Pharm II final exam (female and male repro, heart meds)

Estrogen adverse effects and CI

Adverse effects

- Endometrial hyperplasia and cancer -> give progestin to reduce risk

- breast cancer

- breast tenderness

- CV thrombotic events

- HTN

- peripheral edema

- gallbladder disease and cholestatic jaundice

- headache, migrains

- nausea

- chloasma -> facial discoloration

Contraindications

- Hx of DVT, PE, MI, stroke

- pregnancy

- vaginal bleeding w/out known cause

- liver disease

- ER positive breast cancer

- estrogen dependent cancer

Progestin adverse effect

Adverse effects

- breast tenderness, HA, arthralgias

- sleepiness

- decrease production of cervical mucus

- involution of endometrial layer (thinning) -> spotting, breakthrough bleeding, irregular menses

- in combo w/ estrogen -> increases risk of breast cancer in postmenopausal women

Menopausal hormone therapy

Low dose of estrogen (17-beta estradiol commonly)

Two regimens:

- estrogen alone (ET)

- estrogen + progestin (EPT) -> for pt w/ a uterus

Estrogen -> control menopausal symptoms

- less: hot flashes, urogential atrophy, osteoporosis

- enhanced: sleeping, libido, cognition, mood

- DO NOT give unopposed estrogen to pt w/ intact uterus

Progestin -> counterbalance estrogen-mediated stimulation of the endometrium

- decrease risk of endometrial hyperplasia/cancer

- DO NOT prescribe for pts w/ hysterectomy

Routes of administration for ERT

Oral -> most commonly used route

- needs higher dose than transdermal bc undergoes first-pass metabolism

- higher risk: dyslipidemia, venous thromboembolism, GI side effects

Transdermal -> emulsion, spray, gels, patches

Advantages

- total dose of estrogen is greatly reduced

- less N/V, lower risk for DVT, PE, Stoke

- blood levels of estrogen fluctuate less

Preferred for women with:

- history of VTE

- migrain w/ aura

- elevated triglycerides

- gallbladder disease

Recommendations for MHT

Ideal candidates: healthy, symptomatic women

- age: younger than 60yr OR within 10 yrs of menopause

- risk of complications is lower when used for ~ 5 yrs

- NOT for women over 60 starting MHT for first time

- women w/ multiple risk factors should consider diff therapy

Lowest effective dose for shortest duration necessary

- standard: 5 yrs and not beyond age 60

- recommended non-HT if symptoms persist

Menopausal symptom management

Vasomotor symptoms (hot flashes)

HT is most effective

- but some women are too high risk

Alternatives:

Selective serotonin reuptake inhibitors (SSRIs)

- escitalopram, citalopram, paroxetine (if not using tamoxifen)

Gabapentin

CBT

Genitourinary syndrome of menopause -> dryness, irritation, uncomfortable intercourse

Estrogen is most effective

- topical estrogen is best choice if this is pts ONLY symptom

- options: creams, inserts, rings

Gender affirmation dug therapy for transgender females

Goal: promote development of physical changes that match her gender identity

Medications:

Hormonal therapy

- estrogen: 17-beta estradiol

Testosterone suppression: if testes are present

- spironolcatone

- GnRH agonist (leuprolide)

Monitoring:

Estrogen levels

- physiologic female range

Serum total testosterone

- suppress to female range

Using spironolactone

- serum potassium

Breast cancer screening

Prostate screenings

Combination oral contraceptives (MOA and CI)

Estrogens used: ethinyl estradiol, estradiol

Progestins used: norethindrone, levonorgestrel, norgestrel

MOA: inhibiting ovulation, reduces fertility

- thickens cervical mucus

- alters endometrial lining

Estrogen

- suppresses release of follicle-stimulating hormone from pituitary

- inhibits follicular maturation

Progestin

- acts in hypothalamus and pituitary to suppress midcycle LH surge

- prevents ovulation

Absolute contraindications

- Hx of thromboembolism -> progestin only

- age >35 and smoking

- multiple CVD risk factors (age, smoking, DM, HTN)

- HTN (systolic >160, diastolic >100)

- VTE, ischemic heart disease, stroke, CVD

- abnormal liver function

- known or suspected breast cancer

- undiagnosed abnormal vaginal bleeding

- known or suspected pregnancy

- post-partum <21 days and <6 wks w/ breastfeeding

- migraine WITH aura

- heavy smokers

Relative contraindications

- HTN of any stage

- CAD

- diabetes

Adverse effects of COC

Adverse effects:

- HTN

- N, breast tenderness, edema, increase appetite, fatigue

Thromboembolic disorders increased risk with:

- smoking, hx, thrombophilia, diabetes, HTN, CVD, CAD, surgery/immobilization

Cancer

- promote (not cause) breast cancer growth

- protect against ovarian and endometrial cancer

- no effect on cervical cancer

Abnormal uterine bleeding

- can eliminate or reduce flow, cause spotting

Glucose intolerance

- can increase levels

Smoking increases risk of serious cardio side effects

Use in pregnancy/lactation

- contraindicated in pregnancy

- COCs can enter breast milk.

- Progestin-only during lactation

Stroke in women w/ migraines

- COCs can increase risk of thrombotic stroke

- can still use if: <35, no smoking, healthy, no aura

COC dosing schedule

Most dosed in a cyclic pattern for 28 days

- pills should be takes at same time every day

- prescribed w/ one year supply

28 day schedule:

Monophasic (preferred inititally)

- estrogen and progestin remain constant throughout the cycle of use

21 days of active pill followed by 7 days of either:

- no pill taken

- inert pill taken

- iron pill taken

Biphasic/triphasic/quadriphasic

- estrogen and progestin change as cycle progresses

Methods of starting:

- quick start method

- first day on menstrual period -> no backup needed

- first sunday after onset of menses -> backup for 7 days

Missed pills:

Missing single pill

- take ASAP, continue as normal

Missing > 2 pills

- take ASAP

- backup contraception for 7 days

- if during 1st week: emergency contraception if unprotected sex

- if during 3rd week: finish last week, skip placebos, immediately move to new pack

Combo contraceptive other routes

Transdermal contraceptive patch

- estrogen and progestin, same MOA as orals

- applied once a week

- AE and CI same as COCs

- if detached for >24 hrs backup contraception

Vaginal contraceptive ring

- estrogen and progestin

- one ring inserted each month

- comes out > 3 hrs backup contraception

- AE and CI same as COCs

Progestin only oral contraceptive

AKA minipill

- contains progestin NOT estrogen

- MOA: altering cervical secretions makes endometrium less favorable for implantation

Pros

- does not cause: thromboembolic disorders, HA, N

Cons

- less effective

- more likely to cause irregular bleeding

MUST take on time everyday

- if taken a few hours late backup protection is needed

- if two pills missed and no menstrual bleeding starts -> pregnancy test

Dosing is not cyclic, taken every day (no sugar pills)

- when starting use backup contraception for 7 days

Subdermal etonogestrel implants

Long-acting contraceptives

Route: 4-cm rod containing etonogestrel (progestin)

- implanted sub dermally in groove between biceps and triceps in non-dominant arm

- lasts 3 years

- can be used during breastfeeding after post-partum day 21

MOA:

- suppresses ovulation

- makes endometrium hostile to implantation

AE: irregular bleeding

Depot medroxyprogesterone acetate

Long-acting contraceptive

Progestin medication

- IM or SQ

- lasts 3 months

- fertility takes ~9 months to return

MOA:

- inhibits secretion of gonadotropins

- inhibits follicular maturation and ovulation

- thins endometrium to make implantation unlikely

AE

- menstrual disturbances

- weight gain, bloating, HA, depression, decreased libido

- decreased bone density

Intrauterine devices

Long acting contraceptive

Hormone-free copper IUD

- causes foreign body reaction w/ chemical changes that are toxic to sperm -> interferes w/ fertilization

- good for pts sensitive to hormones

- AE: heavier menstrual bleeding

- lasts 10 years

Levonorgestrel (progestin) containing IUD

- inhibits ovulations, prevents implantation

- AE: bleeding irregularities

- lasts 8 years

Emergency contraceptive pill

Emergency contraceptive pill

Progestin-only products

Plan B one-step or Next choice one dose (OTC)

