Read the following case study then: * Identify and briefly discuss the pathophysiology of Rodney’s medical condition. * Describe the pharmodynamics of each of the drugs Rodney was prescribed linking this to the pathology. * Justify the pharmacological regime, including choice of drug, changes to the regime, dosages and scheduling, and routes of administration. * Critically discuss the mechanisms associated with resistance of either antibiotic OR antiviral drugs. Rodney S was once a patient in a hospital in a major city of Australia.
The records office of this hospital then suffered from accidental flooding due to a burst water pipe. Many records were damaged by the water, leaving much information irretrievable, including most of Rodney’s clinical details. Rodney has since died and his death has resulted in a coronial inquiry. The Coroner’s Office has asked for Rodney’s clinical records from the hospital, and the information that could be obtained from the waterlogged records is given below. This refers mainly to the drug therapy used in the treatment of Rodney over the past two years and an occasional decipherable diagnosis.
The drugs are listed in the order given from Rodney’s initial admission date until his death. 12/11/99-14/02/00 Commenced zidovudine capsules 100 mg po q 5hr. 15/02/00-17/02/00 Zidovudine dose increased to 200 mg po q 4hr. 18/02/00-25/02/00 Cepacine (benzocaine and cetylpyridinium chloride) mouthwash prn q 12hr. 18/02/00-27/02/00 Zidovudine syrup 200 mg po q 4hr. 18/02/00-27/02/00 2 Amphotericin lozenges to be sucked slowly qid. 28/02/00 Zidovudine capsules 200 mg po q 4hr. Ketoconazole 200 mg d with food. 28/02/00-07/05/00 Ketoconazole shampoo. Twice weekly for 4 weeks.
15/04/00-01/06/00 Didanosine tablets 150 mg bd to be chewed. 02/06/00- Zalcitabine tablets 750 g tds. 02/06/00-14/06/00 2 cm ‘Capsaicin’ (0. 075%) cream to painful area tds. 31/07/00- Protein purified derivative (PPD) skin test given which resulted in an indurated area of 9 mm. 06/08/00-06/06/01 Isoniazid tablets 100 mg tds. 06/08/00-06/06/01 Pyridoxine hydrochloride tablets 25 mg om. 03/07/00-06/08/00 Trimethorprim + sulpamethoxazole double strength (‘Bactrim DS’) bd pc. 23/07/00-06/08/00 Pentamidine aerosolized 300 mg/d. Pentamidine IV 300 mg/d. 07/08/00-09/09/01 Pentamidine aerosolized 300mg/monthly.
Developed severe diarrhoea. 09/09/01-16/09/01 Vancomycin 1g IV bd by slow infusion. 16/09/01- Kaposi’s sarcoma diagnosed. No cytotoxic therapy recommended. 18/09/01-25/10/01 Sulphadiazine 1. 5 g q 4hr by slow IV infusion. Pyrimethamine 50 mg stat, 25 mg d. 18/10/01-20/10/01 Calcium folinate 3 mg Im d. Introduction The patient’s condition in this case study can be identified by his medications and the pharmacological regime. Examination of the pharmacodynamics of each of the drugs and their application, helps illustrate the pathology of the illness and the mechanisms involved in antiviral resistance.
Identify and briefly discuss the pathophysiology of Rodney’s medical condition Although available clinical documentation concerning Rodney S is incomplete, enough information is available to make inferences about the patient’s condition. More specifically, by examining the drugs administered for treatment (including sequencing, dosage and scheduling), in combination with diagnoses made at the time – we are able to ascertain that the patient is suffering from the symptomatic phase of HIV infection.
Lehne (2001:1028-1031) defines the pathophysiology of HIV infection in terms of the characteristics of the virus, its transmission, and the clinical course of infection. She states that HIV is a retrovirus, incorporating itself into the genetic material of CD4 white blood cells (T cells). This process is called reverse transcription, and it enables HIV to replicate rapidly. It leads to destruction of the CD4 cells and damage to the immune system. HIV follows a triphastic clinical course – seroconversion phase, asymptomatic phase, and symptomatic phase.
