Chapter 1 history and trends of healthcare worksheet answer key

The μ1-receptor it produces the effects of analgesia.

The μ2-receptor is also associated with other effects such as “sedation, reduced blood pressure, itching, nausea, euphoria, decreased respiration, miosis (constricted pupils) and decreased bowel motility often leading to constipation”

Opioids are agents of choice for

Severe acute pain

Moderate to severe cancer pain

Moderate to severe chronic non-malignant & severe neuropathic pain (third or fourth line) has gained more acceptance in recent years

Reserved for moderate to severe infrequent headaches as “Last resort” due to contraindication or failed response to conventional therapies (eg "triptans")

Opioids do not have a "ceiling effect". The analgesic ceiling effect of a drug refers to the dose beyond which there is no additional analgesic effect.

Initiation of therapy

Pharmacological effects (Tolerance to most side effects occurs within first week)

See Table 34-3

Analgesia

Euphoria

Sedation

Respiratory depression

Cough suppression

Nausea / Emesis

CNS irritability

Constipation - TOLERANCE DOES NOT DEVELOP TO THIS SIDE EFFECT

Because constipation is a predictable effect of opioid therapy, providers should advise patients to begin using laxatives prophylactically when initiating treatment. Although first-line therapy for constipation generally involves increasing exercise, fluid intake, and dietary fiber, these interventions are usually not effective for preventing or treating opioid-induced constipation, and pharmacological management is indicated.

Because opioids affect both peristalsis and the fluid content of the stool, treatment and prophylaxis should target these mechanisms. Stimulant laxatives are commonly used to promote motility; the agents of choice are senna and bisacodyl. A stool softener can be used to counteract the drying and hardening effects of increased transit time; docusate is the most widely used.

Goal: 1 non-forced BM every 1-2 days in average patient

Other options are available

Peripheral opioid antagonists Does not affect analgesic response or promote withdrawal because it does not cross the BBB

Agents specifically used for OIC will not be addressed in the class (eg. methylnaltrexone)

Allergenicity - For a patient with a true allergy to codeine (or related compound), the risk of cross-reactivity with another opioid can be reduced if an analgesic from a different chemical class is used. It is important to note that use of an opioid from a different chemical class does not eliminate the risk of an allergic reaction. For patients with severe or life-threatening reactions, non-narcotic analgesics, such as non steroidal anti-inflammatory agents or acetaminophen, should be considered.

cross allergenicity of compounds in the same column:

· Phenanthrenes

· Phenylpiperidines

Phenylheptanones (diphenylheptanes)

· Morphine

· Meperidine

· Methadone

· Hydromorphone

· Fentanyl

· Levomethadyl

· Oxymorphone

· Sufentanil

· Levorphanol

· Alfentanil

· Codeine

· Hydrocodone

· Oxycodone

Conversion guidance

Determine the total 24-hour dose of current opioid

Using the estimated equi-analgesic dose (see attached), calculate the equivalent dose of new analgesic for the desired route of administration

Converting dose should be decreased by 1/2-2/3 to allow for incomplete cross-tolerance

Take the 24 hour starting dose of new opioid and divide by the frequency of administration to give the new dose

Consider rescue opioid therapy during the conversion process

Please be sure you are comfortable with conversions such as seen in the practice conversions discussion thread

Important Definitions - Terms recognized and encouraged by American Academy of Pain Management, American Pain Society and American Society of Addiction Medicine

Addiction - A primary, chronic, neurobiologic disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. Characterized by one or more of the following: impaired control over drug use, compulsive use, continued use despite harm and craving

Physical Dependence - A state of adaptation manifested by a drug class-specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood levels, and/or administration of an antagonist

Tolerance - A state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more opioid effects over time

Aberrant drug-related behavior - A behavior outside the boundaries of the agreed on treatment plan which is established as early as possible in the doctor-patient relationship

Abuse – Any use of an illegal drug, or the intentional self-administration of a medication for a non-medical purpose such as altering one’s state of consciousness

Opioid Antagonists

Naloxone

Indication: the treatment of opioid agonist-induced respiratory depression and known / suspected overdose of opioid

Reverses both toxic and clinical effects of opioids

Naltrexone

Indication: the adjuvant treatment of alcoholism and nicotine dependence

Used off-label for opiate agonist dependence and withdrawal

Weight loss

Neuropathic Pain:

There are many types of neuropatic pain, but we will limit to DPN since we have already discussed DM. Treatment modalities are similar regardless of the type. Diabetic neuropathies are the most prevalent chronic complications of diabetes.

Treatment does NOT fall into the WHO step wise approach to other types of pain

        Image result for neuropathy algorithm

Consider either pregabalin or duloxetine as the initial approach in the symptomatic treatment for neuropathic pain in diabetes. A

Gabapentin may also be used as an effective initial approach, taking into account patients’ socioeconomic status, comorbidities, and potential drug interactions. B

Although not approved by the U.S. Food and Drug Administration, tricyclic antidepressants are also effective for neuropathic pain in diabetes but should be used with caution given the higher risk of serious side effects. B

Given the high risks of addiction and other complications, the use of opioids, including tapentadol or tramadol, is not recommended as first- or second-line agents for treating the pain associated with DSPN. E

Diabetes Care 2017 Jan; 40(1): 136-154

NOTE: A calculator (that is not part of a smart device) is permitted for the exam along with a clean sheet of scrap paper

NOTE: Conversion guide will be provided if needed

Additional Considerations for Opioid Use and Safety

What are the basic pain pathways and endogenous opioid peptides and the mechanism by which opioid and other analgesics work

What are some considerations when initiating opioid therapy

https://www.healthquality.va.gov/guidelines/Pain/cot/VADoDOTCPG022717.pdf

https://www.cdc.gov/drugoverdose/pdf/Guidelines_Factsheet-a.pdf

https://www.cdc.gov/mmwr/volumes/65/rr/pdfs/rr6501e1.pdf

When is it reasonable to consider use of long-acting formulations

How should breakthrough pain be managed and proper dose determined

Why are genetic polymorphisms important when considering the use of opioids

What is medication assisted therapy for opioid use disorder

who is at increased risk

https://academic.oup.com/painmedicine/article/19/5/928/4098277

what products are available

what concerns are there with naloxone administration

Headache - Headache” is one of the most common complaints .2% of all visits to emergency departments; One of the Top 10 presenting complaints in ambulatory care

International Headache Society (IHS) classification

Migraine

Tension-type headache

Cluster headache

Migraines - goals should include provision of rapid and consistent treatment, Restore functional ability, Use lowest, effective dose of abortive therapy , Minimize adverse events

Non-pharmacological interventions

Patients should maintain a headache diary as part of the treatment regimen to identify potential triggers and practice avoidance as well as possibly the use of ice, rest, bio-feedback

(table 35-2)

Urgent medical evaluation is also imperative with "red flag" symptoms (table 35-1)

Abortive therapies (similar abortive therapies + oxygen used in cluster type headache, but prophylaxis is key)

APAP alone is not recommended

Oral NSAIDs and combination analgesics with caffeine: first-line treatment choices for mild to moderate attacks or severe attacks that have responded in the past to similar treatment

Butalbital-containing products: limit and monitor use due to overuse, medication-overuse headache, and withdrawal

                         

Triptans - First line therapy for moderate to severe migraines, especially when nonspecific (including OTCs (e.g. Excedrine Migraine)) medications are ineffective

Clinical response varies among patients. If there is no response to one triptan, it is reasonable to try another.

CIs - History of ischemic heart disease, uncontrolled hypertension, CAD, stroke, PVD, Prinzmetal's angina, myocardial infarction, pregnancy

Mechanism of action will help to explain contraindication in some of the concominant diseases

Ergotamines - Moderate to severe migraine attacks. Usually considered after other treatment failures

CIs - Contraindicated among patients with/at risk for CAD, stroke, PVD, uncontrolled HTN, liver/kidney disease, strong inhibitors of CYP3A4, pregnancy (category X)

Opioids - Reserved for moderate to severe infrequent headaches

“Last resort” due to contraindication or failed response to conventional therapies

Antiemetics: adjunctive therapy to relieve nausea/vomiting and migraine attack

Prophylactic therapy - there is no commonly accepted indication for starting prophylactic treatment, but should be considered when

quality of life, business duties, or school attendance are severely impaired

frequency of attacks ≥ 2 per month

migraine attacks do not respond to acute drug treatment

frequent, very long, or uncomfortable auras occur

Selection of an agent Based on side-effect profile, previous treatment and patient’s comorbidities (Table 35-4)

Beta-blockers (e.g. propranolol) - Ideal for healthy patients or comorbid hypertension, angina, or anxiety

avoid in reactive airway disease, heart block, bradycardia

TCAs (e.g. nortriptyline, amitryptiline) - Good choice for patients with comorbid depression or insomnia

avoid in urinary retention, BPH, glaucoma or where anticholinergic effects are problematic

Anticonvulsants (e.g. valproate, topirimate) - Good choice for patients with comorbid seizure disorder or manic-depressive illness

many drug-drug interactions

CCBs (e.g. verapamil) - generally considered second or third line for migraine headaches, but first line for prophylaxis of cluster type headache

NSAIDs: Use for migraines with predictable pattern (Example: menstrual cycle)

Should be initiated 1-2 days prior to the expected onset of headache

total duration of use limited due to risk of GI events

Botox: 15 or more headache days a month, each lasting 4 hours or more

CGRP Antagonists: The calcitonin gene-related peptide (CGRP) is a therapeutic target in migraine because of its hypothesized role in mediating trigeminovascular pain transmission and the vasodilatory component of neurogenic inflammation. There is little evidence to guide the use of the CGRP antagonists in specific populations (eg, children, elderly, and women during pregnancy and lactation). Effective in randomized trials but are expensive and lack long-term safety data.

Attachment(s):

Equivalent Analgesic Doses.pdf (64.97 KB) 

Quiz I Review Feb 13, 2019 2:47 PM -

Following each exam, an analysis of grades will be conducted and an exam review will be made available through Panopto (or other technology). The purpose of this review will be to "identify the informational source(s) of the questions" missed, "identify the strategies you could have employed to make information more meaningful and memorable" and to "generate a study plan to repair the deficiencies encountered in the analysis." The attached documents may help with this self-analysis / remediation exercise. These documents are for your own use and do NOT need to be submitted to me for review.

Panopto Link: https://wilkes.hosted.panopto.com/Panopto/Pages/Viewer.aspx?id=b04ae349-c44e-498e-9c2a-a9f30141a49e

The information contained in this media clip is confidential, privileged and only for the information of the intended recipient(s) and may not be used, published or redistributed for any reason.

This link will be available until 02/22/2019

The review address only those questions that needed additional attention. Take note of where you may have seen these topics addressed, emphasized, repeated and highlighted ..

Text book

The Fuel for Active Learning Thread

Weekly Recap

Study Guide

These tools will undoubtedly support your efforts in gaining mastery of the topic(s) at hand. We are called upon to be leaders, not followers. We can learn a tremendous amount from each other. Don't be shy about participating and asking me and each other questions.

Overall, everyone is doing a great job. Thank you for your active participation. If there are any additional questions regarding this review, please ask.

Regards,

Dr D.

Attachment(s):

Post-Exam_Survey Part 1.docx (36.98 KB) 

Post-Exam_Survey Part 2.docx (45.67 KB) 

Study Guide Quiz 2 (Modules V-VIII) Feb 13, 2019 11:41 AM -

Please find attached a study guide for exam 2 (modules 5-8).

Based on student feedback, I am providing you this as a way to identify areas of priority in the material presented. Using this, along with the highlights in the "Weekly Recap" and "Fuel for Active Learning" threads will undoubtedly provide you with the direction the exams will take. I will once again share some important announcements I posted:

We will be covering a great deal of information, so it is prudent that you do not fall behind.

