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PHARM 344 Cardio > Lecture 5,6,7 Dyslipidemia > Flashcards

Lecture 5,6,7 Dyslipidemia Flashcards

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1
Q

Definition of dyslipidemia

A

Abnormal fats in the blood

Elevation of >1 lipoproteins or reduced HDL-C

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2
Q

Four primary categories proteins

A

Low-density lipoproteins (LDL-C) = Bad
High density lipoprotein (HDL-C) = Good
Total cholesterol (TC) = all lipoproteins
Triglycerides (TG)

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3
Q

Types of dyslipidemia

A

Primary = genetic cause
- known as hypercholesterolemia
- most common cause of ASCVD in children

Secondary = Other causes
- most common cause in adults
- sedentary lifestyle
- excessive dietary intake of fat or EtOH
- diseases
- cigarette smoking
- Drugs

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4
Q

Familial hypercholesterolemia (FH)

A

Autosomal dominant genetic disorder

High LDL-C level
- normal LDL-C = 2-5 mmol/l
-Heterozygous FH (1/5000): LDL-C, 5-13mmol/l
-Homozygous (1/1000000): >13mmol/l

Requires aggressive treatment:

Statins
LDL-C apheresis

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5
Q

Drugs causes of dyslipidemia

A

Amiodarone
Beta blocker
Carbamazepine
Clozapine
Corticosteroids
Cyclosporine
Loop diuretics
Oral contraceptives
Olanzapine
Phenobarbital
Phenytoin
Protease inhibitors
Retinoids
Thiazide diuretics

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6
Q

T/F there is a positive associated between high TC or LDL-C and CAD

A

TRUE

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7
Q

Signs and symptoms of dyslipidemia

A

Most are asymptomatic

Possible signs: xanthoma/xanthelasma, Corneal arch’s, carotid bruits

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8
Q

Who to screen with fasting or non fasting TC, TG, HDL-C, calculated LDL-C and non-HDL-C with ApoB when appropriate.

A

Men> 40, women > then 40 or postmenopausal at younger age in indigenous and south Asian individuals

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9
Q

What are risk factors of atherosclerotic cardiovascular disease

A

Hypertension, dyslipidemia, smoking, alcohol, unhealthy diet, physical inactivity, aging, gender, race,genetic predisposition, obesity, diabetes

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10
Q

Framingham risk score risk assessment

A

Risk prediction tool

Estimated 10 year risk of total CVD=CAD, stroke, PAD, heart failure

Reported as percent

Used in practice to determine risk level, treatment recommendation, therapeutic targer

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11
Q

Framingham risk score component

A

Age

HDL-C and TC ( not LDL-C)

SBP

DM ( yes or no)

Smokin status (yes or no)

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12
Q

When to consider pharmacotherapy in risk Managment ( low risk, med risk, high risk)

A

Low risk ( FRS <10%): Therapy not recommended for most low risk indicates, health behaviour modification like smoking cessation, diet, excercise

Med/high risk ( 10-20+ FRS) : discuss healthy modification, initiate statin, discuss add on therapy with patient if levels still high

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13
Q

What are examples of CVD

A

MI, ACS

Stable angine or documented CAD by coronary angiogram

Previous CABG surgery

ACS

Stroke, transient ischemic attack

PAD

Abdominal aortic aneurysm- an abdominal aorta measuring >3.0cm or previous AAA surgery

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14
Q

Additional high risk patient

A

Most patients with DM, or microvascular complications

CKD: Age > 50 yrs and >3 months duration with eGFR <60nl/min/1.73m^2 or ACR > 3mg/mmol

Familial hypercholesterolemia: LDL-C > 5.0 mmol/l or documented FH, after excluding all secondary causes

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15
Q

T/F multiple FRS by x3 for any patient with positive family history or premature CVD