During the symptomatic phase, CD4 T cells drop below a critical level (200 cells/µl). In the late stage of this phase, the patient is rendered highly vulnerable to opportunistic infections, certain neoplasms and neurologic complications which are considered indicators of AIDS (Acquired Immune Deficiency Syndrome). Describe the pharmacodynamics of each of the drugs Rodney was prescribed linking this to the pathology. Justify the pharmacological regime, including choice of drug, changes to the regime, dosages and scheduling, and routes of administration. 12/11/99-14/02/00 Commenced zidovudine capsules 100 mg po q 5hr.
Hudak (2001:1039-1040) includes the following factors in her outline of Zidovudine. Pharmacodynamics & patient pathology: Zidovudine (AZT) interferes with reverse transcriptase enzymes thus slowing the replication process. It is approved for the treatment of all HIV positive people whose CD4 count is less than 500. Pharmacological regime: The standard dosage initially is 200 mg po q 4hrs, and after 1 month, 100 mg po q 4hrs. Zidovudine is available in capsule, syrup, and IV preparations. Applications to case study It can be confirmed that Rodney has a CD4 count less than 500.
The dose, scheduling and route of administration comply with standards (if preceded by an initial first month at higher dosage). Records are not available to confirm this. It is usual to commence treatment with two nucleosides and a protease inhibitor – to hinder drug resistance. If implemented, this may have improved outcomes for the patient. 15/02/00-17/02/00 Zidovudine dose increased to 200 mg po q 4hr It is likely that the dosage was increased because the patient wasn’t responding to the therapy. 18/02/00-25/02/00 Cepacaine (benzocaine and cetylpyridinium chloride) mouthwash prn q 12hr.
The MIMS Annual (2000:733) includes the following factors in its outline of Cepacaine. Pharmacodynamics & patient’s pathology: A topical anesthetic and antiseptic. The anesthetic effect is achieved by stopping axonal conduction, and the anti-microbial action is achieved by causing membrane leakage. Cepacaine is administered for relief sore throat, due to inflammation of the oral mucosa. Pharmacological regime: Recommendations are to gargle or rinse 10-15 ml full strength for 10-15 seconds and expel the liquid; repeating every 2 to 3 hours if necessary. Applications to case study.
Use of the medication follows recommendations. It is possible Rodney is suffering from ulceration to the mouth and/or fungal infection causing difficulty in swallowing. Other modifications to his pharmacological regime implemented at the same time reinforce this. 18/02/00-27/02/00 Zidovudine syrup 200 mg po q 4hr The dosage is maintained however it is being administered in syrup form – indicating the patient is having difficulty swallowing. 18/02/00-27/02/00 2 Amphotericin lozenges to be sucked slowly qid Carpenter (2001:33-35) includes the following factors in her outline of amphotericin.
Pharmacodynamics & patient pathology: Amphotericin works by changing fungal membrane permeability to produce leakage of intracellular components. In lozenge form, its’ primarily uses is the treatment of candidal infections of the oral and perioral areas. Pharmacological regime: Recommendations are for one 10 mg lozenge to be sucked and allowed to dissolve slowly in the mouth 4 times a day for the duration of 7-14 days. Applications to case study It is likely that Rodney has a candidal infection of his oral and perioral areas which was not cleared by cepacaine.
The dosage administered in this case, is twice that recommended. There is no apparent reason for this. 28/02/00- Zidovudine capsules 200 mg po q 4hr. Ketoconazole 200 mg d with food Loebl (2000:179-181) includes the following factors in her outline of ketoconazole. Pharmacodynamics & patient pathology: Ketoconazole works by inhibiting purine transport as well as DNA, RNA and protein synthesis. Additionally, it increases cell wall permeability. Ketaconazole is recommended for systemic treatment of esophageal candidiasis or mycoses which fail to respond to topical treatment. Pharmacological regime:
The recommended dose for adults is 200 mg po daily in a single dose – until the fungal infection has subsided. Applications to case study It appears that the patient is able to swallow better because he has been placed back on the capsule form of zidovudine and is taking ketoconazole with food. Because ketoconazole as a systemic treatment is applied until the terminal stages of Rodney’s illness, it is possible that he has developed a distended candidial infection – such as esophageal candidiasis. Administration is as recommended. 28/02/00-07/05/00 Ketoconazole shampoo. Twice weekly for 4 weeks.
