pdat 10 final exam study guide...pdat 10 final exam study guide questions can be knowledge-based,...

PDAT 10 Final Exam Study Guide Questions can be knowledge-based, comprehension-based, or application based in nature.

The exam is cumulative. Block 1 Objectives: Identify appropriate rate and rhythm control treatment options for acute management of atrial fibrillation in hemodynamically stable and unstable patients (DPo)

Definition of Hemodynamic Stability: There is not a specific or clear definition, but a hemodynamically stable patient can be recognized by AOx3 (~capable of having a conversation), and adequate organ perfusion (MAP > 65 mmHg).

❏ Hemodynamically unstable is more noticeable, as the patient will be decompensated with symptomatic hypotension. If you do not like the image below, I’ve listed the AHA/ACC 2014 Guidelines on the next page.

LINK TO OTHER STUDY GUIDE FOR REFERENCE/COLLABORATION

-----Recommendations from the 2014 AHA/ACC Clinical Practice Guidelines for AFib-

Hemodynamically Stable – Management of Acute AFib with Rate Control ❏ Drug Therapy: Intravenous administration of a beta blocker or non-DHP CCB is recommended to slow the ventricular

heart rate in the acute setting with patients without pre-excitation (AHA/ACC 2014, Class: I, LOE: B) ❏ Beta Blockers

❏ Metoprolol tartrate: 2.5 – 5.0 mg IV bolus over 2 mins, repeat up to 3 doses. ❏ PO dose 25-100 mg BID

❏ Esmolol: 500 mg/kg IV bolus over 1 min, then 50-300 mg/kg/min IV ❏ Non-DHP

❏ Verapamil: 0.075-0.15 mg/kg IV bolus over 2 min, may give an additional 10 mg after 30 min if no response. Then start a continuous infusion 0.005 mg/kg/min infusion

❏ Diltiazem: 0.25 mg/kg IV bolus over 2 min, then 5-15 mg/hr ❏ Target of therapy:

❏ A heart rate control (resting HR < 80 bpm) strategy is reasonable for symptomatic management of AF (AHA/ACC 2014, Class: IIa, LOE: B).

❏ A lenient rate-control strategy (resting HR < 110 bpm) may be reasonable as long as patients remain asymptomatic and left ventricular systolic function is preserved (AHA/ACC 2014, Class: IIb, LOE: B)

Hemodynamically Unstable – Management of Acute AFib ❏ Decision to cardiovert the patient

❏ Electrical Cardioversion is indicated (AHA/ACC 2014, Class: I, LOE: B) ❏ Pharmacological Cardioversion: Flecainide, dofetilide, propafenone, and intravenous ibutilide are useful

for pharmacological cardioversion of AF or atrial flutter, provided contraindications to the selected drug are absent (Class I, LOE: A)

❏ Direct-current cardioversion is recommended when a rapid ventricular response to AF or atrial flutter does not respond promptly to pharmacologic therapies and contributes to myocardial ischemia, hypotension or HF. (Class I, LOE: C)

Anticoagulation ❏ [>48h]: For patients with AF or atrial flutter of more than 48 hours’ duration or unknown duration that requires

immediate cardioversion for hemodynamic instability, anticoagulation should be initiated as soon as possible and continued for at least 4 weeks after cardioversion unless contraindicated (AHA/ACC 2014, Class: I, LOE: C)

❏ [<48h]: For patients with AF or atrial flutter of less than 48 hours’ duration and with high risk of stroke, intravenous heparin or LMWH, or administration of a factor Xa or DTI, is recommended as soon as possible before, or immediately after cardioversion, followed by long-term anticoagulation therapy.

● Determine appropriate indications for proton pump inhibitors and identify risks and benefits associated with their use. (HALEY)

○ Indications for PPI: ■ PUD - 1st line ■ GERD, erosive esophagitis, maintenance for severe erosive esophagitis or Barrett’s

esophagus. ■ Zollinger-Ellison Syndrome - high doses for hypersecretion ■ NSAID-associated ulcers - primary prevention in NSAID use ■ Eradication of H. pylori - PPIs are component of first-line and salvage therapies

○ Risks:

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https://docs.google.com/document/d/1NKBuutvDFg-_e2OFsflbRVHTEClAodmCVXdSRfmkjis/edit?usp=sharing


■ Drug interactions - CYP2C19, clopidogrel, HIV protease inhibitors, methotrexate ■ C. diff infection - increased risk ■ Malabsorption of minerals and vitamins

● Magnesium malabsorption ● Calcium and fracture risk , reduced calcium uptake ● Vitamin B12 malabsorption ● Iron malabsorption

■ Hypergastrinemia, Microscopic colitis, Atrophic gastritis ■ Kidney disease - acute interstitial nephritis (AIN), increased risk CKD

○ Benefits of PPI’s in the Long-Term (J Neurogastroenterol Motil 2018;24(2):182-196): ■ Long-term inhibition of gastric acid secretion is necessary for GERD maintenance therapy ■ Prevention of occurrence of drug-related (ASA/NSAIDs) gastroduodenal ulcers.

