg) in children <5 years of age is higher than in children ≥5 years of age

Time to Peak

Immediate release: Infants 1 month to Children 12 years: 2 to 3 hours; Adults: 2 to 4 hours; Extended release: 8 hours

Half-Life Elimination

Infants 1 month to Children 12 years: 4.7 hours

Adults, normal: 5 to 7 hours; increased half-life with decreased renal function; anuric adult patients: 132 hours; adults during hemodialysis: 3.8 hours

Protein Binding

<3%

Gabapentin Side Effects

Applies to gabapentin: oral capsule, oral solution, oral suspension, oral tablet

Along with its needed effects, gabapentin may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking gabapentin:

More common

  • Clumsiness or unsteadiness
  • continuous, uncontrolled, back-and-forth, or rolling eye movements

More common in children

  • Aggressive behavior or other behavior problems
  • anxiety
  • concentration problems and change in school performance
  • crying
  • depression
  • false sense of well-being
  • hyperactivity or increase in body movements
  • rapidly changing moods
  • reacting too quickly, too emotional, or overreacting
  • restlessness
  • suspiciousness or distrust

Less common

  • Black, tarry stools
  • chest pain
  • chills
  • cough
  • depression, irritability, or other mood or mental changes
  • fever
  • loss of memory
  • pain or swelling in the arms or legs
  • painful or difficult urination
  • shortness of breath
  • sore throat
  • sores, ulcers, or white spots on the lips or in the mouth
  • swollen glands
  • unusual bleeding or bruising
  • unusual tiredness or weakness

Incidence not known

  • Abdominal or stomach pain
  • blistering, peeling, or loosening of the skin
  • clay-colored stools
  • coma
  • confusion
  • convulsions
  • dark urine
  • decreased urine output
  • diarrhea
  • dizziness
  • fast or irregular heartbeat
  • headache
  • increased thirst
  • itching or skin rash
  • joint pain
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • loss of appetite
  • muscle ache or pain
  • nausea
  • red skin lesions, often with a purple center
  • red, irritated eyes
  • unpleasant breath odor
  • vomiting of blood
  • yellow eyes or skin

Some side effects of gabapentin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

  • Blurred vision
  • cold or flu-like symptoms
  • delusions
  • dementia
  • hoarseness
  • lack or loss of strength
  • lower back or side pain
  • swelling of the hands, feet, or lower legs
  • trembling or shaking

Less common or rare

  • Accidental injury
  • appetite increased
  • back pain
  • bloated or full feeling
  • body aches or pain
  • burning, dry, or itching eyes
  • change in vision
  • change in walking and balance
  • clumsiness or unsteadiness
  • congestion
  • constipation
  • cough producing mucus
  • decrease in sexual desire or ability
  • difficulty with breathing
  • dryness of the mouth or throat
  • earache
  • excess air or gas in the stomach or intestines
  • excessive tearing
  • eye discharge
  • feeling faint, dizzy, or lightheadedness
  • feeling of warmth or heat
  • flushed, dry skin
  • flushing or redness of the skin, especially on the face and neck
  • frequent urination
  • fruit-like breath odor
  • impaired vision
  • incoordination
  • increased hunger
  • increased sensitivity to pain
  • increased sensitivity to touch
  • increased thirst
  • indigestion
  • noise in the ears
  • pain, redness, rash, swelling, or bleeding where the skin is rubbed off
  • passing gas
  • redness or swelling in the ear
  • redness, pain, swelling of the eye, eyelid, or inner lining of the eyelid
  • runny nose
  • sneezing
  • sweating
  • tender, swollen glands in the neck
  • tightness in the chest
  • tingling in the hands and feet
  • trouble sleeping
  • trouble swallowing
  • trouble thinking
  • twitching
  • unexplained weight loss
  • voice changes
  • vomiting
  • weakness or loss of strength
  • weight gain

You can not take Prescription for a long time, you need find a way to treat your pain without prescription. Exercising is the best way to relieve your pain. because exercising can enhance your immune system and increase your muscle strength and make your nerve strong.