Rodney possibly has a topical fungal infection to his scalp such as severe seborrhoeic dermatitis or severe scaling due to dandruff. Choice of medication, dosage, scheduling and route of administration are all standard for these conditions. 15/04/00-01/06/00 Didanosine tablets 150 mg bd to be chewed Street (1993:84-85) outlines the following facts about Didanosine. Pharmacodynamics & patient pathology: Didanosine suppresses HIV replication by inhibiting reverse transcriptase, and terminating DNA chain growth. It can inhibit replication in zidovudine resistant strains. Pharmacological regime:
Bioavailability of the tablets form is about 20 percent greater than that of the oral solution. Doses of between 50 mg twice-a-day and 200 mg twice-a-day are recommended (depending upon body weight). Applications to case study It is possible that didanosine has been implemented at this point, because the patient’s clinical condition is deteriorating, and he may be developing resistance to zidovudine. Dosage complies with recommendations, the chewable tablets having a higher bioactivity. Overlapping toxicities mean didanosine shouldn’t be used at the same time as zalcitabine.
In addition, because it can cause peripheral neuropathy, didanosine needs to be used carefully with pentamidine and isoniazid – which can also cause the condition. The patient’s available records don’t indicate the concurrent use of these risky drug combinations. 02/06/00- Zalcitabine tablets 750 g tds The US website AEGIS – AIDS Education Global Information System at www. aegis. com includes the following information about Zalcitabine. Pharmacodynamics & patient pathology: Zalcitabine inhibits viral DNA synthesis by causing premature termination of the growing DNA strand.
It is most often used in combination therapy against HIV often when the patient has developed resistance to other antivirals. Pharmacological regime: Recommended daily dose of zalcitabine is 750 g three-times-a-day. Applications to case study Zalcitabine is usually implemented when the CD4+ cell count is less than 300 cells per mm”. This is likely to be the case with Rodney, his disease having progressed while on zidovudine and didanosine (perhaps indicating resistance). The choice of drug, dosage, scheduling and route of administration, follows recommendations.
02/06/00-14/06/00 2cm ‘Capsaicin’ (0. 075%) cream to painful area tds Carpenter (2001:897) includes the following facts in her outline of capsaicin. Pharmacodynamics & patient pathology: Capsaicin may increase release of substance P (a principal neurotransmitter for pain), from peripheral type C (sensory fibres to central neurons). Capsaicin is indicated in the temporary relief of neuropathy. Pharmacological regime: Capsaicin is applied topically as a cream to affected areas not more than qid. Applications to case study The patient is using capsaicin for the relief of neuropathy.
This condition may be related to use of didanosine and zalcitabine. It is possible that didanosine use was discontinued (as recommended), because clinical signs of neuropathy occurred. 31/07/00- Protein purified derivative (PPD) skin test given which resulted in an indurated area of 9mm Carpenter (2001:938-939) outlines the use of PPD as a test for tuberculosis. It is used I. D. into flexor surface of the forearm. An indurated area of 9 mm resulted from Rodney’s test, indicating that he is positive for tuberculosis. 06/08/00-06/06/01 Isoniazid tablets 100 mg tds.
Galbraith (2001:726) outlines the following facts about isoniazid. Pharmacodynamics & patient pathology: Isoniazid (administered alone) is used for prophylaxis in HIV infected patients who have a positive PPD test, but lack evidence of active tuberculosis. The drug suppresses bacterial growth by inhibiting cell-wall synthesis. Presence of TB is more frequent when the CD4+ cell count is less than 200/mm. Pharmacological regime: Recommended administration is 4 to 5 mg/kg bodyweight daily po in divided doses up to a maximum of 300 mg – usually continued for 6 months to 2 years.