- single dose levonorgestrel

- take w/in 72 hrs of unprotected intercourse

- MOA: delay or stop ovulation

- does NOT harm existing fetus or terminate existing pregnancy

Ulipristal acetate (UPA)

- taken w/in 5 days of unprotected intercourse (RX only)

- MOA: selective progestin receptor modulators

Insert a copper IUD

- w/in 5 days of unprotected intercourse

- MOST effective option

- expensive and not found quickly

Medical abortion

Mifepristone w/ misoprostol

Mifepristone

- MOA: synthetic steroid that blocks receptors for progesterone and glucocorticoids

Use: termination of early intrauterine pregnancy

- requires cotreatment w/ misoprostol

- w/in 12 wks of conception

- alternative to surgery for termination

AE of mifepristone and misoprostol:

- abdominal pain -> NSAIDs, heating pad

- vaginal bleeding -> 9-15 days

- infection

Contraindications

- ectopic pregnancy, hemorrhagic disorders, anticoagulation use

Follow up w/ hCG ~ 5 wks

Testosterone replacement

Indicated for:

- symptomatic men w/ primary, secondary, or mixed hypogonadism

confirmed low T (<230-350)

- must be measured in early morning

- requires confirmation of low w/ repeat level 4 wks later

NOT indicated for:

- normal T

- asymptomatic hypogonadism

- isolated ED

Testosterone pretreatment screening

Age >40

- screen for breast cancer, BPH, and prostate cancer (PSA and DRE)

Cautions

- severe sleep apnea, edema, CHF, hx of MI

Contraindications

- untreated prostate cancer

Baseline lab tests

- hematocrit, LFTs

Androgen medication classifications

Testosterone and testosterone esters

- testosterone

- testosterone cypionate

- testosterone enanthate

- testosterone undecanoate

17-a-alkylakted compounds

- fluxymesterone

- methyltestosterone

- oxandrolone

Androgen preparations for male hypogonadism

Oral

Native testosterone absorbed well but extensive first-pass metabolism makes it ineffective for hypogonadism

Oral testosterone undecanoate

- bypasses first-pass metabolism

Methyltestosterone, fluoxymesterone (17-a-alkylated androgens)

- NOT first line agents due to hepatotoxicity

Transdermal testosterone

- patches, gel (3 formations), liquid solution (1 formulation)

- FIRST-LINE -> most normal and stable testosterone conc.

Testosterone Gel

- advantages: less irritation than patches, cannot fall off

- disadvantages: can wash off, avoid bathing/swimming for 5-6hrs after application

- can be transferred to other by skin-to-skin: wash hands and any any contaminated skin

Parenteral testosterone

- advantage: dosing in wks instead of daily

- disadvantage: variable testosterone levels

Long acting -> testosterone enanthate/testosterone cypionate

- dosing every 1-2 wks injection

Extra-long acting: testosterone undecanoate

- dosing every 10 wks

Adverse effects of testosterone

Adverse effects

Virilization

- in women, girls, boys

Premature epiphyseal closure

- decrease in adult height

- perform xray hand and wrist Q 6 months

Hepatotoxicity

- 17-a-Alkylated androgens

- periodic LFTs

Effects on cholesterol

- lower HDL, elevate LDL

Prostate cancer

- does not cause but can promote growth

Thromboembolic events

Elevated Hematocrit

Breast enlargment -> T converted into estrogen

Testosterone monitoring

Testosterone targets:

- adjust dosage to achieve level of 450-600

- measure morning levels

- schedule midway between doses for injectable

- anytime for transdermal

- do NOT adjust dose based on single abnormal rest, need two consecutive level out of range

Monitor for improvement

- libido, mood, ED may take up to 6 months

Follow-up timeline

- every 2-3 months during initiation and dose adjustments

- once stable and w/in target range: annual

Serum LH

if pt has primary hypogonadism:

- if dose is adequate= LH normalizes

- elevated LH = under-treatment

Bone density -> if low density was presenting sign

- repeat DEXA every 2 yrs until normal

Prostate exam and PSA

- 3 months and then 1yr after starting T

- annually if stable

Hct

- 3-6 months after start of tx, then yearly

- stop testosterone if > upper limit of normal

Hormonal therapy for transgender men

Goal to induce physical changes to match gender identity

- stop menses

- induce virilization

- maintain hormone levels in the normal male physiological range

Principal medication: testosterone

- easiest to achieve w/ IM or SC testosterone

Monitoring:

- serum testosterone: Q3 months, then 1-2 times a year

- monitor for clinical signs of virilization, blood counts, lipid profiles

Phosphodiesterase-5 inhibitors for ED

Sildenafil, tadalafil (duration of action: 36hrs), vardenafil, avanafil

- improved erection hardness and duration in ~70% of men

- effects can last up to 4 hrs, fade after 2 hrs

MOA: Selective inhibition of PDE-5

- increases and preserves cGMP levels in penis

- MUST have stimulus

Adverse effects

Common

- headache, flushing, congestion, dizziness, dyspepsia

Serious

Hypotension

- significant drop in BP w/ nitrate (absolute contraindication), a-blocker (caution and spacing)

- can lead to syncope, cardiac events, or shock

Priapism: painful erection >6 hrs

- left untreated can permanently damage penis

- >24 hrs may never have sex again

- have to aspirate blood from corpus cavernosum, irrigated w/ vasoconstrictor

Nonarteritic ischemic optic neuropathy (NAION)

- irreversible blurring or loss of vision

Sudden hearing loss

Contraindications

Nitrates: nitroglycerin, isosorbide dinitrate

- both PDE5i and nitrates increase cGMP -> vasodilation and hypotension

- life-threatening hypotension, DO NOT combine

a-blocker: doxazosin, BPH meds

- cause arteriolar dilation

- may cause symptomatic orthostatic hypotension

- need to stagger dosing when using these and PDE5i

Caution in med w/ coronary heart disease or cardiac risk

Avoid use:

- recent CV event in last 6 months (MI, stroke, arrhythmias)

- unstable CV conditions (resting hypo/hypertension, unstable angina, decompensated heart failure)

Premature ejactulation

First line -> SSRI

MOA: serotonin can cause delay in ejaculation

- SSRI prevents reuptake of serotonin

Paroxetine is most effective

- lower dose then used for depression

Topical anesthetics -> lidocaine, prilocaine

Decrease sensitivity to glans penis

- disadvantage: transfers to partner and can delay or prevent orgasm

- use w/ condom

5-a-reductase inhibitors

Finasteride, dutasteride

- men w/ large prostates, mechanical obstruction (static)

DOC: for enlarged prostate

MOA: acts in reproductive tissue to inhibit 5-a-reductase

- enzyme that converts testosterone to DHT

- promotes regression of prostate epithelial tissue

- decreases mechanical obstruction of urethra

May take 6-12 months to have prostate shrinkage

- won't relieve acute symptoms

Adverse effects:

- decrease ejaculate volume

- decreased libido

- gynecomastia

- teratogenic to male fetus

- decrease PSA levels -> if not falling as expected, inspect for prostate cancer

a1-adrenergic antagonists

Doxazosin, tamsulosin, alfuzosin, terazosin, silodosin

DOC for mod-severe symptoms of BPH

MOA: blockade of a1 receptors relaxes smooth muscle in:

- bladder neck

- prostate

- prostatic urethra

Decrease dynamic obstruction of the urethra

- good for acute symptom relief w/ BPH

- to maintain benefits must be taken lifelong

Sildosin and tamsulosin: selective for a1a recpetors

- mostly found in prostate

- no/little effect on bp

Alfuzosin, terazosin, doxazosin: non-selective for a1-receptors

- causes vasodilation in blood vessels

- lowers bp

- do NOT combine w/ other vasodilators

Adverse effects

Non-selective agents: doxazosin

- hypotension -> caution w/ nitrates, PDE5i

- fainting (first-dose effect)

- dizziness

- somnolence

- nasal congestion

Selective agents: Tamsulosin

- abnormal ejaculation

BPH meds (PDE5i and anticholinergics)

Tadalafil -> PDE5i

- treats erectile dysfunction due to 5-alpha-reductase inhibitor

- improves BPH symptoms only, does NOT help w/ enlarged prostate

- use w/ pt who has mild BPH and ED

Oxybutynin -> anticholinergic

MOA: relax bladder detrusor muscle

- improve the urine storage capacity of the bladder

- useful for irritative voiding symptoms only (overactive bladder)

