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ADV PHARM I > HYPERLIPIDEMIA > Flashcards

HYPERLIPIDEMIA Flashcards

(50 cards)

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1
Q

hyperlipidemia

A
  • elevation of lipids in blood stream
  • cholesterol, cholesterol esters, phospholipids, triglycerides
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2
Q

lipoprotein types

A
  • chylomicrons
  • very low density lipoproteins (VLDL)
  • intermed density lipoproteins (IDL)
  • low density lipoproteins (LDL)
  • high density lipoproteins (HDL)
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3
Q

atherosclerosis
- define
- goal for tx ds
- risks

A
  • slow progressive ds
  • deposition of fatty substances, fibrous tissue, and calcium on intimal lining of BVs
  • aim is to lower total cholesterol and LDL OR raise HDL —> slow progression of ds + reverse it
  • inc risk of CAD
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4
Q

total cholesterol levels
- desirable
- borderline high
- high

A
  • desirable: <200
  • borderline high: 200-239
  • high: >= 240
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5
Q

LDL cholesterol levels
- optimal
- near optimal
- borderline high
- high
- very high

A
  • optimal: <100
  • near optimal: 100-129
  • borderline high 130-159
  • high: 160-189
  • very high: >= 190
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6
Q

HDL cholesterol levels
- low
- high

A
  • low: <40
  • high: >=60
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7
Q

TG levels
- nl
- borderline high
- high
- very high

A
  • nl: <150
  • borderline high: 150-199
  • high: 200-499
  • very high: >=500
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8
Q

therapeutic lifestyle changes

A
  • dietary mods: low cholesterol (<200), sat fats, calories, avoid trans fats
  • wt reduction
  • exercise
  • quit smoking

attempt TLC and diet mods first (depend on LDL and RFs)

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9
Q

monounsaturated (MUFA) v. polyunsaturated (PUFA) fatty acids

A

MUFA (oleic acid)
- found in olive, canola, safflower, sunflower oil
- foun in walnuts, almonds, peanuts, sesame seeds, olives, avocados

PUFA
- linoleic acid (omega 6): in vegetable oils
- alpha-linoleic acid (omega 3): found in certain fish, marine oils, flaxseed, and linseed oils

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10
Q

Coronary Heart ds
- major RFs
- others

A

MAJOR RFs
- age (men >45, women >55)
- DM
- FHx of early CHD (men <55, women <65)
- HTN
- smoking
- low HDL

other RFs
- obesity
- sedentary lifestyle
- atherogenic diet

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11
Q

ASCVD risk calculated based on what RFs

A
  • sex
  • age
  • race
  • total cholesterol
  • HDL
  • systolic BP
  • treated for HBP
  • DM
  • smoker
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12
Q

classes of drugs

A
  • HMG-CoA reductase inhibitors (statins)
  • bile sequestering agents
  • fibric acid derivatives
  • nicotinic acid
  • misc
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13
Q

HMG-CoA Reductase inhibitors/Statins
- MOA
- effects

A

MOA
- block rate limiting step in cholesterol synth (conversion HMG CoA to mevalonic acid)

effect
- lowers LDL (by 20-60%) and TG (15-60%), raises HDL (3-15%)

INC efficacy w higher doses + more potent statins

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14
Q

statins
- CI
- ADRs in pregnant pts

A

CI
- breast feeding
- ACTIVE heaptic ds (safe in non alc fatty liver ds and hep C)
- pregnancy (category X)

can cause fetal abnorm such as:
- spontaneous abortion
- congenital anomalies: polydactyly, cleft lip, trisomy 18, club foot, AV septal defects, fetal skeletal malformations

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15
Q

statins
- therapeutic benefit

A
  • plaque stabilization
  • improve coronary endothelial dysfunc
  • inhibit platelet thrombus formation
  • anti inflamm activity
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16
Q

first line medication to reduce LDL?

