Essay Example: Pharmacology Of Chlorpromazine

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1- Pharmacology Of Chlorpromazine

The symptoms of schizophrenia, acute psychosis, and bipolar disorder can be managed and treated with the help of a medication called chlorpromazine (Bertolote & Fleischmann, 2002). It is classified as a conventional antipsychotic, also sometimes referred to as a neuroleptic or a medicine from the first generation of antipsychotics. This activity outlines the indications, action, side effects, and contraindications of chlorpromazine treatment in healthcare settings used by healthcare professionals to manage people with dementia, bipolar disorders, and connected psychoses. It also demonstrates why chlorpromazine can help alleviate nausea and vomiting. Other necessary infrastructural of chlorpromazine treatment are also covered in this task.

Pharmacodynamics

Chlorpromazine belongs to the conventional antipsychotic or neuroleptic medication class, often known as antipsychotics of the first generation (FGAs). It exerts its antipsychotic action by inhibiting post-synaptic D2 sites in the mesolimbic system. However, its extrapyramidal adverse effects are instigated by inhibiting D2 receptors in the nigrostriatal pathway (Hosoya et al., 2017). The antiemetic action of chlorpromazine results from a combination blockage of the vomiting agency’s histamine H1, dopamine D2, and muscarinic M1 receptors. Because chlorpromazine is a phenothiazine, it possesses sedative properties and exacerbates the depressed mood of the central nervous system (CNS).

It is not clear how exactly the action is carried out. It is well established that dopamine uptake at postsynaptic D2 receptors can be inhibited by chlorpromazine. Additionally, it acts as an antagonist at the alpha-1 adrenergic receptors. It is crucial for the medical professional to watch chlorpromazine’s tranquilising effects and its enhancement of overall depression. It may be necessary to modify therapy sessions owing to fatigue or other adverse effects (Hosoya et al., 2017).

Pathophysiology of Hiccups

The hiccup reflex consists of the afferent pathway (through the vagal and phrenic nerves and the sympathetic chain), the central hiccup centre (located in the hypothalamus), and the efferent pathway (through the phrenic nerve to the diaphragm and the accessory nerves to the intercostal muscles). It is poorly understood. However, neurotransmitters such as dopamine and GABA appear to play a role. Cancer patients are more likely to experience prolonged hiccups if they are male and older compared to younger ones.

The only FDA-approved medication for the therapy of hiccups is chlorpromazine (Wikes 2017). However, chlorpromazine is ineffective for some individuals, and its adverse effects include severe drowsiness, disorientation, urine retention, hypotension, and QT interval prolongation. It is believed that the anti-dopaminergic impact is the mode of action. The normal dosage for this purpose is 25 mg TID for several days.

Drug of Choice

Chlorpromazine is the only pharmaceutical product approved for managing hiccups by the Food and Medicine Administration in the United States. For many years, it’s been the medicine of choice.   Chlorpromazine is dimethylamine that was created from phenothiazine. It does this by blocking dopamine activity in the hypothalamus, where the central effect is felt. As a result of the fact that it could cause side effects such as hypotension, glaucoma, urinary retention, and delirium, it is no more suggested as a primary therapeutic option. The typical dosage is 25 milligrammes, taken four times a day. However, this can be raised to 50 milligrammes taken daily if required (Woelk, 2011).

Pharmacokinetics

In particular, the pharmacokinetics of chlorpromazine is not completely understood, and they differ from person to person depending on the mode of administration. On the other hand, the kidneys are responsible for excreting between 43 and 65 per cent of the daily dose within twenty-four hours. Four of the five clinically relevant metabolites are considered active in the body’s physiological processes (Hosoya et al., 2017).

It is generally accepted that the clearance half-life consists of numerous phases, with the early phase lasting between one and two hours, the middle phase lasting fifteen hours, and the late phase lasting anywhere from thirty to sixty days. The effects of this drug can remain in the body for a longer period if its half-life is lengthened. Consequently, the physical therapist needs to be made aware of the possibility that undesirable effects will continue even after the dose has been administered (Bertolote & Fleischmann, 2002).