● Also effective in preventing the recurrence of ASA-induced gastroduodenal ulcers ■ Prevention of neoplastic transition of Barrett’s esophagus to dysplastic Barrett’s esophagus ■ Prevention of GERD-induced adenocarcinoma (Gastroenterology 2000;118:S9-S31) - low quality

evidence, controversial - this is the hypergastrinemia thing.

● Describe safe and effective use of medications to treat asthma and COPD (HALEY and Natalia)

● Recommended Revision of ‘Stepwise Approach’: Before the 2018 GINA guidelines were published, there was insufficient data on the infrequent and new-onset asthmatics with ICS therapy. Though, it had been known that chronic airway inflammation is found these populations, and that ‘treatment with regular daily low-dose ICS is highly effective at reducing asthma symptoms, reducing the risk of asthma-related exacerbations, and death.’ As shown in report to right, data is now available confirming that treatment with SABA’s alone increases the risk of exacerbations, AND the early treatment with ICS is critical for asthma control.

● Step1: ○ PRN low-dose ICS-LABA -OR-

■ Formoterol prefered ○ Low-dose ICS taken concurrently with

SABA PRN puffs -OR- ○ Low-dose ICS-LABA, PLUS SABA PRN -OR- ○ ICS-LABA as maintenance AND PRN reliever

■ Preferred product is budesonide-formoterol (symbicort) ● If you’re interested in reading more about these spicy developments, basically just google ‘GINA 2019’ and

go to their website. Although the official guidelines have not yet been released, you can download their 2019 Guideline Pocketbook.

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Asthma

● Rule of 2: (Rule of two defines populations indicated to receive controller meds - beware the latest (GINA 2019 guidelines) support ICS upon diagnosis, but 2018 and prior are aligned with ‘rule of two’)

○ Asthma symptoms/albuterol use >2x/week ○ Nighttime awakenings >2x/month ○ Refilling albuterol >2x/year ○ Peak flow varies >20% baseline

● Stepwise Approach: Admittedly, as excited as I am to input the updated guidelines, there’s also a chance that our test is actually representative of the former 2018 guidelines. OH F’in WELL

○ Step 1: Albuterol PRN ○ Step 2: Low dose ICS ○ Step 3: Low dose ICS/LABA OR medium dose ICS ○ Step 4: Med/high dose ICS/LABA ○ Step 5: Refer for add-on treatment (tiotropium, anti-IgE, anti-IL5/5R) ○ AVOID LABA ALONE

● Initial Controller Tx for Adults and Adolescents per GINA ○ SABA <2x month, no waking, no exacerbations in the past year → NO CONTROLLER ○ SABA >2x/week → Low dose ICS ○ Troublesome symptoms most days, waking due to asthma 1+/week → Med/high dose ICS + LABA

■ Severely uncontrolled asthma or acute exacerbation → short course of OCS + high dose ICS (or moderate dose ICS/LABA)

■ Exacerbation: ● O2 needed, SABA (MDI or neb), corticosteroid (PO preferred or IM/IV-continue

for 5 days), +/- tiotropium, ICS

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Initial management

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○ COPD: ■ Gold Grades:

● GOLD 1 = FEV ≥ 80 ● GOLD 2 = FEV 50-79 ● GOLD 3 = FEV 30-49 ● GOLD 4 = FEV <30

■ Post bronchodilator FEV/F ● VC <0.7

■ Avoid ICS alone!!!

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● Recommend treatment for tobacco dependence based upon patient’s history ● This is from Dr. Wilken’s smoking cessation clinic note

Medication

Precautions Dose Duration of

use:

Bupropion () Hx of seizures

() Hx blackouts

() Anxiety

() Insomnia

() Anorexia

() Alcohol use

() Liver impairment

() Renal impairment

150 mg QAMm x3d then

150 mg BID 12 W

Varenicline () Psych issues

() Renal impairment

() GI issues

0.5mg qAM d1-3

0.5 BID d4-7

1 BID w 2-12

12W

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() Insomnia

Nasal spray () Chronic nasal

disorders

() Asthma

Patch () Dermatologic

conditions

21 if >10cig/d

14 is <10 taper over 10

weeks

taper over 8

weeks

Lozenge () Mouth sores

Gum () Dental issues

() Mouth sores

<30 min s/p waking 4 mg

2mg if >30 min

Inhaler () Bronchospasms

() Mouth sores

● Smoking Cessation Options ○ NRT

■ Gum, lozenge (2 mg, 4 mg OTC) ● 1st cig/cravings ≤ 30 min after waking → 4 mg ● Gradually increase dosing intervals over 12 weeks.

