Medication Management During End-of-life Care

John M. Swegle, PharmD, BCPSAssociate Professor (Clinical)

University of Iowa College of Pharmacy

Mercy Family Medicine Residency

Disclosures

• None

General Goals

• Reduce suffering– Many involved with this

• Patient, family, healthcare provider• Patient, family, healthcare provider

• Know your medications– Limitations

• Drugs are not always the answer

– Appropriate use

General Goals

• Focus on symptoms that are bothersome to the patient– Through conversations/observations– Through conversations/observations

• Family wishes/perceptions– Make sure the patient is the focus of the

conversation

– Must have realistic goals• All parties need to hear the same message

General Goals

• Be prepared for additional therapy– Example: not all pain will be alleviated despite

your best effortsyour best efforts

• If something doesn’t work, try something else

• Make sure and include other disciplines– Social work, spiritual care, nursing, etc.

General Goals

• Must weigh the risks of treatment vs. benefit one hopes to receive– Often depends on prognosis of the patient

– Realize the benefit of a medication may not be immediate

• Example – use of warfarin vs. use of antibiotic

• Assess ongoing need of chronic medications

General Goals

• Location of patient often dictates approach to care– Selection of medications– Selection of medications

– Route of administration

– Aggressiveness of titration• Need for reassessment

– Access to healthcare professional

Limit Waste

• Limited supply in the home– Do not obtain a month supply for:

• Those who are actively dying• Those who are actively dying

• Those requiring escalation/de-escalation of dosing

• New medications

• Healthcare reform may have a big impact on this

Common Symptoms Encountered

• Pain

• Dyspnea

• Nausea/vomiting• Nausea/vomiting

• Constipation

• Anxiety

• Fatigue

• Confusion

• Secretions

Various Etiologies for Pain

• Physiologic– Nociceptive (somatic/visceral)– Neuropathic

• Emotional• Emotional– Anxiety, depression, anger

• Social– Interpersonal issues (family, loneliness, financial)

• Spiritual– Non-acceptance, abandonment, paying for previous

transgressions

Things to Remember

• Severity of the pain• Barriers to successful pain management• Appropriate use of analgesics• Appropriate use of analgesics

– Route of administration– Dosing– Management of adverse events

• Education of patients/families/caregivers/other

Pain Medications

• Acetaminophen

• NSAID’s/COX-2 inhibitors

• Combination opioid/non-opioid agents• Combination opioid/non-opioid agents

• Opioids

• Agents for neuropathic pain

General Opioid Rules

• Do not be fearful of them but treat them with respect

• There is not one agent that is better than anotheranother– Everyone responds differently– Selection takes into account other patient factors

(age, renal function, other disease states, other medications, etc)

• Working with opioids is an art with some science behind it

Myths about Opioids

• Once someone goes on morphine, it means they will die– Morphine does not affect the underlying

pathophysiology of the disease processpathophysiology of the disease process

• All patients become “addicted”– Also not true….some patients may develop

characteristic behaviors however most minimize the use of these agents

• Respiratory depression is a common side effect

Opioids

• Main uses in palliative care:– Pain (typically reserved for moderate to severe)– Shortness of breath– Overall improvement in function

• Potential benefits– Sedation – Calming effect– Improvement in quality of life

Opioids• Dosing:

– Individualized• Some do poorly on 5 mg oral morphine• Some require doses in excess of 12,000 mg of oral • Some require doses in excess of 12,000 mg of oral

morphine per day

• One agent isn’t necessarily better than another– Some are clearly worse or more troublesome

than others– Opioid rotation

Selecting Opioids for Geriatrics

• Liver function was historically viewed as the important pharmacokinetic aspect

• Renal function• Renal function– The more important factor to consider

• Accumulation of opioid metabolites may lead to greater potency and adverse effects

– Higher likelihood of renal function decline in the elderly population

• Even those with “normal” serum creatinine

Drugs Aging 2007;24:761-776

Opioid Selection

• Agents commonly used:– Morphine

– Hydromorphone

• Agents which are not ideal choices– Meperidine

– Codeine– Hydromorphone

– Fentanyl

– Hydrocodone

– Oxycodone

– Methadone (additional training required)

– Codeine

– Any partial agonist or agonist/antagonist

Am J Kidney Dis 2003:42:217-228Drugs Aging 2007;24:761-776

Opioid Adverse Effects

• Constipation – Address and prevent

• CNS: sedation, confusion

• Nausea/vomiting

• Urinary retention

• Pruritis

• Respiratory depression

• HyperalgesiaDrugs Aging 2009;26(suppl 1):63-73Canadian Family Physician 2007;53:426-427

Dyspnea

• Definition of dyspnea– Bad or difficult breathing

• Subjective symptom (similar to pain)• Subjective symptom (similar to pain)– Many people are unable to relate to dyspnea

– Unable to always correlate dyspnea with objective findings

• As with pain, focus more on what the patient tells you rather than what you or the family may observe

Assessing Causes of Dyspnea

The BREATH AIR acronym to identify the etiology:

Bronchospasm *Anxiety*Rales Interpersonal issues*Rales Interpersonal issues*Effusions Religious concerns*Airway obstructionThick secretionsHemoglobin low

