Far

Eastern University – Nicanor Reyes Medical Foundation sterolemia LDL receptor tendon
PHARMA: DRUGS USED TO TREAT HYPERLIPIDEMIA (heterozyg xanthomas,
ous) corneal arcus
Dra. Ravelo, MD
Familial Absent LDL ↑LDL-C LDL-C: >450 Family history of
CORE PRINCIPLES hyperchole receptors mg/dl premature CHD,
- The risk of cardiovascular disease is directly related to serum sterolemia tendon
cholesterol levels particularly the lipoproteins. For every 1% (homozygo xanthomas,
increase in cholesterol, there is a corresponding 1-2% us) corneal arcus.
increase in the risk for CHD Develop CHD at
2nd decade of life
- Of all the lipoproteins, LDL-C is the primary target for
Familial Defective ↑LDL-C LDL-C:250- Family history of
intervention apoB on
Defective 450 mg/dl CHD, tendon
- Patients diagnosed with dyslipidemia should therefore be apoB-100 LDL and xanthomas
evaluated of his risks for developing coronary heart disease VLDL
Dysbetalipo ApoE2:E2 ↑remnan LDL-C:300- Palmar xanthomas,
- Causes of dyslipidemias should be addressed
proteinemia phenotype t VLVL 600 mg/dl Tuberoeruptive
- A goal for cholesterol level should be set (Type III TG:400-800 xanthoma
- Therapeutic lifestyle changes should be instituted immediately hyperlipide ↓VLDL ↑IDL mg/dl
but concurrent use of pharmacotherapy should likewise be mia) remnant
started especially for those at high risk clearance
Familial ↑Apo B and ↑Chole, LDL-C:250- Family history of
combined VLDL 350 mg/dl CHD and
TG or
DYSLIPIDEMIA hyperlipide production both TG:200-800 hyperlipidemia
- Disordered lipid metabolism which results to one or more mia mg/dl
Familial ↑Apo B ↑ Apo B Apo B: >125 None
abnormalities in blood lipids hyperapob production mg/dl
- CAUSES etalipoprot
o Genetics: caused by genetic mutations passed on einemia
Hyperalpha ↑ HDL ↓HDL-C HDL-C: None
by one (heterozygous) or both parents lipoprotein metabolism <40mg/dl
(homozygous) emia
o Lifestyle
o Secondary causes: DM, hypothyroidism, obesity, drugs COMMON SECONDARY CAUSES OF DYSLIPIDEMIA
etc. ↑ Total Chole & - Hypothyroidism
- EPIDEMIOLOGY LDL-C - Nephrosis
o estimated annual incidence of MI: 550,000 new and (HYPERCHOLEST - Dysgammaglobulinemia (SLE, MM)
20,000 recurrent attacks EROLEMIA)
- Progestins or anabolic steroid treatment
o average age at first MI: 65.1 years for men and 72.0 - Cholestatic disease of the liver due to
years for women abnormal lipoproteins as in primary biliary
o DYSLIPIDEMIA: major risk factor for ASCVD cirrhosis
o Epidemiologic data a suggest that hypercholesterolemia - Anti-HIV drugs like protease inhibitors
and perhaps coronary atherosclerosis itself are risk ↑TG & VLDL-C - Chronic renal failure
factors for ischemic cerebrovascular accident (CVA) (HYPERTRIGLYCE - T2DM
RIDEMIA) - Obesity
CHARACTERISTICS OF COMMON LIPID DISORDERS - Excessive alcohol intake
DISORDER METABOLLIC LIPID MAIN LIPID DIAGNOSTIC - Hypothyroidism
EFFECT EFFECT PARAMETER PROCEDURES
- Antihypertensive medications
Polygenic ↓ LDL ↑LDL-C LDL-C: 130- None
hyperchole clearance 250 mg/dl (b blockers, thiazide, diuretics)
sterolemia - Corticosteroid therapy
Atheroscler ↑VLDL ↑triglyce TG: 150- Central obesity - Orally administered estrogens & oral
otic secretion ride 500 mg/dl or DM contraceptives
dyslipidemi HDL-C: <40 - Protease inhibitors for HIV
as ↑Apo C III ↑remnan mg/dl
synthesis t VLDL



