Pharmacokinetics and Pharmacodynamics - Literature review Example

Pharmacokinetics and pharmacodynamics Introduction Pharmacology is the study of connections between living tissues and chemicals and provides the rational basis for therapeutics. It is a field that is comprised of many divisions, among them, pharmacokinetics and pharmacodynamics. In order to deliver the right amount of drug for a reasonable length of time so as to get desired beneficial outcomes while reducing adverse effects, it is important to consider the relationship between the drug’s pharmacokinetic and pharmacodynamic properties. This article focuses on the basic principles of pharmacokinetics and pharmacodynamics (Evans, and 2001). Definitions of pharmacokinetics and pharmacodynamics Pharmacokinetics, abbreviated as PK, refers to the movement of drug into, through and out of the body. It is often described as what the body does to a drug, illustrating the time course of the drug’s absorption, bioavailability, distribution, metabolism and excretion (Evans, and 2001). Practically, this discipline is usually applied to drug substances, but in principle, it concerns all types of compounds ingested or delivered externally, such as hormones, metabolites, toxins or nutrients, into an organism. Pharmacokinetics of a drug depends on the chemical properties of the drug as well as patient related factors such as sex, age and genetic makeup (Franconi, et al, 2007). Pharmacokinetics is normally studied in concurrence with pharmacodynamics. Pharmacodynamics, a branch of pharmacology and abbreviated as PD, is the science of the drug action. It actually looks into the physiological effects of drugs on the organism’s body and the mechanisms of drug action describing the relationship between the drug effect and concentration. It is normally depicted as what a drug does to the body and involves receptor binding, post receptor effects and chemical interactions. Relation between pharmacokinetics and pharmacodynamics For many practical people such as animal breeders and industrial producers, variation in their product is a great bother. In medicine too, variation is a practical art and on a superficial level, it can be considered that variation in response to drug therapy is also a great bother (Franconia, et al, 2007). Variations therefore, are the main reason why people study genetics. A drug can be defined as any substance, whether synthetic or natural, that has the ability to change the physiological state of a living organism. It may have either a toxic or therapeutic effect. However, the response to a drug differs from one individual to another due to various reasons such as genetic factors, diseases and environmental factors (Wilkinson, 2008). Drug therapy entails four basic processes, namely, pharmaceutical process, pharmacokinetic process, pharmacodynamic process and the therapeutic process. The pharmaceutical process concerns drug administration into the patient. The process depends on the properties of the drug formulation and patient compliance, which will determine whether the drug will be absorbed from the gut, skin, muscle or not. The pharmacokinetic process is concerned with the drug getting to its site of action and depends on absorption, distribution, metabolism and excretion of the drug (Graham-Smith and Aronson, 1992). The pharmacodynamic process is concerned with the effects exerted by the drug at its site of action. The effect may either be therapeutic or adverse. Variations from one individual to another may cause the various processes of drug therapy to vary, hence giving a variation in drug response (Galbraith et al, 2007). Factors which lead to individual variation in response to drug therapy Age The effects of drugs vary among people of diverse age groups. Drug metabolism is poor in young children because the hepatic clearance is slow, thus prolonging the half life of drugs. Children have different drug pharmacodynamics compared to adults. For instance, antihistamines which tranquilize adults may be excitatory in children (Galbraith et al, 2007). In neonates, renal excretion of drugs is also said to be slow. Among the elderly, the function of the excretory organs and body composition deteriorate with age. The levels of body fluid reduce with age as the amount of fatty tissue increases. Fat soluble drugs are dispensed in adipose tissues, lessening the amount of free drug at the receptors and extending the duration of action. There is also increased sensitivity to adverse effects of drugs such as hemorrhage from anticoagulants (O’Mahony and Woodhouse, 1994) Gender The differences in gender may affect the bioavailability of certain drugs. For example, the bioavailability of oral drugs differs from females to males, due to the difference in the concentration of enzymes responsible for drug metabolism and gastrointestinal motility between men and women (Franconia et al, 2006). There is also a variation between the metabolism rates of certain drugs between men and women. Moreover, lipophilic drugs are more widely distributed among women as compared to men since women contain a higher proportion of fats. In addition, Franconia et al (2006) highlight that renal excretion of drugs is more in men than it is in women. Pharmacodynamic processes