Pharmacy Care Application for antihyperlipidemic and diuretic drugs

Question 1

Antihyperlipidemics

Answer 1

Used in a wide variety of disease states:
- Cerebrovascular Disease (CVD)
- Coronary Heart Disease (CHD)
- Atherosclerotic Cardiovascular
- Disease (ASCVD)
- Acute Myocardial Infarction (AMI)
- Angina
- Stroke
- Diabetes

Question 2

STATIN

Chemical Nomenclature

Answer 2

Statins derive their name from molds or fungi
Available statins:
- A bunch with statin in their name (Rosuvastatin: most common)

Question 3

STATIN

Pharmacological Nomenclature

Answer 3

3-hydroxyl-3-methylglutaryl/Coenzyme A Reductase inhibitor (HMG CoA Reductase Inhibitors)
- HMG CoA reductase is the rate limiting enzyme in cholesterol synthesis
- By inhibiting this enzyme => compensatory increase in LDL receptors => stimulates LDL catabolism
- Additionally, they possess a pleiotropic effect
– Decreases inflammation at site of coronary plaque, inhibits platelet aggregation, and anticoagulant effects

Question 4

Cholesterol Reduction

Answer 4

Lowers low-density lipoproteins (LDL )
- Low-density lipoproteins (LDL) are referred to
as bad cholesterol

Lowers triglycerides (TG)
- Triglycerides (TG) are the main constituents of
body fat

Raises High-density lipoproteins (HDL)
- High-density lipoproteins (HDL) are referred
to as good cholesterol

Question 5

Long term benefits

STATIN

Answer 5

Targeting hypercholesterolemia
- Reduced risk of CHD
- Reduced risk of atherosclerosis, stenosis, strokes and MI: “Pleiotropic effect”
- Reduction of LDL-C
- Improvement of HDL-C

Statins with healthy lifestyle help patients regardless of cholesterol counts!
It is recommended patient stay on statins with co-morbid conditions if have ASCVD risk factors regardless of cholesterol levels

Question 6

STATIN

Therapeutic uses

Answer 6

Antihyperlipidemic drugs are used in a wide variety of disease states for primary & secondary prevention:
- Hypercholesterolemia
- Hypertriglyceridemia
- Cerebrovascular Disease (CVD)
- Coronary Heart Disease (CHD)
- Atherosclerotic Cardiovascular Disease (ASCVD)
- Acute Myocardial Infarction (AMI)
- Angina
- Stroke
- Diabetes

Question 7

STATIN

Adverse reactions, dosing and monitoring

Answer 7

Adverse drug reactions:
- Diarrhea
- Arthralgia
- Nasopharyngitis
- Insomnia
- Malaise
- Increased hepatic function tests

Dosing/Monitoring
- Pregnancy category X
- Statin should be administered before bedtime (except: Atorvastatin and Rosuvastatin (more side eff)
- Many interact with grapefruit
- Simvastatin can only be used at certain doses when used concurrently with CCBs

Question 8

Individual STATIN compounds

Answer 8

SimvaSTATIN (Zocor®)
PravaSTATIN (Pravachol®)
FluvaSTATIN (Lescol®)
AtorvaSTATIN (Lipitor®)
LovaSTATIN (Mevacor®)
RosuvaSTATIN (Crestor®)
PitaSTATIN (Livalo®, Zipitamag®)

Question 9

Combination STATIN products

Answer 9

Advicor® - lovastatin + niacin ER
Simcor® - simvastatin + niacin ER
Vytorin® - simvastatin + ezetimibe (most common)

Question 10

CHOLES

Chemical Nomenclature

Answer 10

All contain the prefix “Choles-”
Available on the market:
- Cholestyramine (Questran®)
- Cholestipol (Colestid®)
- Cholesevelam (Welchol®)

There is no combination products and all come in powder packets

Question 11

CHOLES

Pharmacological Nomenclature

Answer 11

Bile acid sequestering agent
Mechanism of action: Forms a non-absorbable complex with bile acids and releases chloride ions in the process
- Inhibits reuptake of intestinal bile salts and increases fecal loss of LDL-C