↓LPL activity ↓HDL

↓VLDL ↑small
removal
dense
LDL

Familial Reduced ↑LDL-C LDL-C:250- Family history of
hyperchole functional 450 mg/dl premature CHD,

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 DRUG INDUCES HYPERLIPIDEMIA MAJOR ATHEROSCLEROTIC CARDIOVASCULAR DISEASE RISK
EFFECTS ON PLASMA LIPIDS FACTORS
DRUGS Chole (%) Trigly HDL-C (%) Comments MAJOR RISK ADDITIONAL RISK NON TRADITIONAL
(%) FACTORS FACTORS RISK FACTORS
Diuretics - Advance age - obesity - Increase Lp(a)
- Thiazide Inc 5-7 No Inc 1 Effect is transient; - Increase - abdominal obesity - Increas
initially; change monitor long term total serum - FH of hyperlipidemia e
0-3 later s effect cholesterol - increase small dense clotting
- Loop No No Dec to 15 - Increase Non- LDL-C factors
change change HDL-C - Increase
- increase Apo B
- Indapamide No No No - Increase LDL-C - increase inflammator
- Metolazone change change change - Low HDL-C LDL particle y markers
- K-sparing - DM - Increase
concentrati
Beta-blockers - Hypertension homocystein
on
- Non- No Inc 20- Dec 10- Selective beta - CKD - Fasting/postprandi e levels
selective change 50 15 blockers have - Cigaret al - Apo E4 isoform
- Selective No Inc 15- Dec 5-10 greater effects than
te hypertriglyceridem - Increase uric
change 30 non-selective; smokin ia acid
BB with ISA or alpha g - PCOS - Increase TG
blocking property - Family history of - Dyslipidemic triad rich remnants
are lipid neutral ASCV
Alpha 2 Dec 0-10 Dec 0- Inc 0-15 In general, drugs D
agonist 20 that affect alpha
(clonidine) receptors dec
ATHELOSCLEROTIC CARDIOVASCULAR DISEASE RISK CATEGORIES
& selective cholesterol and
AND LDL-C TREATMENT
alpha 1 inc HDL-C
RISK RISK FACTORS/ 10 YR RISK TREATMENT GOALS
blocker
(Prazosin) CATEGORY LDL Non-HDL Apo B
ACE inhibitors No No No (mg/dl) (mg/dL)
change change change Extreme 1. Progressive ASCVD <55 <80 <70
CCB No No No risk including unstable angina
change change change after achieving LDL <70
Oral Contraceptives 2. Established clinical
- Alpha Inc 5-20 Inc 10- Inc to 15 Effects caused by cardiovascular dse in
monophasi 45 dec 15 reduced lipolytic patients DM, CKD or HeFH
cs activity or inc 3. History or premature
- Alpha Inc 10- Inc 10- Inc 5-10 VLDL synthesis; ASCVD (<55 male, <65
mainly caused by female)
triphasics 15 15
progestin Very high Established or recent <70 <100 <80
component, risk hospitalization for ACS,
estrogen alone is coronary, carotid or peripheral
protective vascular disease, 10 yr risk >
Glucocorticoid Inc 5-10 Inc 15- 20%, DM or CKD ¾ with one or
20 more risk factors, HeFH
Ethanol No Inc up Inc Marked elevation in High risk ≥2 risk factors and 10 year risk <100 <130 <90
change to 50 patients with 10-20%, DM or CKD ¾ with no
hypertriglyceridemia other risk factors
Isotretenoin Inc 5-20 Inc 50- Dec 10- Changes may Moderate ≤2 risk factors and 10 year risk <100 <130 <90
60 15 reverse 8 weeks risk <10%
after Low risk 0 risk factor <130 <160 NR
stopping the drug
Cyclosporine Inc 15- No No CLASSIFICATION OF ELEVATED TG LEVELS
20 change change
TG CATEGORY TG CONCENTRATION GOAL