Adverse Effects:

- dry mouth, constipation

- tachycardia

- urinary retention

- agitation, confusion, drowsiness

- blurred vision

Iron deficiency (oral vs. IV and diff meds)

Oral vs. IV iron

Oral

- uncomplicated iron deficiency anemia

IV

- severe anemia (Hbg <7)

- malabsorption condition: gastric bypass, IBD, celiac

- older pts

- 2nd/3rd trimester w/ Hgb <10.5

- dialysis pt

Oral medications

Ferrous salts

- ferric citrate, ferric maltol, ferrous fumarate, ferrous gluconate, ferrous sulfate

- polysaccharide-iron complex

IV medications

- ferric carboxymaltose (FCM), ferric gluconate (FG), ferumoxytol, iron sucrose (IS), ferric derisomaltose, iron dextran

Give iron until ferritin and transferrin saturation normalizes

Oral meds for IDA

Dosing schedule: one tablet, once a day

- daily doing

- every other day: reduced GI side effects

Duration of therapy: different options

- stop when hemoglobin levels normalize -> helps detect anemia from further blood loss

- 6 months of treatment after Hgb normalized -> completely replenishes iron studies

6-8 wks to fully ameliorate the anemia

6 months to replete iron stores

Enhance absorption

Do not give w/ food

- take separately from calcium-containing food and beverages

- take w/ vitamin C to increase absorption

pH: needs acidic environment

- give 2 hrs before or 4 hrs after ingestion of antacids

Adverse effects

- constipation

- metallic taste

- itching

- black/green stools

Re-evaluate in 2 wks after starting medication

- check Hgb, reticulocyte count, iron tolerability by pt

- Hgb should rise by at least 1g/dL

IV meds for IDA

When to use:

- poor adherence to orals, GI side effects w/ oral

- prefer shorter tx course

- ongoing blood loss (ex. menorrhagia)

- malabsorption (gastric bypass, CKD)

- coexisting inflammatory state (IBD, celiac)

Adverse effects:

Infusion reactions: <1% of pts

- always do a test dose w/ any parenteral formulation

- consider pre-medicating asthmatics/allergies

Fishbane rxn

- flushing, myalgias of chest and back

Arthritic flare w/ inflammatory arthritis

Risk of infection

- bacteria like iron

Re-evaluate 4-8wks after iron administration

- can get an early spike in iron, need to wait to get true level

Vitamin B12 deficiency

Cyanocobalamin

- oral, IM, deep SubQ, sublingual, nasal

- NOT given IV as most will be excreted in urine

- most pts do oral therapy

Symptomatic pts: parenteral administration

- severe symptomatic anemia OR neuro findings

- switch to oral once symptoms resolve

Folic acid

Hazards

- does NOT treat neurologic damage

- treat the anemia but mask B12 deficiency

- should NOT be treated w/ folic acid alone

- check both folate and vit B12

Adverse effects: none

- excess vitamin is excreted when stores are adequate

Duration

Lifelong:

- gastric bypass, strict vegans, pernicious anemia

- need blood work every 3-6 months

Discontinue once corrected:

- diet

Folic acid deficiency

Consequences

Developing fetus: neural tube defects (spina bifida, anencephaly)

- imperative women of reproductive age ensure adequate folic acid levels BEFORE pregnancy occurs

- should consume 400-800 supplemental folic acid + what they get from food

Treatment

- if poor diet: correct w/ dietary measures (unless pregnancy)

- if malabsorption: need supplemental folate

Oral folic acid

- if reversible cause: 1-4 months of tx OR hematologic recovery

- if chronic cause: indefinitely

IV folic acid

- if cannot take oral meds (vomiting, obtunded)

- severe or symptomatic anemia

Sickle cell

Treatment -> Hydroxyurea

MOA

- increases fetal hemoglobin level >>> dilutes abnormal hemoglobin S

Use

- reduce frequency of pain crises, ACS, transfusions

Side effects:

- bone marrow suppression, monitor CBC every 2-4 wks

- cutaneous vasculitis/ulcerations

- teratogenic

Pain management

Mild-mod pain

- NSAIDs, acetaminophen

Mod-severe vaso-occlusive crisis:

- morphine, hydromorphone, oxycodone

Intro to diuretcis

Classified according to their site of action

- MOA: blockade of sodium and chloride reabsorption to decreased reabsorption of water

Greater the reabsorption blocked -> greater the diuresis

- act early in nephron -> block greatest amount of reabsorption, greater diuresis

- act late in nephron -> block very little

Loop diuretics

Furosemide, bumetanide, torsemide

MOA: inhibit the luminal Na/K/2Cl co-transporter in the ascending limb of loop on henle

- increased loss of: Na, Cl, H2O, K, Mg, Ca

- most potent diuretics

- "high ceiling diuretics" bc they can inhibit reabsorption of 25% of filtered sodium

Site of action: loop of henle

Adverse effects

Electrolyte distrubances:

- hyponatremia, hypocholeremia, hypokalemia (U wave), hypomegnesemia, hypocalcemia

Dehydration

- minimize risk -> start low, go slow, monitor weight

- dry mouth, unusual thirst, oliguria, excessive weight loss -> withhold furosemide

Tinnitus (ototoxicity) -> dose related

- ALL are ototoxic

Hypotension -> substantial drop in BP

- symptoms: dizziness, lightheadedness, fainting

- minimize postural symptoms by rising slowly

- if occurs -> discontinue

Other SE

- possible metabolic alkalosis, hyperuricemia (relative contraindication in gout), hyperlipidemia, hyperglycemia

Thiazide diuretics

Chlorthalidone, chlorothiazide, hydrochlorothiazide

MOA: inhibiting the Na/Cl symporter in the distal convoluted tubule

- only 10% of filtered Na -> less diuresis than loops

- amount of diuresis dependent on kidney function

- NOT effective in GFP < 15-20

Site of action: early distal convoluted tubule

Side effects

Electrolyte disturbances:

- hypokalemia, hypochloremia, hypomagnesemia

- hypercalcemia

- check Cr and electrolytes 1-2 wks after starting

Possible metabolic alkalosis

Hyperuricemia

- relative contraindication in gout

Hyperlipidemia, Hyperglycemia

Potassium sparing diuretics

Aldosterone antagonists:

- spironolactone, eplerenone

Non-aldosterone antagonists (ENAC blockers):

- triamterene, amiloride

Therapeutic use:

Hypertension

- usually in combo w/ thiazide or loop to combat K-wasting

Edema in CHF

- produces direct effects on the heart to reduce aldosterone-induced cardiac remodeling that impairs contractility and diastolic relaxation

Side effects

Hyperkalemia esp when used alone

- can cause fatal dysrhythmias if K>5

- monitor K levels and Cr

Spironolactone specific SE

- gynecomastia, menstrual irregularities, impotence, hirsutism, deepening of the voice

Trimterene specific SE

- N/V, leg cramps, dizziness

Aldosterone antagonists vs. non-aldosterone antagonists potassium sparing diuretics

Aldosterone antagonists/mineralocorticoid receptor antagonists (MRAs)

- spironolactone, eplerenone

MOA: competitive antagonist of aldosterone in late DCT and collecting ducts

- BLOCKS action of aldosterone

- retention of potassium

- increased sodium excretion (prevents reabsorption)

- scant diuresis -> decreased SV

Site of action: distal nephron

Non-aldosterone antagonists (ENAC blockers)

- Triamterene, amiloride

MOA: inhibit sodium channels in the late distal tubule and collecting ducts

- reduction in potassium secretion (increase K)

- decreased sodium reabsorption (decreased Na)

- scant diuresis

Site of action : distal nephron

- used in HTN

Angiotensin converting enzyme inhibitor

End in -pril (ex. lisinopril)

MOA

- inhibit ACE to block conversion of angiotensin I to angiotensin II

- decreases angiotensin II formation

- increase levels of bradykinin

Vasodilation -> decreased SVR -> decreased BP

Decreased aldosterone decretion -> decreased SV

- prevent of reverse pathologic changes in heart and blood vessels

- increase excretion of sodium and water

Therapeutic use:

- HTN, heart failure, MI

- LV dysfunction

- diabetic nephropathy

Avoid use/or use caution in:

