Drugs as stated by Luty and Harrison (1997) are chemical compounds which produce a desirable physiological or psychological effect when administered. This essay will discuss two different drugs which are used in the treatment of Parkinson’s disease, co-beneldopa and selegiline hydrochloride. All drugs are absorbed, distributed and then excreted (Luty and Harrison, 1997), so this essay will discuss pharmacokinetics and look at what happens to the drug once it has been administered and what effects the drug has on the body (Neal, 1992), It will also look at pharmacodynamics, the way the body affects the drug (Neal, 1992).
Parkinson’s disease is a neurodegenerative condition and second to Alzheimer’s disease (Allcock, 2007). It is a progressive neurological condition and affects one person in every five hundred, which is about one hundred and twenty thousand people in the United Kingdom (Parkinson’s UK, 2011). Most Parkinson’s disease sufferers are aged fifty or over but younger people can get it too, one in twenty is under the age of forty (Parkinson UK, 2011). An earlier onset can be due to acute encephalitis, carbon monoxide poisoning or metallic poisoning (Beckford-Bell, 2006). The disease results in motor symptoms including tremor, rigidity, postural instability and bradykinesia a slow ability to move and continue movements.
Parkinson’s disease is the steady deterioration of dopamine releasing neurons in the substania nigra (Luty and Harrison, 1997). Without dopamine people can find that their movements become slower so it takes longer to do things (Parkinson’s UK, 2011).
Parkinson’s disease process develops as the cells in the Substantia nigra, the crescent shaped cell mass in the brain stem are destroyed (ADAM, 2011). Parkinson’s disease affects movement, muscle control, and balance. Nerve cells in the substantia nigra send out fibres to tissue located in both sides of the brain. There the cells release essential dopamine neurotransmitters that help control movement and coordination (ADAM, 2011).
Currently, there is no cure for Parkinson’s disease and as yet no knowledge as to why people get the condition (Parkinson’s UK, 2011). Parkinson’s doesn’t directly cause people to die, but symptoms do get worse over time (Parkinson’s UK, 2011). Parkinson’s doesn’t directly cause people to die, but symptoms do worsen over time (Parkinson’s UK, 2011) which does have a contributory factor to mortality rates.
Pharmocokinetics is a branch of pharmacology that is concerned with both the rates at which the drug is absorbed and eliminated and what influences the time the drug moves between one biological compartment and another (Hollinger, 2003). Most drugs are given orally and enter the blood stream by passing through the gut wall (Neal, 1992). Most drugs are recognised by the liver as a toxin and are broken down into metabolites (Campbell, 2011). First pass metabolism is when the strength of a drug becomes reduced before they can be circulated throughout the entire system satisfactorily (Disease.com, 2010).
The first pass refers to the first trip ingested drugs take through the liver, once it has passed through only a small amount of the drug is passed on to the rest of the system. First pass metabolism is usually only associated to drugs that are taken orally. After certain drugs are ingested by the body, they are absorbed by the digestive system after being metabolised through digestion (Disease.com, 2010). After the drugs have gone through first pass metabolism the absorbed drugs enter the hepatic portal system, where they are carried by the portal vein to the liver (Disease.com, 2010). If first pass metabolism occurs, it means that the liver will not allow enough of the drugs to pass into the blood stream to be effective at helping the condition they are being taken for (Disease.com, 2010).
This is known as bioavailability, which is a term to describe the proportion of the drug administered reaching the systemic circulation. If a drug is taken by intravenous injection the bioavailability is one hundred percent as it is not metabolised through the liver. The bioavailability of a drug does vary with different drugs and from patient to patient (Neal, 1992). A standard reaction of the liver is first pass metabolism and it is a reaction to certain drugs, or a particular drug or a number of drugs (Neal, 1992). This may be caused by a deficiency of the drug or a patient may have a condition than can affect the drug (Neal, 1992). When it is the drug that is the problem, the pharmaceutical company have many options to resolve it.
For example, keeping the drug in the same preparation, they can increase the concentration of the drug, or combining other compounds which are designed to facilitate the passage of the drug through the digestive system and the wall of the gut. Although, this can be risky as an excess amount of the drug can impair metabolic function and in turn lead to harmful quantities in the systemic system (Neal, 1992).
