Question

Discussion: Pharmacokinetics and Pharmacodynamics

As an advanced practice nurse assisting physicians in the diagnosis and treatment of disorders, it is important to not only understand the impact of disorders on the body, but also the impact of drug treatments on the body. The relationships between drugs and the body can be described by pharmacokinetics and pharmacodynamics.

Pharmacokinetics describes what the body does to the drug through absorption, distribution, metabolism, and excretion, whereas pharmacodynamics describes what the drug does to the body.

When selecting drugs and determining dosages for patients, it is essential to consider individual patient factors that might impact the patient’s pharmacokinetic and pharmacodynamic processes. These patient factors include genetics, gender, ethnicity, age, behavior (i.e., diet, nutrition, smoking, alcohol, illicit drug abuse), and/or pathophysiological changes due to disease.

For this Discussion, you reflect on a case from your past clinical experiences and consider how a patient’s pharmacokinetic and pharmacodynamic processes may alter his or her response to a drug.

To Prepare

• Review the Resources for this module and consider the principles of pharmacokinetics and pharmacodynamics.
• Reflect on your experiences, observations, and/or clinical practices from the last 5 years and think about how pharmacokinetic and pharmacodynamic factors altered his or her anticipated response to a drug.
• Consider factors that might have influenced the patient’s pharmacokinetic and pharmacodynamic processes, such as genetics (including pharmacogenetics), gender, ethnicity, age, behavior, and/or possible pathophysiological changes due to disease.
• Think about a personalized plan of care based on these influencing factors and patient history in your case study.

By Day 3 of Week 1

Post a description of the patient case from your experiences, observations, and/or clinical practice from the last 5 years. Then, describe factors that might have influenced pharmacokinetic and pharmacodynamic processes of the patient you identified. Finally, explain details of the personalized plan of care that you would develop based on influencing factors and patient history in your case. Be specific and provide examples.

Answer 1

? pharmacodynamics processes of a patient and assess the details of a personalized plan of care that you develop based on influencing factors and patient history. You will also evaluate and analyse ethical and legal implications and practices related to prescribing drugs, including disclosure and nondisclosure, and analyse the process of writing prescriptions to avoid medication errors.

? As an advanced practice nurse, understanding these fundamental pharmacotherapeutic concepts is important to ensure that the prescription drugs you recommend for your patients will be safe and effective to treat and/or manage their symptoms. Additionally, as the advanced practice nurse, it is your responsibility to ensure that when prescribing prescription drugs, you adhere to the ethical and legal principles set forth for prescribing drugs as an added layer of protection and safety for the patients you will treat.

? Learning Objectives

?· Analyse factors that influence pharmacokinetic and pharmacodynamic processes in patients

?· Assess patient factors and history to develop personalized plans of care

?· Evaluate ethical and legal implications related to prescribing drugs

?· Analyse ethical and legal practices of prescribing drugs

?· Analyse strategies to address disclosure and nondisclosure

?· Justify advanced practice nurse strategies to guide prescription drug decision-making

?· Analysethe process of writing prescriptions to avoid medication errors

? Case studies

?The diagnosis of myasthenia gravis can be confirmed by the ‘edrophonium test’. Edrophonium
is injected i.v. (2 mg initially which if tolerated; followed by 8 mg after 30–60 sec). Reversal
of ptosis, diplopia and increase in the strength of affected muscles lasting 5–10 min constitutes
✨positive result.
In case edrophonium is not available, the test can be performed with neostigmine 1.5 mg
i.v. Atropine 0.6 mg may be given i.m./i.v. to block the muscarinic side effects of edrophonium/
neostigmine.
✨ Myasthenia gravis is an autoimmune disorder due to production of antibodies against the nicotinic
receptor at the muscle end-plate. No drug is curative. Both anticholinesterases (neostigmine,
etc.) and corticosteroids (other immunosuppressants as well) afford only symptomatic relief
till administered. The former preserve ACh and improve neuromuscular transmission, while
the latter inhibit the immunological reaction, without removing the cause of the illness.
✨ In many cases (especially older men), thymus is the source of the nicotinic receptor antigen.
As such, thymectomy has been found to lower disease activity and even induce long-lasting remission

?. The symptoms and intraocular pressure (i.o.p.) of this patient indicate that she is having
gluaucoma in both eyes. Phenylephrine (10%) eyedrop would be the suitable mydriatic for
her. Phenylephrine is an α1 adrenergic agonist that dilates the pupil by increasing the tone
of radial muscles of iris, which are adrenergically innervated. It does not produce cycloplegia
because the ciliary muscles lack adrenergic motor innervation. Cycloplegia causes blurring
of near vision and is not required in this patient. Phenylephrine is not likely to raise i.o.p.
in glaucoma patients. On the other hand, antimuscarinic mydriatics like tropicamide,
cyclopentolate, etc. produce both mydriasis and cycloplegia, and tend to raise i.o.p. in glaucoma
patients. Therefore, antimuscarinics are to be avoided in glaucoma patients.