■ Transdermal patch (7 mg, 14 mg, 21 mg) ● >10 cig/day → 21 mg, taper over 10 weeks ● <10 cig/day → 14 mg, taper over 8 weeks

■ Nasal Spray (10 mg/mL) ● Nasal irritation, not recommended for chronic nasal conditions or reactive airway

conditions ■ Oral inhaler (10 mg cartridge, delivers 4 mg)

● Not for asthma/pulmonary disease ● Mimics hand/mouth ritual

○ Bupropion ■ 150 mg PO QAM x3 days then 150 mg BID, max 300 mg/day ■ Begin therapy 1-2 weeks PRIOR to quit date (Good if patient wants more time before

quitting - was a quiz question) ■ Avoid taking before bed, tapering not necessary, 7-12 week duration. ■ May be beneficial for those with depression ■ DON'T USE IN SEIZURES ■ Can be used with NRT ■ May delay weight gain

○ Varenicline ■ D1-3 = 0.5 mg PO QAM, D4-7 0.5 mg PO BID, weeks 2-12 1 mg PO BID ■ Begin therapy 1 week prior to quit date ■ Most efficacious smoking cessation option (per slides/assignment 3b) ■ Offers a different MOA if patient has failed other treatments in the past

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■ neuropsychiatric side effects (dream disorder)

● List the proper steps for metered-dose inhaler technique (Haley)

○ 1. Take off Cap ○ 2. Shake inhaler for 5 seconds (Prime if not used in last 1 week) ○ 3. Place index finger on top of canister and thumb on bottom of mouthpiece. ○ 4. Stand/sit up straight

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○ 5. Take a deep breath in, tilt head back slightly and blow out completely to empty lungs ○ 6. Place mouthpiece of inhaler/spacer/VHC in mouth and close lips around it to make a tight seal ○ 7. As you start to inhale, press down firmly on canister to release medicine, breath in slowly and

deeply for 3-5 seconds. ○ 8. Hold breath for 10 seconds or as long as you can. ○ 9. Take inhaler out of mouth and exhale slowly ○ 10. If you need to take another puff, wait 30 sec - 1 min before administering next dose

● Complete medication reconciliation (Haley)

○ Med Rec: Comprehensive evaluation of a patient’s med regimen any time there is a change in therapy and/or setting in an effort to avoid medication errors such as omissions, duplications, dosing errors, or drug interactions.

○ Resources in Med Rec: ■ Medication list, bottles/boxes, third party claims data, family, OHS ■ ILPMP

● Detect medication related problems

○ Medication Related Problems: ■ Appropriate/Effective: Untreated indication, dose, monitoring, optimal therapy ■ Safety ■ Adherence ■ Access

● Identify barriers to transitions of care ○ Transitions of Care: A set of actions designed to ensure the coordination and continuity of health

care as patients transfer between different levels of care within the same location and transfers between healthcare settings/providers.

■ Pharmacist Role in Transitions of Care ● Hospital admission, intra-hospital transfer, hospital discharge, post-discharge

■ Barriers: ● Lack of communication → word-of-mouth oftentimes and may be

misunderstandings ● Lack of documentation or other resources

Block 2 Objectives: ● Identify pharmacist’s role in preventing medication error ● Develop a guideline-based drug therapy for a patient with HTN, DM, HL, CHF (Dpo),

and/or CKD. Diabetes: Diabetes Treatment Algorithm (adapted from 2019 ADA guidelines)

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HF:

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Hypertension Treatment

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Hyperlipidemia - (2019 Guidelines below)

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When in doubt, moderate-intensity statin.

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CKD

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CKD+MBD (on next page)

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CKD+MBD

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CKD-MBD (continued)

CKD-Anemia (next page)

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CKD ANEMIA

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CKD-Anemia (continued)

Week 4 Frank and Nita

● 1. Identify appropriate resources to understand drug recall issues. ○ News - only real news not that fake stuff ○ Medscape - https://www.medscape.com/ ○ FDA - https://www.fda.gov/drugs/drug-safety-and-availability/drug-recalls ○ Google - make sure the source is credible

● 2. Recommend appropriate first line agents for the treatment of hypertension. ○ Non-Black: ACE-I, ARB, CCB, Thiazide (CKD: ACE-I/ARB are preferred > CCB) ○ Black: Thiazides, CCBs > ACE-I, ARB (CKD: proteinuria = ACE-I/ARB, none =

Thiazide/CCB ■ HF/CHD: BB and ACE-I/ARB [Bold = preferred]

● 3. Recommend alternative drug therapies for patients unable / unwilling to continue current antihypertensive med Second line is more comorbidity oriented

- Gout: no thiazides, Preg: no ACE/ARB/Renin inhibitors (Aliskiren); Asthma no BB; HFrEF avoid

non-DHP CCB (diltiazem verapamil) bc reduce HR ;HyperK: caution with ACE/ARB/Spiro

- Patients with CAD/MI/CHF have increased indication for BB ● Identify monitoring parameters for assessing safety and efficacy of antihypertensive medications

BP ALL BetaBlocker: sx bradycardia: lower dose; sx hypotension: if d/t diuretic dec diuretic

If worsening of HF (SoB, edema) augment diuretic and/or slow titration

Monitor renal function Potassium for ACE/ARB (1-2 weeks s/p initiation or change) and diuretics

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https://www.medscape.com/

https://www.fda.gov/drugs/drug-safety-and-availability/drug-recalls


Week 6 ● 1. Perform medication reconciliation, by considering renal dosing/dialyzability of

medications and creating an appropriate medication administration schedule for a dialysis patient. - Henry (I added this to both study guides, feel free to add as you see fit)