Applications to case study Rodney has tested positive for tuberculosis in the PPD test and probably has a CD4+ cell count of less than 200/mm. Mode of treatment follows recommendations for prophylaxis. Because isoniazid can decrease serum levels of ketoconazole (concurrently being used), Rodney should be carefully monitored for antifungal effect. 06/08/00-06/06/01 Pyridoxine hydrochloride tablets 25 mg om The AEGIS website, AIDS Education Global Information System at http://www. aegis. com includes the following information about pyridoxine. Pharmacodynamics & patient pathology:
Pyridoxine functions as a coenzyme in the metabolism of amino acids and proteins. It is used to treat neurotoxicity associated with the use of drugs such as isoniazid. Pharmacological regime: Pyridoxine is available in tablet, solution and IV form. For protection against isoniazid-induced deficiency, the dosage is 25 to 50 mg/day. Applications to case study The mode of administration indicates the patient is receiving pyridoxine hydrochloride tablets as a preventative against isoniazid-associated peripheral neuropathy. 23/07/00-06/08/00 Trimethoprim + sulpamethoxazole double strength (‘Bactrim DS’) bd pc.
The MIMS Annual (2000:519) outlines the following about trimethoprim + sulpamethoxazole. Pharmacodynamics & patient pathology: Trimethoprim is used in combination with sulpamethoxazole for prophylaxis of pneumocystis carnii pneumonia (PCP). This combination and dosage also confers cross protection against toxoplasmosis. Both drugs work by decreasing bacterial folic acid synthesis. Prophylactic therapy is recommended for all patients with a CD4 T-cell count below 200 cells/µl. Pharmacological regime: Trimethoprim plus sulpamethoxazole, given as one double strength tablet each day is the preferred medication for prophylaxis of PCP.
Applications to case study Rodney’s history at this point indicates that he is severely immunocompromised, with his CD4 T-cell count remaining below 200 cells/µl. The dosage, scheduling and route of administration, complies with recommendations for prophylactic therapy. 23/07/00-06/08/00 Pentamidine aerosolized 300 mg/d. Pentamidine IV 300 mg/d Lehne (2001:1093) assesses pentamidine as follows. Pharmacodynamics & patient pathology: Pentamidine is active against pneumocystis carinii. It works by disrupting synthesis of DNA, RNA, phospholipids, and proteins. Pharmacological regime:
The inhaled form is used to prevent PCP in high-risk HIV positive patients (those with a history of PCP episodes or CD4 lymphocyte counts less than 200 cells/mm”). It is administered 300 mg once every 4 weeks. The IV form is used to treat active PCP and is dispensed in 300 mg single dose vials with dosage being 3-4 mg/kg IV daily for 2-3 weeks. Applications to case study It is possible that Rodney wasn’t tolerating the TMP-SMZ and was switched to pentamidine. However he is receiving the aerosolized and IV forms concurrently. This may indicate that he has developed PCP and the condition is being treated locally and IV.
The combined dosage exceeds recommendations. Pentamidine may increase the blood levels of zalcitabine (being used concurrently). Close monitoring is required because of the increased risk of pancrestitis. 07/08/00-09/09/01 Pentamidine aerosolized 300 mg/monthly. Developed severe diarrhea Rodney’s pentamidine dosage, scheduling and route of administration, have been changed back to that consistent with prophylactic therapy. He may now require the drug for maintenance/preventative treatment only. 09/09/01-16/09/01 Vancomycin 1g IV bd by slow infusion Carpenter (2001:166-168) outline vancomycin use as follows.
Pharmacodynamics & patient pathology: Vancomycin works by hindering bacterial cell-wall synthesis. It is indicated in severe infections when other antibiotics are ineffective or contradicted. Pharmacological regime: For treatment of systemic infection, the drug is administered by intermittent infusion over 60 minutes or more. Recommended dose of 2 gm/day is administered in divided doses at 6-12 hour intervals. Applications to case study The dosage, scheduling and route of administration would seem to indicate that Rodney is suffering from severe systemic infection possibly methicillin-resistant staphylococcus aureus.
This may be causing his severe diarrhea. 16/09/01- Kaposi’s sarcoma diagnosed. No cytotoxic therapy recommended KS is the most common AIDS related cancer and is considered an AIDS defining condition. Cytotoxic therapy has not have been recommended for Rodney at this stage of his illness because it would compromise his immune system further. 18/09/01-25/10/01 Sulphadiazine 1. 5 g q 4hr by slow IV infusion. Pyrimethamine 50 mg stat, 25 mg d. The MIMS Annual (2000:536) outlines the following factors about combined Sulphadiazine/Pyrimethamine treatment.