Mainly decreases LDL-C, with lesser effect on other cholesterol

Question 12

CHOLES

Therapeutic uses

Answer 12

FDA approved:
- Dyslipidemia

Off-label: Main use
- Chronic diarrhea due to bile acid malabsorption
- Hyperthyroidism
- Pruritus associated with cholestasis

Question 13

CHOLES

Adverse reactions, dosing and monitoring

Answer 13

Adverse reactions:
- Abdominal pain
- Constipation
- Flatulence
- Abnormal hepatic function tests
- Myalgias
- Osteoporosis

Interactions/monitoring
- Warfarin – monitor for decreased INR
- Statins/fibrates – monitor for increased incidence of myalgias
- Amiodarone– may decrease availability/effectiveness of amiodarone

Question 14

Fibrate

Chemical Nomenclature

Answer 14

All contain “–fibr-”
Available on the market:
- Gemfibrozil (Lopid®)
- Fenofibrate (TriCor®)
- Fenofibric Acid (Trilipix®)

Question 15

Fibrate

Pharmacological Nomenclature

Answer 15

Fibric acid derivatives

MOF: Exact mechanism is unknown: In theory, inhibits lipolysis and decreases hepatic fatty reuptake as well as inhibit secretion of VLDL

Very good triglyceride lowering agents: Also decrease LDL and increase HDL

Question 16

Fibrate

Therapeutic Use

Answer 16

FDA approved:
- Hypertriglyceridemia
- Hypercholesterolemia
Off-label:
- Primary biliary cholangitis

Question 17

Fibrate -

Adverse reactions, dosing and monitoring

Answer 17

Adverse reactions:
- Increased serum transaminases
- Abdominal pain
- Abnormal hepatic function tests
- Myalgias

Interactions/monitoring:
- All can increase incidence of myalgias when combined with statins
- Gemfibrozil has several drug-drug interaction that
are contraindications
– All statins, ezetimibe, any CYP2C8 substrates (many
antiretrovirals): Also use with caution in patient on warfarin

Question 18

OCUMABS

Answer 18

PCSK-9 inhibitors
- Mechanism of action: Human monoclonal antibodies that aid in clearance of LDL (lower LDL primarily)

Counseling points: Rotate injection sites, injections are given in the thigh, belly, or upper arm

Two agents available:
- Alirocumab (Praluent®) – 75mg/mL, 150 mg/mLpen injectors
- Evolocumab (Repatha®) – 140 mg/mL syringe

Relatively newer medications and place in
therapy in not completely known currently

Question 19

Miscellaneous antihyperlipidemics

Niacin (nicotinic acid, Vitamin B3)

Answer 19

MOF: Not fully understood, potentially related to
inhibition of release of free fatty acids from adipose tissue

Adverse reactions: flushing, pruritus, GI distress, vomiting, diarrhea, hepatotoxicity

Clinical pearls: Different products of niacin are not
interchangeable

Increases HDL while lowering LDL and TG

Question 20

Miscellaneous antihyperlipidemics

Omega-3 polyunsaturated Fatty acids

Answer 20

MOF: Reduction in hepatic production of TG-rich very low-density lipoproteins + reduction in hepatic synthesis of TG

Adverse reactions: Diarrhea, nausea, fishy burps

Available products:
- Lovaza® – high grade fish oil
- Vascepa® – Icosapent Ethyl

Clinical Pearls: Primarily used in hypertriglyceridemia secondary to its effect lowering of TG after other 1st line options

Question 21

Ezetimibe (Zetia®)

Answer 21

MOA: cholesterol absorption inhibitor at the brush border of the small intestine

Adverse reactions: Diarrhea, arthralgia, fatigue, increased serum transaminases

Clinical pearls:
- Generally used as adjunctive therapy with statins
or in addition to dietary changes
- Works primarily lowering LDL but also slightly
lowers TG and raises HDL

Question 22

Bempedoic Acid (Nexletol®)

Answer 22

Mechanism of action: adenosine triphosphate- citrate lyase (ACL) inhibitor which lower LDL by inhibiting synthesis in the liver
- Enzyme upstream of HMG CoA reductase

Adverse reactions: abdominal pain, arthralgias,
gout, increased serum transaminases

