Question

You are working as a nurse in the medical-surgical unit. You are preparing the discharge instructions for your patient Mr. Jones. After you explained his list of medications with him his wife asks you how does the pill that he is going to be prescribed gets to his heart.

1. Use the four processes of pharmacokinetics to describe how medications work.
2. identify the pharmacodynamics and pharmacokinetic changes related to age in older adults. Identify the physiologic changes associated with increased age related to pharmacokinetics.

Answer 1

Four processes of pharmacokinetics are Absorption, Distribution, Metabolism, and Excretion (ADME).

1) ABSORPTION

It is defined as the passage of drug from the site of administration into the circulation of the body.For a drug to reach the site of action, it has pass through different membranes depending on the route in which the drug is administered. Absorption occurs either by passive diffusion or active transport.

Factors influencing rate and extent of absorption are:

1. Disintegration and dissolution of the drug.
2. Formulation
3. Particle size
4. Lipid solubility
5. Ph and ionization- ionized drugs are poorly absorbed while unionized drugs are lipid soluble and well absorbed.
6. Area and vascularity of the absorbing surface - Larger the area better the absorption.
7. Gastrointestinal motility.
8. Presence of food.
9. Metabolism
10. Diseases of the gut like malabsorption and achlorhydia result in reduced absorption.

2) DISTRIBUTION

After a drug reaches the systemic circulation, it should cross cross various barriers before reaching the site of action. Some of the factors affecting distribution are:  

1. PLASMA PROTEIN BINDING - After reaching circulation, most drugs bind to plasma proteins and the free unbound fraction of drug will be available for action. Protein binding prolongs the duration of action of the drugs.

2.TISSUE BINDING - For example, lipid soluble drugs like thiopentone sodium are bound to adipose tissue. It also serves as a reservoir of the drug.

3. BLOOD-BRAIN BARRIER(BBB) - only lipid soluble, unionized drugs can cross this BBB.

4. PLACENTAL BARRIER - lipid soluble and ionized drugs readily cross the placenta while lipd insoluble drugs cross to a much lesser extent.

3) METABOLISM or BIOTRANSFORMATION

• It is the process of biochemical alteration of the drug in the body. The most important organ of metabolism is the liver.
• Through metabolism, generally drugs are inactivated, but some drugs may be converted to to active forms. Prodrug is an inactive drug which gets converted to active form in the body.

Chemical reactions of metabolism takes place in two phases.

1. PHASE 1 REACTIONS - converts the drug to a more polar metabolite by oxidation, reduction or hydrolysis. If it is not sufficiently water soluble to be excreted, it undergoes phase 2 reactions.

2. PHASE 2 REACTION - water soluble substances like glucuronic acid, sulfuric acid, glutathione or an amino acid combine with the drug to form a highly polar compound which is inactive and readily excreted by the kidneys. Larger molecules are excreted through bile.

4) EXCRETION

  Drugs are excreted after being converted to water soluble metabolites while some are eliminated without metabolism.

1. RENAL EXCRETION - kidney is the most important organ of drug excretion. The three processes involved in the elimination are glomerular filtration, active tubular secretion and passive tubular secretion. Highly lipid soluble drugs are reabsorbed in the renal tubules, therefore their excretion is slow.
2. FECAL AND BILIARY EXCRETION - unabsorbed portion of the orally administered drugs are eleminated through feces. Large waters soluble conjugates are excreted in the bile.
3. PULMONARY EXCRETION - lungs are the main route of elimination for gases and volatile liquids.
4. Small amounts of some drugs are eliminated through sweat and saliva.

  2) The pharmacokinetics of many drugs change with age in altered response in extremes of age. For example , in newborns, the liver and kidneys are not fully mature to handle certain drugs, such as chloramphenicol can produce grey baby syndrome. As the blood brain barrier is not well developed, the drug can easily reach tge brain and can cause adverse effects.

• The gastric acidity is low, intestinal motility is slow, skin is delicate snd and permeable to drugs applied topically. Hence, the calculations of the dose to be administered should appropriate depending on the body weight to avoid toxicity.
• Pharmacodynamic differences can also exist such as barbiturates which produce sedation in adults may produce excitation in children.
• In old age people also the capacity of liver and kidneys to handle the drugs would be reduced. For instance, they are at high risk of ototoxicity and nephrotoxicity by streptomycin.

3) When we look into the psychological changes associated with increased age related to pharmacokinetics, we can see that there exist different factors depending on the mentality of the individual.

One half would consider that his/her condition is worsening day by day as he/she has to take these many medications to stay healthy. This can cause negative psychological effects which can affect the body functions as well.

Whereas, the other group of people may believe that these medications will help them stay healthy and the proper administration of these medications will lead to a better health condition. This type of mentality can lead to PLACEBO EFFECT. In which the patient receives psychological benefits moreover physiological benefit.