Studies have demonstrated a link between the therapeutic dosage of chlorpromazine and the alleviation of psychiatric symptoms. The hepatic P450 enzyme CYP2D6 metabolises the medicine, and its half-life is nearly 30 hours. It is eliminated from the body through urine and bile. Researchers have shown that individuals undergoing continuous chlorpromazine medication have reduced plasma levels than those getting an acute oral dosage of chlorpromazine.

Additionally, the concurrent administration of anticholinergics can alter the plasma levels of chlorpromazine. Children and adults have different plasma levels and response thresholds for clinical symptomatic relief and toxicity while using chlorpromazine.

Risk Factors

If an individual has a history of hypersensitivity or intolerance to phenothiazines, it is imperative that chlorpromazine not be given to them (Mann & Marwaha, 2022). Patients taking antihypertensive medicines should exercise extreme caution when utilising the drug because of the risk of experiencing severe hypotension. It should not be used in conjunction with medicines intended to impair the central nervous system, nor should it be given to persons with persistent epilepsy (Hosoya et al., 2017). This medicine has not been given the green light for use in the treatment of psychosis linked with dementia.

Dopamine agonists like levodopa or cabergoline may have less of a therapeutic impact when combined with chlorpromazine because of the D2 receptor-blocking effect of chlorpromazine. When used with chlorpromazine, medications that inhibit selective serotonin reuptake, such as citalopram and escitalopram, are considered to be unsafe. According to the findings of several studies, chlorpromazine may be an appropriate medication for use while breastfeeding if the potential advantages outweigh the potential risks and the nursing mother is under the supervision of a medical professional (Mann & Marwaha, 2022).

Clinical Pharmacology

Two substantial case series from the 1950s demonstrate the effectiveness of intravenous chlorpromazine in treating chronic hiccups.   In contemporary practice, this medicine is used orally for standard treatment; however, the effectiveness of this method of administration was not mentioned during our search (Jeon 2020). Despite scant published evidence, chlorpromazine orally became the norm of therapy, and subsequent studies frequently cited “lack of response to [oral] chlorpromazine” as the justification for attempting therapeutic trials with alternative pharmacological agents. If a cause can be found, it should be targeted in the treatment of hiccups.

It’s possible to treat infections. Steroids or radiation may have an impact on brainstem lesions. Biochemical imbalances may be corrected. Idiopathic causes of chronic hiccups are common. Consider adding the medicine to treat the hiccups if they are frequent and unpleasant, keeping in mind that doing so may cause drug interactions and negative effects (Woelk 2011).

Efficacy and Dosage

Chlorpromazine has been regarded as the most effective treatment for intractable hiccups (Steger et al., 2015). In the hypothalamus, chlorpromazine, a dimethylamine derivative of phenothiazine, works centrally by antagonising dopamine. Apparently, chlorpromazine is approved for the management of hiccups. The treatment for persistent singultus is the oral administration of 25 to 50 mg of chlorpromazine every 6 to 8 hours i.e. 3 to 4 times a day (NICE 2022). If hiccups remain after two to three days of oral therapy, intramuscular or intravenous chlorpromazine is used.

Comparison with other Drugs

Multiple medicines have been found to relieve hiccups. The medicine of choice appears to be chlorpromazine (Steger et al., 2015). Successful usage of haloperidol and metoclopramide has been documented. Several anticonvulsant drugs (e.g., phenytoin, valproic acid, and carbamazepine) have been shown to be useful in treating intractable hiccups. Gabapentin has demonstrated efficacy in individuals with central nervous system (CNS) lesions as well as in other patient populations (Lee et al., 2010).

When hiccups are recognised as a consequence of palliative care, a specialised referral for medication or other treatments to reduce hiccups may be warranted, so it may be essential to consult a palliative care specialist for guidance (BNF 2019). If an individual has a liver, sinus, or cerebral tumour, dexamethasone (4–8 mg oral in the am) may lessen compression or discomfort. If a benefit is observed after one week, it should be discontinued (NICE 2022b).

