1. Therapeutics 1 Tutoring
Sarah Darby
August 26, 2016

2. Lectures Covered Atherosclerosis and Dyslipidemia
Ischemic Heart Disease
CV pharmacology review
Ischemic stroke
Hemorrhagic stroke

3. Atherosclerosis and Dyslipidemia NLA
NLA Risk Factors
Age
Males 45 and older
Females 55 and older
Family Hx
Male first degree relative <55 years
Female first degree relative <65 years
Smoking
HTN
BP > 140/90 or on medication
Low HDL
Males <40mg/dl
Females <50mg/dl
NLA Categories of Risk
Low
0-1 risk factors
Moderate
2 risk factors
High
3 or more
DM factors
CKD 3B or 4
LDL above 190
Very High
Clinical ASCVD
DM + 2 or more, end organ dam.

4. Atherosclerosis and Dyslipidemia NLA
NLA Categories of Risk
Low
0-1 risk factors
Moderate
2 risk factors
High
3 or more
DM factors
CKD 3B or 4
LDL above 190
Very High
Clinical ASCVD
DM + 2 or more, end organ dam.

5. Atherosclerosis and Dyslipidemia NLA
JA is a 56 yo male
Currently taking Lisinopril 10mg daily for hypertension
Well controlled
No other medical problems
Lipids
TC = 205
HDL = 45
LDL = 135
Family history is negative for CVD
Smokes 1/2PPD, denies alcohol or illicit drug use
Based on NLA guidelines, what risk category is he?
Low
Moderate
High
Very high

6. Atherosclerosis and Dyslipidemia NLA
JA is a 56 yo male
Currently taking Lisinopril 10mg daily for hypertension
Well controlled
No other medical problems
Lipids
TC = 205
HDL = 45
LDL = 135
Family history is negative for CVD
Smokes 1/2PPD, denies alcohol or illicit drug use
Based on NLA guidelines, what is his treatment goal?
Non-HDL <100mg/dl
LDL < 130mg/dl
Non-HDL < 130mg/dl
ApoB < 90mg/dl

7. Atherosclerosis and Dyslipidemia
When do triglycerides become the primary target of lipid lowering therapy?
When TG > 200mg/dl
When TG > 500mg/dl
When HDL-C < 35mg/dl
When a patient has a hx of pancreatitis

8. Atherosclerosis and Dyslipidemia
True or False
Raising HDL-C using drug therapy is supported by clinical trials and published in the literature.

9. Atherosclerosis and Dyslipidemia
Additional therapies only for:
Statin intolerant and need a replacement
Inadequate response to statin
Be sure to counsel on med adherence and lifestyle changes first
Which agents?
ACC = ezetimibe, BAS, or PCSK9 inhibitors
NLA = ezetimibe, BAS, or niacin

10. Atherosclerosis and Dyslipidemia Add-on therapy
ACC
1st: Ezetimibe
2nd: PCSK9 or BAS depending on Pt
NLA
1st: Ezetimibe
2nd: Colesevelam
3rd: Niacin ER
PCSK9 inhibitors:
Alirocumab (Praluent)
Evolocumab (Repatha)
- SQ administration, decreased dosing frequency, expensive

11. Atherosclerosis and Dyslipidemia Add-on therapy
Ezetimibe – reduced cholesterol absorption
PCSK9 inhibitors – monoclonal antibody that binds to LDL receptor to promote LDL degradation
Bile-acid sequestrants – disrupts enterohepatic recirculation of bile acids which increases conversion of cholesterol to bile acids

12. Atherosclerosis and Dyslipidemia Add-on therapy
63 yo female in clinic for check-up
Started Atorvastatin 40mg at last visit.
Lipid levels from 4 mos ago:
TC=240, LDL=145, HDL=30
Lipid levels today:
TC=130, LDL=70, HDL=32
What do you recommend for treatment?
Change to Simvastatin 20mg
Add Ezetimibe
Decrease to Atorvastatin 20mg
Maintain current therapy

13. Atherosclerosis and Dyslipidemia Add-on therapy
68 yo male in clinic for check-up
Started Atorvastatin 80mg at last visit.
Lipid levels from 4 mos ago:
TC=410, LDL=320, HDL=40
Lipid levels today:
TC=250, LDL=150, HDL=40
What do you recommend for treatment?
Change to Rosuvastatin 20mg
Add Ezetimibe
Add Colesevelam
Maintain current therapy