The heart of this course will be discussions (please see rubrics) (30% of final grade)

Please be very cognizant of deadlines 

Although each student is only requires to post once and reply once, I Strongly encourage you to take an active role in other discussions.

Unless specifically stated otherwise, you will not be asked to memorize dosages or lab values.

Exam Exception

For this exam ONLY, you will be permitted to use a calculator that is not part of a smart device .. like a calculator from the Smithsonian

For this exam ONLY, you will be permitted to have a "clean" sheet of paper to use as scrap

The ability to synthesize and manipulate concepts as they relate to clinical situations will be emphasized.

Your text book offers an online "Student Center" with learning objectives and self-assessment quizzes: http://www.mhpharmacotherapy.com/0071835024.php?c=student.

Regards,

Dr. D.

Attachment(s):

Study Guide Exam II.docx (20.53 KB) 

Week 4 Weekly Recap (Psych) Feb 4, 2019 8:15 PM -

Early Posting of Recaps-

Since this is an exam week, I have posted the recap early in the week to help with your quiz preparation.

The recaps along with the study guide and fuel for active learning threads will be very helpful tools for you to use

Depression - One theory is that Depression is due to a deficiency in the amount or function of cortical and limbic 5-HT and NE . All currently used antidepressants ↑ 5-HT, DA and/or NE levels in the brain. This theory does not explain everything, but is a strong foundation why the medications we use may be beneficial

When a patient has depressive symptoms, it is necessary to investigate the possibility of a medical, psychiatric, and/or drug-induced cause. You will find these exclusions also listed in DSM5. All depressed patients should have a complete physical examination, mental status examination, basic laboratory work-up and suicide risk evaluation (There is an increased risk of suicide at the beginning of the antidepressant therapy)

Pharmacological causes of depression

Antihypertensive drugs (propranolol, methyldopa, clonidine)

Hormones (oral contraceptives, glucocorticoids)

Acne therapy (isotretinoin)

Antidepressants are used in treatment of depression, as well as some anxiety, pain and eating disorders, but not bipolar disorder

Principles: Most studies find combination of pharmacotherapy + cognitive therapy more efficacious than either therapy alone. Efficacy of different antidepressants is generally comparable across and within classes. For patients with unipolar major depression who are initially treated with antidepressants, newer agents such as SSRIs / SNRIs rather than other antidepressants should be tried. It is critical to take into account patient specific factors such as prior response to a given class of medications, tolerability of adverse effects, comorbid conditions (eg. avoiding anticholinergics in glaucoma or BPH; avoiding bupropion in seizure disorders), etc

All antidepressants take 4-6 weeks to achieve their full effect. Adequate trial is necessary prior to making changes.

There is an increased risk of suicide at the beginning of the antidepressant therapy

Potential for withdrawal symptoms with abrupt discontinuation

In patients with mild to moderate major depression who obtain little symptom relief from an initial antidepressant, switching to an antidepressant from a different class as first-line treatment, rather than augmenting the initial antidepressant with a second drug is recommended (After an adequate trial)

For patients who obtain little symptom relief despite repeated (eg, one to three) antidepressant switches, augmentation with a second medication is recommended

For patients who obtain definite symptom relief that is not satisfactory and can tolerate the initial antidepressant, we suggest augmentation as first-line treatment

Aripiprazole, quetiapine, risperidone, and olanzapine

Lithium

Triiodothyronine (levothyroxine)

SSRIs - Selective serotonin re-uptake inhibitor

Currently most often prescribed initial drug of choice because of low side effect profile and not lethal if overdose as single agent

Nearly all SSRIs undergo hepatic oxidative (P450) metabolism with fluoxetine having an extremely long T 1/2 because of its active metabolite. In fact, the "wash out period" for fluoxetine is about 5 weeks (eg to prevent serotonin syndrome if starting a MAOI, John's Wort, etc)

Some SSRIs inhibit P450 enzymes

Fluvoxamine inhibits CYP1A2, 3A4, 2C9, 2C19

Fluoxetine and paroxetine inhibit CYP2C9 and 2D6

Citalopram, escitalopram and sertraline do not block P450 enzymes

Generally well tolerated.

May be associated with n/v, weight gain (especially paroxetine), etc.

30-40% of patients report loss of libido, delayed orgasm or diminished arousal 

Class effect

Fluoxetine and TCAs have greatest reproductive safety

SNRIs - SNRIs block both SERT and NET (re-uptake of serotonin an norepinephrine)

examples include venlefaxine, duloxetine, desvenlefaxine

Similar indications and side effect profile to SSRIs with different MOA

Higher doses of some agents (venlafaxine) may be associated with increases in DBP, but not seen with others (duloxetine)

Not only indicated in MDD, but also used in treatment of chronic pain disorders (including neuropathies and fibromyalgia), generalized anxiety, stress urinary incontinence (duloxetine), and vasomotor symptoms of menopause

TCAs -Because of their side effects and potential for lethal overdose (even if taken alone), TCAs have essentially been replaced (ie. NOT initial therapy) by SSRIs and SNRIs as the first choice for treatment of depression. They still are used in refractory cases and for other indications (enuresis, migraine prophylaxis, neuropathies, etc)

Significant anticholinergic effects (Anti-SLUD - salavation (ie dry mouth), lacrimation (ie dry eyes / blurred vision), urination (ie urinary retention), defication (ie constipation)).

       

Avoid in:

Patients with benign prostate hyperplasia

Patients with closed-angle glaucoma

Patients with cardiac disease

Patients with hepatic impairment

Elderly patients

Due to anticholinergic, CV and sedative properties

please refer to BEERs list / STOPP-START criteria

Alpha-blocking properties - orthostasis, falls

H1 blocking properties - drowsiness, sedation, weight gain

Sexual side effects

QTc prolongation

CNS depression, especially if combined with other CNS depressants (benzo's, EToH, opiates)

5HT2 antagonists - Trazodone was among most commonly prescribed antidepressants before introduction of SSRIs. Use now primarily limited to insomnia

Unicyclic / tetracyclic antidepressants

Bupropion - Also known as norepinephrine-dopamine reuptake inhibitor (NDRI)(also used in smoking cessation)

Reasonable 1st line option in select patients where weight gain is a concern, patients w/ ADRs from SSRIs (eg. sexual dysfunction), where smoking cessation is also a consideration, etc.

Treatment for Tobacco Use [ http://search.ebscohost.com.ezproxy.wilkes.edu/login.aspx?direct=true&db=dme&AN=905141&site=dynamed-live&scope=site ]

Active metabolites (including amphetamine-like compounds)... note side effects in relation to this fact and yes, this will cause a positive urine test

CNS stimulant effects, such as decreased appetite, anorexia,[weight loss], insomnia, agitation, tremor, seizures

May NOT be a good choice for monotherapy if anxiety is part of the clinical picture

Contraindications: seizure disorder; history of anorexia/bulimia; patients undergoing abrupt discontinuation of ethanol or sedatives, including benzodiazepines, barbiturates, or antiepileptic drugs --> because bupropion lowers seizure threshold!

Very Low likelihood of sexual dysfunction. Sometimes used as add on therapy to offset the sexual dysfunction caused by other antidepressants or in place of other antidepressants

Mirtazapine -

Blockade of 5-HT2A, 5-HT2C and 5-HT3 * receptors

Also blockade of H1 receptors and presynaptic α2-adrenoreceptors

good choice if weight loss part of clinical picture and weight gain is desired

Significant sedative effects, weight gain, dizziness

does NOT cause sexual dysfunction

MAOI-Used only for refractory cases of MDD

By blocking the enzyme that breaks down 5-HT, NE and DA, MAO inhibitors increase the levels of these NTs in the brain

Several significant drug interactions

Drugs that can precipitate hypertensive crisis... Ephedrine, pseudoephedrine, phenylephrine

Serotonin syndrome with other antidepressants, narcotic analgesics (esp. meperidine (Demerol®)), St. John’s wort, linezolid (Zyvox®)

Washout period of 14 days necessary when switching from an MAOI to another antidepressant or from another antidepressant to an MAOI (5 week washout when switching from fluoxetine to an MAOI)

See attached PPT on Serotonin Syndrome

Drug -food interactions precipitating hypertensive crisis

The "Wine and Cheese Reaction"

Anxiety (GAD)

Anxiety -Excessive anxiety or difficult to control worry, occurring more days than not for at least 6 months, about a number of events or activities (such as work or school performance). There are many medical conditions and medications that can cause "anxiety-like" symptoms:

           

There is little evidence that one agent is more effective than another

Primary therapy should address underlying issues and should be managed accordingly (i.e. with SSRIs,SNRIs, etc.)

Citalopram, sertraline, fluvoxamine, and fluoxetine are not FDA-approved for the treatment of GAD. However, the efficacy of SSRIs in GAD appears to be a class effect, and there are uncontrolled data to support the use of all SSRIs in the pharmacotherapy of GAD.

¤Generally, treatment of GAD should be continued for at least one year

BZDs

Most prescribed agents for the acute treatment of anxiety (and in conditions such as depression with there is an anxious component -"bridge therapy")

Efficacy is similar among the available agents

Use (of BZDs) should be limited to short term (2-6 weeks) until "other therapies (SSRI, SNRI)" takes effect

¨Benzodiazepine tapering: 25% per week reduction until 50% of dose is reached, then decrease by 1/8th every 4-7 days.

> 8 weeks of therapy: 2-3 week taper

>6 months of therapy: 4-8 week taper

> 1 year of therapy: 2-4 month slow taper

Should not be used in patients with past or current substance and/or alcohol abuse or dependence     

Prefer those agents with longer half-life due to better coverage of anxiety (this is not the same in elderly patients or for insomnia)

BZDs may paradoxically produce an increase in irritability and aggression in some individuals (particularly if short- acting drugs are given (triazolam)

Benzodiazepines, shown to affect memory, can produce anterograde amnesia (i.e., a loss of memory for events occurring forward in time). Following the ingestion of a benzodiazepine, short-term memory is not affected, but long-term memory is impaired.

Caution: patients are often prescribed BZDs for different reasons (muscle spasm, anxiety, insomnia, etc) by different providers. Always be aware of potential therapeutic duplications

All benzodiazepines are lipid soluble (easy access to the CNS) and can cause profound CNS depression, especially if combined with other CNS depressants

Efficacy is similar between different agents

Duration of action:

Short-acting: alprazolam, triazolam

Intermediate-acting: lorazepam, oxazepam

Long-acting: diazepam, flurazepam, chlordiazepoxide ... The half lives of the parent compound and active metabolites are extensive (up to 100 hours)and can accumulate. AVOID in the elderly.

Boldface drugs available for clinical use in various countries; * = active metabolite.

Note those with short half-lives and those which are conjugated and have no active metabolites.

Buspirone - Anxiolytic drug, but NO sedative, hypnotic, anticonvulsant or muscle relaxant properties

Comparable efficacy to benzodiazepines in the treatment of GAD, but some trials reported inconsistent findings. Considered second line overall

Slow onset of action (2-3 weeks)

lack of activity against comorbid conditions (e.g., depression, panic disorder, social phobia) is a drawback in some patients.

Abrupt discontinuation of buspirone does not cause withdrawal effects as seen in BZDS

TCAs / antihistamines (1st generation) - Limited / Selective used in practice due to adverse effects (see above)

Tricyclic Antidepressants (TCAs)

Agents: imipramine (Tofranil®), nortriptyline (Pamelor®), amitriptyline (Elavil®), doxepin (Sinequan®)

It is equivalent to benzodiazepines in anxiolytic effect.