However, if a drug is highly sensitive to first pass metabolism, then the pharmaceutical company will find another way to administer the drug which will bypass the digestive system and the liver, sending the drug directly into the systemic circulation. Administrating drugs this way, avoids the liver and is in the systemic circulation fully concentrated to be carried through the system, an example of this would be sublingual administration (Neal, 1992). The other factor that can affect first pass metabolism is the liver itself. Chronic liver disease can lead to an increase in bilirubin which may compete for binding sites on protein (Laurence, Bennett and Brown, 1997).
Once administered and the drug has gone through first pass metabolism, the drug attaches to plasma proteins which are formed in the liver (Campbell, 2011). The main binding protein is albumin (Laurence, Bennett, Brown, 1997). It has a complex structure which binds drugs but is also readily releases them (Laurence, Bennett, Brown, 1997). Protein binding reduces the availability of a drug for diffusion or transport into the target organ because only the unbound form of the drug is capable of diffusion across membranes (Golan et al, 2008). Plasma bound drugs are confined to the vascular system and are not able to exert their pharmacological actions (Neal, 1992).
There are many factors that can effect drug distribution with regards to plasma protein binding. One is the administration of two drugs both of which are highly bound to plasma protein, which would result in higher than expected plasma concentration of the free form of one or both drugs (Golan et al, 2008). This increase of free drug has the potential to cause an increase in therapeutic and/or toxic effects of the drug (Golan et al, 2008). A decrease in plasma protein binding capacity in the elderly is another factor that affects drug distribution and it has been attributed to changes in renal failure and its decrease is fifteen to twenty five percent (Ginsberg et al, 2005). The reduced protein binding capacity can lead to a higher potential to drug-drug interactions (Ginsberg et al, 2005).
As an active drug decreases in its concentration in the blood, drug metabolism and excretion shorten the time during which a drug is capable of acting on the target organ (Golan et al, 2008). Half life of a drug is defined as “the amount of time over which the drug concentration in the plasma decrease to one-half of it original value” (Golan et al, 2008). Having the knowledge of a drugs half-life allows a clinician to estimate the frequency of dosing required to maintain plasma concentration of the drugs therapeutic range (Golan et al, 2008).
When arranging a drug regime, careful consideration should be made as the effects from a drug with a long half life, as it may last for a number of days (Golan et al, 2008). Purse (2007) states that no matter what the half life of a drug, it will always take four half lives for the concentration of the drug in the system to reach a steady rate. For an example taking a medication with a half-life of twenty four hours, on the fifth day the rate of intake of the drug will approximately equal the rate of elimination. If the half-life is twelve hours, it will reach that state at the beginning of the third day (Purse, 2007).
As mentioned earlier two drugs used in the treatment of Parkinson’s disease are selegiline hydrochloride and co-beneldopa. Selegiline is a selective monoamine oxidase B inhibitor, however in larger doses it loses its specificity and will also inhibit monoamine oxidase A (Drugsupdate.com 2011). A monoamine oxidase B inhibitor prevents the breakdown of dopamine in the brain by blocking the enzyme monamine oxidase type B, Ahlskog, (2009 and Grosset et al, (2009) cited by Lindahl and MacMahon, (2011)). In the early progression of Parkinson’s disease, selegiline can be used as a monotherapy or later on in the progression of the disease with levodopa (Chan et al, 2004).
The use of selegiline can delay the need for treatment with levodopa. Neal (1992) states that there is evidence to show the progression of the disease may slow with the use of selegiline. Although Chan et al (2004) states that any claims of treatment with any Parkinson’s disease drugs slow down the disease progression or repair neuronal degeneration should be viewed with scepticism. A study was undertaken in Sweden to study the effects of selegiline in monotherapy and in combination with levodopa in the early phase of Parkinson disease.
One hundred fifty-seven Parkinson’s disease patients were randomly chosen in a controlled study for a duration of 7 years, to look at the long term effects of the drugs. The results for selegiline as a monotherapy showed that it significantly delayed the initiation of levodopa therapy vs placebo. The study concluded by confirming earliy findings indicated that selegiline delays the progression of the signs and symptoms of Parkinson disease (Neurology, 2006)