14. Atherosclerosis and Dyslipidemia Add-on therapy
Which treatment is recommended for homozygous familial hypercholesterolemia?
Evolocumab
Ezetimibe
Alirocumab
Colesevelam

15. Atherosclerosis and Dyslipidemia Add-on therapy
What should be your response if a Pt complains of cognitive changes after initiating a statin?
Continue therapy; it will resolve on its own
“Man, you’re crazy! It’s not the statin!”
Rule out other causes
Assess risk vs. benefit of therapy
Consider switching to a more hydrophilic statin
A and B
C, D, and E

16. Atherosclerosis and Dyslipidemia Add-on therapy
What side effect are we most concerned about with statin use?
Abdominal pain
Headache
Increased blood pressure
Myalgia

17. Atherosclerosis and Dyslipidemia Add-on therapy
Who is more likely to experience statin- induced myopathy?
Males or females?
Aged 65 or 85?
Hyper- or Hypothyroidism?
Simvastatin or Rosuvastatin?
Apple juice or grapefruit juice?

18. Atherosclerosis and Dyslipidemia Add-on therapy
HT is a 59 yo female who started Atorvastatin 40mg due to MI 3 mos ago. She has returned to the clinic today with complaints of severe muscle pain. What do you recommend?
Increase to Atorvastatin 80mg
Switch to Simvastatin 40mg
Hold the Atorvastatin, and restart at lower dose in 2 weeks C

19. Atherosclerosis and Dyslipidemia Add-on therapy
Other possible actions for myopathy:
Consider drug interactions and avoid certain CYP enzymes
Choose statins with longer half life to reduce dosing frequency
Rosuvastatin and Atorvastatin
Combine lipid lowering agents and use lower doses

20. Atherosclerosis and Dyslipidemia
TY is a 58 yo female recently discharged from hospital after suffering MI. During her stay, she developed a mild candida infection and was treated with Fluconazole. She comes to you with complaints of uncomfortable muscle pain.
Rx: Metoprolol, Lisinopril, Atorvastatin, Metformin, and Warfarin
What is causing her muscle pain and through what mechanism?
Azole antifungals inhibit CYP3A4, increasing her Atorvastatin concentration
Azole antifungals inhibit CYP2C9, increasing her Atorvastatin concentration
Azole antifungals induce CYP3A4, decreasing her Atorvastatin concentration
Azole antifungals induce CYP2C9, decreasing her Atorvastatin concentration

21. Ischemic Heart Disease
Ranolazine
Indicated for chronic angina
Works by inhibiting late inward sodium channel, which leads to decreased calcium influx = reduced ventricular tension and oxygen consumption
No hemodynamic changes
MARISA
Improved time to angina onset and total exercise duration as compared to placebo
CARISA
Improved angina when used in combination with other therapies
TERISA
Similar improvements in angina in patients with diabetes
MERLIN-TIMI 36
No difference in terms of CV death or MI compared to placebo
Decreased rate of ischemia compared to placebo

22. Ischemic Heart Disease
Ranolazine
Dose: 500mg BID up to 1000mg BID
Concern for prolonged QT interval
No torsades de pointes occurred during clinical trials
Contraindications
Pre-existing QT prolongation
Simultaneous QT-prolonging drug use
Strong CYP 3A4 inhibitors or inducers
Significant hepatic impairment
Drug Interactions!
Weak inhibitor of 3A4
Moderate inhibitor of 2D6 and Pgp
Substrate of 3A4 (also 2D6 and Pgp)

23. Ischemic Heart Disease
Which of the following will increase plasma concentrations of Ranolazine?
Rifampin
Ketoconazole
Phenytoin
Metoprolol
Which of the following will decrease plasma concentrations of Ranolazine?
Ritonavir
Diltiazem
Lisinopril
Carbamazepine

24. Ischemic Heart Disease
Which of the following should not be used in combination with Ranolazine?
Amiodarone
Simvastatin
Verapamil
Gentamicin
Which of the following does NOT have a contraindication with Ranolazine?
SSRIs
Methadone
Carvedilol
Haloperidol

25. Ischemic Stroke
BP: only treat when > 220/120 mmHg or aortic dissection, acute myocardial dysfunction, pulmonary edema, hypertensive encephalopathy
Why?