Principles for Management of Dyspnea

• Focus on the symptom and not the sign

• Determine and treat underlying cause if possible

• Relieve dyspnea without creating new problems

• Assess whether treatment with worthwhile based on patient/family desires

• Discuss treatment options with patient/family

Common Respiratory Medications

• Bronchodilators– These will help to open airways

• Not always able to see objective improvement but the patient may claim to feel better

– Oral/nebulized/IV all are available depending on which agent is selected

• Corticosteroids– Target inflammation – Dose appropriately and be aware of objective

improvement versus “steroid effect”

Semin Oncol 2011;38:450-459

Respiratory Depressants –Bezodiazepines

• Main agents to use:– Diazepam

– Lorazepam

• Mechanism of action– Depression of hypoxic or hypercapnic ventilatory

response

– Alter the emotional response to dyspnea

• Avoid widespread use unless there is underlying anxiety

J Palliat Med 2012;15:106-114

Respiratory Depressants –Opioids

• Morphine– Most frequently used opioid for treating

dyspneadyspnea

– Not always useful for treating dyspnea• Similar to the idea that not all pain should be treated

with morphine

• Do not rely completely on opioids that the overall picture is ignored

Respiratory Depressants –Opioids

• Morphine:– Mechanism of action (multiple theories)

• Shifting of central PCO2 perception• Shifting of central PCO2 perception– Resetting of the homeostatic control of PCO2

– Will allow the body to tolerate higher levels of CO2

without feeling respiratory fatigue

• Preload reduction

• Relaxation effect?

• Miscellaneous mechanisms

Am J Respir Crit Care Med 2011;184:867-869

Respiratory Depressants –Opioids

• Other opioids used for dyspnea– Hydrocodone 5 mg po every 4 hours– Oxycodone 5 mg po every 4 hours– Hydromorphone 0.5-1 mg po every 4 hours

• General titration of opioids– Increase the dose by 20-40% every 12 hours– Supposedly there is not a tolerance problem

once the appropriate dose is established

Nausea

• Entirely subjective experience– Sensation which typically precedes vomiting

• Epidemiology is uncertain due to • Epidemiology is uncertain due to methodological challenges – Heterogeneity of patient populations, various

study settings, etc.

• Fair to say that the symptom is very disturbing

Clin Interv Aging 2011;6:243-259

Nausea

• Similar to many symptoms, it’s best to try and identify the etiology– Or at least identify the receptors you wish to target– Not always possible (multiple causes may be involved)– Not always possible (multiple causes may be involved)

• Areas of involvement– Chemoreceptor trigger zone– Labyrinths– Peripheral afferents

• Do not forget the bowels

Nausea

• Predominate receptors targeted for nausea:– Dopamine (D2)

– Serotonergic (5-HT3)

– Histaminic (H)– Histaminic (H1)

– Muscarinic (M1)

• Receptors targeted to a lesser extent:– Steroid

– Benzodiazepine

– Neurokinin 1 receptor (NK1)

Clin Interv Aging 2011;6:243-259

Medications for Nausea

• Antihistamines– Target etiologies related to motion

• Limited efficacy beyond this• Limited efficacy beyond this

– May be used as adjunctive agents

– Need to watch for adverse effects (dry mouth, constipation, urinary retention)

Antihistaminic Agents for Nausea

Selected Medications Comments

Diphenhydramine (Benadryl) Useful agent but sedating

Dimenhydrinate (Dramamine) Often used for “motion sickness”Dimenhydrinate (Dramamine) Often used for “motion sickness”

Meclizine (Bovine, Antivert) Often prescribed for “dizziness”

Promethazine (Phenergan) Predominately an antihistamine but has small amount of dopamine blocking properties

Medications for Nausea

• Dopamine receptor antagonists– Work by blocking dopamine 2 (D2) receptors

– Useful group of medications for nausea– Useful group of medications for nausea• Often used as first-line for generalized nausea

– Adverse effects may be limiting factor• Dystonic reactions, akathesia, sedation

Dopamine Receptor Antagonists

Selected Medications Comments

Prochlorperazine (Compazine)

Preferred agent to use in many acute situations; Less sedating than promethazinepromethazine

Haloperidol (Haldol) Negative views on this agent has led to decreased use; newer antipsychotics also used but more expensive

Metoclopramide (Reglan) Overall use has declined secondary to the introduction of 5-HT3 agents

Dual mechanism: blockade of dopamine receptors and prokinetic agent on GI tract

Medications for Nausea

• Serotonin antagonists (i.e. – ondansetron)– Block serotonin (5-HT3) receptors through

blockade of localreceptors in the GI tract blockade of localreceptors in the GI tract (primary) and will block serotonin receptors centrally (secondary)

– Key concept….. These agents are very useful for emetogenc causes which are associated with release of serotonin

Serotonin Antagonists

• Main uses:– Prevention of

chemotherapy-induced nausea/vomiting

• Other uses:– Generalized nausea

although not ideal

– Use has increased as nausea/vomiting(early)

– Prevention of post-op nausea and vomiting (PONV)