A

statins

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17
Q

statins
- precautions
- ADRs

A

precautions
- dose adj if DDI

ADRs
- GI (n/v/d)
- elevated LFTs, hepatotox
- myopathy (myalgia, rhabdo–>rare)
- CNS: dec cog func, memory loss (reversible if d/c drug)
- small incidence of hyperglycemia and inc A1C but benefit>risk in DM

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18
Q

statins and myopathy RFs
- patient factors
- drug properties

A

PT factors
- age >80
- female
- small body frame
- dec hepatic/renal func
- hypothyroidism
- diet (grapefruit juice)
- polypharmacy

drug properties
- lipophilicity (prava and rosuvastatin least)
- high F
- limited protein binding
- CYP substrate

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19
Q

statins
- DDIs

A
  • CYP 450 3A4 substrates: lovastatin and simvastatin >atorvastatin
  • CYP2C9 substrate: fluvastatin
  • pravastatin and rosuvastatin have the least DDIs
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20
Q

statin DDIs
- 3A4 inhibitors
- 2C9 inhibitors

A

3A4 inhib
- grapefruit juice, amiodarone, azole antifungal, macrolides

2C9 inhib
- amiodarone, cimetidine, azole antifungals, SSRIs , zafirlukast

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21
Q

statins
- monitoring parameters

Study These Flashcards
A

lipid profile
- measure baseline
- then 4-8 wks after tx initiate or dose changes
- then q6-12 months after

LFTs
- baseline
- periodically after or if S/Sx of liver ds

CPK (CK)
- baseline
- if pt has myalgia sx

22
Q

statin types (list names)

Study These Flashcards
A

atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin, pitavastatin

23
Q

statins
- dosing implications
- which meds do not need to follow dosing implication

Study These Flashcards
A

dose at bedtime to mimic nl circadian rhythm
- atorvastatin and rosuvastatin do not have to be given HS (they have >24 hr half life)

rule of 6s

24
Q

statin dosing
- rule of 6s

Study These Flashcards
A

initial doses produce most substantial reduction in LDL, so start pt on highest necessary dose to get goal
- each doubling after only produces 6-7% reduction in LDL