○ Considerations in renal dosing (Via HW 6A + Week 6 Lecture) ■ Dose/frequency reductions for ESRD/reduced clearance ■ Dialyzability of medication

● What aspects of a drug affect dialyzability? ○ Molecular weight, volume of distribution, protein binding,

charge/polarity, plasma clearance, dialysis flow rates ● If drug removed by dialysis:

○ Reschedule dose for after dialysis ○ Give supplemental dose ○ Increase dose to account for increased clearance from

dialysis ■ Special consideration with blood pressure:

● Patients should hold bp meds before dialysis bc they will be hypotensive and we won’t be able to remove adequate amounts of fluids from dialysis... pt may not be able to take these meds before dialysis

Drugs Removed by Hemodialysis (Examples)

Most Antibiotics and Chemotherapeutic agents Alcohols

Sedatives/anticonvulsants/barbiturates Certain HTN drugs: Atenolol

Metoprolol, Sotalol, Nadolol, Propranolol Isosorbide dinitrate

ACE-inhibitors

Lithium Colchicine

Salicylates APAP

2. Assess pertinent data in patients with chronic kidney disease with complications of bone mineral disease (BMD) and anemia.

○ Dialysis Specific Labs ■ Hepatitis B: Antibody, antigen ■ Anemia: Hgb, MCV, TSAT, Ferritin, TIBC, SFe

● Need to wait a minimum of 7 days after giving IV iron to get labs ● TIBC should be >200, otherwise TSAT will be falsely elevated ● Ferritin can be elevated during infection and inflammation

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■ Mineral and Bone Disease: iPTH, Ca, Alb, Ph, 25-OH vitamin D ● iPTH isn’t super accurate

○ Cinacalcet must be held a minimum of 12 hours prior to testing for iPTH otherwise it will be falsely low

● If albumin <4g/dL, need to use corrected calcium ○ CCa = (4-measured albumin) * 0.8 + measured Ca

3. Utilize the current guidelines from the Kidney Disease Improving Global Outcomes (KDIGO) to develop appropriate therapeutic treatment plans for patients with chronic kidney disease and BMD and/or anemia. LOOK BACK - We completed the KDIGO CKD BMD + Anemia on previous pages

Block 3 Objectives: Week 1 1. List signs and symptoms of chemotherapy extravasation. Daisy

Extravasation of a vesicant drug has the potential to cause blister and tissue necrosis with a more severe and/or lasting injury. Vesicant extravasation may result in loss of the full thickness of the skin and, if severe, underlying structures. The anthracyclines (e.g.doxorubicin, daunorubicin) are among the most important cytotoxic chemotherapy agents that cause extravasation injury.

2. Describe the pharmacological treatment options for an anthracycline extravasation. Daisy -Use central line to avoid extravasation. Avoid butterfly needles. -Dexrazoxane - Antidote for anthracycline extravasation. MOA: strong chelator to prevent formation of ROS, therefore it reduces oxidative stress and the risk for tissue necrosis Additional use: Prevent cardiotoxicity during the use of anthracyclines such as doxorubicin. Very specific FDA labeling for metastatic breast cancer- and only after they reached the max dose of 300 mg/m2

3. Identify patient-related factors in which cyclophosphamide or doxorubicin would require dose adjustments. Nita

Cyclophos: CI if platelets <50K or neutrophils <1500

Doxo: dec 50% if Tbili 1.2-3, dec 75% if Ttbili 3.1-5

4. List anti-cancer medications as discussed in class that may cause heart failure.

○ Main one from 509/Block 3 DI questions: Doxorubicin ○ From Micromedex: anthracyclines, including daunorubicin (Cerubidine),

doxorubicin (Adriamycin, Doxil), epirubicin (Ellence), idarubicin (Idamycin), and valrubicin (Valstar)

○ Targeted therapy, including bevacizumab (Avastin), trastuzumab (Herceptin), lapatinib (Tykerb), sunitinib (Sutent), and sorafenib (Nexavar)

5. Describe the clinical impact of drug-drug interactions with SSRI’s and guideline recommended anticoagulants commonly prescribed for cancer patients. --Natalia

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Answer: It has been suggested that antidepressants, particularly SSRIs and SNRIs, may lead to an increased risk of bleeding through several different mechanisms, such as impairment of platelet aggregation, depletion of platelet serotonin levels, and reduction in platelet count. SSRIs: Fluoxetine and fluvoxamine are thought to have the highest potential for inhibiting warfarin metabolism and therefore enhancing warfarin’s anticoagulant effect. Fluoxetine is a mild inhibitor of 3A4 and a moderate inhibitor of 2C9, while fluvoxamine is the only SSRI that is a potent inhibitor of 1A2 and is also an inhibitor of 2C19, 3A4, and 2C9 TCAs: Particularly nortriptyline and amitriptyline, have been shown to increase prothrombin time (PT) in a dose-dependent manner. The effect of the TCAs (nortriptyline and amitriptyline) on the metabolism of warfarin was greatest with nortriptyline. When used as monotherapy, the TCAs do not appear to increase the risk of bleeding; however, when they are used with warfarin there may be an increased risk of bleeding secondary to their effect on the metabolism of warfarin

