Hydroxyurea

Hydroxyurea

1. Drug class, description/indication.

Hydroxyurea belongs to a class of medications termed as antimetabolites. These are drugs that alter one or more enzymatic processes that are involved in DNA synthesis (Ware, 2010). It finds application in the treatment of various diseases (Ware, 2010). Some of the notable ailments treated by it include; cancer, sick cell disease, carcinoma of the neck and head, cervix, ovary and neck, chronic myeloid leukemia among, among others.

2. Mechanism of action.

Hydroxyurea interferes with enzymatic processes involved in DNA synthesis. It slows down the production of deoxyribonucleotides through inhibiting the enzyme ribonucleotide reductase, which interferes with the normal functionalities of tyrosyl free radicals, which are responsible for the reduction of nucleoside diphosphates (Ware, 2010). Seemingly, in sickle-cell diseases, hydroxyurea raises fetal hemoglobin containing 2-gamma globulin chains, in place of the intended two beta globulin (Ware, 2010). This action is vital in the sense that the latter is genetically malformatted, and as a consequence, it reduces the number of attacks. Notably, the aforementioned processes are further made possible due to the increment in nitric levels, which causes the activation of guanylyl cyclase, leading to the rise of cyclic GMP (Ware, 2010). In turn, the process allows for the activation of the gamma-globin gene necessary for fetal globulin.

3. Initiation of drug therapy for the condition (first-line therapy and second-line therapy pharmaceutical agents).

Hydroxyurea is suitable for use in both adults and children. This assertion is based on the fact that it minimizes the severity of the disease, in patients suffering from sickle anemia (Willen, Shah, Thornburg & Rothman, 2012). Notably, HbF at the initiation of hydroxyurea can be used to predict HbF response, however, the relationship involving the age of hydroxyurea age initiation and HbF response has not yet been ascertained. Hence, researchers have hypothesized that commencing hydroxyurea at an early may have positive outcomes, as it may improve hematological and clinical response (Willen, Shah, Thornburg & Rothman, 2012). Ostensibly, as much as it was previously reserved primarily for adults, the National Heart, Lung, and Blood Institute (NHLBI) recommended that it could be used broadly, including offering it to children and infants over the age of nine months, regardless of clinical severity (Willen, Shah, Thornburg & Rothman, 2012). Therefore, hydroxyurea plays the role of primary and secondary therapy because of the vast research done on it to ascertain its credibility.

4. Pharmacokinetics and pharmacodynamics of selected pharmaceutical agent.

In relation to pharmacokinetics, hydroxyurea can be divided into four stages, including absorption, distribution, metabolism, and excretion. Firstly, it is readily absorbed after one to four hours when plasma levels area realized (Simoneaux, 2019). Following increased doses, it is also vital to observe AUCs and disproportional peak plasma levels for better results. Notably, there is currently no proven evidence suggesting any effect of food on the absorption of hydroxyurea. Secondly, hydroxyurea distributes widely and rapidly in the body (Simoneaux, 2019). The estimated volume of distribution is about that of the total body water. Also, the plasma to ascites rations varies from 2:1 to 7.5:1, meaning, hydroxyurea is more concentrated in erythrocytes and leucocytes (Simoneaux, 2019). Thirdly, approximately 60 percent of the overall dose of the drug undergoes conversion through metabolic pathways. Notable examples of such pathways include saturable hepatic metabolism and the degradation by urease present in intestinal bacteria (Simoneaux, 2019). Finally, the excretion of hydroxyurea in human beings is essential; a linear first-order renal process.

Alternatively, the pharmacodynamics of hydroxyurea encompasses a dose-dependent synergistic activity with cisplatin in vitro. This manifestation means that, in vivo, its activity involves the combination with cisplatin against the CALU-6 human lung xenografts and LX-1 (Paule et al., 2011). However, minimal interactions can be witnessed with the NCL-H460 or NCI-H520 xenografts (Paule et al., 2011). Thus, subsequent continuous exposure to hydroxyurea for approximately four hours with cisplatin can result in more significant interactions.

5. Adverse effects/side effects of the pharmaceutical agent selected.

Side effects of hydroxyurea can be grouped into two categories: common and adverse side effects. Common side effects include loss of appetite, nausea, vomiting, or diarrhea, constipation, and weight gain (Cunha, 2020). Furthermore, the patient may experience sores evidenced around the mouth or throat, rashes, pale skin, headaches, mild dizziness, hair loss, and the darkening of the skin or nails (Cunha, 2020).

Seemingly, serious side effects are devastating, and efforts should be in place to ensure that the patient quickly gets the services of a medical doctor. Notable examples of severe side effects include: shortness of breath, fast heartbeat, extreme tiredness or weakness, itching, pain, redness, swelling, blisters, or sores on the skins, and constant pain that may be experienced in the stomach, but may also spread to the back (Cunha, 2020). Moreover, the patient may be predisposed to seizures, difficulties in urination, persistent diarrhea, confusion, and hallucinations (Cunha, 2020).

6. Contraindications associated with a pharmaceutical agent selected.

Hydroxyurea can be contraindicated in patients marked with bone marrow depression, such as leukopenia. These patients consequently suffer from hypersensitivity to hydroxyurea, which may result in marrow suppression, or rather myelosuppression (PDR, 2020). Hence, before the administration of hydroxyurea, patients should first be evaluated for their hematologic statuses, to identify any potential culmination of bone marrow depression. Additionally, hydroxyurea can also be contraindicated in patients suffering from HIV infection (PDR, 2020). Meaning, probable outcomes such as hepatoxicity and peripheral neuropathy may be experienced due to the interaction of antiretroviral drugs and hydroxyurea.

7. Four essential points for patient education.

Hydroxyurea should be handled with utmost care. Notable points, therefore, include: wearing disposable gloves when handling the drug or their containments, washing your hands before and after interacting with the drug or its containment bottles (Laurin, Nachman, Desai, Ataga & Derebail, 2013). Also, in case the drug powder is spilled on the floor, it should be wiped immediately with a damp disposable towel and disposed of in a closed container (Laurin, Nachman, Desai, Ataga & Derebail, 2013). Finally, the medication should be kept away from the reach of children and pets.

8. Special considerations of pharmaceutical agents selected

Renal excretion acts as a vital pathway for elimination, hence special attention should be adhered to by reducing the dosage of hydroxyurea in individuals suffering from renal failures or impairments (Laurin, Nachman, Desai, Ataga & Derebail, 2013). More so, careful and close monitoring of the hematological parameters should be emphasized in patients suffering from renal impairment.

9. Dosing Regimen, titration, and maximum allowable dose.

For the treatment of CML, the oral dosage for adults is 20 to 30 mg/kg daily as a single dose, while for the advanced squamous cell head and neck cancer is 80 mg/kg every third day accompanied by chemoradiation therapy. Alternatively, for the treatment of sickle-cell anemia, the dose is 15 mg/kg daily for adults, while for children it can range from 10-20 mg/kg and titrated as tolerated (mean dose 21.4 +/- 5.2 mg/kg/ day).