Pharmacological Case Study: Pharmacokinetics and Pharmacodynamics

Pharmacokinetics refers to the study of the time course of drug absorption, distribution,
metabolism, and excretion. Clinically, pharmacokinetics refers to the application of the
pharmacokinetic principles to the safe and effective therapeutic management of drugs in a patient
depending on how their body absorbs, distributes, metabolizes, and excretes drugs from the
system (van den Anker et al., 2018). Simply put, this is the study of what the body does to the
drug after administration. On the other hand, pharmacodynamics refers to the study and
understanding the effects and mechanisms of action of drugs and what they do to the body after
administration (Sahinovic et al., 2018). It entails the relationship between drug concentrations at
the site of action and the resulting effect, including the intensity and time course of the
therapeutic and adverse effects determined by the drug’s binding receptor.
Pharmacokinetics affects medication by considering the bioavailability of drugs in the
same class or different formulations of the same drug, half-lives, or dose concentration curves.
Additionally, it determines the dosing schedule and influences interindividual variability in
dosing requirements (ADA, 2022). On the other hand, pharmacodynamics is essential to
selecting medication options according to their therapeutic index. Therefore, drugs with the dose
required to cause adverse effects against that required for drug efficacy are essential to
medication selection. Additionally, pharmacodynamics determines the steepness of the dose-
response curve that determines dose titration in different drugs. Avoiding adverse drug effects
can also be achieved by understanding the selectivity for receptor subtypes.

Part 2: Dosing and Side Effects

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Pharmacokinetics determines dosing frequency according to their specificity for the
target organ, metabolism or excretion in the liver, adverse effects on tissues reached, and the
likelihood of causing drug interaction through cytochrome P450 inhibition. Dosing frequency
can also be used to determine or encourage adherence to medication. Drugs with low plasma
concentration and therapeutic index require maintenance in a narrow therapeutic range and are
used in a sustained release formulation (Maxwell, 2016). Dosing intervals of about a half-life are
suitable for medications with half-lives between 8-24 hours and should be administered once,
twice, or three times daily. Pharmacokinetics also requires that drugs with shorter half-lives
should not be administered frequently. Additionally, medications can be administered at longer
intervals than the half-lives if they have a large therapeutic index associated with a large degree
of fluctuation over the dosing interval without toxicity at high peak concentrations.
Part 3: EBP Guidelines and Pharmacokinetic Impact
a) Patient Assessment 1: Diabetes Mellitus Type II with Hypertension (HTN)
i. Medication and dosing frequency
Metformin 500mg two tabs bid (twice a day), taken with the evening and morning meals.
The doctor can increase the dosage accordingly until blood sugar levels are successfully
regulated.
ii. Side Effects
More common side effects of Metformin include sleepiness, difficult or painful urination,
cramping or muscle pain, side or lower back pain, general feeling of discomfort, chills or fever,
shallow or fast breathing, diarrhea, reduced appetite, hoarseness of cough, and stomach or
abdominal discomfort. Less frequent symptoms include dizziness, labored or difficult breathing,
depression, pale and cool skin, confusion, coma, cold sweats, chest discomfort, blurred vision,

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anxiety, increased hunger, headache, feeling warmth, shakiness, seizures, nightmares,
nervousness, nausea, and pounding/irregular/fast/racing pulse or heartbeat.
iii. Pharmacokinetics Impact
With an oral bioavailability50-60 percent, Metformin is slowly absorbed under fasting
conditions. Therefore, the drug takes relatively longer periods to lower intestinal glucose
absorption and hepatic glucose production while improving insulin sensitivity by enhancing
peripheral utilization and uptake of glucose. Overall, this lowers blood glucose levels. However,
the drug does not result in hypoglycemia or hyperinsulinemia. In terms of metabolism,
metformin evidence shows that Metformin is not metabolized in the liver. The drug is negligibly
attached to plasma proteins, thus evenly distributed in the body. Roughly 90 percent of the drug
administered orally is excreted through the urinary system within 24 hours of ingestion. The
urine, blood, and plasma half-lives of Metformin are 5, 17.6, and 6 hours, respectively
(Dumitrescu et al., 2015).
b) Patient Assessment 2: coronary artery disease (CAD)
i. Medication and dosing frequency
The recommended drug for addressing coronary artery disease is low-dose ASA (aspirin)
once a day (Nagelschmitz et al., 2014).
ii. Side effects
Mild side effects include headaches, drowsiness, heartburn, and stomach upsets. In severe
cases, patients might experience pain or swelling lasting more than ten days, fever extending
beyond three days, tarry or bloody stool, vomiting or coughing blood, severe stomach pain or
vomiting/nausea, and seizures (convulsions, rapid breathing, hallucinations, confusion, and
ringing in ears.

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iii. Pharmacokinetics impact
Unlike Metformin, aspirin is quickly absorbed in the upper GI, inhibiting platelet
functions quickly within an hour. The drug has an oral bioavailability of 68 percent, clearance of
39 liters per hour, volume distribution of 10.5 L, and a half-life of 0.25 hours. Preventing blood
clotting in the arteries reduces the risk of coronary artery disease (Nagelschmitz et al., 2014).

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References

ADA. (2022). Cardiovascular disease and risk management: Standards of medical care in
diabetes—2022. Diabetes Care, 45(Supplement_1), S144–S174. https://doi.org/10.2337/DC22-
S010
Dumitrescu, R., Mehedinty, C., Briceag, I., Purcarea, V. L., & Hudita, D. (2015). Metformin-clinical
pharmacology in PCOs. Journal of Medicine and Life, 8(2), 187-192.
Maxwell, S. R. J. (2016). Rational prescribing: the principles of drug selection. Clinical Medicine,
16(5), 459. https://doi.org/10.7861/CLINMEDICINE.16-5-459
Nagelschmitz, J., Blunck, M., Kraetzchmar, J., Ludwig, M., Wensing, G., & Hohlfeld, T. (2014).
Pharmacokinetics and pharmacodynamics of acetylsalicylic acid after intravenous and oral
administration to healthy volunteers. Clinical Pharmacology, 6, 51-59. doi:
10.2147/CPAA.S47895
Sahinovic, M. M., Struys, M. M. R. F., & Absalom, A. R. (2018). Clinical pharmacokinetics and
pharmacodynamics of Propofol. Clinical Pharmacokinetics, 57(12), 1539–1558.
https://doi.org/10.1007/S40262-018-0672-3/TABLES/3
Van den Anker, J., Reed, M. D., Allegaert, K., & Kearns, G. L. (2018). Developmental changes in
pharmacokinetics and pharmacodynamics. The Journal of Clinical Pharmacology, 58(S10),
S10–S25. https://doi.org/10.1002/JCPH.1284