(mg/dl)
CLASSIFICATION OF LDL-C LEVELS IN CHILDREN AND ADOLESCENT Normal <150
CATEGORY LDL-C (mg/dl) Borderline 150-199 <150
Acceptable <100 High mg/dl
Borderline 100-129 High 200-499
High ≥ 130 Very high ≥500

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 DRUGS USED FOR TREATMENT OF HYPERCHOLESTEROLEMIA ADVERSE EFFECTS
STATINS - Generally, well tolerated
o ATORVASTATIN - Mild GI disturbances (dyspepsia, flatus, constipation,
o FLUVASTATIN abdominal pain)
o LOVASTATIN - Headache or rash
o PITAVASTATIN - Elevation of creatinine kinase
o PRAVASTATIN - Myalgia (muscle pain: 2-11%)
o ROSUVASTATIN - Myopathy (muscle weakness)
o SIMVASTATIN - Rhabdomyolysis (muscle disintegration is rare (0.1%) &
* structural analogs of HMG-COA occurs primarily at high doses of drug: can lead to renal
failure and even death (8%)
MECHANISM OF ACTION - Fewer muscle effects are observed with pravastatin
- Inhibit 3-hydroxy-3-methylglutaryl-coA reductase, the key - Elevation on transaminase levels
rate limiting enzyme on hepatic cholesterol synthesis
- Upregulation of hepatic LDL receptor and increased LDL-C Rhabdomyolysis
clearance - Symptoms: fever, malaise, diffuse myalgia and/or tenderness,
marked elevation of serum creatine kinase and myoglobin
PRIMARY CLINICAL EFFECTS present in the urine
- Reduction in LDLs (20-60%) which is dose and drug specific - More common in patients with either acute/chronic renal
- Reduction in TAG (15-45%) failure, obstructive liver disease or hypothyroidism
- 5-10% increase in HDL - Can be observed with drug interaction especially INHIBITORS
OF CYP3A4 ex: cyclosporine, tacrolimus, gemfibrozil,
ADDITIONAL BENEFICIAL EFFECTS ketoconazole, HIV protease inhibitors
- Inhibit monocyte migration and adhesion to o fewer muscle effects are observed with Pravastatin
endothelium o elevation in transaminase levels
- Inhibit monocyte proliferation
- Inhibit oxidation of LDL DRUG INTERACTIONS
- Inhibit immune and inflammatory responses - All statins with the exception of Pravastatin are metabolized
- Stabilize atherosclerotic plaques in the liver by the CYP450 system
- Inhibitors of CYP450 enzymes: increase the
THERAPEUTIC USES concentrations of statin leading to increased risk of
- Drug of Choice for patients with high plasma LDL- C levels adverse effects such as myopathy and rhabdomyolysis
- Patients with familial hypercholesterolemia benefit much less - CYP3A4 inhibitors lead to elevated levels of Lovastatin,
because of defect on LDL receptor Simvastatin & Atorvastatin
- Drug of Choice for patients with high risk of cardiovascular - CYP3A4 inhibitors are associated with increased risk of
disease irrespective of plasma cholesterol levels rhabdomyolysis:
o Immune suppressants: cyclosporine and
PHARMACOKINETICS tacrolimus
- Directly taken up into the liver by a specific anion o Macrolide antibiotics: erythromycin, clarithromycin
transporter OATP2 o CCB: diltiazem, verapamil
st
- Extensive 1 pass extraction in the liver o Anti-arrhythmic: Amiodarone
- Metabolized by CYP3A4: Lovastatin, Simvastatin, o Azole: Itraconazole (Sporanox), Ketoconazole
Atorvastatin (Nizoral)
- Metabolized by CYP2C9: Fluvastatin and Rosuvastatin o Anti-coagulants: warfarin
- Pravastatin: metabolized via the cytochrome P450 o Anti-HIV: Amprenavir, Indinavir, Neflinavir, Ritonavir
pathway - Inhibitors of CYP2C9 increase the plasma concentration of
- T ½ Lovastatin, Simvastatin, Pravastatin & Fluvastatin: 1.5-2 Fluvastatin & Rosuvastatin.
hrs o Ex. Ketoconazole, Itraconazole, Metronidazole,
- T ½ Atorvastatin: 14 hrs Sulfinpyrazone
- T ½ Rosuvastatin: 19 hrs - Grapefruit juice in large amounts (>1L/day): increase
- ALL statins undergo GLUCORONIDATION in the liver plasma concentrations of Lovastatin, Simvastatin &
- Doubling the STATIN dose only results in a 5-6% further Atorvastatin via inhibition of CYP3A
decrease in LDL-C, while increasing potential toxicity - Drugs such as phenytoin, griseofulvin, barbiturates, rifampin
and thiazolidediones: increase expression of CYP3A4 which

