Elementary Pharmacology


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In order to really understand some of the differences between the various drugs, one needs to know some basic pharmacology.  

RECEPTOR This is the part of a nerve cell that responds to the drug you are taking.  There are different types of receptors that respond to morphine.  The pain relief you get from morphine like drugs is mainly through the mu subtype of opiate receptors.  There is also a kappa sub-type of opiate receptor.  This gives additional pain relief.  There are other subtypes of opiate receptors that are not as well studied.  Sedatives, such as Xanax, Valium, Klonopin, and Fioricet will stimulate the GABA receptor.  There is also an NMDA-type glutamate receptor involved in pain transmission and negative emotional states.  

AGONIST This is a drug that stimulates a receptor.  Heroin and Vicodan are agonists at the mu receptor (and kappa as well).  They maximally stimulate the receptor (each molecule is able to fully open the receptor channel.   

PARTIAL AGONIST This is a drug that stimulates the receptor but cannot produce a maximal affect. I find it easy to conceive of it as each molecule of drug is only able to partly open the receptor channel.  This is why buprenorphine cannot give maximal pain relief.   However, it also seems to be the reason why euphoria is less when buprenorphine and other partial opiates are used.  

ANTAGONIST This is a drug that goes into a receptor and does not stimulate it.  However, it will prevent an agonist from stimulating the receptor.    Narcan and Naltrexone are antagonists of the mu receptor and therefore act as blockers of other drugs such as heroin and hydrocodone.  Buprenorphine is an antagonist at the kappa receptor although a partial agonist at the mu receptor.  In order for an antagonist to work, it must have a higher affinity (below) for the receptor than the drug it is trying to block; or, it must be present in a much higher concentration.  

AFFINITY This refers to how tightly the receptor holds the drug.  When a drug is interacting with the receptors, it is constantly falling off and reattaching.  A drug with a higher affinity is more tightly held and will fall off far less.  Eventually, it will come to occupy a majority of the receptor sites and act as a blocker to any other drugs that may be present.  The antagonist medications mentioned above (i.e. Narcan) all have higher affinities for the receptor than heroin, Vicodan etc.  

HALF LIFE This refers to the time it takes for the body to metabolize half the drug in the system.  After one half life there is 50% of the drug left;  after 2 half lives there is 25% of the drug left.  It takes five half-lives for drug levels to stabilize in the bloodstream and for the body to effectively eliminate the drug.   A drug with a short half-life is considered short acting while long acting refers to a drug with a long half-life.  Short acting drugs tend to achieve therapeutic levels in the bloodstream faster; so they work with a much faster onset of action.  Long acting drugs usually need to accumulate over time before they have a therapeutic effect.  Long acting drugs can be given less frequently and still maintain stable drug levels.    When a long acting drug is given with the same frequency as short acting drugs, there is still a benefit since the serum levels will be more stable and the clinical effects more enduring.  For this reason, all else being equal, long acting drugs should be used whenever possible for treatment of symptoms   A drug with a short half-life usually has a quick onset of action.  That quick onset of action seems to be responsible for the euphoria experienced when addictive drugs are used.  The use of a long acting drug will cause less euphoria.  It is therefore less likely to result in cravings and loss of control. It is less addictive.  

DELAYED RELEASE DRUGS   Over the past 15 years, new formulations of drugs have come out.  MsContin, Oxycontin and Duragesic patches are some of theses.  They contain only short acting drugs (morphine, oxycodone and fentanyl respectively).   However, these formulations are designed to release the drug over a longer period of time.  Since the drugs are released over time, the pills do not have to be taken as often.    There are drawbacks compared to true long acting drugs.  The delayed release mechanism can be bypassed, resulting in the quick absorption of a large amount of medication.  That is why the drugs are widely abused.  Also, once fully absorbed, the drugs are more quickly metabolized so that therapeutic effects are quickly lost if a pill is missed and withdrawal can quickly occur.

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