A

False

Multiple by 2

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16
Q

How to screen for dyslipidemia

A

History and physical examination

Standard lipid profile: Total cholesterol, LDL, HDL, non-HDL, triglycerides

Fasting plasma glucose or A1C

Estimated glomerular filtration

Lipoprotein- once in a person lifetimes with initial screening

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17
Q

What is the Calculation for LDL-C and name of it

A

Friedwald equations

LDL-C (mmol/l) = TC - HDL - TG/2.2

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18
Q

Apolipoprotein B

A

Each of the atherogenic lipid particles ( LDL, LP, LDL, VLDL) contains 1 molecule of Apo-B

Serum concentrations of the APO-B reflect total number of these particles

More PARTICICLES = HIGH RISK

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19
Q

Non-HDL-C

A

Alternate measurement instead of ApoB

Provides an estimated sum of all atherogenic lipoprotein

Calculation: TC- HDL- C

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20
Q

ApoB and non-HDL-C for screening and treatment purposes ?

A

Recommend that for any patient with triglycerides >1.5mmol/l, non-HDL-C or ApoB be used instead of LDL-C as the preferred lipid parameter for screening

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21
Q

TG

Causes of hyperrtriglycermia…

A

High dietary fat intake
Excessive EtOH
Poor DM control

Very high TG associated with pancreatitis

Reducing TG with pharmacologic therapy does not reduce CV events

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22
Q

Healthy behaviour modifications

A

Smoking cessation

Diet: caloric restriction, fibre intake > 30g daily, substitute unsaturated fats or saturated/trans fats,fruit and vegetables

Excercise

Limit EtOH intake

Stress Managment

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23
Q

Pharmacological treatment for dyslipidemia

A

Statins
Cholesterol absorption inhibitor ( Ezetimibe)
niacin
Vibrates
Bile acid suquestrants
PCSK9
Icosapent Ethyl (IPE)

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24
Q

Relative effects of different agents

A

Statins :
LDL-C : lowers 30-50%
HDL-L : increases 4-10%
TG: Lowers 20-30% (> effect with higher TG)