Anticholinergic, ↓ seizure threshold, cardiotoxicity, orthostatic hypotension

Antihistamines (1st generation)

¨Hydroxyzine (Atarax®, Vistaril®)

Second-line therapy due to adverse effects and limited efficacy (but commonly used in primary care setting)

Adverse effects: anticholinergic, sedation (within 30 mins)

Should be avoided in elderly population

¨Pregabalin (Lyrica®) / Gabapentin (Neurontin®)

Second-line therapy; not approved in US for GAD

1st line in evidence based guidelines in Europe

Efficacy similar to lorazepam, alprazolam, and venlafaxine

Adverse effects: Sedation, dizziness, dry mouth, abnormal thinking (difficulty concentrating)

β-Adrenergic antagonists (e.g., propranolol) may be helpful in patients with physical symptoms (e.g., palpitations and other cardiovascular complaints) but are not effective for the treatment of GAD.

Insomnia

Proper sleep hygiene should be encouraged.

Basic principles for the rational treatment of insomnia are to use the lowest effective dose, use intermittent dosing (2-3 nights/wk), use short term (2-3 wk at a time), discontinue after slow taper if the patient has been taking it regularly, and use agents with short and/or intermediate half-life to minimize daytime sedation

Dosage, pharmacokinetic properties, and risk-benefit ratio are the key factors in selecting the most appropriate medication

Choice of agents should be based on alleviating particular sleep problems (Eg difficulty falling asleep, decreased TST, early awakening, etc). Short-acting agents are recommended for patients with difficulty falling asleep, while intermediate-acting drugs are indicated for problems with sleep maintenance

Examples of short-acting medications (duration of effect ≤8 hours) include zaleplon, zolpidem, triazolam, lorazepam, and ramelteon.

Short-acting agents taken at bedtime can result in both early-morning wakening and rebound insomnia the following night

may be beneficial if intermediate or longer acting agents result in "hangover" or excessive daytime (morning) sedation

good choice when sleep induction

Examples of longer-acting medications include zolpidem extended release, eszopiclone, temazepam, estazolam

Used for sleep maintenance

Long-acting agents taken at bedtime can result in daytime sedation the following day leading to falls, etc

Avoid long-acting agents, especially in older people, because they cause daytime sedation and impair cognition, thereby increasing the risk of falls.

Influence of manual skills (such as driving performance) due to drowsiness, confusion, amnesia and impaired coordination

enhancement of depressant action of other drugs (in a more than additive way)

Caution and close monitoring is needed in the administration of hypnotics to older people and to patients with hepatic, renal, or pulmonary disease.

Treatment of insomnia in older adults requires careful attention to the role of medical, neurologic, sleep, and psychiatric comorbidities. Vulnerability to side effects increases with age, and medications for insomnia often exacerbate existing age-related impairments such as gait instability, sedation, cognitive dysfunction, urinary and bowel dysfunction, and cardiac arrhythmias. Older adults may have slower drug metabolism, and thus maximum and next-day serum concentrations will be increased.

5 BZDs marketed for insomnia

Flurazepam, triazolam, temazepam, estazolam, quazepam

No respiratory depression in healthy patients, but respiratory depression in patients with COPD or obstructive sleep apnea

Note: Any BZD can be used for sleep. The limitations are the same as described in the GAD section above

"Z Hypnotics" - Zolpidem, zaleplon, eszopiclone. Act on the BZD receptor similar to traditional benzodiazepines

no effect on sleep architecture

minimal rebound insomnia

no anti-convulsant or muscle relaxing properties (as do typical BZDs)

Suvorexant - blocks the binding of wake-promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R, which is thought to suppress wake drive

Increased levels in women and obese patients

An increased risk for hazardous sleep-related activities such as sleep-driving; cooking and eating food, making phone calls, or having sex while asleep have also been noted

Ramelton - Ramelteon is a melatonin receptor agonist that specifically targets the MT1 and MT2 receptors in the brain, believed to be critical in the regulation of the body's sleep-wake cycle

Reduced the latency of persistent sleep with no effects on sleep architecture and no rebound insomnia or significant withdrawal symptoms

Drowsiness, dizziness, increased prolactin levels

NO ABUSE POTENTIAL or Cross tolerance with other CNS depressants(including alcohol)

1st generation antihistamines (eg. diphenydramine, hydroxyzine).

Generally safe but have anticholinergic adverse effects, such as dry mouth, blurred vision, urinary retention, and confusion in older patients

       

Elderly

These medications are a concern and should be avoided in patients with BPH and glaucoma, among others

May reduce "sleep quality"

For Exam Purposes Only, DO NOT worry about the sections on Narcolepsy, Cataplexy, RLS, Obstructive Sleep Apnea or Parasomnias

Attachment(s):

The Serotonin Syndrome.pptx (111.47 KB) 

Opioid Use in Non-Cancer Pain Feb 4, 2019 3:00 PM -

Please note the republished post below.

Just a reminder that this portion of the course is mostly self-directed, meaning there are no "specified" due dates. Please keep in mind, your initial post must answer all of the questions in the case presented (with references) and you will assign a rating for two of your peers posts. In order to allow yourself and your peers enough time to complete .. recall I have recommended the following:

The initial post completed between weeks 4 and 6 (Recommended)

Completing the response posts (Assigning a rating to two peers posts) between weeks 6 and 12 (Recommended)

Completion of the quiz prior to the end of the semester (Open Book)

Chronic non-cancer pain is highly prevalent in our communities and its optimal management is crucial to the health and well being of the community. At both the level of the individual patient and the community, there needs to be focus on using the best available evidence to assess and manage this overwhelming problem. Part of the appropriate treatment for many people will include opioid analgesics for acute pain at least for days to weeks. Simultaneously there is increasing pressure to ensure that prescribing of opioid analgesics is minimized to reduce the risk of dependence and illicit diversion. This is a difficult balance to strike, even with initiatives such as prescription drug monitoring programs.

In order to best explore this important topic, we will use the “Patient Encounter” found in Pharmacotherapy: Principles and practice (4th ed.) chapter 34, Pain Management.

The case is broken up into four parts each with multiple questions to be researched. Your initial post to the completed case (All 4 parts) will follow the same format as other discussion posts. I recommend completing the initial post between weeks 4 and 6.

Once you have completed your case workup and post, you will have the opportunity to evaluate cases posts from two peers (assigned to your group). Based on your research, you will assign the each peer reviewed case from 1 (poor) to 5 (excellent) stars.

This gives you the liberty of seeing alternative presentations of the same case, identification of issues that either you yourself or peer may have missed as well as reinforce other points that you may have agreed upon. I recommend completing the response posts between weeks 6 and 12.

The textbook chapter can be used as an initial resource, but additional guidance can be found on the web page for this topic: Table of Contents > Opioid Use in Non-Cancer Pain > Opioid Use in Non-Cancer Pain (Web Page).

This discussion (initial and response posts) is equally weighted with all other posts

The second segment of this topic is a quiz representing 10% of the course grade. This quiz will consist of 25 multiple-choice questions. The content for the quiz will be taken from textbook readings, resource readings (Dynamed), course objectives and discussion assignment. The quiz will be "open" throughout the semester and may be taken at anytime during the course as adequate preparedness and time allows. The quiz is NOT monitored by ProctorNow and may be considered "open book".

Related image

Week 3 Weekly Recap (M/W Health) Feb 4, 2019 1:53 PM -

Men's health:

Erectile dysfunction -“The inability to attain or sustain an erection adequate for sexual stimulation”

Can be the result of age related changes (e.g. diminished testosterone, altered response to NO, etc), comorbidities (e.g. DM, BPH, depression, etc .. Table 51-1), and medications (Table 51-2. 5-alpha reductase inhibitors, beta-blockers, TCAs, etc).

Diagnosis should include PE (including a check for signs of hypogonadism), medication review, Hx, and labs ( HbA1C, PSA, FLP, testosterone)prior to initiating medications

Treatment should include:

Non-pharmacological interventions (exercise, weight loss, etc)

Co-morbidity (DM, HTN, etc.) management - including (if possible) removal of causal medications

If a medication is removed, consider that it probably will have to be replaced with a reasonable alternative

Table 51-1, 51-2

Examples: SSRIs are a potential cause of ED. A reasonable replacement might be bupropion (assuming no contraindications); dutasteride (for BPH) is a common cause of ED. Tardenafil as a replacement for or in combination with a 5-alpha reductase might be reasonable (assuming no contraindications)

Image result for medication associated with ed

Note: There are occasions where an offending medication can NOT be discontinued because of a compelling indication and / or lack of a reasonable alternative (eg Beta-blockers in heart failure). One must consider if the patient is healthy enough for sexual activity and if so, possible alternatives such as vacuum erection devices or medications (see below) 

PDE5Is - Often considered drug of choice when pharmacotherapy is necessary. There is no convincing evidence that one agent in this class is superior to another. Choice may be based on patient preference, cost, and formularies. If one agent does not work it may be reasonable to try another from the same class.

There is no drug effect without some type of sexual stimulation because these drugs do not cause penile erections; they only provide the ability of the penis to respond to sexual stimulation.

Varying duration of action (most 4-5 h, tadalafil 36h).

Headache and flushing most common ADRs. Serious cardiac events possible.

Significant DIs exist

(+) nitrates - severe hypotension

In an emergent situation, a patient who has taken sildenafil may be given a nitrate after 24 hours; for tadalafil, after 48 hours. Vardenafil does not have a suggested time interval, but blood pressure and heart rate did not change when the drug was taken 24 hours before nitrate administration.

prolonging of QT interval

Serious cardiovascular events have been associated with PDE5 inhibitors; therefore, they should not be used in patients in whom sexual intercourse is inadvisable because of poor cardiac status.

Testosterone replacement (Low-T)-

Testosterone replacement regimens should never be administered to men with normal serum testosterone levels, or in patients with isolated erectile dysfunction as the only sign of hypogonadism.

Before initiating any testosterone replacement regimen in patients 40 years and older, patients should be screened for breast cancer, benign prostatic hyperplasia, and prostate cancer. All are testosterone-dependent conditions and theoretically could be worsened by exogenous administration of testosterone

Thorough medical workup is indicated

Several medications may contribute (cimetidine, spironolactone, ketoconazole, etc).

Several relative and absolute contraindication to use

Alprostadil - PgE1 analog administered by intracavernosal injection & intraurethral inserts

Because PGs bypass many steps in the erectile cascade, they are quite effective at producing an erection, even in cases where PDE5 inhibitors cannot do so.

Most invasive and low patient acceptance. Reserved as second or third line treatment

Image result for intraurethral suppository

Vacuum erection devices (see text)

OTC / Herbals (Yohimbine, etc) - limited evidence. Not recommended

BPH - BPH increases urethral resistance, resulting in compensatory changes in bladder function. Obstruction-induced changes in detrusor function, including smooth muscle hypertrophy, compounded by age-related changes in the functioning of the bladder, lead to urinary frequency, urgency, and nocturia, the most bothersome BPH-related complaints. Not all patients with LUTS have BPH and not all men with BPH have LUTS.

Diagnosis includes components such as symptom assessment (AUA score), PE and PSA (which tends to correlate with prostate size and can be used as a prognostic marker)

Interventions (non-surgical)

This image describes the management of benign prosthetic hyperplasia (BPH) based upon AUASI scores, if the symptoms are bothersome and if there are complications. Treatment may include 

Lifestyle modification - limiting EToH, caffeine, avoid certain medications (Table 52-4)(e.g. decongestants, androgens, etc), weight loss, etc

Watchful waiting is the most conservative approach for patients with mild symptoms or those with moderate symptoms without bother

The level of symptom distress that individual men are able to tolerate is variable

Alpha-blockers - fairly rapid onset (2-4 weeks) with relatively rapid symptom resolution , durable effect (years) with AUA symptom index (AUASI) improving 30-45%. No effect on prostate size (PSA) or disease progression.