● Anticoagulants, From NCCN

Agent Standard Dosing Obesity Dosing (BMI ≥40 kg/m2)

LMWH

Dalteparin 5,000 units SC daily (category 1 for inpatient) Consider 7500 units SC daily

(limited data)

Enoxaparin 40 mg SC daily (category 1 for inpatient) Consider 40 mg SC every 12

hours

Fondaparinux 2.5 mg SC daily(category 1 for inpatient) Consider 5 mg SC daily (limited

data)

UFH 5,000 units SC every 8–12 hours (category 1

for inpatient)

Consider 7500 units SC every 8

hours

Aspirin 81–325 mg daily(for low-risk multiple myeloma outpatients only)

Warfarin Adjusted to INR 2–3

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6. Identify monitoring parameters for initiating anticoagulants. - Sam Warfarin

- Baseline: INR, CBC, risk of bleeding, BMP (renal fxn), LFT. Can consider CYP2C9 and VKORC1

- Continuing monitoring: LFTs every 12 months, after initiation of warfarin INR should be monitored every 1-3 days until stable. Then can check q 1-4 weeks. If INRs are consistently stable, can extend this interval to q 3 months

- Do not change maintenance doses more frequently than every 3 days - Bridging with LMWH/UFH usually required

DOACs - all DOACs are Factor Xa inhibitors except dabigatran which is a direct thrombin inhibitor (Factor II)

- Dabigatran: Renal function (BMP, CrCL), CBC w/ diff, signs/symptoms of bleeding - No bridging necessary

- Rivaroxaban: Renal function (BMP, CrCL), CBC w/ diff, signs/symptoms of bleeding - No bridging necessary

- Apixaban: Renal function (BMP, CrCL), LFTs, CBC w/ diff, signs/symptoms of bleeding - No bridging necessary

- Edoxaban: Renal function (BMP, CrCL), LFTs, CBC w/ diff, signs/symptoms of bleeding - No bridging necessary

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7. Discuss counseling points for venous thromboembolism and adverse effects associated with anticoagulants. - Sam

○ Report any signs of excessive bleeding from cuts or excessive bruising or bruising from unknown cause

○ Stand up and walk around every 1 to 2 hours ○ Do not smoke just before your trip - Smoke as much as you want after your trip ○ Wear loose, comfortable clothes ○ Shift your position while seated, and move your legs and feet often ○ Drink plenty of fluids ○ Wear knee-high compression stockings ○ Avoid alcohol and medicines that make you sleepy, because they can impair your

ability to move around ○ Warfarin-Related - Report any changes in diet (Vit K intake, green

tea/liver/supplements, cranberry/pomegranate/grapefruit) or new medications/supplements

S/Sx of PE:

○ Panting, shortness of breath, or trouble breathing ○ Sharp, knife-like chest pain when you breathe in or strain ○ Coughing or coughing up blood ○ A rapid heartbeat

Warfarin

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\\

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DOACs

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Week 2 Describe the effect that the loading dose and genetic polymorphisms have on the pharmacokinetics and pharmacodynamics of clopidogrel. - Henry

○ Loading Dose - Required to establish antiplatelet effects due to variable and delayed onset of action (Dose-dependent).

○ Genetic Polymorphism (CYP2C19) ■ Normal - *1 ■ ↓ Activity - *2, *3 ■ ↑ Activity - *17 ■ Intermediate (*1/*2, *2/*17) or Poor (*2/*2, *2/*3, *3/*3) Metabolizers - ↑

Risk of cardiac events (USE ALTERNATIVE THERAPY) ● Alternatives - Prasugrel, Ticagrelor

2. Determine the appropriate duration of dual antiplatelet therapy for patients who have had an intracoronary stent placed for the treatment of coronary artery disease, including acute coronary syndrome. - DPo

Associated Guidelines

- 2016 ACC/AHA Focused Update on Duration of Dual Antiplatelet Therapy in CAD [Definition] - Dual Antiplatelet Therapy (DAPT): DAPT is antiplatelet therapy including a combination of ASA + P2Y12 inhibitor. Of the P2Y12 inhibitors, there is clopidogrel, prasugrel, and ticagrelor. Risks

- Thrombosis Risk: ACS, DM, LVEF < 40%, bare metal stent (BMS), strange stents - Patients presenting with ACS should be considered to be at high-risk for thrombosis

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- Bleed Risk: History of prior bleeding, concomitant anticoagulant therapy, advanced age, LBW, CKD< DM, anemia, chronic steroids therapy, chronic NSAID therapy

- Increased risk favors shorter duration DAPT Recommendations (2016, ACC/AHA)

- Duration - In patients with ACS treated with DAPT after BMS or DES, the P2Y12 inhibitor should

be continued for at least 12 months (I, B-N) - In these same patients, who are at low-risk of bleeding, continuation of DAPT

longer than 12 months may be reasonable. (IIb, A) - In these same patients, who are at high-risk of bleeding or experience overt

bleeding, discontinuation after 6 months may be reasonable. (IIb, C-LD) - Drug Therapy

- In patients treated with DAPT, a daily ASA dose of 81 mg is recommended (I, B-NR) - In patients with ACS treated with DAPT after coronary stent placement, who are not at

high risk for bleeding complications and who do not have a history of stroke or TIA it is reasonable to choose prasugrel over clopidogrel.