- pregnant pts -> fetal injury

- pts w/ history of angioedema -> increased bradykinin

- pts w/ B/L renal artery stenosis -> can cause acute renal failure

Adverse effects

- dry cough -> d/t increased bradykinin

- angioedema -> d/t increased bradykinin

- hyperkalemia -> check levels 1 wk after starting

- AKI -> check Cr levels 1 wk after starting

- teratogenic

- first dose hypotension

Angiotensin receptor blocker

end in -sartan (ex. losartan)

MOA

- block effects of angiotensin II at the receptor level

- decreases angiotensin II action -> vasodilation -> decrease SVR

decrease aldosterone secretion -> decrease SV

- prevents pathologic changes in the heart and vessels

- increase excretion of sodium and water

More complete blockage of angiotensin II than ACEi

- does NOT affect bradykinin levels

Therapeutic uses:

- HTN, heart failure, MI, diabetic nephropathy

Avoid use/or use caution in:

- pregnant pts -> fetal injury

- pts w/ history of angioedema -> increased bradykinin

- pts w/ B/L renal artery stenosis -> can cause acute renal failure

Adverse effects

- cough -> less then ACEi

- angioedema -> less than ACEi

- hyperkalemia -> check 1wk after starting

- AKI -> check C levels 1wk after starting

- first dose hypotension

Aldosterone antagonists

Eplerenone, spironolactone

MOA

- blocks aldosterone receptors at the mineralocorticoid receptor

- promotes K retention and Na/H2O loss

- decreases BP

Therapeutic uses

- HTN, heart failure

Adverse effects

- eplerenone has less antiandrogen side effects

- gynecomastia

- hyperkalemia

Calcium channel blockers (dihydropyridines)

End in -dipine (ex. amlodipine, nifedipine)

MOA

- blocks CC in vascular smooth muscles

- promotes vasodilation

- little blockage in the heart -> cannot be used for dysrhythmias

Hemodynamic effects

- primarily cause arterial vasodilation (NOT venous)

- decrease BP

- may cause reflex tachycardia due to decrease BP

- do NOT alter contractile force

Adverse effects

- postural hypotension

- facial flushing

- gingival hyperplasia

- headache

- edema of ankles and feet

- reflex tachycardia -> increases cardiac oxygen demand -> increases anginal pain -> combine with BB to prevent

Calcium channel blockers (non-dihydropyridines)

diltiazem, verapamil

MOA

- blocks CC in the vascular smooth muscles AND the heart

- promotes vasodilation (less than DHP)

- decrease HR and contractility

Hemodynamic effects

- have more balanced effect on both the heart and blood vessels

- lower blood pressure through vasodilation

- decrease HR and contractility

Adverse effects

- MC complaint is constipation

- dizziness, facial flushing, headache

- gingival hyperplasia

- edema of ankles and feet

Cardiac effects

- SA node: bradycardia

- AV node: partial or complete AV block

- Myocardium: decreased contractility

Do NOT use in pts w/:

- sick sinus syndrome

- second or third degree AV block

- decompensated heart failure

Beta-adrenergic antagonists aka beta-blockers

Nonselective -> B1=B2

- propranolol, sotalol, timolol

Cardioselective B1>>B2

- atenolol, metoprolol

W/ vasodilating actions -> mixed alpha and B1=B2

- carvedilol

- labetalol

Mechanism of action -> all BBs

​Heart​

- Block action of norepinephrine and epinephrine at β1 receptors on cardiac muscles​

- inhibit nodal cell from firing​ -> reduce HR ​

- inhibit contractile cell from firing​ -> reduce contractility ​

- Overall Effect: decreased CO/SV = decreased BP​​

Kidney​

- Decrease renin release from juxtaglomerular cells → decreased SVR=decreased BP​

Adverse effects

- Bradycardia​

- Hypotension- Reduced CO​

- Precipitation of Heart Failure​

- AV heart block​

- Rebound cardiac excitation- with abrupt cessation​

- Impotence​

- Fatigue​

B2 blockage

- bronchoconstriction

- hypoglycemia awareness decreased

Caution and CI

All BBs

- Avoid and/or use caution in:​ Patients on concurrent non DHP CCBs​, Patients with bradycardia ​, Heart block​

Nonselective BBS

- avoid/use caution in: pts w/ asthma and COPD and in diabetics

Central alpha-2 agonists

Clonidine, methyldopa

MoA: Stimulate central α-2 receptors in the central nervous system (α-2 agonist)​

- Suppress central sympathetic outflow​

- Suppresses release of NE​​ -> decreased BP

Avoid use in:

- older adults -> sedation, hypotension, dizziness

Side effects

All​

- Orthostatic hypotension​

- Dizziness​

- Headache​

- Sedation/Drowsiness​

- Dry mouth​

- Constipation​

- Confusion​​

Methyldopa ONLY​

- Fluid retention​

- Lupus-like syndrome​

- Hepatitis​ -> Monitor LFTs​

Advantages

- Clonidine is fast acting​ -> good for urgent blood pressure control​

- Methyldopa ONLY​ -> can be used in pregnancy​

Disadvantages

- rebound HTN when abruptly stoped

alpha-1 blockers

-zosin Doxazosin, prazosin, terazosin

MOA: Block effect of norepinephrine at arterial α-1 receptors (α-1 blocker). Non-selective.​

- Vasodilation → decreased SVR​​

Avoid and/or use caution in:​ Elderly​

- Orthostatic hypotension

Adverse effects

- “First-dose” phenomenon​

- Orthostatic hypotension​

- Dizziness​

- Headache​

- Syncope​

- Fluid retention​

​

Advantages​

Effective for management of BPH​​

Disadvantages​

Evidence demonstrating less efficacy in reducing CV events​​

ACC/AHA HTN initial tx recommendations

Initiate single agent if meets any of the following

- ASCVD​

- CKD​

- Diabetes​

- Calculated 10-year ASCVD risk greater than ≥ 10%​

- Anyone with BP >160/100, regardless of risk ​

Choose from following first-line agents

- ACE, ARB, CCB (-dipine or verapamil/diltiazem), thiazide diuretic

Elevated BP (120-129/<80)

- lifestyle modification

Stage 1 HTN (130-139 OR 80-89)

- consider single agent

Stage 2 HTN (>= 140 OR >= 90)

- 2 meds from 2 diff classes

Start w/ 2 meds from 2 diff classes with:

- stage 2 HTN

- SBP is >20 or DBP >10 from goal

- in AA pts

Individualizing therapy for HTN

Renal disease

All classes work: ACEI/ARBs work best​

- Most cases also add diuretic​

- Advanced renal insufficiency thiazide is not useful- use a loop​

Diabetes

Preferred meds: ACEI/ARBs​

- slow progression of renal damage ​​

Other Meds:​

- BB: can decrease morbidity and mortality​, use with caution can mask hypoglycemia​

- Thiazide and loop diuretics: cause hyperglycemia​, use with caution​

Older adults >55 y/o

Follow same general treatment principles​:

