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The contents of this blog contain topics relevant to end of life care written by our own hospice clinical pharmacists. Continue to check this site regularly for the newest post or subscribe to the RSS feed below.
Michelle Mikus, PharmD

Rectal Medication Seizure Management Options

In end of life care, often times the oral route of medication administration is not an option. However, it is important that seizure prophylaxis be maintained beyond the patient's ability to swallow and that treatment options are known. The good news about rectal administration of seizure medications is that many antiepileptics that patients take orally can be given rectally. In addition, the dosages of these medications do not need adjusted from oral to rectal.

Phenobarbital is one of the oldest medications used for seizure prophylaxis. This medication is weight based and also takes 4-5 hours to reach peak concentration. For that reason, phenobarbital should not be used for acute seizure episodes. Dosages are most often 1-3mg/kg orally or rectally in divided doses (1-2 times daily). Note phenobarbital is sedating.

Carbamazepine immediate release tablets can be used rectally. Ideally, the same daily oral dosage is given rectally in 6-8 small, divided doses and the crushed tablets are put in a gelatin capsule when possible. Most patients require daily doses between 800-1200mg. Note carbamazepine serum concentrations should be monitored. Carbamazepine suspensions can also be used and would need to be diluted with an equal volume of water.

Valproic acid and divalproex sodium are of the most commonly used medications for seizure prophylaxis. Fortunately, they too can be used rectally when oral administration is not possible. If using the liquid formulations, dilute with an equal volume of water. Optimal response is seen at doses below 60mg/kg/day, in divided doses.

Lastly, a lamotrigine rectal suspension can be prepared out of the immediate release or chewable tablets. This is done by crushing the tablets and mixing into 6-10mL of room temperature water. Most patients find success at a dose of 250mg twice daily.

Benzodiazepines such as diazepam and lorazepam are commonly used rectally for acute seizures and should not be excluded from this overview.

There are many reasons that a patient may need to be on an antiepileptic drug: epilepsy, brain metastases, and even disease progression, to name a few. Using the above information, management of these medications beyond the oral route is possible and dose conversions are not necessary.


References:
1. Connelly, J., & Weissman, D. Fast Fact #229: Seizure Management in the Dying Patient. Retrieved September 4, 2015, fromhttps://www.capc.org/fast-facts/229-seizure-management-dying-patient/
2. Krouwer H, Pallagi J, Graves N. Management of seizures in brain tumor patients at the end of life. J Palliat Med. 2000;3:465-475

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Lori Osso-Connor, PharmD, CGP

Serotonin Syndrome in the Elderly

Serotonin Syndrome or serotonin toxicity occurs when there is overstimulation of the peripheral and central serotonin receptors which causes serotonin to accumulate in the body. Increased serotonin levels can occur through the following mechanisms: increased serotonin production, inhibition of serotonin reuptake, inhibition of serotonin metabolism, increased serotonin release, and/or stimulation of the serotonin receptor. Any medication or combination of medications that can increase the concentration of serotonin can cause serotonin syndrome. The medications most likely to be involved in contributing to serotonin syndrome include selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitor (SNRIs), tricyclic antidepressants (TCAs) or serotonin modulator antidepressants (trazodone).

SSRIs are often used in the treatment of depression. The elderly population is at increased risk of experiencing depression due to disability, co-morbid conditions, and/or the death of loved ones. Therefore, the use of antidepressants in the elderly is common. SSRIs exert their effect by blocking the reuptake of CNS neuron serotonin in the brain. Some examples of SSRIs include: Prozac (fluoxetine), Paxil (paroxetine), Celexa (citalopram), Lexapro (escitalopram), and Zoloft (sertraline).

Serotonin syndrome is often underdiagnosed and clinicians must be aware and identify early symptoms. Serotonin syndrome is diagnosed through clinical symptoms. The hallmark feature of serotonin syndrome is agitation. The common signs are usually a triad of features including: neuromuscular excitation (clonus, rigidity, hyperreflexia), autonomic stimulation (tachycardia, fever, sweating, diarrhea, hypertension), and changes in mental status (confusion, agitation, coma). The Hunter Serotonin Toxicity Criteria is recommended for diagnosing serotonin syndrome.

Serotonin syndrome may occur within minutes to hours of use of the offending medication(s). The severity could range from mild to severe, even resulting in death. Treatment consists of discontinuing the causative medication. Diazepam has been used to decrease hypertonicity. Serotonin antagonists such as cyproheptadine and chlorpromazine also have been used.
It is important for the pharmacist to be aware of medications that have the potential to cause serotonin syndrome and recognize to the signs and symptoms associated with it.