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 can reduce plasma concentrations of Lovastatin, Simvastatin (~50% lower than a statin alone )
& Atorvastatin - cam be used to relieve pruritus (itching) due to accumulation
- Gemfibrozil inhibits metabolism of ALL STATIN drugs of bile acids in patients with biliary obstruction
(including pravastatin) by inhibiting statin glucorinidation; - Drug of Choice: hypercholesterolemia in children and
increases the risk of myopathy and rhabdomyolysis women of child bearing age who are lactating, pregnant or
- Gemfibrozil – inhibit the OATP2 transporter-mediated become pregnant
uptake of statins into the liver
PHARMACOKINETICS
CONTRAINDICATIONS - Not absorbed or metabolically in altered by the intestine
- Pregnancy: shown to induce birth defects - Totally excreted in the feces
- Patients with liver disease
- Patients taking Gemfibrozil – increased risk of myopathy and ADVERSE EFFECTS
rhabdomyolysis - GI disturbances: most common side effects. (Constipation,
bloating, epigastric fullness, nausea and flatulence)
BILE-ACID BINDING RESINS o (Colesevelam: less GI intolerance)
o CHOLESTYRAMINE - At high doses, Cholestyramine and Colestipol, but NOT
o COLESTIPOL Colesevelam can impair absorption of fat soluble vitamins:
o COLESEVELAM A, D, E, and K

MECHANISM OF ACTION DRUG INTERACTIONS
- acts as anion exchangers which bind bile acids/salts in the - Cholestyramine and Colestipol but not Colesevelam
small intestine preventing their absorption interferes with the intestinal absorption of many drug.
- Resin/bile acid complexes are excreted in the feces o Ex Tetracycline, Phenobarbital, digoxin, warfarin,
(~10-fold increase in excretion) paravastatin, fluvastatin, aspirin and thiazide diuretics.
- disrupts the normal enterohepatic recirculation (These drugs should be taken either 1-2 hours before or
of bile acids 4-6 hours after bile acid-binding resins)
- the reduced concentration of bile acids upregulated the
expression of cholesterol 7-a-hydroxylase (rate-limiting CONTRAINDICATIONS
enzyme in the synthesis of bile acids) promoting hepatic - Dysbetalipoproteinemia and raised Triglycerides (>400
conversion of cholesterol bile acids mg/dL) due to risk of further increasing Triglyceride levels
- this lowers the concentration of hepatic cholesterol thereby
increasing expression of LDL receptors (via activation of INHIBITORS OF INTESTINAL STEROL ABSORPTION
SREBP), which promotes the hepatic uptake of LDL from the o EZETIMIBE
plasma, resulting in an overall decrease in the plasma LDL
concentration MECHANISM OF ACTION
- decreased hepatic cholesterol can lead to increased - inhibits Niemann-Pick C1-like protein (NPC1L1) involved in
expression of HMG-CoA reductase, resulting in increased the absorption of both dietary and biliary cholesterol in the
hepatic cholesterol synthesis and the generation of small intestine
additional VLDLs à that can actually increase serum - reduction in hepatic cholesterol result in increased
triglyceride levels in patients with type III expression of LDL receptors, promoting increased LDL
dyslipoproteinemia clearance