Gabapentin Breastfeeding Warnings

Benefit should outweigh risk.

Excreted into human milk: Yes

Gabapentin and breastfeeding

If your doctor or health visitor says your baby is healthy, you can take gabapentin while breastfeeding. It’s important to keep taking gabapentin to keep you well.

Gabapentin passes into breast milk in small amounts. It has not been known to cause any side effects in breastfed babies.

If your baby is not feeding as well as usual, seems unusually sleepy, has a stomach upset, or if you have any other concerns about your baby, talk to your doctor, pharmacist, health visitor or midwife.

Gabapentin and fertility

There’s no evidence to suggest that taking gabapentin reduces fertility in either men or women. However, discuss your pregnancy plans with a doctor. They may wish to review your medicine and prescribe a higher dose of folic acid for you to take (5mg a day) before you become pregnant.

Speak to a pharmacist or your doctor before taking gabapentin if you’re trying to get pregnant.

Comments:
-The effects in the nursing infant are unknown.
-Limited information indicates that maternal doses up to 2.1 g daily produce relatively low levels in infant serum.
-Breastfed infants should be monitored for drowsiness, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants and when using combinations of anticonvulsant or psychotropic drugs.

You can not take Prescription for a long time, you need find a way to treat your pain without prescription. Exercising is the best way to relieve your pain. because exercising can enhance your immune system and increase your muscle strength and make your nerve strong.

 

Gabapentin Pregnancy Warnings

Animal studies have revealed evidence of fetotoxicity involving delayed ossification in several bones of the skull, vertebrae, forelimbs, and hindlimbs.

Gabapentin 800mg
Gabapentin 800mg

Hydroureter and hydronephrosis have also been reported in animal studies. There are no controlled data in human pregnancy.

To provide information regarding the effects of in utero exposure to this drug, physicians are advised to recommend that pregnant patients enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/.

AU TGA pregnancy category B1: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have not shown evidence of an increased occurrence of fetal damage.

US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

This drug should be used during pregnancy only if the benefit outweighs the risk.

AU TGA pregnancy category: B1
US FDA pregnancy category: C

Comments:
-Women on antiepileptic drugs (AEDs) should receive prepregnancy counseling with regard to the risk of fetal abnormalities.
-AEDs should be continued during pregnancy and monotherapy should be used if possible at the lowest effective dose as the risk of abnormality is greater in women taking combined medication.
-Folic acid supplementation (5 mg) should be started 4 weeks prior to and continued for 12 weeks after conception.
-Specialized prenatal diagnosis including detailed mid-trimester ultrasound should be offered.
-The risk of having a child with a congenital defect as a result of antiepileptic medication is far outweighed by the dangers to the mother and fetus of uncontrolled epilepsy.

Gabapentin and pregnancy

Gabapentin is not generally recommended in pregnancy as there is not enough information about whether it’s safe for your baby.

However, from the small amount of information that is available, there’s no clear evidence that it’s harmful. It should only be taken if the benefits of the medicine outweigh the risks.

If you take gabapentin for epilepsy, it’s important that this is well treated during pregnancy, as seizures can harm you and your baby. Keep taking gabapentin, but talk to your doctor urgently. They may recommend you change to a different medicine.

If you’re trying to get pregnant or have become pregnant while taking gabapentin, it is recommended to take a high dose of folic acid (5mg a day). You can get this from your doctor or midwife.

Ideally you’ll take high dose folic acid for 3 months before you start trying to get pregnant and for the first 12 weeks of pregnancy. Do not worry if you have not taken it before you get pregnant, but start taking it as soon as possible once you know that you are pregnant. It helps your baby to grow normally.

If you take gabapentin around the time of giving birth, your baby may need extra monitoring for a few days after they’re born. This is because they may have withdrawal symptoms from gabapentin.

We do not know what the long term effects of taking gabapentin in pregnancy may be on childhood learning and development. For safety, you’ll usually be advised to take it only if the benefits of the medicine outweigh the risks. Talk to your doctor about the benefits and risks.