- Initiate at lower doses- ½ of younger adult dose​

- Titrate doses slower​​

Increased risk of orthostatic hypotension and dizziness​

- Cardiovascular reflexes are blunted​

- Avoid central α-2 agonists and α-1 blockers​

HTN stepped care approach w/ NO compelling indications

Step 1

- ACEi/ARB or CCB or Thiazide

Step 2

- ACEi/ARB plus CCB or Thiazide

Step 3

- ACEi/ARB plus CCB plus Thiazide

Step 4

- ACEi/ARB plus CCB plus Thiazide

- plus Spironolactone

Loop diuretics for HF

First-line for fluid retention in HFrEF & HFpEF​

- ↓ Symptoms of congestion (edema, dyspnea)​

- Helps maintain euvolemia​

- Associated with ↓ hospitalizations (not mortality)​

​

When to Use:​

- Patients with current or prior signs of fluid overload​

​

Mechanism of Action:​

- Inhibits Na⁺/K⁺/2Cl⁻ co-transporter in the ascending loop of Henle​

- ↓ Sodium and water reabsorption → ↑ diuresis​

Side effects

- ​Hypokalemia (15%) – prophylactic potassium repletion may be needed​ ​

- Hypomagnesemia (15%)​

- Acute kidney injury (pre-renal)​- > Increased SCr​

- Ototoxicity​

- Hypotension​

- Hyperuricemia (often asymptomatic) (18%)​

- Hyponatremia (7%)​​

ACEi (-pril) for HF

- Improve functional status and reduce mortality by ~47%​

​- Recommended for all HF patients without CI

​- Favorably influence cardiac remodeling​

​​

Hemodynamic Benefits:​

Arteriolar dilation:​

- ↑ Stroke volume (SV) and cardiac output (CO)​

- ↑ Renal blood flow → ↑ sodium and water excretion​

Venous dilation:​

- ↓ Venous pressure → ↓ pulmonary congestion, preload, cardiac dilation​

Aldosterone suppression:​

- ↑ Sodium and water excretion​

Potassium retention​

Net Effect:​

- ↓ Preload and afterload → ↓ cardiac workload​

​​

AE: hypotension, hyperkalemia, cough, angioedema, renal failure, teratogenic​

ARB (-sartan) of HF

Similar effect to ACEI​

- Less effect on cardiac remodeling than ACEI -> ACEI is preferred​

- Use: HF who can’t tolerate ACEI​

​

Hemodynamic Benefits:​

Arteriolar dilation: ↑ Stroke volume and cardiac output, ↑ renal blood flow, ↑ Na⁺/H₂O excretion​

Venous dilation: ↓ Venous pressure → ↓ pulmonary congestion, preload, cardiac dilation​

Aldosterone suppression: ↑ Sodium/water excretion, potassium retention​​

Net Effect: Arterial and venous vasodilation → ↓ preload and afterload → ↓ cardiac workload​

​

AE: hypotension, hyperkalemia, cough, angioedema, renal failure​

Aldosterone antagonists for HF

Spironolactone and eplerenone

Indication:​

- Stage II–IV HFrEF​

- Reduce morbidity and mortality​

​

Mechanism: Block aldosterone receptors in heart and kidneys​

- ↓ Cardiac remodeling and fibrosis​

- ↓ Sympathetic nervous system activation​

- ↓ Baroreceptor reflex activation​

​​

AE: hypotension, hyperkalemia, gynecomastia (with spironolactone), impotence (with spironolactone)​

ARNi for HF

Sacubitril/valsartan (entresto)

Indications:​

HFrEF with NYHA Class II–III symptoms​

- Reduces morbidity and mortality​

- Preferred over ACEi/ARB in appropriate patients​

- ACEi/ARB reserved for those who cannot tolerate ARNi​

​​

Components:​

- Valsartan: ARB → blocks angiotensin II receptors​

- Sacubitril: neprilysin inhibitor → prevents breakdown of natriuretic peptides​

​- Net Effect: ↑ Natriuretic peptides → promote vasodilation, natriuresis, and ↓ blood volume/preload​

​​

Important Pearl:​

- Sacubitril must be combined with an ARB because neprilysin inhibition alone increases angiotensin II levels​

- The ARB component blocks the effects of excess angiotensin II

Side Effects:​

- Hypotension​, hyperkalemia​, increased SCr​, Angioedema​

​​

Important Precautions:​

- Do not administer with an ACEi or within 36 hours of last ACEi dose (risk of angioedema)​

- Contraindicated in patients with a history of angioedema from any cause​

​

​Monitoring: Similar monitoring requirements as ACEi/ARB

- Serum potassium (K)​

- Renal function​

- Blood pressure​

Beta-blockers for HF

ONLY -> carvedilol, metoprolol succinate, bisoprolol

- First-line therapy for all patients with HFrEF​

- Reduce all-cause mortality and hospitalizations​

- Improve ejection fraction (EF)​

Clinical Considerations:​

- Start only when HF is stable and patient is euvolemic​​

- Dose must be carefully titrated to avoid worsening HF​​

- Benefits may take 1–3 months to manifest​

MOA -> block B1-adrenergic receptors in heart

- reduce sympathetic effects

- ↓ Heart rate​ -> allows more ventricular filling time​

- ↓ Contractility initially​ -> reduces workload and oxygen demand​​

Long-term: improves ventricular function by reversing remodeling​

- ↓ Risk of arrhythmias by stabilizing cardiac electrical activity​

AE:

- Fluid retention and worsening HF​ -> especially if started too quickly​

- Fatigue​

- Hypotension​

- Bradycardia​

- Heart block​

Cardiac glycoside for HF

Digoxin

Indications:

- Add-on therapy for patients still symptomatic despite standard HF meds​

- Rate control in HF patients with afib and low BP​

- Reduces hospitalizations only — no mortality benefit​

Toxicity risk

- seen w/ levels >2

MOA

Inhibits Na⁺/K⁺ ATPase pump in myocardial cells​

- ↑ Intracellular Na⁺ → ↑ Ca²⁺ influx via Na⁺/Ca²⁺ exchanger​

- Net effect: increased cardiac contractility (positive inotrope)​

Common Symptoms:​

- Fatigue, weakness​, confusion, delirium, psychosis​

- Nausea, vomiting, anorexia​

- Visual disturbances: halos, photophobia, red-green or yellow-green vision​

​

Cardiac Effects:​

- Arrhythmias: ventricular tachycardia, Vfib

- AV block, sinus bradycardia​​

Risk Factors for Cardiac Toxicity:​

- Low magnesium (↓Mg)​

- Low potassium (↓K)​

- Low calcium (↓Ca)​

​

Reversal Agent:​

- Digibind® — antibody fragments that bind digoxin for renal excretion​

Stages of HF

Stage A -> high risk for developing HF, but no Sx

Aggressive RF control

- HTN -> ACEi or ARB

- CV risk reduction -> stop smoking, manage dyslipidemia

- diabetes -> SGLT2i

Stage B -> no sx but stuctural heart disease

Goals

- prevent symptomatic HF and cardiac injury

- delay remodeling and LV dysfunction progression

Treatment plan

- ALL stage A tx

- plus ACEi/ARB and BB

Stage C -> structural HD plus HF symptoms

All stage A tx

- change to ARNi

- BB, aldosterone, SGLT2i

- Loop diuretic PRN

Additional options

- digoxin -> rate control esp. in hypotensive pts

- hydralazine + isosorbide dinitrate -> for AA pts

Stage D -> marked sx w/ recurrent hospitalizations

All treatments of stage A-C

- chronic inotropic meds -> symptom relief

- LVAD

- palliative care

Other recommendations for HF

Calcium channel blockers​

Avoid Diltiazem and Verapamil​

- May worsen HF and increase mortality​

Amlodipine / Felodipine​

- Do not improve HF outcomes​

- Can be used for uncontrolled HTN (target BP <130/80)​

​

The following are not indicated for HF by itself, but should be used if indicated for other disease states are present​

- Anticoagulation​

- Antiplatelets (including aspirin)​

- Statins​

​

Omega-3 fatty acids may be reasonable in patients with NYHA II-IV symptoms ​​

HMG-CoA reductase inhibitors

Statins

MOA

- Inhibit HMG-CoA reductase​

- rate limiting step in cholesterol biosynthesis​​

Effects on lipid profile​

- Decrease LDL (20 – 55%)​

- Decrease TG (10-30%)​

- increase in HDL (5-15%​)

Statin therapy recommended for:

Clinical ASCVD or LDL >190

- high intensity

LDL 70-189:

- dibetes -> moderate intensity statin

- multiple RF and 50-75 -> high intensity

ASCVD risk

- >20% -> high intensity

- 7.5-20% -> moderate intensity

- 5-7.5% -> lifestyle vs. moderate intenisty

- <5% -> lifestyle

Adverse effects:

Most common SE:

- constipation, diarrhea, dyspepsia, nausea, abdominal pain​​

Myopathy: ​

- Affects 5–10%: muscle aches, tenderness, weakness​

- Rare: Myositis → very rare: Rhabdomyolysis​

- Rosuvastatin = highest risk​

- Get CK at baseline and if symptoms develop​

- Discontinue if CK >10x ULN​​

Hepatotoxicity:

- Check baseline LFTs, repeat if symptomatic​​

New-Onset Diabetes: 1 in 500​

- Benefit >risk. Keep taking​​

Teratogenic​

Monitoring and interactions for Statins

Monitoring

Lipid panel​

- Baseline​

- 4-6 weeks after starting treatment​ then annually​​

Liver Function Tests​

- Baseline for all patients​

- Follow-up only if symptomatic

Creatine phosphokinase​

- Baseline CK​

- Recheck if muscle symptoms​​

Interactions

CYP Enzyme Interactions​

- CYP inhibitors → ↑ statin levels → ↑ risk of myopathy​

- Rosuvastatin & Pravastatin = least CYP interactions​​

Grapefruit juice​

- Inhibits CYP3A4​: ↑ absorption and ↓ metabolism of atorvastatin, lovastatin, simvastatin​

- Moderate intake OK​: ≤ 8 oz/day or ½ grapefruit/day​​

Amlodipine

- ↑ levels of atorvastatin, lovastatin, and simvastatin​​

Gemfibrozil

- contraindicated with statins​

- ↑ risk of severe myopathy/rhabdomyolysis​

Switching statins

- if drug/food interaction choose pravastatin

- if need high intensity -> rosuvastatin

Cholesterol absorption inhibitors

Ezetimibe

MOA

- Inhibits cholesterol absorption in the small intestine​​

Effects on lipid profile​

- Decreases LDL (18-23%)​

- Decrease TG (5-10%)​

- Increase HDL (1-3%)​

​

Reduction in ASCVD events s/p MI when combined with a moderate intensity statin​

​- Contraindicated in active liver disease or persistent elevations in LFTs​

​

Adverse effects: generally well tolerated​

- Myalgias, diarrhea, arthralgia​

Adenosine triphosphate-citrate lyase inhibitor

Bempedoic acid

MOA

- inhibits ATP-citrate lyase (ACL)​

- ACL is upstream of HMG-CoA reductase in cholesterol synthesis​

- Works only in the liver, not active in skeletal muscle​​

Effects on lipid profile​

- Decreases LDL (20-25%)​, better when added to statin

​

Reduction in ASCVD events​

​

Adverse effects: generally well tolerated​

- Hyperuricemia (caution in gout), back pain, muscle spasm, tendon rupture​

Bile acid resins

Cholestyramine, colesevelam

MOA

- Bind bile acids in intestine → form complexes → excreted in feces​

- This depletes bile acid, forcing liver to use cholesterol to make more bile acids → lowers LDL​​

Effects on lipid profile​

- Decrease LDL (15-20%)​

- Increase or no change in TG (5%) ​

- DO NOT USE IN PATIENTS WITH TG ≥ 300 mg/dL- can -reflex cause hyperTG​

- Increase HDL (3-5%)​

​​

Adverse effects & drug interactions: not absorbed through the GI tract, so devoid of systemic effects​

GI side effects:

- constipation, abdominal pain, cramping, bloating, gas, dyspepsia​

Decreased absorption of fat-soluble vitamins (A, D, E, K) - - especially with cholestyramine​

May impair absorption of other meds

- administer other drugs 1 hour before or 4 hours after​

Fibrates

Fenofibrate, gemfibrozil

MOA

- Activate PPAR-α (peroxisome proliferator-activated receptor-alpha)​

- ↓ VLDL production → ↓ triglycerides​​

Effects on lipid profile​

Decrease LDL (5-20%)​

Decrease TG (20-50%)​

Increase HDL (15%)​

​

Contraindicated in severe liver disease, gall bladder disease​

​

Adverse effects​

- Increase LFTs​

- Myopathy- increased risk with used with statin (especially Gemfibrozil)​

- Gallstones: upper abdominal discomfort, intolerance of fried foods, bloating​

​

Monitoring​

- LFTs, renal function ​

PCSK9 inhibitors

Alirocumab, evolocumab, inclisiran

MOA

- Monoclonal antibody (“biologic”) that inhibits proprotein convertase subtilisin kexin type 9 (PCSK9)​

- Net effect: increased LDL clearance​

- Dramatic decrease in LDL when combined with a statin (60%)​​

Administered subcutaneously, every 2-4 weeks​

​​

Adverse effects​

- Injection site reactions​

- Nasopharyngitis​

​

Monitoring​

- LDL at baseline and then at 4-8 weeks to assess response ​

Niacin

Niacin

MOA

- Decreases rate of hepatic synthesis of VLDL and LDL​​

Effects on lipid profile​

- Decrease LDL (5-25%)​

- Decrease TG (20-50%)​

- Increase HDL (15-35%)​

​

Do not use in active liver disease, peptic ulcer disease​

​

Adverse Effects:​

- Hepatotoxicity ​

- Can increase blood glucose-benefit outweighs risk for most patients​

Most common

- Flushing​ -> Pre-med w/ aspirin 325 mg 30-60 min prior to niacin (may use other NSAIDs)​

- Take with food, but avoid alcohol, hot beverages, spicy foods with administration​​

Increase Uric Acid Levels-caution in Gout​

Monitoring

- LFTs at baseline then every 6 months​

- Blood glucose/A1c (if DM)​

- Uric acid (if gout)​

Omega-3 fatty acids

OTC fish oil

MOA -> unknown

- used for severe hypertriglyceridemia (>= 500)

Affect on lipid panel

- Decreases TG by 25-45%​

- May increase LDL by as much as 45%​

- Minimal effect on HDL​

Adverse effects:

- Dyspepsia, fishy burp, diarrhea, GI discomfort​

- Reduction in platelet aggregation​ -> increased risk of bleeding ​

- Caution in patients with fish or shellfish allergy​

Aspirin

Anti-platelet

MOA -> suppresses platelet aggregation

- irreversible inhibition of thromboxane 2 (TXA2) via COX-1

- COX-1 inhibition -> decrease TXA2 -> decrease platelet aggregation

- last for life of the platelets (7-10 days)

Indications

- ischemic stroke, TIA

- chronic stable angina, unstable angina

- coronary stenting

- acute MI, previous MI, prevention of MI

Prophylactic dosing

- used only for prophylaxis NOT treatment of VTE

Adverse effects

- dyspepsia

- nausea

- bleeding/bruising

Do NOT take NSAIDs w/ aspirin

- NSAIDs block aspirins access to COX-1, antagonising its irreversible platelet inhibition

- if need to: take aspirin first than NSAID 2+ hours later

Clopidogrel

Anti-platelet

MOA -> suppresses platelet aggregation

- irreversible inhibition P2Y12 ADP receptor on platelets

- ADP inhibition -> decrease GPIIb/IIa complex -> decrease platelet aggregation

- last for life of the platelet (7-10 days)

- slower onset than aspirin

Indications

- ischemic stroke, TIA

- coronary stending

- acute MI, previous MI, prevention of MI

Prophylactic dosing

- prevent recurrence of thrombotic event

- drug-eluting stent -> 6-12 months

- post-MI or stroke -> 12 months

Side effects

- bleeding/bruising

- rare: thrombotic thrombocytopenia purpura (TTP)

- do NOT take w/ PPIs

Ticagrelor

Anti-platelet

MOA -> suppresses platelet aggregation

- reversibly inhibits the P2Y12 ADP receptor on platelets

- platelet function recovers faster after stopping

- preferred over clopidogrel in high-risk ACS pts

Indications

- ischemic stroke, TIA

- coronary stending

- acute MI, previous MI, prevention of MI

Side effects

- bleeding/bruising

- dyspnea

Prophylactic dosing

prevent recurrent of thrombotic event

- generally at least 12mo post-MI or stent

Unfractionated Heparin

Anticoagulants

MOA -> binds and enhances antithrombin III

- potentiates inhibition of factor Xa and factor IIa (thrombin)

- prevents conversion of fibrinogen to fibrin

Indications

- prophlaxis and treatment of venous thromboembolism (VTE)

Adverse effects

- bleeding and bruising -> requires monitoring

- heparin-induced thrombocytopenia (HIT) -> MC complication of HIT is VTE

- epidural/spinal hematoma risk

HIT treatment

- stop ALL heparin and warfarin products

- AVOID platelet transfusion unless actively bleeding

Start non-heparin anti-coag

- argatroban, fondaparinux, DOACs (apixaban, rivaroxaban)