PRIMARY CLINICAL EFFECTS PRIMARY CLINICAL EFFECTS
- modest 10-25% reduction in LDLs (less effective than - reduces LDL levels by ~18%
statins) - minimal effect on HDL and TAG
- increase in serum TAG by 3-10%
THERAPEUTIC USES
THERAPEUTIC USES - For patients with primary hypercholesterolemia
- SECOND LINE drugs used mainly for treatment of primary - Significant LDL lowering effects when combined with a
hyperlipidemias in the young (<25 yrs.) and in patients for statin: a further 25% decrease in LDL
whom statins do not effectively lower plasma LDL- - Ezetimibe together with statin allow lower dosing of statin
cholesterol drug, thereby avoiding potential statin- associated adverse
- can be used together with low dose statin in combination effects (ex. Rhabdomyolysis)
therapy to aggressively reduce serum LDL-C concentrations

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 PHARMACOKINETICS - 10-30% increase in HDL
- Rapidly absorbed by the enterocytes
- undergoes entero-hepatic recirculation several time/day THERAPEUTIC USES
- Lowers both plasma cholesterol and Triglycerides
ADVERSE EFFECTS - Treatment of familial combined hyperlipidemias
- Generally well tolerated &familial dysbetalipoprotenemia (elevation of both
- Flatulence is the most common Triglycerides and cholesterol)
- Diarrhea and myalgia can occur - Most Effective Agent in Elevating HDL Levels
- Low incidence of impaired liver function (reversible) - Often combined with other lipid lowering drug such as
statin or a resin
DRUG INTERACTION - Reduced the incidence of myocardial reinfarctions and
- Cyclosporine increases concentration of Ezetimibe overall mortality in patients with a history of previous MI
- Bile acid resins interfere with absorption of Ezetimibe and if - Use of niacin is often limited by poor tolerability
used concurrently should be taken several hours apart
PHARMACOKINETICS
CONTRAINDICATIONS - Administered orally
- Hypersensitivity to Ezetimibe - Converted in the body to nicotinamide & incorporated to
- patients with mild to severe hepatitis NAD+
- Pregnant women- due to insufficient studies - Excreted in the urine unmodified and as several
- Metabolites
DRUGS USED FOR HYPERTRIGLYCERIDEMIA
NIACIN (NICOTINIC ACID/ VITAMIN B3) ADVERSE EFFECTS
o NICOTINIC ACID/VITAMIN B3 - Skin flushing, itching (pruritus), and a sensation of warmth
(this prostaglandin-mediated effect can be diminished by
- Water soluble vitamin that at physiological concentrations is prior treatment with Aspirin or ibuprofen)
used in the synthesis of NAD and NADP - GI distress, nausea and abdominal pain
- Pharmacological effects of niacin require Large Doses (1500- - Inhibits tubular secretion of uric acid & therefore
3000 mg/day) and are independent of conversion to NAD & predisposes to hyperuricemia & gout (20% of patients)
NADP - May cause insulin resistance (generally reversible) &
hyperglycemia may be worsened in susceptible patients
MECHANISM OF ACTION ex. Type 2 DM
- Acts via its GI-coupled GPCR (GPR109A) expressed in adipose - Hepatic toxicity
tissue to inhibit CAMP-induced lipolysis (stimulated via the - Can exacerbate peptic ulcer
GS-coupled beta-adrenergic receptor) thus reducing the - Poor tolerability often limits the use of the drug
release of free FFA to the liver
- Decreased FFA in the liver causes reduced synthesis of CONTRAINDICATIONS
Triglycerides which in turn reduces production of VLDLs - Peptic ulcer disease
- Reduced VLDLs reduces production of LDL-C - Patients with a history of gout
- Increases the half-life of apoAI, the major apolipoprotein - Caution should be observed in diabetics
present in HDL, which increases plasma concentration of HDL - Caution should be observed in patients with impaired liver
and promotes reverse cholesterol transport function
- Reduces the levels of Lp(a) lipoprotein which is modified form
of LDL covalently coupled to the Lp(a) protein. FIBRATES
o The Lp(a) protein is homologous to plasminogen and is o FENOFIBRATE
found in atherosclerotic plaques, where it is thought to o GEMFIBROZIL
contribute towards atherosclerosis by antagonizing the
- derivatives of fibric acid
activation of plasminogen thereby inhibiting
- acts as ligands for nuclear hormone transcription factor:
thrombolysis.
peroxisome proliferator-activated receptors alpha (PPAR-a)
o Niacin is the ONLY lipid lowering drug to significantly