3. Evaluate and recognize signs and symptoms of serious adverse effects associated with the use of antiplatelet, anticoagulant, and fibrinolytic drugs used to treat acute coronary syndrome. 4. Identify patients for whom the use of intravenous beta-blockers should be avoided due to increased risk of adverse events.

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Week 3 - Henry ● 1. Compare/contrast the pharmacokinetics, toxicity, and expected efficacy of

colistin and polymyxin B ○ PK: Polymyxin B is given as the active drug, whereas Colistin is administered as

the prodrug colistimethate sodium (CMS) and has variable and slow (hours) conversion to the active moiety. CMS is excreted in the urine and requires renal adjustment while polymyxin B does not require dose adjusting.

○ Toxicity: Polymyxin B is associated with a lower risk of nephrotoxicity than colistin, which can cause significant nephrotoxicity.

○ Efficacy: Based on the PK and comparative adverse effect profile, I would expect polymyxin B to be more effective and less toxic in this patient. This patient has an acute kidney injury and colistin has been shown to be more nephrotoxic than polymyxin B especially in patients with preexisting renal insufficiency. Colistin also requires renal adjustment while polymyxin b doesn’t which is another factor to consider when deciding on a treatment.

● 2. Interpret recent studies related to the optimal treatment of KPC-producing bacteria and apply to patient care

○ TANGO II is a randomized clinical trial conducted from 2014 to 2017 to evaluate the efficacy and safety of meropenem-vaborbactam monotherapy versus the best available therapy (BAT) for CRE.

■ The results of the study showed that patients treated with meropenem–vaborbactam had higher rates of clinical cure than BAT at both end of treatment (with 65.6% vs 33.3%) and test of cure (59.4% vs 26.7%). In addition, there was lower rates of day-28 all-cause mortality (15.6% vs 33.3%) when compared to BAT

○ Colistin vs ceftazidime/avibactam ■ Superior to colistin in initial treatment of kpc

● 3. Identify appropriate monitoring parameters for the polymyxins ○ Nephrotoxicity - Hematuria, proteinuria, oliguria ○ Neurotoxicity - Dizziness, weakness, paresthesia, vertigo, visual disturbances,

confusion, ataxia ○ Considered to be more potent at smaller doses and has less variable PK profiles

compared to colistin. ○ Polymyxin does NOT require renal dose adjustment ○ Incidence of Nephrotoxicity - Less than Colistin in recent studies

● 4. Identify monitoring parameters, including therapeutic drug monitoring, for phenytoin in critically ill patients

○ Drug Interactions ■ CYP2C9/2C19 Inhibitors - ↓ Phenytoin Cl ■ CBZ, PB, PR, Rifampin - ↑ Phenytoin Cl

○ Phenytoin Serum Levels - 10-20 mcg/mL (5-7 half-lives/7-10 days after initiation of treatment or dose change)

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○ Monitoring Parameters - Seizure control, emergence/worsening depression, suicidal thoughts/behavior, or changes in mood/behavior

■ Vital signs, hemodynamic status ■ Hydration status, electrolytes, blood glucose, lactate level ■ Renal function (impact on drug clearance) ■ EEG monitoring

● 5. Identify appropriate drug choice and route of therapy for patients with witnessed generalized seizure.

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Block 4 Objectives: ● Collect information needed to assess a pediatric patient’s response to drug therapy

Identify appropriate pediatric-specific drug information resources Nita ○ LexiComp Pediatric and Neonatal Dosage Handbook is preferred over

Micromedex ○ Hydration Assessment (10b):

■ Number of wet diapers, intake, any vomiting or diarrhea ■ Vital signs, BUN/Scr, specific gravity of urine ■ Physical appearance, e.g., temperature, color, capillary refill ■ Consideration for IV therapy

● Toxic, unable to take in oral, infants < 2 months old, unable to adhere to regimen

● Recognize age-related differences in vital signs, laboratory values, and pharmacokinetic parameters Nita FEVER: <3 mo with Tm> 100.4° (rectal) > 3 mo with rectal Tm≥ 104°

● In children less than 3 years old (like assessment 10A), a rectal assessment of temperature is the most accurate and a temperature over 100.4 degrees in this case is considered a fever.

● Other generally accepted values depending on site of measurement include over 99.5 if oral, over 100 if tympanic, over 100.3 if temporal and within 3-47 months old, and over 99.3 if axillary.