25
PCSK9 Mab inhibitors - names - indications
- alirocumab SC, evolocumab SC indications - familial hypercholesterolemia (homozygous, 2 defective genes)--->use in combo w other lipid lowering tx) - primary heterozygous familial hypercholesterolemia (1 defective gene) ---> use in combo w statin - primary hypercholesterolemia, atherosclerotic CV ds-->in combo w a statin
26
PCSK9 Mab inhibitors - MOA
monoclonal Ab inhibits binding of proprotein convertase subtilisin/kexin type 9 (PCSK9) to LDL receptors---> reduces degradation of the LDL receptors - inc receptors---> avail to clear LDL cholesterol from circulation and therefore lower LDL levels
27
PCSK9 Mab inhibitors - ADRs
- injx site rxns - nasopharyngitis - influenza - allergic rxns
28
PCSK9 siRNA inhibitors - name - indications
- Inclisiran indications - **adjunct** to diet/statin tx for adults w primary hyperlipidemia ---> including heterozygous familial hypercholesterolemia (HeFH) to reduce LDL cholesterol
29
PCSK9 siRNA inhibitors - MOA - freq
MOA - binds to mRNA precursor for PCSK9, inclisiran inhiitors PCSK9 gene expression and results in INC hepatocyte recycling and membrane expression of LDL receptors---> dec levels of LDL-C freq - twice yearly injx
30
recommendation tx to reduce ASCVD risk - clinical ASCVD
clinical ASCVD - age =< 75 yo + no safety concern ----> high intensity statin - age >75 yo OR safety concern---> mod-intense statin
31
recommendation tx to reduce ASCVD risk - primary prevention for: DM+ LDL 70-189, NO DM + LDL 70-189, and LDL>190
primary prevention - DM 40-75 yo + LDL 70-189 ----> mod intenstiy statin, consider high intensity if >= 7.5% 10yr ASCVD risk - NO DM 40-75 yo + LDL 70-189 ---> estimate 10yr ASCVD risk - primary LDL >= 190 ----> R/o secondary causes ---> age >= 21 yo --> high intensity stain ----> acheive min of 50% dec LDL ----> LDL lowering non statin tx
32
highest intensity statins
- atorvastatin (40-80mg) - rosuvastatin (20-40mg)
33
bile sequestering agents - MOA - CI
MOA - binds to bile acids, forms complex that is excreted--> less bile acids avail to emulsify fats in GI-->inc conversion cholesterol to bile acid--> dec LDL + inc TG CI - in hypertriglyceridemia (TG>400)
34
bile sequestering agents - PK (pharmacokinetics) - ADRs
PK - not absorbed from gut, excreted in feces ADRs - GI (n/v/constipation, flatulence, statorrhea, ano, heartburn) - inc TGs
35
bile sequestering agents - DDIs - guidelines
DDIs - binds with and prevents absorp of almost all drugs--> take 1 hr before or 4 hrs after (especially digoxin, thyroxin, warfarin) guidelines - can add when pts dont reach LDL goal with statin or can't tolerate statins
36
bile sequestering agents - names - freq - formulation
cholestyramine - QID to Q4H, avail as powder - can use in overdose tox agents colestipol - BID, avail as tabs or granule packets - can use in overdose tox agents colesevelam - QD-BID, avail as tabs, take w meals (may also have glucose lowering effect in DM2) can take several weeks for max effect
37
fibric acid derivatives - MOA
MOA- activation of peroxisome proliferator activator receptors (PPARs) - activates lipoprotein lipase -->dec TGs - dec expression apo CII--> dec TGs - inc expression apo AI + AII--> inc HDL
38
fibric acid derivatives - indications - CI - types
indications - hypertriglyceridemia or marked HDL deficiency CI - severe renal/hepatic failre - biliary + gallbladder ds types - gemfibrozil - fenofibrate
39
fibric acid derivatives - ADRs - DDIs
ADRs - GI - fatigue, HA - impotence - dyspepsia - rash, urticaria, alopecia - inc LFTs - myopathy and rhabdo - gallstones DDIs - competes w warfarin and sulfonylurea for protein binding sites (monitor)
40
nicotinic acid (niacin) - MOA - guidelines
MOA at HIGH DOSES - inhibit lipolysis--> dec circulating free fatty acids--> dec TG synth--> dec hepatic VLDL production+secretion - also inc HDL guidelines - 2nd line choice to add when pts dont reach LDL goal w statins or cant tolerate ## Footnote avail alone or combo w lovastatin
41
nicotinic acid (niacin) - ADRs + how to minimize
ADRs - vasodilation, flushing, pruritis-->more w SR form (reduce w ASA pre treatment or slowly inc dose) other ADRs - GI (take w food to minimize) - PUD - inc LFTs--->hepatic dysfunc (more w SR form) - hyperuricemia - hyperglycemia
42
misc- ezetimibe (zetia) - MOA
MOA - inhib absorp cholesterol at brush border of small intestine--> dec delivery cholesterol to liver--> inc cholesterol clearance
43
misc- ezetimibe - ADRs - DDIs
ADRs - chest pain, dizzy, fatigue, HA, GI (diarrhea, abd pain, arthralgia) DDIs - cyclosporine - FIBRIC ACID DERIVATIVES
44
combo products
- ezetimibe + simvastatin - nicotinic acid + lovastatin - nicotinic acid + simvastatin - amlodipine + atorvastatin - pravastatin + ASA - ezetimibe + atorvastatin
45
misc- probuchol (lorelco) - effect - ADRs
effect - lowers LDL and HDL (limited to certain types of hereditary high cholesterol and/or cases where other meds are ineffective) ADRs - n/d - bloating, dizziness | RARELY USED bc of inc effectiveness statins
46
other misc options
- vit E - garlic - HDL infusions - alt therapies: artichoke extract, soy, walnuts, fish oils, plant stanols/sterols, fiber - dietary supplements
47
fish oils (omega-3 fatty acids) - MOA - efficacy
MOA - dec synth and secretion VLDL, reduce TG transport - contains 2 PUFAs and DHA (avail as Rx lovaza) efficacy - 1-5 g/day can reduce TG 20-50% - only effective for high TGs, does not lower total cholesterol or LDL
48
fish oils + CVD - efficacy
- fish oil from dietary sources/supplements reduce ASCVD risk + mortality - 1gm/day--> dec risk MI, stroke, progression of atherosclerosis
49
fish oils - recc dosing - ADRs/side effects
dosing - safe in doses <=3 g/day - 2-4g for hypertriglyceridemia - rx product is 2g BID ADRs/side effects - GI (flatulence, diarrhea, dyspepsia) - body odor - rx lovaza has less ADRs than OTCs - higher doses--> anticoag effect and inc risk bleeding or suppress immune response
50
dietary sources of fish oils ADRs
- large amts fatty fish may have high amts toxins (mercury, PCB, dioxin) ADRs - tremor, numbness, tingling, difficulty concentration, vision problems ## Footnote fatty fish---> shark, swordfish, king mackerel, filefish, farm raised salmon

ADV PHARM I (13 decks)

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