? ?Since carbimazole inhibits further synthesis of thyroid hormones (T3, T4) without affecting
their release or action, the hormone stored in the gland continues to be released and produce
effects. Moreover, thyroxine has a long plasma t½ of 6–7 days. Thus, the effect of carbimazole
starts manifesting only after 2–3 weeks and peaks after 2–3 months.
Many of the symptoms of thyrotoxicosis are due to sympathetic overactivity. Blockade of
β adrenergic receptors (β1 and β2) by propranolol or similar drug affords rapid symptomatic
relief, without affecting thyroid status. A nonselective β-blocker given to her along with
carbimazole could have controlled palpitation, tremor, etc. within a few days. This drug could
be withdrawn when carbimazole had taken effect.
?The reappearance of neck swelling without any symptom of thyrotoxicosis indicates that it
is due to deficient feedback inhibition of TSH by a suboptimal thyroid hormone level as a
result of higher maintenance dose of carbimazole. This is supported by the mild hypothyroid
symptoms experienced by the patient and the raised TSH level alongwith low normal FT4
level. The raised TSH is stimulating the thyroid so that despite its low functional status, deficiency
is not marked. Since the disease activity in Graves’ disease may decline after some time, the
maintenance dose of carbimazole needs to be adjusted from time-to-time according to the
assessed clinical and laboratory thyroid status of the patient. This patient requires temporary
discontinuation of carbimazole followed by a lower maintenance dose as assessed later.

?. This is a case of advanced metastatic prostate carcinoma, for which only palliative
therapy with androgen deprivation (tumour cells remain androgen dependent) is
possible. When orchidectomy has been refused, the most effective method of androgen
deprivation is to give a long acting GnRH agonist. Thus, the choice of triptorelin is correct.
The GnRH agonists initially increase LH (also FSH) release for 1–2 weeks, followed by receptor
desensitization and nearly total blockade of LH secretion by 3–4 weeks. The raised LH levels
in the beginning stimulate testis to secrete more testosterone which activates tumour cells
resulting in increased bone pain and bladder obstruction noticed after 1 week of therapy
in this patient.
?The initial flaring of symptoms can be avoided by pretreating with an antiandrogen bicalutamide
50 mg orally daily for 3 days before starting triptorelin injection and then continuing both
drugs together. The stimulatory effect of excess testosterone on tumour cells would be blocked
by bicalutamide so that no flaring of symptoms would occur. The combined androgen blockade
with GnRH agonist + androgen antagonist is the favoured approach.
? The patient can be given an antiresorptive drug in addition to relieve bone pain. A potent
parenteral bisphosphonate like zoledronate infused i.v. over 15 min every 1–4 weeks is the
most effective drug for this purpose. It may also retard growth of the bony metastasis for
some time.

?The parkinson’s disease of this patient appears to have advanced over the last 5 years and
he is now experiencing ‘wearing off effect’ of levodopa-carbidopa. He is also developing
dyskinesia, a late adverse effect of the drug. At this stage, antiparkinsonian medication cannot
be withdrawn, because he will develop marked rigidity, immobility and tremor hampering
life activities. He is already experiencing an adverse effect of his medication; therefore, the
dose should not be increased further.
Since levodopa-carbidopa is the most efficacious and cheapest medication for parkinsonism,
it may be prudent to continue it at a reduced dose and supplement it with another longer
acting drug to smoothen the therapeutic effect. The options available as supplementary
medication are:
? A direct dopamine agonist like ropinirole/pramipexole can be gradually added to levodopa-
carbidopa whose dose should be reduced in steps. Both drugs can be taken concurrently
3 times a day. Ropinirole/pramipexole being longer acting will smoothen symptom control.
They also produce less dyskinesia.
?A MAO-B inhibitor like selegiline 5 mg twice a day or rasagiline 1 mg once a day in
the morning will prevent degradation of dopamine in the brain, prolonging and smoothening
effect of levodopa-carbidopa.
?Entacapone 200 mg with each dose of levodopa-carbidopa can also potentiate and prolong
levodopa action by inhibiting another metabolizing enzyme COMT. It can also be an additional
third drug to levodopa-carbidopa + selegiline for greater symptomatic relief.

⚫Passage of dark urine indicates bleeding in the kidney. This along with blood loss per vaginum
has resulted in acute fall in Hb level. The rise in INR value is indicative of excessive deficiency
of clotting factors, especially of prothrombin, factor X and factor VII due to relative warfarin
overdose. The obvious cause in this patient is the additive hypoprothrombinaemic action
of inj ceftriaxone given for treatment of pelvic infection.
This complication could have been prevented either by selecting an antibiotic that does
not cause hypoprothrombinaemia/interact with warfarin or by reducing the dose of warfarin
when ceftriaxone was started. The new warfarin dose should have been arrived at by repeated
determination of INR value till ceftriaxone was being given.
☔Further warfarin dose must be stopped immediately and vit K 10 mg injected i.m. at the
earliest. The patient must be put on bed rest to reduce bleeding. Because Hb level is
9 g/dl, blood transfusion is not required at this stage, but must be kept handy in case she
bleeds further. Repeat doses of vit K (5.0 mg i.m.) should be guided by frequent INR measurement
and the severity of bleeding, avoiding too much vit K that would interfere with the protective
effect of warfarin subsequently. Changing the antibiotic to one which does not cause
hypoprothrombinaemia or bleeding may be considered on the basis of bacteriological sensitivity
of the organism causing pelvic infection.