Clinical pearls:
- Generally used as adjunctive therapy with statins or in addition to dietary changes
- Works primarily lowering LDL
- Also available in a combo product with ezetimibe
(Nexlizet®)
- Marketed as the alternative for patients with statin
induced myalgias

Question 23

Inclisarin (Leqvio®)

Answer 23

Mechanism of action: Utilizes the RNA interference mechanism and directs catalytic breakdown of mRNA for PCSK-9
- Increase LDL receptor recycling and uptake

Adverse reactions: antibody development, injection site reactions, arthralgias, bronchitis

Clinical pearls:
- Generally used as adjunctive therapy with statins
or in addition to dietary changes
- Works primarily lowering LDL
- Works through patient’s medical insurance instead
of Rx insurance
New to the market in 12/2021

Question 24

PIB

Answer 24

Not currently on the market for use

Potentially promising category of drugs
- Mechanism: inhibits cholesterol ester transfer protein resulting in increases in HDL and decreasing LDL

Currently in the pipeline:
- Torcetrabpib
- Anacetrapib
- Evacetrapib

Question 25

Diuretics

Answer 25

General clinical pearls:
- Thiazides are 1st line therapy for HTN
- Loop diuretics are first line for fluid management in CHF and other disorders with fluid retention such as
cirrhosis
- K-sparing diuretics are primarily indicated in patient with systolic CHF
- Osmotic diuretics are generally used for intracranial
pressure reduction not hypertension

Off label:
- Calcium nephrolithiasis
- Diabetes Insipidus
- Osteoporosis

Question 26

Hypertension classifications

Answer 26

HTN is a major risk factor for CV and renal disease
- Only about 35-40% of Americans with HTN are controlled
- Normal BP: systolic (SBP) < 120 mmHg AND diastolic (DBP) < 80 mmHg
- Elevated BP: SBP – 120-129 mmHg or DBP > 80 mmHg
- Stage 1 HTN – SBP 130-139 mmHg or DBP – 80-89 mmHg
- Stage 2 HTN – SBP > 140 mmHg or DBP >
90 mmHg

Question 27

THIAZIDE - Chemical Nomenclature

Answer 27

THIAZIDE is a chemical reference to these S- containing synthetic compound, with some structure similarities to sulfonamides

Available thiazide diuretics:
- ChloroTHIAZIDE (Diuril®)
- HydrochloroTHIAZIDE (HydroDiuril®)
- Chlorthalidone (Hygroton®)
- Metolazone (Zaroxlyn®)

Question 28

THIAZIDE - Pharmacological Nomenclature

Answer 28

Mechanism of action: Inhibits reabsorption in the distal convoluted tubules causing increased excretion of sodium, potassium and water
- Block reabsorption of Na+ and Cl- increasing their excretion
- Also decrease Ca2+ excretion

Question 29

THIAZIDE - Therapeutic uses

Answer 29

FDA approved:
- Hypertension (HTN)
- Fluid retention in HF (mild)
- Edema

Clinical Pearl:
- Considered one of the 1st line options for the management of HTN
- Metolazone is the exception and is used in our CHF
patients to assist in fluid management

Question 30

THIAZIDE Adverse reactions, dosing and monitoring

Answer 30

Adverse drug reactions:
- Orthostatic hypotension
- Dizziness
- Photosensitivity
- Hyponatremia
- Hyperuricemia
- Leg cramps

Dosing/Monitoring
- Monitor patient closely if they are concurrently using dofetilide or lithium

Question 30

THIAZIDE Adverse reactions, dosing and monitoring

Answer 30

Adverse drug reactions:
- Orthostatic hypotension
- Dizziness
- Photosensitivity
- Hyponatremia
- Hyperuricemia
- Leg cramps

Dosing/Monitoring
- Monitor patient closely if they are concurrently using dofetilide or lithium

Question 31

Loop diuretic: Chemical/Pharmacological
Nomenclature

suffix “–semide”

Answer 31

Mechanism of action: Inhibits reabsorption of sodium and chloride in the ascending loop of Henle which causes its natriuretic effect

Adverse reactions and cautions are similar to the thiazide diuretics

Clinical Pearl: Primarily used for fluid management and as alternative agents for HTN
Furosemide (Lasix®)
Torsemide (Demadex®): no IV
Bumetanide (Bumex®)