RR: 0-12mo: 30 -57 HR: 0-6 mo: 120-160 6-12: 110-150 12-24: 100-140

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Hypotension: 1 month to 12 m: < 70 mmHg in infants (BP 65/40 mmHg in week 12 case) Vd: highest in neonates → higher loading dose (eg. Aminoglycosides) Clearance: slowest in neonates but increases significantly in infants/children

● Discuss characteristics of various medication formulations that create potential barriers to use in pediatric patients

○ Tablets vs solution vs suspension ○ Labeling may not always match dosing device ○ Dosing device may not always be provided ○ Correct syringe technique ○ Dosing in infants and children compared to adolescents adults

■ Duration ■ Weight-based calculations – not per day vs per dose ■ Rounding to something measurable, but usually within 10% of

recommended dose (if dose 4.4 mg, round to 4.5 mg not 5 mg) ■ Become familiar with appropriate oral dosing devices

Block 5 Objectives: Identify and apply the basic principles of geriatric medicine, including assessment, pharmacotherapy, prevention, sensory deficits, and palliative care to the care of older adults with multiple chronic conditions.

Hypertension in older adults

A stringent goal of <130/80 may not be appropriate for all pts! Two guidelines to consider when

setting a new BP goal are: JNC 8 guidelines and ADA guidelines (from the ACCORD trial).

*When it comes to elderly patients, it’s especially important to treat the patient, NOT THE NUMBER. A

patient may report feeling well when their BP was high; we can adjust their goal accordingly. Lowering

blood pressure too quickly in older adults can cause ischemic stroke!

Key take-aways from “JNC 8 Guidelines for the Management of Hypertension in Adults” (2014):

● In adults 60+, initiate pharmacologic tx when BP is 150/90 mmHg or higher and set goal of

<150/90. (Strong Recommendation - Grade A)

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● Setting a goal of <140/90 in adults 60+ provides no additional benefit compared with a higher

goal.

● In patients with BOTH HTN and DM, pharmacologic tx should be initiated when BP is 140/90

mmHg or higher -- regardless of age!

Key take-aways from ACCORD BP trial (2010):

● Intensive anti-HTN therapy did not significantly reduce the primary CV outcome or rate of death

from any cause.

● No significant benefit in targeting a systolic BP of 120 compared with a goal of 140 among

patients with type 2 diabetes at high risk for CV events.

Manage geriatric syndromes including dementia, delirium, depression, falls, insomnia and pain.

○ Dementia

■ *Optimize non-pharmacological management*

■ Cholinesterase inhibitors (donepezil, rivastigmine, galantamine)

● Donepezil = longest acting cholinesterase inhibitor; eliminated

hepatically

○ When deprescribing, must titrate down

● Rivastigmine = shortest acting cholinesterase inhibitor; eliminated

renally ← remember ‘r’ for renal!

■ Memantine

■ Use beyond 1 year is minimal; weigh benefit vs. risk

■ Predominant side effects to counsel on: diarrhea*, nausea (esp. rivastigmine)*,

vomiting, headache

■ Avoid initiating more than one agent at a time

■ Monitoring: TSH

Agitation or psychosis in patients with dementia

○ If patient needs antipsychotics for managing NCSD/BPSD: risperidone 0.25mg BID is the

most reasonable choice

○ MUST be tapered down and withdrawn after 4 weeks in absence of response OR

withdrawn after 4 months in older adults who have been responding

○ Delirium

■ Difference between Dementia and Delirium: Acuity of onset

● Medications associated with delirium: Jimson weed, digoxin, diazepam,

hydroxyzine

■ Management:

● Principles: ensure safety, identify and reverse causes, thoroughly search

and treat any organ system failure, avoid polypharmacy and d/c

unnecessary medications, minimize opioids and BZDs, repeat physical

exam/further labs/radiologic study

● Nonpharmacologic strategies: adequate light, control source of excess

voice, provide clear side pose in the pt location including clock and

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calendar and a chart of day schedule, place objects from the pt’s home

in the room, use TV/radio for relaxation and help the pt maintain

contact with the outside world, maintain diurnal cycle, communication

and interaction with the pt (identify correct sensory impairment, no

medical jargon, arrange tx to allow maximum period of uninterrupted

sleep)

● Pharmacologic strategies: ANTIPSYCHOTICS FOR BEHAVIORAL PROBLEM

SHOULD BE STRICTLY AVOIDED UNLESS NON-PHARMACOLOGICS HAVE

FAILED and THE OLDER ADULTS COULD POTENTIALLY HARM

THEMSELVES OR OTHERS -> then haloperidol may be appropriate. It’s

important to: dose according to severity, assess need for medications

on a daily basis, prescribe an effective dose for 48 hours and taper

gradually over 1-5 days

● Prevention: perform admission cognitive function test to assess

baseline, remove catheter asap, assure hearing aid/glasses/teeth

traveling with pt while transferring thru facilities, encourage family

participation in the hospital, good sleep hygiene, empower the pt by

providing self-care strategies, suggest to maintain activity level

(ambulatory pt to walk 3x daily, unambulatory pt should do full range of

movement exercise at least 15 mins 3x daily)

○ Depression

■ Screening: Geriatric Depression Scale, Center for Epidemiologic Studies

Depression Scale, Patient Health Questionnaire-2. Should also acquire nutrition

status and conduct basic lab test, inquire if pt can do normal life activities of

daily living and social function, review med list/mobility/balance, get sitting and

standing blood pressure

■ Prescribing med for depression: low initial dosing and monitoring for AEs,

continue antidepressants for 4-6 weeks after titrating to therapeutic dose.