Medication Class Examples
Selective Serotonin Reuptake Inhibitors (SSRIs) citalopram (Celexa), fluoxetine (Prozac), fluvoxamine (Luvox), olanzapine/fluoxetine (Symbyax), paroxetine (Paxil)
Selective Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) duloxetine (Cymbalta), sibutramine (Meridia), venlafaxine (Effexor)
Triptans

almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Imitrex),

zolmitriptan (Zomig)

Miscellaneous

Medications- buspirone (Buspar), carbamazepine (Tegretol), cocaine, cyclobenzaprine (Flexeril), Fentanyl, 5-hydroxytryptophan, linezolid (Zyvox), lithium, L-tryptophan, meperidine (Demerol), methadone (Dolophine), methamphetamine (Desoxyn), methylene blue, metoclopramide (Reglan), mirtazapine (Remeron), ondansetron (Zofran), phenelzine (Nardil), selegiline (Eldepryl), St. John’s wart, tramadol (Ultram), tranylcypromine (Parnate), trazodone (Oleptro), valproic acid

Medication Classes- Ergot alkaloids, Tricyclic antidepressants

 


References:
1. Brown, Charles. "Drug-Induced Serotonin Syndrome." U.S. Pharmacist 17 Nov. 2010: Web. 27 Aug. 2015. 
2. Nguyen, Timothy, and Billy Sin. "A Case of an Older Adult Patients and Drugs Associated with Serotonin Syndrome." The Consultant Pharmacist 30.8 (2015): 455-57. 

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Irene Petrides, PharmD

Hyperkalemia in the Elderly

Hyperkalemia or a rise in serum potassium concentration is an electrolyte disorder that has the potential to be a life threating condition. With increased aged there is increased risk for hyperkalemia. In the elderly, the loss of renal mass and comorbid conductions results in decreased renal function.1,2 Therefore the common regulatory mechanism of managing potassium is disrupted.3 Many medications can be associated with contributing to hyperkalemia including potassium supplements, potassium sparing diuretics, nonsteroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors, beta adrenergic blocking agents, heparin, digoxin, and trimethoprim-sulfamethoxazole.4 In order to avoid hyperkalemia certain precautions should be taken. This includes renal dosing and avoiding concomitant use of potassium altering medications. Signs and symptoms of hyperkalemia often are associated muscle paralysis, dyspnea, palpitations, nausea or vomiting and paresthesia. It is imperative to recognize these signs and symptoms as for hyperkalemia can be quickly fatal, resulting in respiratory paralysis or cardiac arrest.3

Management of hyperkalemia depends on severity and renal function. In patients with moderate potassium elevation and normal renal function, treatment simply results in identifying and removing the source of increased potassium levels and/or increasing the excretion of potassium.3 This includes a loop diuretic, aldosterone analogue, or initiating the controversial cation exchange resin (Kayexalate®).2 In patients with severe hyperkalemia and impaired renal function, aggressive treatment may comprise of intravenous insulin along with glucose, inhaled nebulized intravenous beta-2 agonist, intravenous calcium for cardiac toxicity, sodium bicarbonate to correct severe metabolic acidosis, and ultimately emergency dialysis.3

Kayexalate® (sodium polystyrene sulfonate) is a medication used in treatment of hyperkalemia. However it is important to keep in mind the safety label posted by the US Food and Drug administration in 2009.1 Kayexalate® is reported to cause colonic necrosis and other serious gastrointestinal adverse events including bleeding, ischemic colitis, and perforation.1,2 Therefore it is not recommended to use Kayexalate® with Sorbitol®.1,2,3 Due to this labeling, a more appropriate strategy in the treatment of mild to moderation hyperkalemia may be decreasing potassium intake increasing potassium depletion with the use of loop diuretics.1,2

In conclusion it is important to keep in mind prevention is key. A drug medication review is always necessary. All medications need to be evaluated especially over the counter medications. Many patients are on potassium supplements, non-steroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors. Decreased renal function in addition to medications associated with drug induced hyperkalemia is a recipe for disaster in the aging population Ultimately, appropriate prevention is desired in addition to close monitoring as well as treatment when necessary.3,4


REFERENCES:

1 Kamel, K. S., and M. Schreiber. 'Asking The Question Again: Are Cation Exchange Resins Effective For The Treatment Of Hyperkalemia?'. Nephrology Dialysis Transplantation 27.12 (2012): 4294-4297. Web.

2 Sterns, R. H. et al. 'Ion-Exchange Resins For The Treatment Of Hyperkalemia: Are They Safe And Effective?'. Journal of the American Society of Nephrology 21.5 (2010): 733-735. Web.