Relax smooth muscle in bladder neck, urethra & prostate

(Blue dots indicate the distribution of alpha receptors surrounding the bladder and prostate). It is clear why these agents would provide rapid relief of symptoms 

New second generation (alfuzosin) and third generation (tamsulosin and silodosin) agents are preferred because of uroselectivity, no need for dose titration and limited orthostasis

Older agents also have an indication for hypertension and have more CV ADRs (e.g. orthostasis, reflex tachycardia, etc).

dose titration should follow the "start low, go slow" paradigm 

Most guidelines advocate for the individual management of BPH and hypertension

5 alpha reductase inhibitors - Management of moderate to severe BPH in patients with enlarged prostate glands

Reduce prostate size (and PSA) and thus outlet obstruction

(less subjective symptom improvement)

Reverse / Slow disease progression

Decrease the risk of disease complications

Note: although dutasteride blocks both the Type I and Type II iso-enzymes of 5-alpha reductase while finasteride only blocks Type II, there is not a clinically significant difference in outcomes when either is used

Peak effect 6-12 months, effect is only durable as long as drug is continued

ADRs -- (androgen insufficiency) decreased libido, impotence & ejaculatory disorder, breast tenderness & enlargement

PDE5Is (tadalafil) - Treatment of the signs and symptoms of benign prostatic hyperplasia +/- ED

Comparable efficacy to alpha-blockers for LUTS, but does not increase flow rate or reduce PVR

Peak onset 1-4 weeks

Combination therapy

Alpha-blocker offer immediate relief; 5 alpha-RIs reduce prostate enlargement over time

In patients with an enlarged prostate gland and an elevated PSA ≥1.4 ng/mL, combination drug therapy with an α1-adrenergic antagonist and a 5α-reductase inhibitor is more beneficial than single drug therapy.

Rationale

alpha-blocker offer immediate relief

5 alpha-RIs reduce prostate enlargement

PDE5I with an α-adrenergic antagonist, patients experienced significant improvements in LUTS, increased urinary flow rates, and decreased PVR volume

Herbals: No dietary supplement, combination phytotherapeutic agent or other nonconventional therapy is recommended for the management of LUTS secondary to BPH. …

Women's Health

General Information:

FDA Categories- 5 categories (ABCDX) Based on clinical data (animal, human) and estimated risk: benefit ratio if drug is given.

Category A: “Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester (and there is no evidence of a risk in later trimester), and the possibility of fetal harm appears remote.”

Category B: “Either animal-reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the first trimester (and there is no evidence of a risk in later trimesters).”

Category C: “Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.” Pregnancy Category C is given to medicines that have not been studied in pregnant humans but that do appear to cause harm to the fetus in animal studies.

Category D: “There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective.)”

Category X: “Studies in animals or human beings have demonstrated fetal abnormalities or there is evidence of fetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.”

Note: Because of certain limitations (as seen in discussion threads), This system is being replaced, but is still widely used

Pregnancy and Lactation Labeling Rule (PLLR)

Red Flag medications -

Warfarin, Phenytoin, Valproic Acid, Carbamazepine, Lithium, ACE inhibitors/ARBs, Thalidomide, Ethanol, statins .. etc

Note: this is NOT a comprehensive list, but a good representation for exam purposes

Table 47-3

Combined Oral Contraception: - choosing a formulation based on fertility goals, patient preference, discussion of risk/benefits, Hx (to rule out contraindications .. see US MEC attached)

World Health Organization and the Food and Drug Administration recommend using the lowest dose pill that is effective

Risks can include, but not limited to cancers, CV events/HTN, VTE, drug interactions

Concomitant use of broad spectrum antibiotics and combination contraceptives may result in decreased contraceptive efficacy; however this is Category 1 under US MEC

If a typical failure rate of 1% to 3% is a concern for the patient, consider additional or alternative forms of birth control

Concomitant use of P450 enzyme inducers (rifampin, phenytoin, carbamazepine, phenobarbital) may result in decreased contraceptive efficacy

If use COC – use higher doses (at least 35 mcg EE) + high progestin, shorten hormone free interval to 4 days or less

Avoid low progestin – the patch, POP

Consider additional or alternative forms of birth control

Table 48-5

Concomitant use of Anti-HIV protease inhibitors can either increase or decrease serum levels of estrogens and progestins – may need backup method

Drospirenone can cause hyperkalemia, especially if used with other agents that can increase potassium (ACEIs, heparin, aldosterone antagonists, etc)

Benefits can include favorable effect on bone, menstrual effects, improved acne, improved PMDD, etc

Managing concerns Table 48-4:

Estrogen

Excess – N/V, cervical mucorrhea, hypertension, headache, breast tenderness, edema, melasma, bloating

Deficiency – Early or mid-cycle breakthrough bleeding, increased spotting, hypomenorrhea, vasomotor symptoms

Progestin

Excess – breast tenderness, headache, fatigue, changes in mood

Deficiency – Late break through bleeding, hypermenorrhea, dysmenorrhea

Androgen

Excess – increased appetite, weight gain, acne, oily skin, hirsutism, decreased libido, increased breast size, breast tenderness, increased LDL, decreased HDL

¨

Amenorrhea - rule out other causes. Can increase to more estrogenic formulation or to triphasic formulation to decrease amenorrhea.

Not a concern if patient is happy.

Acne/ oily skin/ hirsutism - Rule out other causes. Switch to less androgenic formulation of progestin (or decrease progestin content)

3rd generation Desogestrel, norgestimate

4th generation drospirenone

Dienogest

GI- typically resolves in 1-3 months. Decrease estrogen component will help with nausea. Decrease progestin component to help with bloating and constipation

Bleeding /spotting - Common (30-50%) when first initiated. Often resolves by 3rd or 4th cycle

Other manipulations of estrogen and progestin depend at the point of the cycle bleeding / spotting occurs

First rule out other causes including medications (eg. Medications that increase metabolism)

If spotting or bleeding before completing active pills (late cycle (days10-21)) – increase progestin to enhance endometrial support

Monophasic with higher progestin or triphasic with ­ing progestin

If spotting after withdrawal bleeding (early cycle (days 1-9))– increase estrogen or decrease progestin in the early pills(triphasic)

If mid-cycle spotting/bleeding – increase both estrogen/progestin midcycle

Headaches - If headaches start or worsen after starting OC, need to rule out other causes (take BP, ask about headache, any focal neurologic symptoms)

If related to OC use and are not serious - Discontinue OC, Lower estrogen dose, Lower progestin, Eliminate pill free interval (only if HA occur during pill free interval)

Decreased Libido

Ask about depression

If due to decrease in vaginal lubrication, switch to vaginal ring contraception

Increase estrogen

Hypertension - COCs can cause small increases (i.e., 6 to 8 mm Hg) in blood pressure, regardless of estrogen dosage

Low -dose COCs is acceptable in women younger than 35 years with well-controlled and frequently monitored hypertension

Discontinuing the COC usually restores blood pressure to pretreatment values within 3 to 6 months

VTE / Thromboembolism

Estrogens - increase hepatic production of factor VII, factor X, and fibrinogen in the coagulation cascade, therefore increasing the risk of thromboembolic events

Progestins

Newer 3rd and 4th generation progestins – greater effect on procoagulant, anticoagulant, and fibrinolytic pathways

Increased resistance to the anticoagulant effect of activated protein C by some progestins

Higher levels of sex hormone binding globulin

For women who are at an increased risk of thromboembolism - Consider low-dose oral estrogen contraceptives containing older progestins or Progestin -only contraceptive

See US MEC

Progestin Only oral contraceptives - indicated in Breastfeeding (post-partum phase), older women, women who cannot take estrogen

The failure rate is higher than other progestin-only methods or COCs

Effectiveness is lowered when taken as little as a few hours late

Other conditions in pregnancy:

DM I / II / GDM

Treatment

ADA diet

Insulin – drug of choice

–Regular insulin or NPH

–Insulin lispro (Humalog)

–Insulin aspart (Novolog)

◦Insulin requirements will increase beginning around 28 weeks gestation and continue to increase due to placental hormones

◦Increasing data on safety of insulin glargine in pregnancy

oral agents (metformin / glyburide) 2nd line

HTN

–when SBP reaches 160 or DBP reaches 110

–Continue treatment when multiple hypertensive's were required before pregnancy or when end organ damage is present

methyldopa / labatolol 1st line

hypothyroidism

◦Levothyroxine – DOC

◦Attain normal thyrotropin concentrations

◦Women who received thyroid replacement prior to pregnancy can expect an increased dosage requirement of 25-50% during pregnancy

depression

No psychotropic drugs with labeling approved by the FDA for use during pregnancy and lactation

1st line – psychotherapy, but not always an option

SSRI’s

◦Avoid paroxetine (D) during first trimester

–CV malformations

◦Fluoxetine (C) citalopram (C) sertraline (C)

–Literature is reassuring, best data

◦Risk of PPHTN after 20 weeks gestation with SSRI’s

◦Risk of neonatal withdrawal or adaptation syndrome1

–d/c 2 weeks before term

TCA’s

◦Literature is reassuring

◦Possible withdrawal symptoms

Atypical antidepressants

◦Limited data

Menopause

Goals - Alleviate or reduce symptoms, Improve QOL, Minimize ADRs

Non-pharmacological interventions - avoid vasomotor triggers (hot beverage, spicy food, EToh, etc), exercise, water based lubricants

Pharmacotherapy - hormone therapy remains the most effective treatment for vasomotor symptoms and vulvovaginal atrophy, especially in women with moderate to severe symptoms, provided there is not CHD, significant CHD risk factors or history of breast cancer

Oral Estrogens - FDA approved for moderate to severe vasomotor symptoms, vulvovaginal atrophy and prevention of post-menopausal osteoporosis.

Note, oral estrogens should NOT be used for osteoporosis prevention in the absence of vasomotor symptoms of menopause or for patients with local symptoms ONLY

The HOPE trial demonstrated low dose provided equivalent efficacy relief as standard doses

Oral progestins - Used in women with an intact uterus to reduce endometrial hyperplasia and endometrial cancer with estrogen monotherapy.

Must be taken minimum of 12-14 days/month

NOT necessary s/p hysterectomy

Length of therapy - The benefit to risk ratio appears to be best if HT is started close to the time of menopause. Typically can stop 2-3 years after starting. Longer durations may be associated with CHD, stroke, VTE, various cancers etc.

Can abruptly stop hormone therapy or can taper. No evidence that tapering of HRT reduces the recurrence of hot flushes compared with sudden discontinuation

1 out of every 4 will need to be re-initiated due to bothersome vasomotor symptoms

Strong consideration for tapering in those on higher doses of estrogen or long duration.

Tapering options

Dose taper - Progressively decrease dose of estrogen

May require 3-6 months in some women

Do not decrease again until symptoms are tolerable and improve

Day taper

Decrease the number of days per week HRT is taken

Do not decrease again until symptoms are tolerable and improve

Combination of dose and day tapering

Note- progesterone is not tapered, only the estrogen component is. Progesterone is stopped at the end of the taper when completely stopping HRT

Vulvovaginal complications during menopause can range from vaginal dryness to atrophy , dyspareunia (painful coitus) and lower urinary tract symptoms (urge incontinence / OAB)

Local or systemic estrogen therapy for symptom relief

Estrogen can help to restore thickness, elasticity, and lubrication

Estrogen can help reduce the risk of recurrent urinary tract infections

In the absence of vasomotor symptoms, local/ topical (vaginal) estrogen therapy should be used. There is minimal systemic absorption (with exceptions) and does not require the concomitant administration of a progestin

Attachment(s):

USMEC for Contraceptive Use 2017.pdf (322.96 KB) 

APA Style Reference / Scholarly Resources Jan 30, 2019 7:00 AM -

Rubric: "Correct APA format, including references and citations, writing mechanics, grammar, spelling, and punctuation are used."