Low molecular weight heparin (LMWH)/enoxaparin

Anticoagulant

MOA

- selectively inhibits factor Xa > IIa

- works via antithrombin III prothrombin

Uses

- prophyaxis and tx of VTE

- used inpatient and outpatient DVT/PE tx and bridge therapy

Side effects

- bleeding and bruising

- risk of HIT

- spinal/epidural hematomas w/ spinal puncture

Dabigatran

Oral direct thrombin inhibitor, anti-coag

MOA -> direct, reversible inhibiton of factor IIa (thrombin)

Use:

- prevention of systemic embolism in Afib

- treatment of DVT/PE

- prevention of recurrence of DVT/PE

Adverse effects

- bleeding and bruising

- GI: dyspepsia, gastritis-like symptoms -> take w/ food/PPI

- epidural or spinal hematomas

Warfarin

Vitamin K inhibitor, anti-coag

MOA -> inhibits vit K epoxide reductase

- reduced activation of vit K-dependent clotting factors (II, VII, IX, X)

- also affect natural anti-coags protein C and S

Dosing and initiation:

- NOT used alone to start VTE treatment

- requires overlap (bridging) w/ a rapid-acting anti-coag (ex. enoxaparin, heparin)

- overlap continues for minimum 5 days and until 2 consecutive INR readings > 2 at least 24hrs apart

INR goals

- standard anti-coag: 2-3

- prosthetic heart valve: 2.5-3.5

- low-intensity warfarin: 1.5-2.5

Drug interactions

FAB5 potentiate effect (increase INR interaction w/ warfarin -> takes even longer to clot)

- metronidazole, amiodarone, bactrim, fluoroquinolones, fluconazole

Vit K rich food (decrease INR)

Adverse effects

- exacerbates bleeding/bruising

- induced skin necrosis

- purple toe syndrome

Factor Xa inhibitors

Rivaroxaban, apixaban, edoxaban

MOA -> direct inhibiton of factor Xa, preventing activation of thrombin and clot formation

Use

- prevention of stroke in afib

- treatment/prophylaxis/reduce risk of recurrence DVT/PE

General warning

- concurrent antiplatelets, SSRIs, NSAIDs increase risk of bleeding

Side effects

- bleeding and bruising

Fibrinolytic agents

Alteplase, tenecteplase

MOA -> tissue plasminogen activator (tPa)

- enhances conversion plasminogen to plasmin, initiating fibrinolysis

- degrades the fibrin matrix of the thrombus

Side effects

- bleeding, hemorrhage (GI, ICH)

Use:

- unstable PE or severe iliofemoral DVT

- restoring catheter and shunt function

Absolute and relative contraindications

- pregnancy

- healing wounds

- Hx of CVA

- brain tumor

- intracranial bleeding

- metastatic cancer

VTE treatment

Treatment for DVT and PE similar

Basic approach

- initial phase (5-7 days) -> aggressive anti-coag

- maintenance phase (3-6 months) -> full-dose anti-coag

- extended phase -> unprovoked (higher recurrence risk) or provoked (lower recurrence risk)

Preferred agents

DOACs: apixaban, rivaroxaban

Special populations

Pregnancy

- preferred -> UFH and LMWH (does not cross placenta)

- avoid -> warfarin

- lactation -> warfarin, LMWH, UFH all safe

- DOACs -> NOT recommended

Cancer

- first-line: LMWH

- DOACs (rivaroxaban, apixaban, edoxaban) as alternative

Invassive procedures

- assess bleeding risk vs. thrombotic risk

- short half-life agents preferred

- bridging may be needed for high-risk pts on warfarin

Anticoagulation reversal agents

Warfarin

Vitamin-K (phytonadione)

- slower effect -> takes ~24hrs to significantly raise INR

- if immediate reversal needed -> consider FFP or prothrombin complex concentrate (PCC)

UFH and enoxaparin (LMWH)

Protamine sulfate IV

- neutralizes UFH completely

- partially reverses LMWH (enoxaparin)

Stopping/starting blood thinners and procedures

Warfarin

- stop 5 days before procedure

- bridge w/ LMWH is high thrombotic risk (stop LMWH 24hrs before procedure)

- re-start 12-24hrs post procedure

DOACs -> apixaban, rivaroxaban, dabigartran, edoxaban

- low bleeding risk procedure -> stop 24hrs before

- high bleeding risk procedure -> stop 48-72hrs before

- restart 24-72hrs post pocedure

LMWH (enoxapain)

Therapeutic dosing -> stop 24hrs before procedure

- low bleeding risk -> restart 24hr post-op

- high bleeding risk -> restart 48-72hrs post-op

Prophylactic dosing

- stop -> 12hrs before procedure

- restart -> 12-24hrs post-op

UFH -> IV infusion

- stop 4-6hrs before procedure

- restart 6-12hrs post-op

Aspirin (ASA)

- can continue for minor or moderate risk procedures

- stop 5-7days before major high-risk bleeding

Clopidogrel

- stop 5-7 days before

Ticagrelor

- stop 5 days before

Dual antiplatelet therapy

- dealy elective surgery for at least 6-12 months post stent

Antidysrhythmic drugs

Class 1: sodium channel blockers

- quinidine

- lidocaine

Class 2: BB

- propranolol

Class 3: potassium channel blockers

- amiodarone

Class 4: CCB

- verapamil

Class 5: others

- adenosine, digoxin

Class 1: sodium channel blockers

Quinidine

MOA -> binds Na+ channels -> prevents Na+ influx

- delays repolarization -> prolongs action potential

- strong anticholinergic effects -> increases SA node automaticity and AV conduction

- may cause ventricular tachycardia (fast ventricular rate)

Pre-treat w/ BB, verapamil, or digoxin to control ventricular rate

Uses

- treat SV and ventricular dysrhythmias

Indications

- long-term suppression of SVT, atrial flutter, afib, sustained VT

Adverse effects

cinchonism:

- tinnitus, headache, nausea, vertigo, blurred vision

anticholinergic:

- dry eyes, dry mouth, urinary retention, constipation

cardiotoxicity at high doses

Class II: BB

Metoprolol, propranolol, atenolol, esmolol

MOA -> block B-receptors, reducing effects of catecholamines

- decrease HR

- decrease contracility

- depress automaticity

Use -> control ventricular rate

- Afib, atrial flutter

Contraindications

- bradycardia

- 2nd or 3rd degree heart block

- concurrent use w/ non-DHP CCB (verapamil)

Class III: potassium channel blockers

Amiodarone

- most effective antiarrhythmic

Side effects and monitoring

Hyper- and hypo- thyroidism

- TSH/T4 baseline and every 6 months

blue-gray skin discoloration

- PE at every office visit

fulminant hepatitis

- LFTs baseline and every 6 months

pulmonary fibrosis

- CXR baseline and every 12 months

corneal microdepositis

- slit-lamp exam

Class IV: CCB

Verapamil, diltiazem

MOA -> block inward calcium current during plateau and phase 4 of action potential

Use

- supraventricular arrhythmias

- control of ventricular rate in Afib and atrial flutter

Adverse effects

- bradycardia, AV block, heart failure, vasodilation hypotension, peripheral edema, constipation

Digoxin for anti-arrhythmia

MOA -> inhibits Na/K-ATPase pump, suppresses AV node conduction, shortens refractory period

- decrease HR, increase contraction (pos inotrope)

- PO or IV

Adverse effects

- dysrhythmias

Monitoring

- ECG, HR, BP, CrCl, drug level, electrolytes, s/s toxicity

Signs of toxicity

- greenish-yellow halos, arrhythmias, blurred vision

Contraindications

- ventricular fibrillation

Atropine

MOA -> antimuscarinic, blocks acetylcholine

- monitor HR, BP, ECG

Indications

- bradyarrhythmia

Adverse effects

- blurred vision, xerostomia, urinary retention, constipation, tachycardia

Adenosine

MOA -> slows conduction time through AV node

- IV only, 6mg dose

DOC for converting acute supraventricular tachycardias (SVT)

- ultra short half life (~10 seconds)

Adverse effects

- chest pain/pressure, flushing, GI distress, dyspnea

Contraindications

- bradyarrythmias

Sinus bradycardia

HR < 60bmp

- can occur w/ sick sinus syndrome or tachy-brady syndrome

Stable -> no treatment

Hemodynamically unstable

- 1st line atropine 0.5mg IV q3-5min (max dose 3mg)