Ketamine has proven to be the most effective anaesthetic agent. Baclofen is especially beneficial for those in whom other medications are contraindicated. Only chlorpromazine is authorised for the therapy of intractable hiccups. However, as described, other medications have also been proven to be effective (Cole & Plewa, 2020).

Safety Aspects

Patients suffering from a liver illness should proceed cautiously when using the drug. Patients who have previously developed jaundice after taking phenothiazine shouldn’t be given Thorazine (chlorpromazine) or any other phenothiazine if it’s at all possible to avoid doing so. If a fever is accompanied by symptoms similar to the grippe, then proper liver testing must be performed. If the tests reveal an abnormality, the treatment should be discontinued. Hold off on exploratory laparotomy unless it is shown that extrahepatic obstruction is present. Liver function tests in jaundice caused by the drug may falsely indicate that extrahepatic obstruction is present (Medscape, 2021).

Warn patients to report any sudden start of sore throat symptoms or any other symptoms associated with an infection. Stop taking medicine and start taking antibiotics or other treatment as necessary as soon as the white blood cell and differential levels indicate signs of cellular depression.

There are many types of neuromuscular reactions, including dystonias, motor instability, Pseudoparkinsonism, and tardive dyskinesia. Occasional symptoms include dry mouth, nasal congestion, nausea, obstipation, constipation, adynamic ileus, urine retention, priapism, miosis and mydriasis, atonic colon, and ejaculatory problems or impotence (Lee et al., 2010). It appears that dose is connected with these reactions.

Potential Drug Interactions

Chlorpromazine and Dexamethasone can cause severe hypokalaemia and potentially increase the risk of polymorphic ventricular tachycardia.

Chlorpromazine and Ondansetron – prolong the QT interval potentially can cause hypokalaemia.

Chlorpromazine and Aprepitant: Decrease metabolism of chlorpromazine

Chlorpromazine and Metoclopramide: Both of the medications you are taking can produce aberrant muscular movements and a condition known as a neuroleptic malignant syndrome, which can be fatal (Lee et al., 2010).

2–CLINICAL GOVERNANCE

Professional Accountability and Relevant legal/ethical issues

A number of frameworks support the practice of prescribing, and patient safety bodies all over the UK have acknowledged that there is a possibility for drugs to cause harm. Significant shifts in clinical practice have been one of the primary motivating factors behind the continuous growth of nurse prescribing, which is still in its infancy.

Prescribers are required to offer a justification in order to maintain their legal and professional accountability.

What exactly is recommended

When it is suggested to use products available without a prescription

Whenever a choice is reached, neither prescribe nor suggest a certain product.

Every prescriber is required to provide high-quality healthcare coverage while adhering to their industry’s most stringent ethical standards and conduct guidelines. The professional code of conduct that governs prescribing practice also serves as an important source of information for the practice of nursing prescribers (NMC 2022). As a result of the Royal Pharmaceutical Society’s (RPS) acceptance in 2016 of a continually updated collection of skills (RPS, 2021), it has been ensured that high standards will continue to be maintained and that skills will be similar across disciplines.

The power dynamic between prescriber and consumer, with the potential for misuse and the ability to exert control, is at the heart of ethical problems around prescribing. As a result, links to regulatory bodies and explicit relationships between morals and codes are provided to remind professionals that objective external norms are required so that they have a benchmark against which to measure their behaviour.

Within the bounds of the non-maleficence principle, deontological ethics, and paternalistic ethical norms, nurse prescribers are allowed to practise their profession. Because prescribing demands a higher degree of career accountability and obligation, the nurse prescriber must be willing to accept the ramifications of any actions or inactions they take while prescribing medications.