APA style referencing in this course

From the content page: Course Resources > APA Style Guide to Electronic References

APA Style Referencing help at Wilkes University

On the library home page under Resources, click on Online Reference Collection. Then, the last item on the Online Reference Collection page is Citation Guides & Style Manuals. http://wilkes.libguides.com/c.php?g=191922&p=1266495

APA Style Wizard works the best if you double check the citation after it is automatically created because sometimes the automatically generated citation contains incorrect capitalization or other small mistakes.

Rubric: "Peer reviewed scholarly resources are used for the 2 required discussion posts. A minimum of 2 references are required (other than the course textbook)."

Here is a time saver for you. When you are looking for scholarly resources, go to your Dynamed links for that topic. In the summary pane to the left, find the section titled "Guidelines and Resources". You will find the most current information available as far as guidelines as well as supporting review articles.

Wikipedia, Scientific American, Live Strong, US News, etc. are NOT scholarly resources

In accordance with national standards, including those of the Agency for Healthcare Research and Quality's National Guideline Clearinghouse, guidelines (and articles) more than 5 years old that have not yet been updated to ensure that they reflect current knowledge and practice can no longer be assumed to be current.

Tips Jan 30, 2019 5:00 AM -

1. As we are progressing into the middle of week three, I would like to remind each of you to revisit the course objectives and rubrics for online grading.

2. Each module has an introductory page with key points, module objectives and other additional resources. If you are not utilizing the Dynamed links, you should. They provide very current information about all aspects of therapy, including guidelines and scholarly literature. You may find this a literature search time saver.

3. Please be sure you are comfortable accessing Proctor Now using the practice quiz. 

Quiz Preparation Jan 28, 2019 5:00 AM -

As you are preparing for the exam, I again encourage you to understand each of the concepts provided in the chapter(s) assigned. The content for examinations will be taken from lecture material (eg. Key points web page), textbook readings, course objectives, discussions and evidence based approaches to therapy (found both in the text and via Dynamed). The ability to synthesize and manipulate concepts as they relate to clinical situations will be emphasized.

During the course of each week, we have discussed some clinical case scenarios. Please remember that these cases certainly are not meant to be all inclusive of that weeks required topics. They are meant to get you to think critically about each disease state and appropriate pharmacotherapy. Along the way I have taken the time to comment and provide module (weekly) recaps. I assume that you have taken the time to review them and each other's posts.

I have previously provided a formal study-guide as a way to identify areas of priority in the material presented. In addition, I have been very "guiding" with responses to posts, the "Fuel for Active Learning" thread and "Weekly recaps". All of the material for the exam were emphasized and can be found in at least one of these places (More likely you will find redundancies .. and for GOOD reason, you will see it again).

If you are NOT actively participating ...

posts limited to mere 150 words just to "get by"

reviewing fellow classmates / my posts

participating in fuel for active learning

using tools such as weekly recaps and study guide ..

... you are missing out on some great information

Do not memorizes doses of medications (in practice I would expect that you would look doses up and confirm dosing accuracy of each medication prescribed) and do not memorize normal lab values needed to make treatment decisions or monitor therapy (if needed in a question, reference ranges will be provided). You should be able to interpret values however.

Example TSH was found to be 3.1mU/L. (nl 0.3-3.04m/)

Your text book offers an online "Student Center" with learning objectives and self-assessment quizzes: http://www.mhpharmacotherapy.com/0071835024.php?c=student. (>For Students > Self Assesment Q&A)

Did you get the right answer? If so great job, but don't stop there. Ask yourself "what made all the other possible choices incorrect". This will certainly help identify area that may need additional time and attention.

Questions, please ask.

Best Regards

Week 2 Weekly Recap - (Endocrine) Jan 27, 2019 9:00 AM -

Diabetes:

In this discussion, please talk about how patients get put on these medications and why/how they should be transitioned to more evidence based treatments. Is it OK to start a patient on a drug (particularly an oral drug) other than metformin as an initial drug? Please cite possible circumstances where this could be reasonable. How can patients and practitioners be convinced to change their behavior?

As you can see from our discussion, treatment approach can vary from patient to patient and from practitioner to practitioner. It is each of our responsibilities to ensure patients are receiving the most appropriate treatment based upon current evidence and patient acceptance. It is also our responsibility to educate each of our patients about long term side effects and benefits so an informed decision can be made.

Throughout the discussions, I made several comments and added some insight. It is my assumption that you each took the time to read them and learn from what was said. Below are some highlights:

How are the "players" (Insulin, glucagon, amylin, incretins) involved in glucose regulation

How does the clinical course of DM I and DM II differ

What are the risk factors for DM II and are they modifiable

Consider lifestyle modifications

What micro- and macrovascular complications are associated with DM and what interventions can be used to prevent or treat them (besides glucose control) ..That is, these medications should be used "adjunctly" to BG lowering interventions in ALL patients with DM, barring contraindications! These intervention have been demonstrated to improve long term outcomes .. Don't forget about them in your comprehensive treatment plan

ACEI (or ARBs) - REGARDLESS BLOOD PRESSURE

There is a "compelling" indication in patients with hypertension and DM

Delay progression in Type 1 with or without HTN and any degree of albuminuria

Delay progression in Type 2 with or without HTN and microalbuminuria

Reduce development of microalbuminuria in Type 2 with or without HTN

ARBs are considered a reasonable alternative for those intolerant of ACEI

Of the agents available to control the complications of diabetes mellitus, cardiovascular drugs, and particularly ACE inhibitors, have a pre-eminent place. Experimental and epidemiological data suggest that activation of the renin-angiotensin-aldosterone system plays an important role in increasing in the micro- and macrovascular complications in patients with diabetes mellitus. Not only are ACE inhibitors potent antihypertensive agents but there is a growing body of data indicating that also they have a specific 'organ-protective' effect. For the same degree of blood pressure control, compared with other antihypertensive agents, ACE inhibitors demonstrate function and tissue protection of considered organs. ACE inhibitors have been reported to improve kidney, heart, and to a lesser extent, eye and peripheral nerve function of patients with diabetes mellitus. These favourable effects are the result of inhibition of both haemodynamic and tissular effects of angiotensin II. Finally, there are a growing number of arguments favouring the use of ACE inhibitors very early in patients with diabetes mellitus.

This is basically everyone with DM

ACEI (or ARBs) - Compelling indication with elevated BLOOD PRESSURE

Cardioprotective dose ASA (IE baby aspirin or clopidrogel as alternative)

Use in ALL diabetics with CV disease (secondary prevention)

Prevention of CV events (primary prevention)

USE in: high CV risk (10-yr CV risk > 10%) - Typically: male > 50 yo or female >60 yo with 1 additional major risk factor (FH of CVD, HTN, smoker, dyslipidemia or albuminuria)

MAY consider: intermediate CV risk (younger patients with 1 or more risk factors, older patients with no risk factors, or 10-yr CV risk of 5-10%)

Note - Many authorities consider DM to be an ASCVD risk equivalent

This is basically everyonewith DM

Statins - ACC/AHA 2013 Guidance

For All patients 40-75 with diabetes (see above)

Moderate intensity statin is indicated regardless of baseline LDL

High intensity statin should be considered in those with a 10 year risk > 7.5%

For patients with diabetes aged <40 years with additional atherosclerotic cardiovascular disease risk factors, consider using moderate intensity or high-intensity statin and lifestyle therapy

For patients with diabetes aged >75 years with additional atherosclerotic cardiovascular disease risk factors, consider using moderate intensity or high-intensity statin therapy and lifestyle therapy

This is basically everyone with DM

Statins - ADA Guidance

no longer recommends specific LDL-C goals in adults

initiation and intensity of statin therapy should be based on cardiovascular risk status rather than specific LDL-C goals, but statins indicated for most adults > 40 years old with diabetes

What are the goals set by ACE /ACCE and are they written in stone for all patients?

Primary target for glycemic control is HbA1C

Individualize HbA1C goal – based on…

Duration of DM

Age/life expectancy

Comorbid conditions

Known CVD or advanced comorbid conditions

Hypoglycemic unawareness

Individual patient considerations

 

Diabetes Care Volume 40, Supplement 1, January 2018: Metformin, if not contraindicated and if tolerated, is the preferred initial pharmacological agent for type 2 diabetes. A

Landmark Study UK-PDS

Reduced macrovascular complications in obese patients

Reduced all-cause mortality and risk of stroke compared to intensive therapy with insulin or a sulfonylurea

Reduced diabetes-related death and MI versus conventional therapy

contraindications to metformin include eGFR < 30ml/min, Severe/worsening CHF (including multiple hospitalizations / exacerbations), lactic acidosis, concurrent radio contrast dye. etc

Please note when transitioning from oral therapy for type II DM to insulin, metformin is retained! Secretagogues are discontinued when prandial (fast/rapid) insulin is to be added

What are the various types of oral and non-insulin medications and what represents a rational combination of medications.

What antidiabetic medications have compelling indications:

for those with underlying ASCVD or at high risk for CVD

for those with CKD

for those with a compelling need to avoid hypoglycemia

for those where weight is an important consideration

What are the precautions, SE, CIs (ex. TZDs association heart disease and HF, weight gain, edema, osteoporosis)

Note other medications highlighted in yellow in the AACE flow chart above and the precautions in the charts below)

Note: neither ADA or ACCE advocates use of > than 3 medications (triple therapy).

Insulin

What are the various insulins and describe the pharmacokinetics (onset, peak, duration)and how are they used (eg basal, basal-bolus, split-mixed, sliding scale (..Ask if you don't understand)).

PKs of Insulins

Insulin Regimen Types

 

Sliding Scale Should NOT be used

Difficult to do in home setting, requires education and understanding of patient and caregiver

Allows patient to become hyperglycemic, better to schedule dosing and prevent rises in BG

Requires frequent blood glucose monitoring, $$$ and compliance issues

Can be used as monotherapy or as add-on therapy for T2DM .. Presenting A1C 9 + symptoms or failure to achieve goal A1C on adequate trial of 2-3 agents at maximally tolerated doses

Often starting with a long acting insulin

When glycemic goals aren’t reached despite basal insulin (Good FBG and pre-prandial BG, but elevated HbA1C), Consider prandial therapy with fast-acting insulin. Begin fast-acting insulin before largest meal.

Variation exists between ADA and ACCE in their recommendations

If HbA1C still elevated, add fast-acting to another meal

Sulfonylurea can continue up until the point where prandial (rapid) insulin is added

Metformin can / should continue !!

Consider insulin in:

Severely uncontrolled hyperglycemia (glucotoxicity)

Elevated glucose despite maximally tolerated oral therapy

Gestational diabetes or pregnancy

Comorbid illness that make control with oral agents difficult (e.g., MI, infection, renal or hepatic disease)

Intolerance to oral medication

Insulin ADRs

Hypoglycemia

Injection site reactions

Lipoatrophy – caused by insulin antibodies; Lipohypertrophy – caused by injections into same sit

Weight gain (increased abdominal fat)

? Cancer

How is therapy monitored and how should the results be interpreted?