– Prevention of nausea secondary to radiation

– Use has increased as prices dropped

• Advantage: not associated with EPSE

Miscellaneous Medications for Nausea

• Corticosteroids– Dexamethasone vs. prednisone

– May benefit if etiology due to inflammatory – May benefit if etiology due to inflammatory process

• Tumor pressing against bowels

– Useful adjunctive agent

– May be compounded with other products • Reglan + Benadryl + Dexamethasone

Constipation/Diarrhea

• Consider causes which may add to the problem– Constipation: anything anticholinergic– Diarrhea: antibiotics, chemo, radiation

• General points– Maintain hydration– Modify diet (if applicable)– Create favorable environment

Management of Constipation

• General agents to use:– Sennosides, docusate, PEG (Miralax)

– As needed: mag citrate/MOM, suppositories, enemas

• General agents that may be used:– Sorbitol/lactulose: taste issues

• Agents often limited:– Bulk forming agents: require adequate water

– Methylnatrexone (Relistor®): other options may be tried first

Anxiety

• Culmination of physical and psychological symptoms mixed in with the reality of the situation– Psychological factors (i.e. – fears of isolation, – Psychological factors (i.e. – fears of isolation,

factors associated with death) may impact the physical findings

• Presents in many ways– Restlessness, insomnia, hyperactivity,

jitteriness, apprehension, worry

Management of Anxiety

• Attempt to identify the etiology– Example: anxiety secondary to dyspnea,

delirium– Drug-induced or drug withdrawal– Drug-induced or drug withdrawal

• Consider non-pharmacologic solutions– Other disciplines: social worker, spiritual care– Family support– Psychological support

Curr Opin Support Palliat Care 2007;1:50-56

Management of Anxiety

• General medications used:– Benzodiazepines

• Lorazepam • Lorazepam

• Clonazepam

– Antipsychotics• Haloperidol

• Quetiapine

– Antidepressants

Curr Opin Support Palliat Care 2007;1:50-56

CNS - Fatigue

• Numerous causes– Pain, medications, deconditioning, anemia,

cytokine release, metabolic abnormalities, depression, infection, dehydration depression, infection, dehydration

– Increased sleep is an expected outcome as end of life gets closer

• Is there a need to treat?– Is it a primary concern to the patient?– Are there reasonable options that minimize

risks?

Management of Fatigue

• Adapt ADL’s: reduce housework/physical activities

• Rearrange schedule • Rearrange schedule

• Avoid using energy for unnecessary things

• Pharmacologic options– Corticosteroids

– Stimulants

Confusion/Delirium

• This is a one hour talk

• General approach:– Look for underlying cause– Look for underlying cause

– Remove or treat cause if possible

– Use of antipsychotics/benzodiazepines

– Create safe environment for all parties

– Maintain patient dignity

Secretions

• Often distressing to caregivers/family• Precise mechanism unclear

– Generally referred to as inability to clear – Generally referred to as inability to clear secretions

– Air flowing over secretions with respiration creates the noise

• Has been referred to as the “death rattle”– Associated with death being near

Secretions – Management

• Non-pharmacologic– Repositioning– Suctioning

• Medications:– Atropine – Glycopyrrolate– Scopolamine– Octreotide

Am J Health Syst Pharm 2009;66:458-464

Other Symptoms Encountered

• Depression

• Behavioral problems

• Anorexia• Anorexia

• Insomnia

• Family crisis situations

Medications Readily Available

• Routine medications for comfort care:– Morphine– Haloperidol– Atropine eye drops– Lorazepam

• Miscellaneous agents:– Dexamethasone– Something for bowels

Discontinuing Medications

• When should this be done?– Suggest not right away (unless clear harm)

• Avoid the perception of giving up• Avoid the perception of giving up

• Do not want to lose the confidence of the patient

– Assess needs and clarify with patient family

– Always good to ask if they (patient) feel as if they are taking too many medications

• Opens the door

Discontinuing Medications

• Do they have an indication for the drug• Goals of therapy

– Have they changed from 5 years ago– Have they changed from 5 years ago

• When will the benefit be realized– Example of diabetes– Use of surrogate endpoints

• Examples: BP, BG, DEXA

• You can always add something back

Discontinuing Medications

• Risk vs benefit– If the risk outweighs the benefit, there is no

reason to continue the medication– Sometimes difficult to determine– Sometimes difficult to determine

• Aspirin for CVA prevention– D/C and patient has CVA next week– Don’t D/C and they develop GI bleed in two weeks

• 85 year-old female taking 3 BP meds; BP: 165/90; complains of lightheadedness at various times during the day

Discontinuing Medications

• Once stopped, discontinue the monitoring– Makes no sense to continue monitoring for

something which is not going to be treated• Diabetes and BG• Diabetes and BG• Hypertension and BP

– If you obtain a result, you often are obligated to do something with it

• Not implying out of sight, out of mind

– All parties need to be on board with this as well

Concluding Remarks

• Be realistic in your expectations from drugs– Not everyone responds the same way

• Include the patient in the discussion• Include the patient in the discussion

• More expensive medications are not always better

• Don’t wait to treat the symptoms

Questions?