emiC -- brain question

[mathman444]

emiC -- brain question

Hi, emiC -- Can you tell me what the drug neurontin does and what it's side effects are? Can it make you irritable and crabby? Or am I just irritable and crabby anyway?

 

[emiC]

Re: emiC -- brain question

"what the drug neurontin does and what it's side effects are"

Some definitions first:

pharmacokinetics: study of what the body does to the drug (simply conceptualize it as how does the body digest/ metabolize and excrete the drug)

pharmacodynamics: study of what the drug does to the body ( mainly at the receptor level)

Neurontin or generic name: gabapentin

It is FDA approved for anticonvulsant (anti seizure/ epileptic drug) It is used by neurologists as adjunct for partial seizure and secondary generalized seizures. Off FDA label, it has been used to decrease anxiety (not exactly an anxiolytic) e.g. social phobia & panic disorder, for chronic pain control, and even to stablize mood (although data on mood stablization is only comparable to placebo)

You are asking a pharmacodynamic question:

GABA is an amino acid neurotransmitter (messenger that transmits messages from one nerve cell to the next) found almost exclusively in the <span style="color:red;">brain</span> There are 3 kinds of GABA receptors GABAa, GABAb, and GABAc

Gabapentin is a GABA (gamma aminobutyric acid) derivative that interestingly has no activity at the GABA receptor or transporter. The exact mechanism of action (why it works therapuetically) is unknown.

Adverse Side Effects include but not limited to : as reported in % adults

Central nervous system: somnolence 20%, dizziness 17%, ataxia 12%, fatigue 11%

Dermatologic: pruritus 1%

GI: wt gain : 3%, dyspepsia : 2%, dry throat: 2%

Neuromuscular: tremor: 7%, back pain : 2%, myalgia (muscle pain): 2%

Ocular: nystagmus 8%, diplopia 6%, blurr vision: 4%

Respiratory: rhinitis: 4%, pharyngitis: 3%, coughing 2%

I am sure it can make people irritable and crabby. It probably makes you crabby, and then you become irritable.

Pharmacokinetics:

T1/2 (half life, same concept as the radioactive half life) is 5 -7 hours. So it takes five half life after taking the last dose for 97% of the drug to be completely cleared from the body. It also takes five half life (and one has to take gabapentin three times a day) for any drug to build up to steady state concentration (Css is the concentration of drug in the body at the point where the amount of drug intake = amount of drug degradation/exceretion)

Gabapentin has to be taken 3 times a day, kind of inconvenient. One has to take a drug as often as half life or < half life (so if a drug has half life of 24 hrs, one can take the drug every 24 hrs or <24 hrs) in order for the drug to build up to Css.

excretion: excreted unchanged by the kidney (Gabapentin actually is not digested or metabolized by the liver at all)

I hope that helps.

<span style="color:red;font-size:medium;">Best Wishes</span>

 

[sk8m8]

Neurontin

Hey mathmann, I can give you the "lay" version of it. I've had it perscribed to me for neuropathy in the extremities. Unfortunetly it is more indicated for the stinging and aching type of neuropathy more than the "numbness" kind.

They oftentimes perscribe elevil( amytriptoline/sp?) which is an old fashioned "anti-depressant" for this condition, but many people can't tolerate it. Neurontin's effects are "serendipitous" in that it is a siezure drug and they have discovered many "side" benefits of the drug that it was not developed for.(as emci listed) It's often times given to "bypass" patients who've required vein grafts from their legs to repair heart damage. It leaves horrible shooting pains down the extrmeties and Neurontin does a great job of relieving the pains.

 

[emiC]

therapeutic and side effects

Kietics and Dynamics again

Drugs have effects on the body. The perfect goal is to have the effect of the drug be therapeutic. Drugs have two kinds of effects: therapeutic effects and side effects. The ideal drug for any therapeutic indication would have only therapeutic effects and no side effects. We have come a long way from amitriptyline, but we are not at utopia yet. There are no perfect drugs, but the best and most commonly used medications have a very high "therapeutic to side effect ratio."

Amitriptyline's therapeutic to side effect ratio is not as desirable as some newer ones.

It is a value judgment, however, whether a particular effect of the drug is a side effect or a therapeutic effect. This happens when drugs that were developed for one particular indication end up getting used for something quite different. One of the best examples of this is minoxidil, which was launched as a treatment for hypertension. It was noted that many people taking minoxidil who were bald started to grow hair back.

Half-life and Steady State again

The half-life of a given medication is how long it takes for the body to get rid of half of the dose. When someone is taking a medication on a regular basis, there is an ongoing process of drug absorption in the form of each dose of the drug and, an ongoing process of drug removal with the drug's metabolism and clearance. Eventually, there comes a point when the amount of drug going in is the same as the amount of drug getting taken out. This is the "steady state." It takes 5 T 1/2 for a medication to reach steady state.

Many drug effects occur primarily when the blood level of the drug is either going up or going down. When the drug reaches steady state, these effects can be either be decreased or completely absent, i.e. these effects only take place if there is <strong>a first derivative other than zero</strong>. Unwanted side effects from a particular compound are great deal more acceptable if they only take place on the way to steady state (transient). Another way to classify drug effects into 2 groups is to classify them into those effects that take place primarily while the blood level is changing and those effects that take place primarily when the blood level is stable at steady state. Ideally, for any drug, all of the unwanted effects would be in the former category and all of the therapeutic effects would be in the latter category.

Return back to gabapentin, it is reported to have a relatively favorable side effect profile. That is the report, I know if I have to experience sedation and dizziness, I would be very irritable myself.

 

[mathman444]

Re: therapeutic and side effects

Thanks for the dope -- I mean, the information -- emiC and sk8m8. I consider myself much the wiser. I don't know why doctors so often seem like they can't be bothered to tell you anything.

Mathman