Safe and Appropriate Prescribing

Safety and effectiveness remain the top prescription priorities. All prescribers must adhere to their own ethical guidelines and scope of practice. In order to obtain a prescription qualification, practitioners must be familiar with their standards of conduct. Consider whether the benefits of medicines outweigh their possible risks. Revie available evidence. Select the optimal formulation, dose, frequency, route, and duration of treatment.

Choose medications based on cost and the requirements of other individuals (healthcare resources are finite). To prescribe properly, prescribers must thoroughly understand pharmacology in connection to the given medications, including pharmacokinetics and pharmacodynamics. Access and utilise credible and confirmed information sources, such as the British National Formulary. Be knowledgeable about typical causes of medication mistakes and how to avoid risk factors.

Determine how favourable and negative effects can be evaluated. Learn how to modify prescriptions based on new facts. Learn how to submit adverse medication events

Consider the patient’s thoughts, concerns, and expectations.

Select drugs that are effective, safe, and economical

Adhere to applicable national rules and local formularies

Ensure medications are provided on the appropriate forms.

Monitor the positive and negative consequences

Value-Based Prescribing

A patient-centred strategy for prescribing is required to investigate patients’ wishes and perspectives. The concepts of public health and primary prevention are interchangeable in the context of prescribing practices and can be used to investigate the positive effects of therapeutic intervention. Clinical work usually makes use of Becker’s (1974) Health Belief Model, which is a tool that assists in better comprehending the actions that patients take regarding their health.

The model is utilised to gain a better understanding of how patients perceive their susceptibility to contracting a disease or illness, as well as how the prescribed treatment relates to the patient’s perception of how serious they believe their situation to be and how it will impact their day-to-day lives (Davis et al., 2013). The chosen treatment option and the chance of concordance will be impacted by a better understanding of the patient’s ethnic background and how it influences the patient’s behaviour.

Collaboration and patient outcomes

It has been demonstrated that collaboration in health care improves patient outcomes, such as decreasing preventable adverse drug reactions and death rates and optimising medication dosages. It has also been demonstrated that teamwork benefits health care personnel, such as minimising additional work and enhancing job satisfaction (Bosch & Mansell, 2015).

Team prescribing to Independent Prescribing

The transition from pharmacist to independent prescriber carries advantages and new obligations. Involving other participants of the MDT in prescription choices is a realistic step newly-qualified PIPs can take to strengthen their clinical reasoning. In secondary care, the pharmacist might discuss the clinical decision with the healthcare staff during ward rounds or MDT meetings. It could be a talk with a primary care physician or specialised colleague before or after a consultation. In either setting, the pharmacist can email or call expert teams in healthcare or the community for guidance.

The organisation should involve supervision (such as senior PIPs or advanced practice professionals) in developing peer review, support, and mentorship programmes. Peer evaluations should be conducted within a framework your organisation agreed upon, focusing on parts of practice that promote constructive reflection and discourage a blame culture. Moving from pharmacist to PIP requires a mental shift and a shift in the demands of patients, coworkers, and the MDT. Despite the fact that patients are usually positive about pharmacist prescription and the pharmacist prescriber’s role in their treatment, there is low awareness regarding this position. Being prepared to describe one’s job can aid in managing patient expectations.

References

Becker. (1974). Models and theories of health behaviour (2): The health belief model. Amac Training. https://amactraining.co.uk/resources/handy-information/free-learning-material/models-and-theories-of-health-behaviour-change-index/models-and-theories-of-health-behaviour-2/#:~:text=The%20Health%20Belief%20Model%20(Becker

Bertolote, J. M., & Fleischmann, A. (2002). Suicide and psychiatric diagnosis: a worldwide perspective. World Psychiatry : Official Journal of the World Psychiatric Association (WPA), 1(3), 181–185. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1489848

BNF. (2019). Dexamethasone. NICE; NICE. https://www.nice.org.uk/

Bosch, B., & Mansell, H. (2015). Interprofessional collaboration in health care. Canadian Pharmacists Journal / Revue Des Pharmaciens Du Canada, 148(4), 176–179. https://doi.org/10.1177/1715163515588106