3 Elliott, M. J. et al. 'Management Of Patients With Acute Hyperkalemia'. Canadian Medical Association Journal 182.15 (2010): 1631-1635.

4 Perazella, Mark A., and Rex L. Mahnensmith. 'Hyperkalemia In The Elderly'. J Gen Intern Med 12.10 (1997): 646-656. Web.

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Jessica Horsley, PharmD

Intranasal Medication Administration: Suitable Drugs and Devices

Compared to intravenous (IV) and other invasive routes of administration, intranasal (IN) administration of medications provides several benefits with regard to safety and efficacy. This route of administration is needleless, requires no sterile technique and is pain-free and well tolerated by patients. The transmucosal drug absorption offered by this route offers a rapid onset of action, with dosing and bioavailability similar to IV dosing.

Variability in intranasal drug absorption can be attributed to both drug and patient-related factors. Drug formulations should be concentrated and potent and of a volume of less than 1mL (preferably less than 0.2mL if possible). Physicochemical drug properties are of importance, as optimal absorption is dependent on the molecular weight and hydro- or lipophilicity of the drug. Lipophilic medications with a molecular weight of less than 300 Da are most suitable for IN administration. The patient’s transepithelial passage proves to be another variable affecting drug absorption. Abnormal nasal blood flow, rhinosinusitis, radiation to the head/neck, diseases affecting mucociliary clearance like cystic fibrosis, and cigarette smoking may all affect mucosal health, and therefore IN drug absorption. Drug interactions for IN administration are considered relative and include phenylephrine and oxymetazoline.

With regard to IN administration, most nursing professionals and even patients are familiar with nose drops or aerosol sprays like sodium chloride nasal spray or fluticasone. For those medications without a commercial nasal dosage form available, options for administration in the past have included compounding into drops/spray, or using a syringe and cotton ball. These methods may prove problematic due to immediate swallowing, rapid clearance, and posterior delivery of medication. A new option, drug atomization, now exists to address these failures in IN drug delivery. An atomized spray delivers small particles to the nasal mucosa rapidly and without regard to patient positioning. Three commercial devices exist for IN drug atomization: Mucosal Atomization Device, Accuspray Nasal Spray and Kurve Controlled Particle Dispersion. Although considered off-label use, the therapeutic uses of IN-administered drugs include seizures, hypoglycemia, opioid overdose, epistaxis and anesthesia. Suitable medications for IN administration applicable to the hospice population include fentanyl, benzodiazepines, ketamine, naloxone and lidocaine.1

2016 06 29 12 57 45

For information regarding nasal atomization products:

LMA MAD Nasal
http://www.lmana.com/pwpcontrol.php?pwpID=6359

BD Accuspray SCF
http://www.bd.com/pharmaceuticals/products/nasal-spray.asp

Kurve CPD
http://www.kurvetech.com/nasaltechnology.asp 

 


References:

1 Jen, C. No IV access, get MAD! Powerpoint presentation at: the American Society for Health-System Pharmacists Midyear Clinical Meeting; Dec 7-11 2014; Anaheim, CA.

2 Wolfe TR, Braude DA. Intranasal medication delivery for children: a brief review and update. Pediatrics. 2010;126(3):532-7.

3 Gallagher EJ. Nasogastric tubes: hard to swallow. Ann Emerg Med. 2004;44:138-41.

4 Pandey RK, Bahetwar SK, Saksena AK, Chandra G. A comparative evaluation of drops versus atomized administration of intranasal ketamine for the procedural sedation of young uncooperative pediatric dental patients: A prospective crossover trial. J Clin Pediatr Dent. 2011;36:79–84.

5 Tsze DS, Steele DW, Machan JT, Akhlaghi F, and Linakis JG. Intranasal ketamine for procedural sedation in pediatric laceration repair: a preliminary report. Pediatr Emerg Care. 2012 Aug;28(8):767-770.

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Delta Campus Pharmacy Student

Use of Nebulized Morphine for the Management of Dyspnea

Dyspnea, or shortness of breath, is a very common complaint in hospice and palliative care. Up to 70% of end stage cancer or COPD patients experience dyspnea.1 Opioids, such as morphine, have been used to relieve the uncomfortable sensation associated with dyspnea. Oral and parenteral morphine are the most well studied routes of administration for this indication. Unfortunately, systemic absorption of opioids can cause adverse events that may be considered unbearable in the hospice population such as nausea, vomiting, drowsiness, constipation, and respiratory depression. Oral administration of morphine takes 15-30 minutes to take effect and lasts about four hours.2,3 While parenteral administration of morphine takes 6-10 minutes to take effect and also last about four hours. Inhaled opioids have a faster onset of action than the oral route and considered less invasive than the parenteral route.2