also vary from female to male. For instance, female are more sensitive to morphine compared to male, and on the other hand, ibuprofen has been found to be more active in men than in women (Franconia et al, 2006) Pharmacogenetics Pharmacogenetics refers to the study of genetic variations that cause variable responses to drugs and includes the study of drug receptors, drug metabolizing enzymes and genetic polymorphism of drug transporters (severino and Del Compo, 2004). Receptor genes mutations can at times make cells to be hypo-responsive to certain ligands. For instance, mutations in the vitamin D receptor may make them to have a lower affinity than the normal vitamin D receptor, thus resulting in decreased responsiveness to hormone and cellular resistance (Lu, 1998). Genetic variations in drug transporters may also lead to pharmacokinetic variations among individuals. For instance, transporters for neurotransmitters reveal genetic variations and have been associated with variations in drug response (Evans and Johnson, 2001). In addition, variations in protein binding have been seen among individuals due to variations in the quantity and quality of the plasma proteins, especially serum albumin and acid glycoprotein (Franconia, et al, 2007). Hepatic and renal function An important site for drug metabolism in the body is the liver. Therefore, liver diseases can lead to accumulation of drugs to toxic levels or prolonged effects of the drug. However, the impact of liver disease depends on the pharmacokinetic properties of the drug (Galbraith et al, 2007). Kidney diseases may also have an effect on the blood concentration of many drugs. Drugs such as digoxin, amino glycosides and penicillin are often unchanged from their administered form and thus, inability to excrete these drugs may result in toxic effects in the bodies of patients with renal diseases (Galbraith et al, 2007) Diet Differences in drug response also come as a result of dietary variations (Wilkinson, 1997). Presence of food in the gut during drug administration may affect absorption as nutrient molecules compete with drug molecules at absorption sites. A diet rich in protein may speed up the clearance of theophylline and antipyrine, while caffeine and cruciferous vegetables such as broccoli, cabbage and cauliflower are known to enhance drug metabolism (O’Mahony and Woodhouse, 1994). Other factors that cause inter-individual variations with regard to drug response include drug disease interaction, occupational activity, alcohol consumption, smoking, pregnancy, body weight and circulatory insufficiency. Adverse Drug Event An Adverse Drug Event, abbreviated as ADE, is an injury resulting from the use of a drug. It includes harm caused by the drug such as overdoses and adverse drug reactions and harm from the use of the drug including discontinuations of drug therapy and dose reductions. Adverse Drug Events may occur as a result of medication errors though most do not. Adverse Drug Reaction This is defined as harm directly caused by the drug at normal doses during normal use. Most adverse drug reactions are quite mild and some may disappear when the drug is stopped or dose is changed. The most common types of drug reactions include nausea, constipation, diarrhea and loss of appetite (Franconia, et al, 2007). Medication error This is a mishap that happens during drug administration, dispensing, prescribing and transcribing. An example of a medication error may include misreading or miswriting a prescription. Difference between Adverse Drug Event, Adverse Drug Reaction and Medication Errors Adverse drug events include injuries caused by overdoses, adverse drug reactions, dose reductions and discontinuations of drug therapies. They may also occur as a result of medication errors. This is an inclusive term describing injuries resulting from the use of a drug either in the correct way or in the manner not prescribed by the doctor. However, adverse drug reactions refer to injuries that happen to an individual as a result of the right use of a drug. It often contradicts the intended therapeutic outcome. It is therefore necessary to note that adverse drug reactions result from the right use of a drug. Medication errors on the other hand are accidents that occur during drug administration or dispensing whereby the clinical officer or patient misread or miswrite a prescription. Factors which can increase the risk of adverse drug events from a patient perspective Many adverse drug events result from known pharmacologic properties, while some result from medication errors (Hussar, 2007). However, some are generated from patient specific factors. Little is known regarding how well hospitalized patients can recognize injuries or errors in their care. Studies show that some of the factors that can increase the risk of adverse drug events from the patient perspective include medication non-adherence, pharmacist-patient miscommunication, and patient medication error, and self-medication, failure to read medication label, polypharmacy and patient characteristics. Research studies also prove that there is a correlation between adverse drug events and increasing age (Vessel, 1991). Frail elderly patients appear to be most vulnerable to adverse drug events and it is