Self-monitoring blood glucose

Target reaching fasting and pre-prandial glucose goals FIRST

Target PPBG if HbA1C goal not met despite meeting FBG and pre-prandial glucose goals

How does treatment in the hospital setting differ from outpatient

NO studies have evaluated oral agents on outcomes in hospitalized patients

"Sick days"

http://www.joslin.org/info/Sick_Days.html

Immumizations

Thyroid Disease:

Hypothyroidism

Autoimmune or Hashimoto’s thyroiditis (most common)

Subacute thyroiditis

Post radioactive iodine therapy

Lithium therapy

Iodine deficiency

Goals: Restore and normalize thyroid hormone concentrations, Attain and maintain euthyroid state, Relieve current symptoms, Reverse any biochemical abnormalities

What agents are used to treat hypothyroid disease? What makes the medications different and what do the guidelines recommend for use 

Recommendation 22.1: Patients with hypothyroidism should be treated with Levothyroxine monotherapy. Grade A

other forms of thyroid replacement may be associated with necessary cost, lack of therapeutic rationale, increase adverse effects and allergenicity (animal based products)

Starting therapy

Normal adult dose: 1.6 mcg/kg/day (~100-125 mcg/day) based on IBW (LBW)

Titration by 25-50 mcg every 4-6 weeks until TSH normalizes

EXCEPTIONS include elderly, chronically ill patients or history of cardiovascular disease . Initially 12.5-25 mcg/day, then titrate to maintenance dose until TSH normalizes

Expect higher requirements during pregnancy

Thyroid hormone demand

Increases in TBG

Destruction of T4 by placental deiodinases

Note adjustments in table

How is treatment monitored and how should results be interpreted as far as therapy changes (the relationship between TSH and T3-4)

Primary hypothyroidism

Monitoring should be every 6-8 weeks after starting or dose/product change. If TSH is not in target range (0.5-2.5 mIU/L) alter dose in 10% to 20% increments. ..

levothyroxine has a T 1/2 of 6-10 days (and NTI .. see below). How does this relate to the fact that after initiating or changing a does or changing a product (IE brand to generic, generic to brand or one generic brand to another), TSH should be checked in about 6 weeks?

Why are thyroid replacement drugs considered to have a narrow therapeutic index ( NTI )and what does that mean clinically?

The therapeutic index (TI) is the range of doses at which a medication is effective without unacceptable adverse events. Drugs with a narrow TI (NTIs) have a narrow window between their effective doses and those at which they produce adverse toxic effects. 

Oral Bioavailability: (erratic) 40-80%

brand vs generic

Highly protein bound (99%)

Half-life

Euthyroid = 6-7 days

Hypothyroid = 9-10 days

Steady State: @ 6 weeks or 4-5t1/2

Consider changes such as brand to generic, different generics

What are some drug-drug, drug-food interactions associated with thyroid replacement (eg. drug binding interactions, di-valent cations, amiodarone, certain antibiotics)

ALL patients should be educated that thyroid replacement should be taken first thing in the morning with water only and at least 30 minutes away from food or other medications.

Where binding interactions are concerned, the window is two hour separation

myxedema coma ?

Hyperthyroidism

Graves’ disease (most common)

Nodular thyroid disease (toxic solitary or multinodular goiter)

Inflammatory thyroid disease

Goals : Reduce the activity of excessive hormone activity, Minimize symptoms, Prevent long-term complications

Medications - Thionamides

RECOMMENDATION 13 Methimazole should be used in virtually every patient who chooses antithyroid drug therapy for GD, except during the first trimester of pregnancy when propylthiouracil is preferred, in the treatment of thyroid storm (inhibition of peripheral conversion), and in patients with minor reactions to methimazole who refuse radioactive iodine therapy or surgery

Delayed onset

Monitoring LFTs, CBC,TSH, Free T4, weight

Drug-drug / drug food interactions ?

- Iodides

-radioactive iodine (RAI)

Instructions for patients receiving RAI?

Beta-blockers role in therapy?

So .. beta blockers are used for Symptomatic relief of hyperthyroidism until more definative therapy is instituted and thyroid levels retun to normal or near normal..

Reduction of peripheral manifestations

Tachycardia, sweating, severe tremor, nervousness

Inhibition of peripheral conversion of thyroid hormones at higher doses (propranolol ONLY)

Small therapeutic effect in magnitude

thyrotoxicosis

Why does amiodarone pose a unique concern to thyroid disorders

"Amiodarone-normal thyroid autoregulation is lost because of the relatively high iodine content" .. this fact can lead to a situation where amiodarone can cauase BOTH hyper- and hypo- thyroidism, depending on the patient, through several process

blocking thyroid peroxidase

blocking proteolysis of Tg and thyroid hormone

altering organification, etc

If there are any questions, please ask ..

Great job everyone!

Week 1 Weekly Recap - (GI) Jan 20, 2019 10:00 AM -

As you have demonstrated, the use of PPIs in GERD is not just as simple as picking up a box of pills at your local pharmacy. Much thought and clinical decision making is necessary if the intended use is going to exceed 2 weeks (patient directed therapy with OTCs). HPIs, CCs, allergies, medication histories, etc. will be part of a more extensive work up.

What would you recommend if a patient is taking Nexium and Plavix together?

"As we have seen through our discussions, there is a lot of information (including an FDA issued statement in the package insert) describing the drug interaction and reduced efficacy of clopidogrel if used with a PPI (primarily omeprazole) (or in patients who are genetically slow CYP2C19 metabolizers); however there is also evidence based information indicating the interaction is not as significant as originally thought.

PPI therapy does not need to be altered in concomitant clopidogrel users as there does not appear to be an increased risk for adverse cardiovascular events. (Strong recommendation, high level of evidence) Am J Gastroenterol 2013; 108:308–328; doi:10.1038/ajg.2012.444

Despite pharmacodynamic evidence that omeprazole interferes with clopidogrel metabolism, COGENT trial found addition of omeprazole to clopidogrel reduced gastrointestinal events without increasing cardiovascular events. ACCF/AHA/SCAI 2011 guideline on percutaneous coronary intervention (Circulation 2011 Dec 6;124(23):e574, Catheter Cardiovasc Interv 2013 Oct 1;82(4):E266, J Am Coll Cardiol 2011 Dec 6;58(24):e44

Again, not a straight forward answer to a complex question.

Evidence-based decision making involves combining the knowledge arising from one’s clinical expertise, patient preferences, and research evidence within the context of available resources. Evidence-based decision making—like all decision making—involves choosing from a discrete range of options, which may include doing nothing or a “wait and see” strategy. All such choices are informed by an evaluation of available information: the process of using clinical judgment. In making evidence-based decisions, research evidence should not be taken at face value and adhered to uncritically, but should be given an appropriate weight in a decision depending on its internal and external validity. Integrating research evidence into decision making involves forming a focused clinical question in response to a recognized information need, searching for the most appropriate evidence to meet that need, critically appraising the retrieved evidence, incorporating the evidence into a strategy for action, and evaluating the effects of any decisions and actions taken. These steps are important components of the active process that is evidence-based decision making. "(Evid Based Nurs 2004;7:68-72 doi:10.1136/ebn.7.3.68)

Please remember, this discussion was only representative of the topics included in GI (week 1) and you are encouraged to dissect related topics (PUD, constipation, diarrhea, n/v) with the same type of critical thinking. As i have stated... The ability to synthesize and manipulate concepts as they relate to clinical situations will be emphasized.

GERD

“Heartburn” – hallmark symptom (i.e. Retrosternal chest pain in association with certain foods or in the first hour or two after eating, or constantly)

May be associated with significant morbidity

May be assocoated with atypical presentation

Treatment goals: Relieve associated symptoms, promote esophageal healing, Avoid complications, Prevent recurrence

Step 1 :

Life style modification / non-pharmacological interventions such as dietary modification, avoid contributing medication, smoking cessation, avoidance of EtOH, weight loss, etc (See Table 17-1)

There are simply too many recommendations and each is too narrowly applicable to enforce the whole set on every patient. However, it is also clear that there are subsets of patients who may benefit from specific lifestyle modifications, and it is good practice to make those recommendations to those patients based on their specific history

+/ - Antacids

Multivalent cations with many precautions, drug interactions and adverse effects. Note comments section below!

Trial of patient-directed OTC therapy(not exceeding 2 weeks) OTC H2RAs (up to BID) or OTC PPIs (up to QD)

Step 2: Lifestyle modification with standard dose (Prescriber directed) acid suppression therapy H2RAs (BID) x 6-12 weeks or PPIs (QD) x 4-8 weeks (↑ to BID with inadequate symptom response )

Note there is no significant difference in efficacy among the H2RAs when given at equipotent doses

Cimetidine is associated with numerous clinically significant DIs

Dose reduction in renal and hepatic insufficiency and in the elderly

Duration of suppression ranges from 6-10 hours and varies with dose

Note there is no significant difference in efficacy among the PPIs when given at equipotent doses

Food may affect absorption. Given 30-60' before a meal. More flexibility in term of dosing with newer agents (eg. dexlansoprazole)

Delayed onset: 3-4 days for full inhibition

Duration of action up to 24 hours due to covalent, irreversible inhibition of proton pump

Step 3: PPIs (QD-BID) x 4-16 weeks

PPI therapy should be initiated at once a day dosing, before the first meal of the day. For patients with partial response to once daily therapy, tailored therapy with adjustment of dose timing and / or twice daily dosing should be considered in patients with night-time symptoms, variable schedules, and / or sleep disturbance.

In patients with partial response to PPI therapy, increasing the dose to twice daily therapy or switching to a different PPI may provide additional symptom relief

Step 4: surgical intervention

Maintenance PPI therapy should be administered for GERD patients who continue to have symptoms after PPI is discontinued and in patients with complications

Risks

Patients with known osteoporosis can remain on PPI therapy. Concern for hip fractures and osteoporosis should not affect the decision to use PPI long-term except in patients with other risk factors for hip fracture (ACG Conditional recommendation, Moderate-quality evidence)

PUD

Peptic ulcers (gastric and duodenal) are defects in the GI mucosa that extend through the muscularis mucosa. Causal relationships associate with H. Pylori infection, NSAIDs and SRMD.

Therapy includes non-pharmacological interventions (similar to GERD) and pharmacological with acid suppression (antacids, H2RAs, PPIs) and/or mucosal protection (sucralfate, colloidal bismuth, misoprostol), and if present, H Pylori eradication

Acid suppression - see GERD

Mucosal protection

Sucralfate - In acid environment it turns into a viscous, sticky polymer that binds selectively to ulcers and erosions creating a protective layer

Efficacy comparable to H2RAs

Chemically, contains Al(OH)3, thus behaves as Aluminum as far as ADRs (eg constipation), DIs (eg chelation)

Bismuth - MOA unclear

Bismuth coats ulcers and erosions, creating a protective layer against acid and pepsin

It may stimulate PG and mucus secretion

It binds bacterial endotoxins and has direct antimicrobial activity against pylori

Misoprostol - it stimulates mucus and bicarbonate secretion, replaces PG stores and enhances mucosal blood flow

Approved for prevention of NSAID-induced ulcers in high-risk patients

H Pylori eradication - Because of the critical role of pylori in the pathogenesis of peptic ulcer, eradication of this infection is a standard care in patients with gastric or duodenal ulcers

All regimens include 2 antibiotics & Acid suppression therapy (PPI or H2RA)

May include Bismuth preparation

Note especially duration and comments sections of the table below!

*Standard dosages for PPIs are as follows: lansoprazole 30 mg p.o., omeprazole 20 mg p.o., pantoprazole 40 mg p.o., rabeprazole 20 mg p.o., esomeprazole 40 mg p.o.

In patients aged 55 yr or younger with no alarm features, the clinician may consider two approximately equivalent management options: (i) test and treat for H. pylori and a trial of acid suppression if eradication is successful but symptoms do not resolve or (ii) an empiric trial of acid suppression with a proton pump inhibitor (PPI) for 4–8 wk. Am J Gastroenterol. 2005 Oct;100(10):2324-37.

NSAID induced ulcers

Prevention: Misoprostol or PPI. H2RAs not recommended for prophylaxis.

