Foundations Quiz 3 (L9 + L10 + L11)

L9

chronic hypertension therapies

• 1st line → ACEi, ARB, thiazide, CCB

• 2nd line → beta-blockers

• resistant htn → alpha blockers

  • used for management of benign prostate hyperplasia (BPH) and some off-label indications

-lol, -olol, -alol, -ilol chemical nomenclature

aryloxypropanoloamines; multi-ring structures

-lol, -olol, -alol, -ilol pharmacologic nomenclature

beta-adrenergic receptor blockers (beta-blockers)

• act at beta-receptors located in various organs in the body

beta1 receptors

catecholamines (norepinephrine) binds to beta1 receptors and cause inc cardiac automaticity and conduction velocity = inc heart rate

• release renin which leads to bp elevation

• more likely located on cardiac muscles, but not exclusively

beta2 receptors

cause relaxation of smooth muscles such as in the lungs

• peripheral vasodilation

• skeletal muscle stimulation (tremors)

• work primarily in the pulmonary tissue and the periphery

alpha1 receptor

• bronchodilation and vasoconstriction effects

• some beta-blockers exhibit alpha-blocking properties

  • labetalol

  • carvedilol

• mixed alpha1/beta-blockers

beta-blocker mechanism of action

• dec BP by competitively blocking both beta1 and beta2 adrenergic receptors

  • results in dec HR and myocardial contractility

• some block alpha1 receptors

  • dec peripheral vasoconstriction (lowers BP)

• intrinsic sympathomimetic activity (ISA)

  • partially stimulate beta receptors while blocking catecholamines

  • do not lower HR to the same degree as other beta-blockers

cardio-selective beta blockers

target beta1 receptors preferentially

• most become more non-selective in nature at higher doses

• cause a larger effect on HR

• have a smaller effect on BP

**does not always correlate w what the specific beta-blockers are used for

non-cardio selective beta blockers

do not lower HR as much as selective beta-blockers

• cause more BP lower by either alpha-blocking properties or NO vasodilation

• can cause bronchoconstriction

  • must be avoided in patient w a history of asthma

  • used w caution in patients w COPD

**does not always correlate w what the specific beta-blockers are used for

beta-blocker therapeutic indications

2nd line treatment for htn unless patient has another indication req it such as

• angina pectoris (help inc O2 supply)

• cardiac arrhythmias (atrial fibrillation)

• myocardial infarctions

• migraine prophylaxis

• heart failure

• tremors

beta-blocker contraindications

• 2nd or 3rd degree AV block or sick sinus syndrome

• cardiogenic shock

• cardiac failure/decompensation

beta-blocker warnings

• caution in patients w diabetes (mask signs of hypoglycemia)

  • except sweating

• use caution w brochospastic diseases

• peripheral vascular disease

• CNS depression

• use in acute decompensated heart failure

beta-blocker ADR/side effects

• bradycardia

• hypotension

• fatigue

• dizziness

• depression

• dec libido

• impotence

beta-blocker drug interactions

• diltiazem/verapamil

• digoxin

• carvedilol, metoprolol, and propranolol are major substrates of CYP2D6

• carvedilol and propranolol are inhibitors of p-gp

  • cyclosporine, dabigatran, digoxin, ranolazine

• diabetes medications

beta-blocker counseling points

• do not abruptly discontinue beta-blockers after using for extended period of time

  • can lead to rebound tachycardia

• taper beta-blockers slowly to avoid rebound effects

• if symptoms of HF appear (SOB, dyspnea, swelling of ankles)

• masks signs of hypoglycemia

  • pt will still have sweating and hunger

non-selective beta-blockers examples

cardio-selective beta-blockers examples

mixed non-selective and alpha1 blockers

ophthalmic beta-blockers

indication → glaucoma

-darone examples

amiodarone indications

• antiarrhythmic agent used for ventricular arrhythmias

  • non-sustainted verticular tachycardia (VT)

  • sudden cardiac arrest due to ventricular fibrillation/pulseless VT

• off label

  • pharmacological cardioversion in atrial fibrillation (Afib)

  • maintenance of sinus rhythm

  • prevention of post operative atrial arrhythmias

• dose used is dependent on the type of arrhythmias being treated

  • lower doses are generally used for atrial arrhythmias (paroxysmal Afib)

amiodarone mechanism of action

**** 24

L11

hyperlipidemia

condition caused by an inc amt of lipids (fat) in the body

• lipids deposit on the side of the artery wall

  • narrows the artery, which impacts blood flow and cause complete blockage

  • plaque can rupture and cause platelet aggregation and form a clot

cholesterol

• LDL (low-density lipoproteins)

• TG (triglycerides)

• HDL (high-density lipoproteins)

low-density lipoproteins (LDL)

“bad cholesterol”

• stores cholesterol in arteries, which can lead to plaque and blockage

Triglycerides (TG)

main component of body fat

high-density lipoproteins (HDL)