Pharmacodynamics & patient pathology: Pyrimethamine works by inhibiting the enzyme dihydrofolate reductase. Sulphadiazine works by inhibiting use of PABA. The combination of these drugs is indicated for the treatment of toxoplasmosis (usually manifesting as encephalitis in AIDS patients). Toxoplasmosis most likely occurs when CD4 T-cell counts fall below 100 cells/µl. Pharmacological regime: The recommended dose of sulphadiazine is 1 to 1. 5 g 4 times a day for 3-4 weeks, and for pyrimethamine it is 25-100 mg daily for 3-4 weeks. Applications to case study.
At this stage Rodney may have a CD4 T-cell count below 100 cells/µl. His body is very susceptible to opportunistic infections including toxoplasmosis. Mode of use complies with recommendations for this condition. 18/10/01-20/10/01 Calcium folinate 3 mg IM d Pharmacodynamics, patient pathology, and pharmacological regime: According to Carpenter (2001:833), calcium folinate is a reduced form of folic acid that is readily converted to other folic acid derivatives. It is indicated in the prevention and treatment of haematologic toxicity from pyrimethamine therapy. Applications to case study.
It was only after one month of treatment with pyrimethamine that calcium folinate was introduced as a preventative/treatment for haematologic toxicity. The dose complies with recommendation for prevention however it was introduced late into the therapy. Critically discuss the mechanisms associated with resistance of either antibiotic or antiviral drugs Antiviral resistance is a major concern in the treatment of HIV positive patients. The website AIDSMeds. com at http://www. aidsmeds. com outlines the mechanisms associated with resistance as follows. “Drug resistance develops because HIV mutates during the replication process.
These mutations cause some viral strains to become stronger and less susceptible to antiviral drugs… The drug-resistant form multiplies, and becomes the dominant strain within the body, reducing the effectiveness of the individual’s treatment. ” Rarely does resistance result from primary infection with a HIV drug-resistant variant. In most cases, it emerges over the course of treatment as the result of several factors including – poor treatment adherence (allowing resistant strains of the virus to grow faster), and poor drug absorption (promoting drug resistant mutations).
The AIDSMeds.com website goes on to detail ways resistance can be minimized. Combination therapy hinders resistance because the different drug groups have different target enzymes. Guidelines recommend the use of two nucleoside reverse transciptase inhibitors (NRTIs) plus one or two protease inhibitors (PIs), or a non-nucleoside reverse transcriptase inhibitor (NNRTI). Resistance tests can also be used to guide drug selection, especially when changing a regime that has failed. Finally education about adherence and the following of dietary guidelines to assist absorption is very important.
Conclusion Examination of the case study concerning Rodney S helps to outline the complexities involved in the treatment of HIV patients. Key to effective treatment is an understanding of the interrelationship between the pharmacodynamics of HIV medications, pathology of the illness, individual pharmacological regimes, and ways to minimize drug resistance. Reference List AEGIS: AIDS Education Global Information System at http://www. aegis. com AIDS MEDS http://www. aidsmeds. com Carpenter, D et al, Ed 2001 Australasia Nursing Drug Handbook. Pennsylvania:
Springhouse Corporation Galbraith, A, Bullock, S & Manias, Ed 2001, Fundamentals of pharmacology. A textbook for nurses and allied health professionals. Australia: Addison-Wesley Hudak, M & Gallo, B Ed 2001, Critical Care Nursing. Philadelphia: J. B. Lippincott Co Lehne, A et al Ed 2001, Pharmacology for Nursing Care. St Louis: W. B. Saunders Company Loebl et al Ed 2000, The Nurse’s Drug Handbook. Delaware: Delmar Publishers Inc MIMS Annual 2000 Ed 24. Sydney: MediMedia Australia Street, AC 1993, ‘Antiviral drugs – clinical applications’ Australian Prescriber 16, 4:81-86.