COX-2 inhibitors are associated with a significantly lower incidence of gastric and duodenal ulcers when compared to traditional NSAIDs. However, this beneficial effect is negated when the patient is taking concomitant low-dose aspirin. The usefulness of these agents has also been reduced by their association with myocardial infarction and other thrombotic CV events

Candidate

History of prior gastrointestinal event

Age over 60 (5x greater risk)

High NSAID dosage

Concurrent use of corticosteroids (4x greater risk)

Concurrent use of anticoagulants, antiplatelets or low dose ASA (12x greater risk)

Treatment

Discontinue NSAID If possible

Eradicate pylori if (+)

H2RAs or PPIs

PPIs heal NSAID-related ulcers more effectively as compared with H2RAs and are therefore the antisecretory drug of choice for treating NSAID-related ulcers, especially when NSAIDs are continued

Patients with NSAID-associated ulcers should be treated with a PPI for a minimum of eight weeks

Sucralfate is an option for healing only if NSAID will be stopped

Stress ulcer prophylaxis

The American Society of Health-System Pharmacists recommends prophylaxis in the following scenarios: coagulopathy(defined as a platelet count <50,000 cells/mm3, an INR >1.5, or a PT >2 times control); mechanical ventilation for longer than 48 hours; history of GI ulceration/bleed within 1 year before admission; head/spinal cord injury; burns on more than 35% of body surface area; ICU patients with multiple trauma; transplant patients perioperatively; and patients with at least two of the following risk factors—sepsis, ICU stay longer than 1 week, occult bleeding for at least 6 days, and use of high-dose corticosteroids (>250 mg daily of hydrocortisone or its equivalent).

As of now, there is no current recommendation for PPIs over H2RAs, as further clinical studies, including pharmacoeconomic analysis, are needed Barkun AN, Bardou M, Pham CQ, Martel M. Proton pump inhibitors vs. histamine 2 receptor antagonists for stress-related mucosal bleeding prophylaxis in critically ill patients: a meta-analysis. Am J Gastroenterol 2012;107:507–520.

Constipation

Approach to treatment should begin with determination of cause(including medications a patient may be on table 21-1)

Opiates

Anticholinergics (eg. tricyclic antidepressant (amitryptiline), diphenhydramine, benztropine, etc)

NDHP-CCB (eg verapamil)

Oral iron preparations

Calcium or aluminum antacids

NSAIDs

Clonidine

Diuretics

Non-pharmacological interventions first (diet (fiber), exercise, fluids)

Probiotics - limited data Best Pract Res Clin Gastroenterol. 2011;25:119–126

Pharmacological

Bulk forming agents (eg. methylcellulose (Citrucel*))

Administer 240 mL of water with each dose to prevent esophageal / GI obstruction and worsening symptom

Physical binding of other substances including medications

Safe in pregnancy

Emollients (softeners) (eg. docuste (Colace*)

Facilitate mixing of aqueous and fatty materials in the intestinal tract

Used for prevention, NOT treatment. Commonly prescribed with medications that may cause constipation (chronic opiate use, iron supplementation)

Safe in pregnancy

Lubricant laxative (mineral oil / castor oil)

Coats stool to allow easy passage / Prevents colonic water absorption

Systemic absorption – can generate immune response

Aspiration – may lead to lipoid pneumonia

Decreases absorption of fat-soluble vitamins à DO NOT use in pregnancy

Hyperosmotics (eg. polyethylene glycol (Miralax*))

Osmotic effects to retain fluid in GI tract

Safe in pregnancy

Saline laxatives - Composed of relatively poorly absorbed ions (Mg+ - sulfate, phosphate, citrate)(eg. MOM*)

Osmotic effects to retain fluid in GI tract

May be used occasionally to treat constipation in otherwise healthy adult

ADRs: fluid and electrolyte depletion, Mg (renal dysfunction) or Na (CHF) accumulation

Stimulant laxatives (senna, bisacodyl) (eg Sennokot*, Dulcoloxa*)

Only recommended for intermittent use – daily use strongly discouraged

New agents available for specific use ONLY (eg. IBS-C, OIC)

NOT discussed in this course

Summary of recommendations:

Slow Transit Constipation

Hyperosmotic laxatives

Senna, bisacodyl and other stimulants are second line

Those who need to avoid straining (eg hemorrhoids, hernia, MI)

Stool softeners or PEG

Children

Diet, fluid exercise

Avoid under 6 years without evaluation

Glycerin suppository, docusate

Diarrhea

Goal of treatment: Identify and Treat primary cause, Manage secondary causes, prevent electrolyte & acid/base disturbances & dehydration , provide symptomatic relief ,

Note the primary goal is NOT ALWAYS to stop diarrhea (see below, Infectious diarrhea)!

Non-pharmacological

Rehydration , oral preferred

Avoid Soda products, Gatorade*, Chicken broth, Tea

Diet

Resume age-appropriate diet once rehydrated

Secondary causes can include medications. An evaluation of medications an possible substitution of offending medications should be considered (if possible)

aluminum containing antacids, metformin, colchicine, antibiotics, etc

Pharmacological agents

Opiates and derivatives - Acts on peripheral (eg loperamide (Immodium*)) and central (eg diphenoxylate/atropine (Lomotil*)) opioid receptors depending on the agent. Those that act on central mu receptors are control substances and prescription only

Noninfectious diarrhea (acute & chronic)

Adverse effects: constipation, fatigue, dizziness

Adsorbents = Works through non-selective adsorption, providing bulk in digestive tract

Not systemically absorbed

Binds 60 times its weight in water

Also used for constipation (absorbs water / fluids)

Can also bind drugs leading to altered drug bioavailability

Bismuth subsalicylate - see GERD

Contraindications

ASA allergy

Nursing or pregnant women

GI bleeding

Immunocompromised patients

Drug interactions

Decrease protein binding of warfarin

Decrease absorption of TCN, quinolones

Octreotide - Prevents the release of secretory substances, Stimulates intestinal absorption

Symptomatic treatment of carcinoid tumors & VIPomas that produce violent watery diarrhea

Adverse effects:

Nausea , abdominal pain, QT prolongation

Cholelithiasis (d/t inhibition of gall bladder activity)

Hyper - / Hypoglycemia ( d/t altered insulin, glucagon GH balance)

Crofelemer - FDA approved for symptomatic relief of non-infectious diarrhea in patients with HIV/AIDS on anti-retroviral therapy

Probiotics - Help maintain normal GI flora, reduce colonization of disease-causing bacteria

Evidence - Vary based on intended use (acute treatment, prevention, antibiotic associated, adults, children), strain of bacterium and timing of administration

Digestive enzymes (lactaid)

Use in patients with lactase deficiency who are lactose intolerant

We do not routinely use empiric antibiotics in patients with acute diarrhea.

Infectious diarrhea:

diff -

The initial step in the treatment of Clostridium difficile infection (CDI) is cessation of the inciting antibiotic as soon as possible

Therapy for nonsevere difficile infection (CDI) consists of oral metronidazole >> oral vancomycin

Limitations of metronidazole include dose-dependent peripheral neuropathy and side effects of nausea and metallic taste.

Use of oral vancomycin is appropriate for initial therapy of nonsevere disease in patients who are pregnant, breastfeeding, or intolerant/allergic tometronidazole

Rifaximin— Small case series have suggested that sequential therapy with vancomycin followed by Rifaximin may be effective for the treatment of recurrent CDI

Traveler's diarrhea - the classic travelers' diarrhea due to enterotoxigenic Escherichia coli (ETEC) generally produces malaise, anorexia, and abdominal cramps followed by the sudden onset of watery diarrhea. The illness is generally self-limited with symptoms lasting for approximately one to five days.

Antibiotics are warranted to treat diarrhea in those who develop severe diarrhea, characterized by more than four unformed stools daily, fever, or blood, pus, or mucus in the stool. In addition, some travelers desire antibiotic treatment for milder disease if the illness is a large burden on a business trip or vacation.

For adults, several different antibiotic options are effective for travelers' diarrhea. In general, fluoroquinolones (eg ciprofloxacin) are the first choice for their efficacy and tolerability. However, for travelers to Asia,azithromycin is preferable because of increasing resistance to fluoroquinolones among enteric pathogens in that region. Azithromycin is also the preferred agent for pregnant women and children. We only use Rifaximin if a fluoroquinolone or azithromycin is not available or appropriate because its efficacy for invasive disease is unknown

Nausea / Vomiting

When choosing an agent,

Focus on individual patient, evaluate risk factors, and rule out other causes.

Agent related variables (efficacy, ADR’s, cost)

Please review mechanisms, ADRs and indications

Example Promethazine -

Block DA2 receptors in the CTZ + have antihistaminic and anticholinergic effects.

ADR’s: EPS, sedation, hypotension

Place in therapy: “general purpose antiemetics”. not very effective in severe n/v (i.e. chemotherapy induced n/v (CINV)

Example Lorazepam -

Benzodiazepines bind to GABA-A receptors. GABA is the major inhibitory NT in the CNS

benzodiazepines are sedatives, not antiemetic agents

Sedative and anti-anxiety effects → reduce anticipatory N/V associated with chemotherapy

ADRs - CNS - sedation, hallucinations, euphoria; CV - hypotension

CINV - Evaluate emetogenic potential of regimen

Mono therapy for chemotherapy with low and moderate emetogenic risk

Aggressive (combination of agents with different mechanisms) antiemetics for highly emetogenic regimens and delayed CINV

Examples

Dexamethasone + metoclopramide + diphenhydramine + lorazepam

Ondansetron + dexamethasone

Ondansetron + metoclopramide

Metoclopramide + dexamethasone 

Ondansetron + dexamethasone + prochlorperazine

Ondansetron + dexamethasone + aprepitant 

Discussion Based Learning Jan 16, 2019 6:00 AM -

Discussion-based learning provides deeply engaging learning experiences, particularly when outcomes are complex, and require application and synthesis. It enables student involvement through instructor-directed questions and student participation. This requires that students contribute and learn from each other.

Although each student is only required to post once and reply once, I encourage you to take an active role in other discussions. I have previously mentioned that the discussion cases are not meant to be all inclusive for a given topic, therefore I will add threads (Fuel for Active Learning), additional posts and ask questions of your and your classmates to stimulate additional conversation. Even if you do not post beyond the required minimum, it is to your benefit to at least review ALL remaining posts.

Benefits / Outcomes:

Improves communication skills: Students learn to articulate their thoughts as part of a larger discussion with their peers and instructors.

Boosts confidence: Students are encouraged to put forth their ideas in a supportive and engaging environment

Builds mutual respect: No one person is in a position to govern the conversation; students learn to listen to their peers and offer their own insights without dismissing opposing viewpoints.

Requires independent preparation: Students must come to class ready to discuss the assigned topic

Encourages critical thinking: Because students must play an active role in learning through discussion, they are required to exercise more critical thinking than is typically needed in a traditional lecture setting.

These items make the foundation for inter- and intra- professional approach to patient therapy.

Quiz Clarification / Note Jan 16, 2019 5:00 AM -

Just so we are all on the same page ..

There are three quizzes in this twelve week course each covering 4 weeks of inclusive information. So for example, quiz 1 "opens" at the end of the fourth week on Friday 02/08/2019 at 7:00 am and "closes" on Monday 02/11/2019 at 11:59 pm and will contain content from module I, II, III and IV. This means that in the fourth week, quiz one will open before your response post for week four is technically due and ... material from week four will be on the first quiz. The same trend continues for quizzes two and three (quiz 2 will contain content from module V, VI, VII, and VIII .. again the response post for week eight is technically due after exam two has already opened).

I am telling you this so that you can prepare accordingly.

Regards,

Dr D.

Study Guide Quiz 1 (Modules I-IV) Jan 14, 2019 9:00 AM -

Please find attached a study guide for exam 1 (modules 1-4).

