Foundations Exam 2 (L9 - L17)

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

• relates to bp

**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

• found in blood vessels

• some beta-blockers exhibit alpha-blocking properties - mixed alpha1/beta-blockers

  • labetalol

  • carvedilol

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; affect heart; more effect on heart rate

• 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

  • or COPD

• 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

• propranolol

• timolol

• nadolol

• pindolol

**cardio-selective beta-blockers examples

**mixed non-selective and alpha1 blockers

• carvedilol

• labetalol

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

• class III antiarrhythmic

• inhibits adrenergic alpha and beta receptors

• affects Na, K, and Ca channels

  • prolongs action potential and refractory period

  • dec AV conduction and sinus node functions

• t ½ = 40-55 days - long

**amiodarone side effects

• seen after patient is on for extended period of time

• affects several systems

  • pulmonary - fibrosis, pneumonitits

  • thyroid - hypo/hyperthyroidism - has iodine in structure

  • ophthalmic - blurred vision, visual halos

  • gastrointestinal - anorexia, nausea, vomiting

  • cardiovascular - hypotension, bradycardia, QT prolongation

  • dermatologic - photosensitivity

  • hepatic - abnormal LFTs

  • no renal toxicity

**amiodarone BBW

• hepatotoxicity

• pulmonary toxicity

• ability to worsen arrhythmias

• use should be limited to pt w life-threatening arrhythmias

amiodarone drug interactions

• drugs that prolong QTc (fluoroquinolones, macrolides)

• warfarin

• substrate - CYP3A4, CYP2C8

• inhibits - CYP2C9, CYP2D6, CYP3A4 (grapefruit juice)

amiodarone examples

**dronedarone

• class III antiarrhythmic for reducing risk of cardiovascular hospitalization

• for pt w paroxysmal or persistent atrial fibrillation or atrial flutter w recent episode

• associated risk factors → age > 70, HTN, diabetes, prior stroke

• structurally similar to amiodarone, but lacks iodine moiety

**dronedarone warnings

• slightly better side effect profile vs amiodarone

  • lacks thyroid toxicity - bc no iodine

  • other side effects are similar

**dronedarone BBW

• inc risk of death when used w patients w class III or IV congestive heart failure (CHF)

• inc risk of death in patients w chronic atrial fibrillation

-(z)osin chemical classification

• quinazolines (piperazine ring and acyl moiety)

• aryl sulfonamides

**-(z)osin pharmacologic classification

• alpha blockers

  • alpha1 - adrenergic receptor blockers on smooth muscle cells of peripheral vasculature

    • dec BP by vasodilation and tot peripheral resistance

    • inc urine flow and dec frequency in BPH bc alpha1 receptors on prostate

  • alpha1a - adrenergic receptor blockers

**-(z)osin indications

• hypertension

• benign prostatic hyperplasia (BPH) - only alpha1a blockers

**-(z)osin warnings and side effects

• priapism (esp w alpha 1a blockers) - rare but serious ADR resulting in painful, prolonged penile erection, leading to permanent impotence if not treated asap

• orthostatic hypotension

• retrograde ejaculation

• nasal congestion, dizziness, tiredness

• sulfonamide allergy (tamsulosin)

-(z)osin examples

-asteride chemical classification

4-azasteroids - synthetic steroid-like structures

**-asteride pharmacologic classification

• androgen hormone inhibitors/ 5 alpha-reductase inhibitors

• competitively inhibit type II 5-alpha reductase → inhibits reduction of testosterone to dihydrotestosterone

**-asteride indications

• benign prostatic hyperplasia (BPH)

• alopecia

**-asteride warnings

• pregnancy category X - contraindicated

• use w care in patient who have diminished urinary flow (obstructive uropathy)

• use w caution in patient w hepatic insufficiency

• not indicated in US for prevention of prostate cancer

-asteride examples

L10

glucocorticoid

• protein, lipid, and CHO metabolism

• brain excitability

• inflammation

• ex: cortisol

mineralocorticoid

• water and electrolyte balance

• ex: cortisol, aldosterone

**steroid therapy

used in many types of disease; corticosteroids are everywhere

ex: leukemias, RA, asthma, etc.

**glucocorticoid activity

• convert protein into CHO (hepatic gluconeogenesis) & dec in uptake of glucose in peripheral tissues

  • may inc glucose levels and worsen diabetes management

• lipolysis

  • may cause hypertriglyceridemia

• redistribution of body fat to upper trunk and face from extremities

  • may cause moon face appearance; accumulation of fat around shoulders

• inc in gastric acid secretion and blood flow to gastric mucosa

  • inc risk of peptic ulceration

• inc in growth hormone secretion

  • inc growth

• potentiation of catecholamines and inc in synthesis of epinephrine from NE

  • inc HR and BP

• modulation of bone cell function

  • can lead to osteoporosis and fractures w longer term use

• influence on brain excitability and patterns

  • influenced mood and behavior, mania or psychosis

• dec eosinophils, monocytes, and basophils; inhibition of recruitment of neutrophils and monocytes; death of B cells and dec in production of antibodies and complement system components

  • immunosuppression, inc risk of infection

**mineralocorticoids activity

• endogenous mineralocortioid = aldosterone

• inc in sodium reabsorption in distal convoluted tubule

  • inc water retntion

• inc in potassium and H renal excretion

  • hypokalemia and metabolic alkalosis

Cushing’s syndrome

excess corticosteroid concentration

• due to excess corticosteroid secretion

• latrogenic disease due to high dose, long-term steroid use

symptoms

• high hp

• weight gan

• fat redistribution - moon face

• hyperglycemia

• osteoporosis

• irritability

• susceptibility to infection

effects of long-term corticosteroid

dec in ACTh production from anterioir pituitary due to suppression

natural feedback look

• get vit D and calcium supplements

• for GI bleed prevention

  • high dose AND on of the following (old age, history of GI ulcer, usage w anticoagulants (warfarin, asprin, aspirin, clopidegral, ibuprofen, naproxen)

  • treatment → PPI

**tapering of steroids to prevent adrenal insufficiency

• if starting at a high dose >20 mg prednisone equivalent and prolonged duration of therapy > 2 weeks

• slow, controlled withdrawal of medication

**short-acting steroid meds

• hydrocortisone

• cortisone acetate - equal glucocort. and mineral. potency

**intermediate-acting steroid meds

• prednisone

• prednisolone

• methylprednisolone

• fludrocortisone - only mineral. potency

• triamcinolone - only glucocort. potency

**long-acting steroid meds

• dexamethasone - only glucocort. potency

• betamethasone - only glucocort. potency - use for childen

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 warnings and 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

only high-intensity (lowers LDL > 50%)

• atorvastatin

• rosuvastatin

only low-intensity (lowers LDL < 30%)

• lovastatin

• simvastatin

• pravastatin

• fluvastatin

• pitavastatin

all used for moderate-intensity (lowers LDL 30-49%)

**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; subQ injection; monoclonal antibodies

**-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 (stomach), upper arm, hip, buttocks

Enlicitide (Lipfendra) - 20 mg tablets

• only oral agent in class

• PCSK-9 inhibitor - dec LDL

• 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 - dec LDL

• FDA approved 02/2026

• adverse effects

  • pain/redness at injection site

  • flu or flu-like symptoms

**PCSK-9 inhibitors

• alirocumab

• evolocumab

• Enlicitide

• Lerodalcibep-liga

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