Cole, J. A., & Plewa, M. C. (2020). Singultus (Hiccups). PubMed; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK538225/

Davis, J. L., Buchanan, K. L., & Green, B. L. (2013). Racial/Ethnic Differences in Cancer Prevention Beliefs: Applying the Health Belief Model Framework. American Journal of Health Promotion, 27(6), 384–389. https://doi.org/10.4278/ajhp.120113-quan-15

Hosoya, R., Uesawa, Y., Ishii-Nozawa, R., & Kagaya, H. (2017). Analysis of factors associated with hiccups based on the Japanese Adverse Drug Event Report database. PLOS ONE, 12(2), e0172057. https://doi.org/10.1371/journal.pone.0172057

Jeon, Y. S. (2020, September 11). BMJ Supportive & Palliative Care | A leading palliative care journal. BMJ Supportive & Palliative Care. http://spcare.bmj.com/

Lee, J. H., Kim, T. Y., Lee, H. W., Choi, Y. S., Moon, S. Y., & Cheong, Y. K. (2010). Treatment of Intractable Hiccups With an Oral Agent Monotherapy of Baclofen -A Case Report-. The Korean Journal of Pain, 23(1), 42–45. https://doi.org/10.3344/kjp.2010.23.1.42

Mann, S. K., & Marwaha, R. (2022). Chlorpromazine. PubMed; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK553079/#:~:text=Chlorpromazine%20is%20a%20member%20of

Medscape. (2021). Thorazine (chlorpromazine) dosing, indications, interactions, adverse effects, and more. Reference.medscape.com. https://reference.medscape.com/drug/chlorpromazine-342970

NICE. (2022a). Chlorpromazine hydrochloride. NICE; NICE. https://www.nice.org.uk/

NICE. (2022b). Scenario: Management of hiccups. NICE; NICE. https://www.nice.org.uk/

NMC. (2022). Professional standards of practice and behaviour for nurses, midwives and nursing associates. NMC. https://r.search.yahoo.com/_ylt=Awr982c_Od5iet0q_F5XNyoA;_ylu=Y29sbwNncTEEcG9zAzEEdnRpZANBMDYzNF8xBHNlYwNzYw–/RV=2/RE=1658759615/RO=10/RU=https%3a%2f%2fwww.nmc.org.uk%2fglobalassets%2fsitedocuments%2fnmc-publications%2fnmc-code.pdf%23%3a~%3atext%3dThe%2520Code%2520contains%2520the%2520professional%2520standards%2520that%2520registered%2csettings%252C%2520but%2520they%2520are%2520not%2520negotiable%2520or%2520discretionary./RK=2/RS=3SVM9fRp5CCVgHU_yUKiJNQ10gY-

Royal College of Nursing. (2012). Non-medical prescribing | Advice guides | Royal College of Nursing. The Royal College of Nursing. https://www.rcn.org.uk/get-help/rcn-advice/non-medical-prescribers

Steger, M., Schneemann, M., & Fox, M. (2015). Systemic review: the pathogenesis and pharmacological treatment of hiccups. Alimentary Pharmacology & Therapeutics, 42(9), 1037–1050. https://doi.org/10.1111/apt.13374

Wikes, G. (2017). Hiccups Treatment & Management. Medscape. https://r.search.yahoo.com/_ylt=AwrgNiyENN5iJOYoyCRXNyoA;_ylu=Y29sbwNncTEEcG9zAzEEdnRpZANBMDYzNF8xBHNlYwNzcg–/RV=2/RE=1658758404/RO=10/RU=https%3a%2f%2femedicine.medscape.com%2farticle%2f775746-treatment/RK=2/RS=557F48_dckD2YBWoBbgI8qCGHnM-

Woelk, C. J. (2011). Managing hiccups. Canadian Family Physician Medecin de Famille Canadien, 57(6), 672–675, e198-201. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114667/#

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