26. Ischemic Stroke Acute Treatment Alteplase (rt-PA) aids in reperfusion.
Gold standard of therapy
Risk? Bleeding
Should be given within 4.5 hours
Increases likelihood of a favorable outcome
LONG LIST of exclusion criteria
Dose: 0.9mg/kg total over 60 minutes
10% given as a bolus over 1 minute
Maximum dose is 90mg

27. Ischemic Stroke 70 yo female, presents to ER 1h after sx onset
Is Alteplase (rt-PA) therapy appropriate?
BP = 200/120
Platelets = 120,000/mm3
Received heparin infusion 24 hours prior
Stable on warfarin with INR of 2.0
Negative history for intracranial hemorrhage

28. Ischemic Stroke 70 yo female, presents to ER 4h after sx onset
Is Alteplase (rt-PA) therapy appropriate?
Hx of DMT2 and ischemic stroke
Stable on warfarin with INR of 1.5
NIHSS = 28

29. Ischemic Stroke 70 yo female, 55.5kg, presents to ER 1h after sx onset
The healthcare team deems Alteplase appropriate. What is her dose?
50mg infusion over 60 min.
5mg bolus over 1 min., followed by 45mg over 60 min.
50mg bolus over 1 min., followed by 40mg over 60 min.
5mg bolus over 1 min., followed by 85mg over 60 min.

30. Ischemic Stroke 65 yo male, 105kg, presents to ER 1h after sx onset
The healthcare team deems Alteplase appropriate. What is his dose?
9.5mg bolus over 1 min., followed by 85mg over 60 min.
95mg infusion over 60 min.
9mg bolus over 1 min., followed by 81mg over 60 min.
95mg bolus over 1 min., followed by 5mg over 60 min.

31. Ischemic Stroke Acute Treatment when not t-PA eligible
Give antiplatelet as soon as possible
Choose Aspirin or Clopidogrel
Don’t pick dipyridamole (bad headaches)

32. Ischemic Stroke Anticoagulation Unclear cause? Monitor heart rhythm
Cardioembolic origin needs anticoagulation
Initiate within 14 days

33. Hemorrhagic Stroke Intracerebral hemorrhage Gradual increase in sx
Causes: think anticoag and HTN
BP:
SBP is mmHg
Decrease to <140 quickly
SBP is >220mmHg
Use CIVI and monitoring to get to <140
Management
Cont. Inf.: Clevidipine and Nicardipine
Boluses: Hydralazine and Labetalol

34. Hemorrhagic Stroke Reversing Bleeds
Kcentra and FEIBA are both 4 factor prothrombin complex concentrates
Difference: FEIBA has activated factor 7
Warfarin
Vit K
Kcentra
FEIBA
FFP
Dabigatran
Kcentra
FEIBA
Hemodialysis
Rivaroxaban
Kcentra
FEIBA
Apixaban
Kcentra
FEIBA

35. Hemorrhagic Stroke DVT Prophylaxis Intracerebral hemorrhage
LMWH started 1-4 days after onset in immobile patients
Subarachnoid hemorrhage
No treatment until aneurysm is protected via surgery
LMWH or UFH started 24 hours after surgery
When to restart anticoag?
No heart valves: wait at least 4 weeks
Aspirin monotherapy can be started back sooner
Controversy over mechanical valves

36. Hemorrhagic Stroke Subarachnoid hemorrhage “worse headache”
Sudden onset
Highest risk of re-bleeding in first 72 hours
BP:
Get below 160mmHg
Use same drugs as ICH, except lower target with ICH
Special: Nimodipine
Only indicated for reducing vasospasm associated ischemia after SAH

37. Hemorrhagic Stroke
72 yo female presents to ER with vomiting and severe headache
Pt currently taking warfarin 5mg daily for AF
Her current BP is 230/135mmHg.
What do you recommend for treatment of her blood pressure?
Labetalol continuous infusion
Clevidipine continuous infusion
Amlodipine bolus
No therapy; she’s fine with that BP! B

38. Hemorrhagic Stroke
78 yo male presents to ER with vomiting and severe headache
Pt currently taking Rivaroxaban 20mg daily for AF
What reversal strategy do you recommend?
Hemodialysis to quickly pull of the Rivaroxaban
Kcentra
Vitamin K
LMWH
No treatment
Kcentra

39. Hemorrhagic Stroke
78 yo male presents to ER with vomiting and severe headache
Pt currently taking Rivaroxaban 20mg daily for AF (no mechanical valve)
When can we safely restart his anticoagulation?
Immediately
7 days
1 year
4 weeks

40. Therapeutics 1 Tutoring Questions?
Sarah Darby
August 26, 2016