Based on student feedback, I am providing you this as a way to identify areas of priority in the material presented. Using this, along with the highlights in the "Weekly Recap" and "Fuel for Active Learning" threads will undoubtedly provide you with the direction the exams will take. I will once again share some important announcements I posted:

We will be covering a great deal of information, so it is prudent that you do not fall behind.

The heart of this course will be discussions (please see rubrics) (30% of final grade)

Please be very cognizant of deadlines 

Although each student is only required to post once and reply once, I strongly encourage you to take an active role in other discussions.

Unless specifically stated otherwise, you will not be asked to memorize dosages or lab values.

The ability to synthesize and manipulate concepts as they relate to clinical situations will be emphasized.

your text book offers an online "Student Center" with learning objectives and self-assessment quizzes: http://www.mhpharmacotherapy.com/0071835024.php?c=student.

Regards,

Dr. D.

Attachment(s):

Study Guide Exam I.docx (25.32 KB) 

Opioid Use in Non-Cancer Pain Jan 14, 2019 8:00 AM -

Chronic non-cancer pain is highly prevalent in our communities and its optimal management is crucial to the health and well being of the community. At both the level of the individual patient and the community, there needs to be focus on using the best available evidence to assess and manage this overwhelming problem. Part of the appropriate treatment for many people will include opioid analgesics for acute pain at least for days to weeks. Simultaneously there is increasing pressure to ensure that prescribing of opioid analgesics is minimized to reduce the risk of dependence and illicit diversion. This is a difficult balance to strike, even with initiatives such as prescription drug monitoring programs.

In order to best explore this important topic, we will use the “Patient Encounter” found in Pharmacotherapy: Principles and practice (4th ed.) chapter 34, Pain Management.

The case is broken up into four parts each with multiple questions to be researched. Your initial post to the completed case (All 4 parts) will follow the same format as other discussion posts. I recommend completing the initial post between weeks 4 and 6.

Once you have completed your case workup and post, you will have the opportunity to evaluate cases posts from two peers (assigned to your group). Based on your research, you will assign the each peer reviewed case from 1 (poor) to 5 (excellent) stars.

This gives you the liberty of seeing alternative presentations of the same case, identification of issues that either you yourself or peer may have missed as well as reinforce other points that you may have agreed upon. I recommend completing the response posts between weeks 6 and 12.

The textbook chapter can be used as an initial resource, but additional guidance can be found on the web page for this topic: Table of Contents > Opioid Use in Non-Cancer Pain > Opioid Use in Non-Cancer Pain (Web Page).

This discussion (initial and response posts) is equally weighted with all other posts

The second segment of this topic is a quiz representing 10% of the course grade. This quiz will consist of 25 multiple-choice questions. The content for the quiz will be taken from textbook readings, resource readings (Dynamed), course objectives and discussion assignment. The quiz will be "open" throughout the semester and may be taken at anytime during the course as adequate preparedness and time allows. The quiz is NOT monitored by ProctorNow and may be considered "open book".

Related image

Getting Started Jan 14, 2019 7:00 AM -

During the course of each week, we will discuss some clinical case scenarios. Please remember that these cases certainly are not meant to be all inclusive of that weeks required topics. They are meant to get you to think critically about disease states, pharmacology of the medications used and appropriate pharmacotherapy.

Taking the time to read and understand my posts / responses, that of fellow students, the "Fuel for Active Learning" thread and study guide will undoubtedly prove to be beneficial. This will create an enriching environment and a foundation for our learning.

Rubrics for Discussion / Grading of Posts Jan 14, 2019 6:00 AM -

Discussions represent 30% of this courses grade. Please make the most of it and do not make the mistake of unnecessarily losing points here! Please familiarize yourself with the rubric used for grading (Table of Contents > Course Resources > Grading Rubric Online Discussion)

"Discussion in the classroom demonstrates comprehension of weekly course material evidenced by responses that are insightful, analytical and promote an engaging classroom environment". Have you researched your post? Can you support your answer with evidence based medicine? Are the guidelines you used current? Have you provoked additional responses to your or other posts?

Please remember this is a 500 level course. Posts should be of high quality caliber

You must demonstrate comprehension via your posts

"The initial discussion response(s) for each weekly question(s) is (are) posted by Wednesday at 11:59 PM ET for each electronic week. This posting is a minimum of 150 words. The required discussion response(s) to 1 peer for each weekly question(s) is (are) completed by Sunday at 11:59 PM ET for each electronic week. These postings are on different days of the week than the initial post(s). This posting is a minimum of 150 words".

Please note, this portion of the rubric dictates deadlines. Therefore, grading for this criterion will either be 20 points (on time) or 0 points (past the deadline). There is no grey area here. The deadline for posts are based on Eastern Time (ET). If you live outside of this time-zone, please plan accordingly so your posts are not late.

I extend to you these anecdotal scenarios:

Is it acceptable draw a trough for vancomycin one hour after it should have been drawn (i.e. 30 minutes after giving a dose vs 30 minutes before the next dose was given)?

Is it acceptable to forget to write a stop order on a medication?

Is it acceptable to delay door-to-needle time when considering initiation of tPA in patient with acute ischemic stroke knowing that delays (hours) can impact outcomes?

Is it acceptable to delay lifestyle modifications when addressing chronic conditions such as GERD, Hypertension, Asthma, COPD, etc?

Please note, this portion of the rubric also dictates a 150 word minimum. I assure you, an insightful, analytical and engaging post will be AT LEAST this length. In text references, casual greetings and anecdotal information will not count toward the 150 words (I will verify word count).

"Peer reviewed scholarly resources are used for the 2 required discussion posts. A minimum of 2 references are required (other than the course textbook)."

Here is a time saver for you. When you are looking for scholarly resources, go to your Dynamed links for that topic (found in the introductory page for each topic). In the summary pane to the left, find the section titled "Guidelines and Resources". You will find the most current information available as far as guidelines as well as supporting review articles you can use to formulate your post / response.

WebMD, Wikipedia, Scientific American, Live Strong, US News are NOT scholarly resources

In accordance with national standards, including those of the Agency for Healthcare Research and Quality's National Guideline Clearinghouse, guidelines (and articles) more than 5 years old that have not yet been updated to ensure that they reflect current knowledge and practice can no longer be assumed to be current.

"Correct APA format, including references and citations, writing mechanics, grammar, spelling, and punctuation are used."

APA style referencing in this course

From the content page: Course Resources > APA Style Guide to Electronic References

APA style referencing help at Wilkes University

On the library home page under Resources click on Online Reference Collection. Then, the last item on the Online Reference Collection page is Citation Guides & Style Manuals. http://wilkes.libguides.com/c.php?g=191922&p=1266495

APA Style Wizard works the best if you double check the citation after it is automatically created because sometimes the automatically generated citation contains incorrect capitalization or other small mistakes.

ProctorNow / Exams Jan 14, 2019 5:00 AM -

For those of you who are familiar with, those who are not familiar with or those that have never used Proctor Now, I strongly encourage you to familiarize (or re-familiarize) yourself with the policies and procedures, accessing the site and computer requirements. For your convenience, there are tutorials in the content folder labeled "Proctor Now" and there is a practice exam (not graded) always available to ensure you have no issues prior to the first official exam. Please access the practice exam. It seems almost inevitable that someone has an issue, don't let it be you.

If you attempt to complete an exam and you are prompted for a password, you are not accessing the exam correctly. Please revisit the tutorial from Proctor Now

Following each exam, an analysis of grades will be conducted and an exam review will be made available through 'Panopto' (or other technology). The purpose of this review will be to "identify the informational source(s) of the questions missed", "identify the strategies you could have employed to make information more meaningful and memorable" and to "generate a study plan to repair the deficiencies encountered in the analysis." The attached documents may help with this self-analysis / remediation exercise. You do not need to submit the analysis to me.

Attachment(s):

Post-Exam_Survey Part 1.docx (36.98 KB) 

Post-Exam_Survey Part 2.docx (45.67 KB) 

Greetings Jan 13, 2019 5:00 AM -

Welcome to NSG 533 Advanced Pharmacology

I am Dr. De Francesco (Dr. D. if you prefer) and will be teaching this course. My contact information can be found in the table of contents under Course resources > Faculty contact information. I request that you use email whenever possible.

We are about to embark on an intensive, but rewarding experience for all of you. We will be covering a great deal of information, so it is prudent that you do not fall behind. With a little hard work everyone should come through with a great deal of knowledge and some very valuable skills.

ASK

As you can see, each module topic provides you with an introduction highlighting key points, objectives, reading from the text as well as other additional resources. A review of the Dynamed links (found under the heading "Evidence-Based Medicine Resources) will provide you access to the most current information, current guidelines and links to additional supporting scholarly resources saving you time when searching for evidence based, supporting literature for posts.

Healthcare is ever-changing and it is my intention to prepare graduates for a lifelong career of continuous self-directed learning and self-assessment.

INQUIRE

The heart of this course will be discussions (please see rubrics) where you can demonstrate your understanding of the material, ask questions, compare literature findings, elicit insightful thought from each other and provide you with an opportunity to practice using that information in patient cases.

In addition, there will be three examinations given during this course. The content for examinations will be taken from lecture material, textbook readings, course objectives, discussions and evidence based approaches to therapy (found both in the text and via Dynamed). Questions I pose and responses I may give to your posts / threads are meant to be "guided" to help you to direct and focus your studies. I will almost always start a thread for each topic entitled "Fuel for Active Learning". This section will not only help "guide" you on points of discussion that need additional emphasis, but will also include relevant points for related topics not specifically discussed in the case(s) provided. To augment and narrow the scope for testing, I will also provide a study guide and "Weekly Recaps". Hopefully, you will be inspired and motivated to develop your own case scenarios, formulate an action plan and ask questions when direction is needed.

In the words of Dr. William Mayo, ‘It has become necessary to develop medicine as a cooperative science; the clinician, the specialist, and the laboratory workers uniting for the good of the patient. Let us do the same in the classroom.

ENGAGE

One of most important aspects of pharmacology, and its extension into your role as future practitioners, is the ability to treat the patient as a whole. Beyond diagnosis is the ability to interpret lab values, select correct drugs and dosages and make adjustments as necessary. It also means understanding that the uses of certain medications have implications beyond their immediate effects, thus affecting long term outcomes (mortality). However, let us not forget the basics either... mechanism of action, side effects, contraindications and drug interactions and patient allergies.

Unless specifically stated otherwise, you will NOT be asked to memorize dosages or lab values.

Application and interpretation is critical.

From the syllabus: "The ability to synthesize and manipulate concepts as they relate to clinical situations will be emphasized."

APPLY

As we embark on our first topic, I encourage you to read the text first to provide a foundation. Access the Dynamed links. Think about some of your current patients. Do you agree or disagree with current treatment? What information did you find to support your decision? Are your changes (if any) warranted? Have you considered compliance (or lack thereof and reasons why) and the patients beliefs? This is the type of methodology that you should approach each case (or question) with.

INTERACT

“Learning is more effective when it is an active rather than a passive process.” – Euripides

Although you are required to post once and provide one response for each discussion topic, I strongly encourage you to engage in more. Response posts to "Fuel for Active Learning" are welcomed and will undoubtedly support your efforts in gaining mastery of the topic(s) at hand. We are called upon to be leaders, not followers. We can learn a tremendous amount from each other.

Finally, your text book offers an online "Student Center" with learning objectives and self-assessment quizzes: http://www.mhpharmacotherapy.com/0071835024.php?c=student. Did you get the right answer? If so ... great job, but don't stop there. Ask yourself "what made all the other possible choices incorrect"? This will certainly help identify area that may need additional time and attention.

I look forward to working with each of you. Best of luck!

Regards,

                Dr. D.

Should any technical issues arise, please notify me without delay