also noted to be the age group that is likely to be getting several medicines. For instance, patients with an already impaired homeostatic or excretory process as a result of weakened reserve capacity such as the elderly are more susceptible to adverse drug events. The very young are also considered more vulnerable to adverse drug events since their immune system is not fully developed and thus some drugs may be too strong for them or may have adverse effects to their bodies (Linotile et al, 1979). Factors which can increase the risk of adverse drug events from the healthcare system perspective Regarding the healthcare system perspective, increased risk of adverse drug events often results from medication errors, such as wrong prescription of drugs, and miscommunication to the patients on how to use the drugs. Medication errors often occur at any point in the medication administration process and particularly during the ordering and administration stages and have an impact on the health of a patient, which is normally considered more adverse among the elderly and young children. How adverse drug events can be avoided or minimize Approximately one million people al over the world die or are injured each year due to adverse drug effects. Adverse drug events lead to various physical consequences ranging from allergic conditions to death. One study indicated that approximately nine point seven percent of adverse drug events resulted in permanent disability. One of the primary causes of adverse drug events is medication errors. These occur at any point in the medication administration process and particularly during the ordering and administration stages. Since most adverse drug events among the elderly are predictable, good communication is crucial (Macleod, 1986). Pharmacists and all those people who prescribe drugs to patients should create an efficient therapeutic partnership with the patients in order to ensure that medication errors are eliminated. The application of computer based decision support systems and electronic prescribing should be encouraged to minimize prescription errors. Also, the nursing medication administration and monitoring systems should be improved to include changes such as bar coding medications alongside additional warnings on medications with higher potential for harm such as anticoagulants. On the patients’ side, a follow up system should be developed in order to ensure that patients adhere to their medications strictly (Franconia, et al, 2007). A better atmosphere should be created for the patients to report any cases of adverse drug events to healthcare professionals without fear of punishment or repercussions. Also patients should be taught about the need to comply to their medication schedule strictly and the effects of not doing so. Conclusion Pharmacokinetics is an essential scientific disciple that strengthens applied therapeutics. Patients should be prescribed appropriate medication for effective outcomes. Pharmacodynamics concerns what the drug does for the body. However, people differ when it comes to response to drugs. In some cases, correct administration of drugs may cause adverse effects to patients, condition known as adverse drug reaction causing disorders such as nausea and bloating. Medication errors also do occur due to factors such as misread prescription. This may counter the therapeutic effect of a drug and therefore, it is important for healthcare professionals to consider these disparities when it comes to drug prescription in order to produce an effective therapeutic effect. Reference: Evans, W and Johnson J. 2001. Pharmacogenomics: The Inherited Basis for Inter-Individual Differences In Drug Response. Annual review of genomics and human Genetics. 2(9), p. 9-39 Franconi, F. Brunelleschi, S. Steardo, L. Cuomo, V. 2007. Gender differences in Drug responses. Pharmacological Research, 55(2), p. 81-95 Galbraith, A. Bullock, S. Manias, E. Hunt, B. Richards, A. 2007. Fundamentals of Pharmacology: An Applied Approach For Nursing And Health. Second edition. England. Pearson Education Limited. Griffin, J.P. The Textbook of Pharmaceutical Medicine (6th Ed.). New Jersey: BMJ Books. ISBN: 9781405180351 Hussar, D A. 2007. Drug Interactions: Factors Affecting Response to Drugs. Available From http://www .merck.com /mmh e/s ec02/ ch013/ch013 c.htm l. Linnoila, M. Malttila MJ. Kitchell BS. 1979. Drug interactions with alcohol. Drugs. 18(4), p. 299-311 Lu, Y H A. 1998. V Drug-Metabolism Research Challenges in the New Millennium: Individual Variability in Drug Therapy and Drug Safety. Drug Metabolism and Disposition. 26 (12). p.1217-122 Macleod, S M and Soldin, S J. 1986. Determinants of drug disposition in man. Clinical Biochemistry. 19, p.67-71 O’Mahony, M S and Woodhouse, K W. 1994. Age, Environmental Factors And Drug Metabolism. Pharmacology and Therapeutics. 61, p. 279-287 Severino, G and Del Zompo, M. 2004. Adverse Drug reactions: role of pharmacogenetics. Pharmacological Research. 49(4), p.363-373 Vesell, E S. 1991. Genetic And Environmental Factors Causing Variation In Drug Response. Mutation Research. 247, p. 241-257 Wilkinson, GR. 2005. Drug Metabolism and Variability among Patients in Drug Response. The New England Journal of Medicine, 352(21), p.2211-2224 Read More