“good cholesterol”

• removes cholesterol from the blood and carries it back to the liver

anti-hyperlipidemics

medications used to lower lipids (fats) in many disease states:

• cerebrovascular disease (CVD)

• coronary heart disease (CHD)

• atherosclerotic cardiovascular disease (ASCVD)

• acute myocardial infarction (AMI)

• angina

• stroke

• diabetes

-Statins examples

derived from molds and fungi

-statin combination products

-statin mechanism of action

HMG CoA Reductase Inhibitors

• HMG CoA Reductase → rate-limiting enzyme in cholesterol synthesis

• limiting it leads to a compensatory inc in expression of LDL receptors, which stimulates LDL catabolism

• pleiotropic effect

cholesterol reduction

• dec LDL

• dec TG

• inc HDL

pleiotropic effect

dec inflammation at the site of coronary plaque, inhibits platelet aggregation, and has anticoagulant effects

-statins indication

hypercholesterolemia

• reduced risk of CHD

• reduced risk of atherosclerosis, stenosis, strokes, and MI

• reduction of LDL

• improvement of HDL

recommended for patients to stay on statins w co-morbid conditions if they have ASCVD risk factors, regardless of cholesterol levels

-statin therapeutic uses

antihyperlipidemic drugs used for primary and secondary prevention

• hypercholesterolemia

• hypertriglyceridemia

• cerebrovascular disease (CVD)

• coronary heart disease (CHD)

• atherosclerotic cardiovascular disease (ASCVD)

• acute myocardial infarction (AMI)

• angina

• stroke

• diabetes

-statin adverse effects

• arthralgia (joint pain)

• myalgia (muscle pain)

• inc hepatic function tests

• diarrhea

• nasopharyngitis

• insomnia

  • malaise

-statin dosing/monitoring

• pregnancy category X

• administered before bedtime

  • exception: atorvastatin, rosuvastatin

• if myalgia → try diff statin as they have diff rates of lipophilicity, leading to diff rates of myalgias

• many interact w grapefruit

• simvastatin can only be used at certain doses when used w CCBs

-statin intensity

choles- examples

bile acid sequestrants

choles- mechanism of action

• forms a non-absorbable complex w bile acids and releases Cl ions in the process

• inhibits reuptake of intestinal bile sals and inc fecal loss of LDL

cholesterol reduction

• dec LDL

choles- therapeutic uses

• dyslipidemia

• diabetes (colesevelam only)

• off label

  • chronic diarrhea due to bile acid malabsorption

  • hyperthyroidism

  • pruritus associated w cholestasis

choles- adverse effects

• myalgias

• constipation

• abdominal pain

• flatulence

• abnormal hepatic function tests

• osteoporosis

choles- dosing/monitoring

• DDI

  • warfarin → monitor for dec INR

  • statins/fibrates → monitor for inc incidence of myalgias

  • amiodarone → may dec availability/effectiveness of amiodarone

-fibr- examples

fibrates; fibric acid derivatives

-fibr- mechanism of action

• not well understood

• theoretical → inhibits lipolysis and dec hepatic fatty reuptake as well as inhibit secretion of VLDL (very low-density lipoprotein)

cholesterol reduction

• dec LDL

• dec VLDL

• dec TG

• inc HDL

-fibr- therapeutic uses

• hypertriglyceridemia

• hypercholesterolemia

• off label

  • primary biliary cholangitis

-fibr- adverse effects

• myalgias

• inc serum transaminases

• abdominal pain

• abnormal hepatic function tests

-fibr- dosing/monitoring

• inc risk of myalgia when used in combo w statins

• gemfibrozil has DDIs that are contraindicated

  • all statins

  • ezetimibe

  • any CYP2C8 substrates (many antiretrovirals)