COMBINING ANTIDEPRESSANTS CAN LEAD TO SEVERE AES.

■ Adverse drug withdrawal symptoms may occur with sudden d/c of the

treatment -> should TAPER THE DOSE to minimize adverse outcomes.

■ Clinical effect size of antidepressant therapies over placebo is minimal.

■ Sertraline or citalopram have the safest side effect profile for elderly pts

■ Routine monitoring parameters include: pulse, baseline EKG, orthostatic blood

pressure, anticholinergic effects.

■ TSH is also a lab we typically monitor in depression

○ Falls

■ #1 risk for falls: CNS POLYPHARMACY

■ Risk Factors

● Past history of falls Lower-extremity weakness

● Elderly

● Cognitive/visual impairment Balance problems

● Psychotropic drugs Arthritis

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● History of stroke Orthostatic hypotension

● Dizziness Anemia

■ High Risk Meds/Drug Classes

● Benzodiazepines Gabapentin

● Antipsychotics Antidepressants - TCA, SSRI, BZD

● Opioids Antiepileptics

● Sedatives Diuretics

● Digoxin Antihistamines

■ Interventions for fall prevention (the following have the highest level of

evidence):

● Strength and balance exercise/ tai chi/ home modification

● Postural hypotension management

● Vit. D supplementation for fall prevention - according to Beer’s has

good level of evidence, but US Preventative Task Force gives it a D rating

sooo take with a grain of salt and if pt not benefiting - DEPRESCRIBE

○ Insomnia

■ Avoid Beer’s list drugs

■ “Sundowning” - state of confusion occuring in the late afternoon and spanning

into the night; can lead to a variety of behaviors including alterations in

sleep-wake cycle

○ Pain (from assessment 16b/NCCN guidelines)

■ If managing pain crisis (score >4) not related to oncologic emergency in opioid

tolerant patients, a rescue dose of 10-20% is warranted to start supplemental to

the patient’s chronic opioid dose.

■ If an oral analgesic is considered, opioid tolerant patients should get an oral

opioid dose equivalent to 10-20% of total opioid taken in the previous 24 hours.

■ When calculating new maintenance dose, take total 24 hour opioid use and

divide by the frequency you want the patient to take the medication (2-3 times

a day) to convert from as needed pain relief to a scheduled opioid dose. De-prescribing considerations: Assess each drug for its eligibility to be discontinued (Natalia)

● No valid indication and/or contraindications: ○ Diagnosis in doubt or not confirmed ○ Confirmed diagnosis but no evidence in literature to support efficacy of treatment

● Risks > benefits of continuing medication: ○ Beer’s criteria

■ Benzodiazepines ■ Digoxin ■ Psychotropics ■ Narcotics

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■ NSAIDs/ASA ■ Anticoagulants ■ Cardiovascular drugs ■ Insulins/hypoglycemics ■ Anticholinergic meds

● If Life Expectancy < Time to Benefit ○ Medication NOT recommended ○ Possible risks of medication without benefit ○ Examples: Statins, bisphosphonates

■ Evaluate utility of preventative medications in patients with severe dementia, metastatic cancer, end-stage organ failure

● If Life Expectancy = Time to Benefit ○ Defer to patient’s values and preferences

● If Life Expectancy > Time to Benefit ○ Medication may help and generally continued ○ Evaluate if TTB < TTH

● “High-risk” drug combinations increase level of toxicity (i.e NSAID + diuretic + ACE inhibitor in CKD)

Part of prescribing cascade:

● Disease or symptom control drug ineffective or symptoms have resolved ○ Sliding scale insulin, oral hypoglycemics in older diabetic patients with multiple

comorbidities ○ Antihypertensive use in frail older patients ○ Ongoing anti-emetic use following resolved episode of

nausea/vomiting

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○ Ongoing PPI use following cessation of NSAIDs or corticosteroid therapy ○ Antihypertensive use if normo-hypotensive with lifestyle modifications ○ Antidepressants for previous but resolved episode of reactive depression ○ Antipsychotics for agitation in dementia

Consider De-prescribing the following:

Post recitation quiz: (Regarding systematic reviews about OTC and pharmacologic interventions to

prevent cognitive decline)

Which of the following was found in persons with normal baseline cognition?

→ Low-strength evidence that ginkgo biloba did not improve neuropsychological

performance or memory.

Which of the following was found in persons with mild cognitive impairment?

→ Low-strength evidence that vitamin E did not prevent Alzheimer’s-type dementia

Which of the following was found in persons with normal baseline cognition?

→ Low-strength evidence that estrogen and estrogen-progestin increase risk for dementia or

mild cognitive impairment.

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Which of the following was found in persons with mild cognitive impairment?

→ Low-strength evidence that testosterone does not slow decline of cognitive test

performance.

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