PCSK9-i:
LDL-C: lowers 50-60%
HDL-C: increases 10-15%
TG: lowers 20-50%

Ezetimibe:
LDL-C : lowers 15-20%

Niacin:
LDL-C: lowers 15-20%
HDL-C: increase >30%
TG: Lowers 20-50%

Fibrates:
HDL-C: increase 5-20%
TG: Decrease 25-50%

IPE:
TG: lowers 30%

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25
When do consider pharmacotherapy in risk Managment in dyslipidemia
Low risk: FRS < 10%, statin therapy not recommend, health behaviour modifications Intermediate risk: FRS 10-19.9%, discuss health behaviour -> initiate statin treatment High risk : FRS >20%, health behaviour modifications, initiate statin treatment.
26
What conditions are statins indicated in
LDL > 5.0 mmol/L Most patients with diabetes: - age >40 - age >30 yrs and DM x > 15 hr duration - microvasculate disease CKD: - Age >50yrs and eGFR <660 ml/min or ACR >3mg.mmol ASCVD (Athersclerotic cardiovasculate disease)
27
Statins Mechanism of action leads to reduced cholesterol synthesis via???
-Upregulation of LDL receptors - decreased VLDL production - these mechanism lead to reduction in TC, LDL-C and TGs MOA: Blocks HMG-Coa reducatse, blocks synthesis of cholesterol in liver
28
Statin LDL lowering comparison
Rosuvastatin : lowers by 40-65% Atrovastatin : Lowers by 35-60% All others are less
29
Statins, recommended dose range
Atrovastatin: 10-80mg Fluvastatin: 20-80mg Lovastatin: 20-80mg Pravastatin: 10-40mg Rosuvstatin: 5-40mg Simvastatin: 10-40mg
30
What is the law of diminishing returns
“Rule of sixes”: double statin dose= 6% additional LDL-C lowering
31
Contraindications of Statins
Active liver disease Pregnancy and lactation Hypersensitivity
32
_____ are the cornerstone of dyslipidemia Managment- recommended as the initial lipid lowering agent of choice for treatment
Statins***
33
______ dose or ________ tolerated statin should be used for all patients in whom treatment is indicated
Maximum, maximally
34
____ % reduction in MVE per 1 mmol/l reduction in ldl-c achieved with statin therapy
20-40
35
Statin metabolism :
Atrovastatin, lovastatin, simvastatin : CYP3A4 Fluvastatin, rosuvastatin: CYP2C9 Pravastatin : not understood
36
What can increase and decrease statin levels
Increase (with CYP3A4 Inhibitors) - macrolide antibiotics - grapefruit juice - azole antifungals - protease inhibitors Decrease: Rifampin Carbamazepine Bosentant Efavirenz Antacids
37
Adverse effects of statins GI MSK Hepatic Endo
GI: nausea/vomiting/diarrhea MSK: Myopathy Hepatic: elevated liver enzymes Endo: diabetes- in those predisposed Nocebo effects: people who have negative expectation about medicine or treatment experience harmful symptoms they otherwise wouldn’t have
38
Terminology CK Myopathy Myalgia Myosin is Rhabdomyolysis
CK: creatinine kinase, tissue enzyme that is released during muscle breakdown Myopathy: muscle related pathology Myalgia: Muscle pain with CK ULN Rhabdomyolysis: Muscle breakdown with CK> 10x ULN +/- serum myoglobin and renal failure
39
Myopathy, incidence rate and risk factors
Incidence 1.5-5% Dose related Occurs usually in first 6 months Risk factors: Hx of myalgias with statins Hypothyroidism Renal or hepatic impairment Female Small body frame Advanced age Drug interactions
40
Rhabdomyolysis
Very rare Diagnosed by : Myoglobinemia -> myoglobinuria ( darkens urine) , can lead to acute renal failure Not well predicted by myalgias Likely dose repeated Increased risk with vibrate combination Discontinue statin and do not rechallenge
41
Approach to monitoring statin use
Baseline CK and TSH in all patients CK-> ULN —-> reasses symtpoms and CK in 6-12 weeks
42
Monitoring CK < 10x ULN CK> 10X ULN
- consider other causes, follow until CK 10x ULN -> hydrate PRN, follow until CK
43
What step do statins inhibit
HMG-CoA -> Mevalonate
44
Coenzyme Q10 effect?
No effect on muscle pain or CK in patients on statin therapy Not recommended as per CCS guidelines
45
Statin induced liver enzyme elevation Incidence Most often will present with ___elevation
0.1-3% ALT Asymptomatic May be dose related
46
Approach to monitoring statin induced liver enzyme elevation
Baseline ALT Check alt ever 6-12 weeks post statin initiation If <3x ULN, no routine ALT monitoring required If >3x ULN, d/c statin and reassess in 6-12 weeks Monitor for signs and symptoms of liver failure, jaundice, fever, malaise, lethargy, abdominal pain
47
New statin safety concerns Diabetes Cancer Cognition Fatigue Cataracts