reduce the levels of Lp(a) lipoprotein
MECHANISM OF ACTION

- Activate PPAR-a, which leads to decrease plasma triglyceride
PRIMARY CLINICAL EFFECTS
concentrations by:
- 30-80% reduction in Triglycerides
o Increasing the expression of lipoprotein lipase in
- 10-20% reduction in LDLs
muscle, resulting in increased muscle lipolysis

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 (enhanced uptake & catabolism of Triglyceride-rich CONTRAINDICATIONS
lipoproteins) - Pregnant/lactating women
o Decreasing hepatic expression of apolipoprotein CIII (a - Severe hepatic dysfunction (due to increased risk of
known inhibitor of lipoprotein lipase), that enhances hepatic damage)
overall lipoprotein lipase activity leading to increased - Severe renal dysfunction
catabolism of TAG-rich lipoproteins - Pre-existing gallbladder disease
o Increasing the expression of genes involved in Fatty - Caution should be observed in patients taking STATIN
Acid transport and Fatty Acid oxidation in because of increased risk of rhabdomyolysis
hepatocytes (results in increased Fatty Acid
catabolism, thereby reducing hepatocyte DRUG INTERACTIONS
Triglyceride synthesis and decreasing the hepatic - Highly protein bound and can displace other protein-bound
production of VLDLs. drugs from albumin
o Increases plasma concentration of HDL by increasing - Potentiates the effects of oral anti-coagulants (ex.
the synthesis of apoAI and apoAII, the major warfarin) leading to increased risk of bleeding.
apolipoprotein found in HDL. (this promotes reverse (anticoagulant drug concentrations should be reduced by
cholesterol transport) 30% when given together with a statin)
o Upregulation of the SR-B1 scavenger receptor in - Enhances hypoglycemic effects of sulfonylureas
hepatocytes, which binds to HDL and promotes - Gemfibrozil increases the serum concentrations of
increased transfer of cholesterol from HLDLs to statins
hepatocytes, leading to increased secretion of - Gemfibrozil inhibits the transporter responsible for hepatic
cholesterol into the bile duct uptake of statins
- Gemfibrozil inhibits statin glucoronidation involved in
PRIMARY CLINICAL EFFECTS the metabolism and excretion of all statins
- 40-60% reduction in TAG - Fenofibrate does not affect statin metabolism and is
- Mild (10-20%) reduction in LDL therefore the doc for use with a statin in combination
- 10-20% increase in HDL therapy
- OVERALL EFFECT: - Renally excreted (drug concentrations are elevated in
o Increase peripheral VLDL clearance patients with renal insufficiency, thereby increasing the
o Decreased hepatic Tag production = decrease serum VLDL risk of drug interactions)