  • use in caution in patients on warfarin

-ocumab examples

PCSK-9 inhibitors

-ocumab mechanism of action

• human monoclonal antibodies that aid in clearance of LDL

• PCSK-9 inhibitors

cholesterol reduction

• lotta dec LDL

-ocumab adverse effects

• pain/redness at injection site

• flu or flu-like symptoms

-ocumab counseling points

• rotate injection sites - thigh, belly, upper arm

Enlicitide (Lipfendra) - 20 mg tablets

• only oral agent in class

• PCSK-9 inhibitor

• FDA approved 07/2026 - very recently

• adverse effects

  • dizziness

  • diarrhea

Lerodalcibep-liga (Lerochol) - 300 mg/1.2 mL syringes

• once monthly injection

• PCSK-9 inhibitor

• FDA approved 02/2026

• adverse effects

  • pain/redness at injection site

  • flu or flu-like symptoms

niacin (nicotinic acid, vit B3) mechanism of action

• not fully understood

• theoretical → inhibits free fatty acid release from adipose tissue

cholesterol reduction

• dec LDL

• dec TG

• inc HDL

niacin (nicotinic acid, vit B3) adverse effects

• flushing

• pruritis

• GI distres

• vomiting

• diarrhea

• hepatotoxicity

niacin (nicotinic acid, vit B3) notes

diff products of niacin are NOT interchangeable - IR vs ER

omega-3 fatty acids examples

omega-3 fatty acids mechanism of action

reduces hepatic production of VLDL and reduces hepatic synthesis of TG

cholesterol reduction

• dec VLDL

• dec TG

omega-3 fatty acids notes

• inc risk of bleeding

• second-line therapy for hypertriglyceridemia

omega-3 fatty acids adverse effects

• diarrhea

• nausea

• fishy burps

ezetimibe (zetia) mechanism of action

cholesterol absorption inhibitor at the brush border of the small intestine

cholesterol reduction

• dec LDL

• dec TG

• inc HDL

ezetimibe (zetia) adverse effects

• diarrhea

• myalgia

• arthralgia

• fatigue

• inc transaminases

ezetimibe (zetia) notes

generally used in combo w statin or in addition to dietary changes

bempedoic acid (nexletol) mechanism of action

adenosine triphosphate-citrate lyase (ACL) inhibitor, which lowers LDL by inhibiting LDL synthesis in liver

• enzyme upstream of HMG CoA reductase

cholesterol reduction

• dec LDL

bempedoic acid (nexletol) adverse effects

• gout

• abdominal pain

• arthralgias

• inc transaminases

bempedoic acid (nexletol) notes

• generally used in combo w statins or in addition to dietary changes

• also available in combo product w ezetimibe (nexlizet)

• marketed as an alternative to patients who cannot tolerate statins due to myalgias

inclisarin (leqvio) mechanism of action

utilizes the RNA interference mechanism and directs the catalytic breakdown of mRNA for PCSK-9

• inc LDL receptor recycling and reuptake

cholesterol reduction

• dec LDL

inclisarin (leqvio) adverse effects

• antibody development

• injection site reactions

• arthralgias

• bronchitis

inclisarin (leqvio) notes

• generally used in combo w statins or in addition to dietary changes

• approved in 12/2021

• works thru the patient’s medical insurance instead of RX insurance

-pib examples

• none are currently available on the market

• obicetrapib → in the pipeline currently

-pib mechanism of action

inhibits cholesterol ester transfer protein (CETP) resulting in an inc in HDL and a dec in LDL

cholesterol reduction

• dec LDL

• inc HDL

hypertension

• condition caused by inc pressure in the blood vessels

  • arterial walls are damaged, which causes thickening

  • thickening walls dec diameter of the blood vessel for blood flow

• only 35-40% of Americans w htn are controlled

• htn is a major risk factor for CV and renal disease

hypertension classifications

diuretics

“water pills”

• causes higher excretion of sodium and water

diuretics therapeutic use

• thiazides → 1st line therapy for htn

• loop diuretics → 1st line for fluid management in chronic heart failure (CHF) and other disorders w fluid retention such as liver cirrhosis

• K-sparing diuretics → patients w systolic CHF

• osmotic diuretics → intracranial pressure reduction not htn

• off label

  • calcium nephrolithiasis

  • diabetes insipidus

  • osteoporosis

-thiazide examples

not all have the same suffix

-thiazide chemical name

sulfur containing synthetic compounds w structural similarities to sulfonamides

-thiazide mechanism of action

inhibits reabsoprtion in the distal convoluted tubule, causing inc excretion of sodium, potassium, and water

• blocks reabsorption of Na and Cl inc their excretion

• dec Ca excretion

-thiazide indications

• hypertension

• fluid retention in HF (mild)

• edema

-thiazide notes

• 1st line therapy for htn

  • exception: metolazone (used more for fluid retention in HF)

-thiazide adverse effects

• photosensitivity

• orthostatic hypotension

• dizziness

• hyponatremia

• hyperuricemia

• leg cramps

-thiazide dosing/monitoring

monitor patient closely if they are concurrently using dofetilide or lithium

-semide examples

loop diuretics

-semide mechanism of action

inhibits reabsorption of sodium and chloride in the ascending loop of Henle, which causes its natriuretic effect

-semide adverse effects

• photosensitivity

• orthostatic hypotension

• dizziness

• hyponatremia

• hyperuricemia

• leg cramps

-semide notes

primarily used for fluid retention and as an alternative agent for HTN

K+ sparing diuretics examples

K+ sparing diuretics mechanism of action

competes w aldosterone for receptor sites in the distal renal tubules, inc sodium and chloride excretion while preserving potassium

K+ sparing diuretics adverse effects

• photosensitivity

• orthostatic hypotension

• dizziness

• hyponatremia

• hyperuricemia

• leg cramps

• gynecomastia

K+ sparing diuretics notes

typically used for congestive heart failure management or resistant HTN