The use of nebulized opioids can be considered an appealing option compared to the oral and parenteral routes of administration. However, nebulized opioids are not routinely recommended. This is because there is conflicting data as to their benefit. There are no large-scale studies testing the efficacy of nebulized opioids, and smaller studies show conflicting evidence. Some studies show that nebulized opioids are less effective compared to oral or parenteral administration while others show that nebulized morphine is equally efficacious to subcutaneous morphine.1,4 Some patients are noted to prefer nebulized morphine over other routes of administration.4

A systematic review of 18 clinical trials that evaluated all routes of opioids in the management of dyspnea found a statistically significant benefit with the oral and parenteral routes of administration but found the nebulized route of administration to be no more effective than nebulized saline. However, the authors of this review did note that there might have been insufficient data with the nebulized route of administration to make this claim.8 Another review of 9 clinical trials looking at efficacy of nebulized morphine in the management of dyspnea found that 3 of the trials had positive results, but the rest failed to show improvement after treatment. The authors note that the small number of subjects, variety of disease states, and different outcome measures limited the interpretation of the results.9 Based upon these varying results, the use of nebulized opioids for the management of dyspnea are not routinely recommended. If you are going to consider a trial of a nebulized opioid, then it is recommended to use an injectable vial and not the oral morphine concentrate. A review of the literature will find no place where the oral concentrate has been evaluated and one article that directly states that the oral elixir should not be used.10 There is some belief that the sugar-free formulation of the oral morphine solution can be used via nebulizer, however, there is not literature to support this. It is of note that all current oral morphine solutions are sugar free and that the sugar containing oral morphine solutions are no longer on the market.7 There is some concern if the injectable vial needs to be preservative free for use via nebulizer. This concern comes from the fact the preservatives can induce bronchospasm in some patients. This is a rare but sometimes serious side effect. The preservatives of most concern are sulfites and edetate disodium (EDTA), found in both oral and parenteral preparations of morphine.5,6 It is not necessary to use preservative-free morphine, but caution should be used in patients susceptible to bronchospasms. If you are not using a preservative free product, then it is recommended to monitor your patient during the first administration of the nebulized opioid for this side effect. Typical starting dose for nebulized morphine is 2.5-10 mg; this can be titrated up to 30 mg per dose. Alternatives to morphine include hydromorphone 0.25- mg or fentanyl 25 mcg.1 Doses can be repeated every 4 hours as needed.3 Morphine for injection should be diluted to 2 mL volume with normal saline solution, if needed.1


Submitted by: Shawn Millsop, PharmD Candidate 2016 at Duquesne University School of Pharmacy and Lorin Yolch, PharmD, CGP, FASCP, Director of Professional Education at Delta Care Rx


References

1 Ferraresi V. Inhaled opioids for the treatment of dyspnea. Am J Health-Syst Pharm. 2005; 62: 319-320.

2 Bausewein C, Simon ST. Inhaled nebulized and intranasal opioids for the relief of breathlessness. Curr Opin Support Palliat Care. 2014; 8: 208-212.

3 Sarhill N, Walsh D, Khawarm E, Tropiano P, Stahley MK. Nebulized hydromorphone for dyspnea in hospice care of advanced cancer. Am J Hosp Palliat Care. December 2000; 17(6): 389-391.

4 Bruera E, Sala R, Spruyt, et al. Nebulized Versus Subcutaneous Morphine for Patients with Cancer Dyspnea: A Preliminary Study. J Pain Symptom Manage. June 2005: 29(6): 613-618.

5 Excipients in the label and package leaflet of medicinal products for human use. European Commission. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003412.pdf Published July 2003. Accessed June 2, 2015.

6 Beasley R, Fishwick D, Miles JF, Hendeles L. Preservatives in nebulizer solutions: risk without benefit. Pharmacotherapy. January-February 1998; 18(1): 130-139.

7 Gold Standard, Inc. Morphine. Clinical Pharmacology [database online]. Available at: http://www.clinicalpharmacology.com. Accessed June 25, 2015.

8 Jennings AL, Davies AN, Higgins JP, Gibbs JSR, Boardley KE. A Sytematic Review of the use of Opioids in the management of dyspnoea. Thorax. 2002;57:939-44.

 9 Brown SJ, Eichner SF, Jones JR. Nebulized Morphine for Relief of Dyspnea Due to Chronic Lung Disease. The Annals of Pharmacotherapy. June 2005;29:1088-92.

10 Ahmedzai S, Davis C. Nebulised drugs in palliative care. Thorax. 1997;52(Suppl 2):S75-77.

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