Diabetes: associated small increased risk, but benefits outweigh risks Cancer: no assocition and may actually improve survival in some population Cognition: no associated Fatigue : poor quality evidence Cataracts: Small association in retrospective cohort data
48
Ezetimibe, dose range, indicated to lower LDL by how much
Ezetimibe - 10mg, lower by 15-20%
49
Ezetimibe contraindications, and drug interaction
Contraindications: - combination with statin in patients with active liver disease or unexplained liver enzyme elevation - hypersensitivity - pregnancy and lactation Drug interaction: - cyclosporine - fibrates - BAS ( Decrease Ezetimibe levels)
50
Fibrates recommended dose range,
Bezafibrate, 400mg Fenofibrate 48-200mg Gemfibrozil 600-1200mg First line therapy to reduce TG ( 20-50%)
51
Fibrates (AE, Indication, contraindication, drug interaction)
AE: GIT, Myositis, galllstones Indication: 1st line for mixed dyslipidemia Drug interaction: increase risk of myopathy when combined with statins Contraindication: patient with impaired renal fx, pregnant, preexisting gall bladder disease
52
Niacin, dose range, LDL lowering %, AE,Indication,contraindication,MOA
Crystalline Niacin 1-3G ER niacin - 500-2000mg hs Lowers lDL by 20% in combo with statin Increases HDL by 20% MOA: Lowers TG, and thus VLDL Synthesis, inhibits diacylglycerol acyltransferase-2 a key enzyme for TG synthesis AE: impaired of glucose tolerance, increase uric acid, reversible increase in liver enzymes -> hepatotoxicity Indication: monotherapy or in combo with Fibrate, resin or statin, patient with High TG and low HDL Contraindication: Gout, peptic uncle, hepatotoxicity, DM
53
What are the 3 types of NIACIN
Crystalline niacin ( OTC) - requires titration to develop tolerance to flushing Extended release niacin (RX only) - reduced incidence of flushing - associated with hepatotoxicity Flush - free niacin (OTC) - studied in rabbits - contains inositol Do not recommend as alternative to niacin
54
Bile acid sequestrants - MOA, 3 drugs, usual dose, lowering of LDL
MOA - make cholesterol absorption easier form the intestine - both endogenous cholesterol (synthesized in the liver and enterhepatically recirculated) and exogenous cholesterol Cholestyramine - 2-24g Colestipol- 5-30g Colesvelam - 1.25-3.75g Lowers LDL by additional 10-15% Multiple GI adverse effects
55
PCSK9 inhibitors
= proprotein convertase subtilisin/ kexin Serum PCSK9 is inversely related to density of LDL-C receptors on hepatocytes PCSK9 modulates formation of atherosclerosis
56
PCSK9 Inhibitors
Evolocumab (Repatha - Sanofi - SQ injection a 2-4 weeks ( 140mg q2 weeks or 420 mg a month) Alirocumab (praluent) - sanofi/regeneron - SQ injection ever 2 weeks : 75 or 150mg q2 weeks
57
PCSK9 inhibitors indications
Lower LDL-C in patients HeFH without clinical ASCVD whose LDL-C remains above target despite maximally tolerated statin therapy with or without Ezetimibe For patients with HeFH and ASCVD whose LDL-C remain above threshold >1.8mmol/l despite maximally tolerated statin with or without Ezetimibe For all secondary prevention CVD patients in whom LDL-C remains above>1.8mmol/l on maximally tolerated statin dose
58
Icosapent Ethyl (IPE) MOA Indication
MOA: reduces hepatic very low density lipoprotein triglycerides synthesis, and/or secretion, and enhances TG clearance from circulating VLDL particles Indication: recommend used of IPE to lower risk of CV events in patients with ASCVD, or with diabetes 1 or more CVD risk factors, who have elevated fasting TG levels of 1.5-5.6mmol/l despite treatment with maximally tolerated statin therapy.
59
What are the potential mechanism of cardio protection for omega-3 fatty acids
Lower TG rich lipoproteins Anti thrombotic effects Antiarrhythmic actions Altered prostaglandin synthesis Anti inflammatory actions Augmented specialized pro-resolving mediators
60
T/F low dose omega 3 mixtures show no significant cardiovascular benefit
True
61
Beyond statins, when to add on intensity therapy
Ensure statin dose optimized Lipid threshold is the current focus of the 2021 guidelines - threshold = the quantitive point at which an action is triggered
62
Prior to initiating lipid lowering therapy, what tests to do
Lipid profile TSH ALT CK Scr FBG
63
Follow up
In 6-8 wk or as planned - LIPID profile - ALT Annual - Lipid profile Suspected myopathy - CK - +/- TSH On going - Signs and symptoms of CV events - signs and symptoms of adverse effects

PHARM 344 Cardio (17 decks)

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