THERAPEUTIC USES FISH OILS
- Hypertriglyceridemia o OMEGA-3 LONG CHAIN POLYUNSATU RATED FATTY
- Severe hypertriglyceridemia at risk of pancreatitis and in ACIDS
those with low HDL-C
- Familial dysbetalipoproteinemia (type III - Polyunsaturated Fatty Acids
hyperlipoproteinemia) - a mixture of eicosapentaenoic acid and Docosahexanoic
- Long term use has been clinically proven to reduce the acids (Omacor/Lorvaza)
incidence of coronary events (22%), stroke (25%) and transient
ischemia events (59%) MECHANISM OF ACTION
- Unclear, but appear to involve the inhibition of hepatic
PHARMACOKINETICS Triglyceride synthesis & the increased Triglyceride clearance
- Completely absorbed after oral administration
- Distributed widely and are bound to serum proteins PRIMARY CLINICAL EFFECTS
- Undergo extra hepatic circulation - Lower serum Triglyceride levels by 50%
- Half-life for gemfribrozil is 1.5 hours and for fenofibrate is 20h - Minor increase in HDL
- Can increase LDLs in some individuals
ADVERSE EFFECTS
- Generally, well tolerated THERAPEUTIC USES
- Most common side effects: mild GI disturbances - Currently approved as an adjunct to diet and lifestyle
- Predisposition to gallstone formation due to increased interventions in the treatment of hypertriglyceridemia in
cholesterol excretion in the bile patients with Triglyceride levels >500 mg/dl
- Myopathy and rhabdomyolysis have been reported
especially when given with a statin ADVERSE EFFECTS
- Hepatitis - Fishy after taste

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 - GI: nausea, bloating, diarrhea, flatulence SUMMARY
- Reduces serum concentrations of vitamin E DRUGS USED FOR HYPERCHOLESTEROLEMIA
STATINS o ATORVASTATIN
DRUG INTERATIONS o FLUVASTATIN
- None o LOVASTATIN
- Unlike fibrates, fish oils are not associated with an increased o PITAVASTATIN
risk of rhabdomyolysis when given together with STATIN o PRAVASTATIN
o ROSUVASTATIN
PCSK9 INHIBITORS o SIMVASTATIN
o ALIROCUMAB
o EVOLUCUMAB BILE ACID BINDING RESINS o CHOLESTYRAMINE
o COLESTIPOL
- PCSK9, a protein that regulates the recycling of LDL o COLESEVELAM
receptors INHIBITORS OF INTESTINAL o EZETIMIBE
STEROL ABSORPTION
MECHANISM OF ACTION DRUGS USED FOR HYPERTRIGLYCERIDEMIA
- inhibit PCSK9 leading to reduced LDL receptors NIACIN o VITAMIN B3
FIBRATES o FENOFIBRATE
PRIMARY CLINICAL EFFECTS o GEMFIBROZIL
- reduces LDL level by approximately 60% when added to
maximum statin therapy FISH OILS o OMEGA-3 LONG CHAIN
- their strong efficacy in reducing LDL-C & possible synergistic POLYUNSATURATED
effects with statins, combined with a favorable safety profile FATTY ACIDS
PCSK9 INHIBITORS o ALIROCUMAB
and tolerability
o EVOLUCUMAB


THERAPEUTIC USES
- For highest risk individuals
- Individuals unable to reach LDL-C goals with maximally
tolerated statin dose
- Both indicated for individuals with HeFH
- As secondary prevention in individuals with clinical ASCVD
who require additional LDL-lowering therapy
- Evolocumab is also indicated for treatment of individuals
with HoFH

COMBINATION DRUG THERAPY
- LDL-cholesterol levels are not sufficiently reduced in high-risk
patients even with the highest dose of STATIN
- a STATIN + either a Resin, Ezetimibe or Niacin Synergistic
reduction of LDL- cholesterol with drug combination
o Both LDL and VLDL levels are elevated (ex. combined
hyperlipoproteinemia)
- STATIN + Niacin: more effective than either agent alone
- STATIN+ fibrate: in cases where Triglyceride and LDL are very
high. However, should be used with caution as increased risk of
myopathy especially with Gemfibrozil (Fenofibrate is preferred
drug in this case)
o When LDL or VLDL levels are not normalized with a single
drug regimen.
o When HDL deficiency co-exist with other hyperlipidemias
- Either Niacin or fibrate is added to increase HDL
o when VLDL levels are increased during treatment of
hypercholesterolemia with a bile acid- binding resin
- Niacin is added to control elevated VLDL levels
Notes from Pharma Manual Only

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