- if refractory: dopamine infusion, epinephrine infusion

Chronic management of sick sinus syndrome

- pacemaker

- HFpEF pts: continue BB + pacemaker

Atrial fibrillation

Goals of treatment

- improve ventricular function

- prevent stroke/systemic embolism

Rate control

strict goal: HR <80bpm

- if symptomatic or HFrEF

lenient goal: HR <110bpm

- if asymptomatic and preserved EF

meds

- BB (metoprolol, atenolol)

- non-DHP CCB (verapamil, diltiazem)

Rhythm control

- goal: maintain sinus rhythm + improve quality of life

- consider in younger, symptomatic pts of failed rate control

Stroke prevention

- risk scoring (CHA2DS2-VASc)

- anti-coag as needed; DOACs preferred

Meds for anginal symptoms and stable angina CAD risk reduction

Anginal rescue relief

- SL NTG

- NTG spray

Anginal symptoms prophylaxis

- BB, CCB, long acting nitrates

- ranolazine

Reduce mortality and prevent future event, pts get all 3:

antiplatelet

- aspirin 81mg OR clopidogrel

ACEi/ARB

- esp if DM, HTN, CKD, HF, prior MI

Statin

- high-intensity for ALL pts w/ known CAD

Nitrates

Rapid Acting Nitroglycerin (glyceryl trinitrate)​

MOA

- Converts to nitric oxide​ → Relaxes vascular smooth muscle​ → Leads to vasodilation​

Use

- Rescue therapy​

- Quickly halt episode of angina once it has begun​

- should be used no more every 2-3 days

1st line for acute angina attacks

- sublingual or translingual to avoid fist-pass metabolism

- call EMS if no relief after 1st dose

Pharmacodynamic actions: vascular dilation​

- Peripheral Arteries → ↓ Afterload​

- Peripheral Veins → ↓ Preload​

- Coronary Arteries → ↑ Blood flow to the heart muscle​

Dosing options

Sublingual SL tablet

- usually 0.4mg PRN for chest pain, max 3 doses

Nitroglycerin pray

- 0.4mg/spray, 1-2 sprays q5min PRN, max 3 doses

Beta blocker for angina

Mechanism of Action: Antagonize adrenergic beta receptors​

- Reduce the workload of the heart​

- Decrease myocardial oxygen demand​

- ↓ heart rate and contractility​

Titrate to resting HR of 55-60bpm

Clinical benefits

- Works at rest and during exertion​

- Reduces both symptomatic and silent ischemia​

- Decreases frequency and severity of angina​

Side effects

- Bradycardia ​

- Heart block​

- Mask the signs of hypoglycemia​

- Impaired glucose tolerance​

- Rebound tachycardia (with abrupt stop)​

- Bronchospasm- especially in non cardio selective​

- Hypotension​

- Fatigue​

- Depression​

- Insomnia​

- Impotence​​

Contraindications

- Bradycardia​

- Hypotension​

- Second/third degree heart block​

- Uncontrolled reactive airway disease​

- Severe peripheral artery disease​

- DM with frequent hypoglycemia​

- HFrEF and unstable fluid status​

CCB for angina

Dihydropyridine (DHP) amlodipine

MOA

- relax vascular smooth muscle -> vasodilation

- use only for long acting formulas

Non-dihydropyridine (Non-DHP) verapamil, diltiazem

MOA

- slow SA/AV node conduction

- decrease HR and contractility

Goal: reduce oxygen demand by decreasing workload

Key points

- Non-DHPs are generally more effective for angina​

- Both types can be used in stable angina​

- Avoid combining Non-DHPs + beta blockers (risk of bradycardia/heart block)​

Side effects

Non-DHPs

- Bradycardia ​

- Hypotension ​

- Heart Block​

- LV depression​

- Headache​

- Constipation (verapamil)​

Fatigue​​

DHP:​

- Ankle/leg edema​

- Reflex tachycardia​

- Hypotension​

- Headache​

- Gingival hyperplasia​

- Fatigue​

Long acting nitrates

Nitroglycerin, Isosorbide Mononitrate, Isosorbide Dinitrate​

MOA

- Cause vasodilation (mostly veins > arteries)​

- ↓ preload by pooling blood in veins → ↓ heart workload​

Important points:

Can cause reflex sympathetic activation → ↑ heart rate and oxygen demand​

- Using a beta blocker can reduce this reflex increase​

Nitrates require a nitrate-free interval daily to prevent tolerance (so no continuous 24-hour coverage)​

- can develop w/in 1-7days of continuous use

- leads to reduced efficacy

- increase dose does NOT overcome tolerance

Dosing strategy

- require 10-14hr nitrate-free interval daily

- commonly dose at night while sleeping

- patches should be removed after 12hrs, do NOT wear for full 24hrs

Caution

- avoid in pts w/ low baseline bp

- use cautiously if combines w/ low doses of CCB or BB that cause hypotension​

Side effects

- Headache​ -> Will likely resolve within 2 weeks​

- Flushing​

- Dizziness​

- Weakness​

- Nausea​

- Postural hypotension​

- Syncope​

- Reflex tachycardia​

- Skin irritation (topical products)​

- Increase ICP​

- Rebound HTN & angina ​-> If abruptly discontinued​

Angina treatment

Sublingual nitroglycerin + long-acting antianginal drug​

1) BB preferred​

- Decrease mortality- especially with prior MI​

- Suppress nitrate-induced reflex tachy​

2) If inadequate or contraindications:​

- substitute NDHPs: If not taking a BB (due to side effects) and no bradycardia, AV block, HF​

- Add OR Substitute: DHPs are safer​: if need to combine w/ BB, good if pt has bradycardia, AV block, HF​

- add/substitute a long-acting nitrate​ -> Need nitrate holiday

3. If inadequate or contraindications:

- add/substitute Ranolazine​

Comorbid conditions preferred medications

​Asthma

- verapamil or diltiazem, AVOID BB

Hyperthyroidism

- BB preferred

Depression

- CCB preferred, avoid BB

Vasospastic angina (cocaine use)

- CCB is drug of choice

Angina treatment algorithm

Rescue Therapy​

- SL nitroglycerin (or spray) as needed​

Initial Maintenance Therapy​

β-Blockers >>> Non-DHP CCB as first line​

- alternative: CCB or long-acting nitrates​

if initial maintenance unsuccessful​

- add on CCB or long-acting nitrates​

- ranolazine may be added on or substituted​

choices depends on HR and BP and responsiveness​

Vasospastic Angina​

CCB’s or long-acting nitrates ​

- may add-on long-acting nitrates to CCB’s and vis versa​

β-blockers may induce alpha reflex vasoconstriction​

- DO NOT GIVE

Aspirin for stable angina

Mechanism of Action​

- irreversible inhibition of thromboxane (TXA2) production via COX-1​

- Effects last the lifespan of the platelet (~7-10 days)​

​

Dosing​ -> 81mg to 162mg by mouth daily ​

- ACS: 325mg loading dose then 81 mg daily​

- higher maintenance doses = no further benefit​

Alternative

- clopidogrel

​

Side-effects / Adverse Events​

- dyspepsia, nausea, bleeding/bruising, thrombocytopenia​​

Clopidogrel for stable angina

Mechanism of Action​

- Inhibits ADP binding to platelet P2Y12 receptor ​

- prevents activation of GPIIb/IIIa complex ​

- ↓ platelet aggregation​

- Irreversible inhibition (platelet lifespan 7-10 days)​

Good for stable angina or lower-risk ACSACS

​

Indications:​

- Alternative to ASA in SIHD patients who can’t tolerate aspirin​

- Used in DAPT for ACS patients (especially post-PCI or stenting)​​

​

Pharmacogenetic factors​

- prodrug needing conversion to active metabolite by CYP2C19​

- Slower onset compared to newer P2Y12 inhibitors​​

Ticagrelor for stable angina

Mechanism of Action​

- Inhibits ADP binding to platelet P2Y12 receptor ​

- prevents activation of GPIIb/IIIa complex ​

- ↓ platelet aggregation​

- Reversible inhibition​

Preferred in ACS

​

Indications:​

- Alternative to ASA in SIHD patients who can’t tolerate aspirin​

- Used in DAPT for ACS patients (especially post-PCI or stenting)​

​​

Pharmacogenetic factors​

- Not a prodrug: does not need conversion to active metabolite​

- Faster onset compared to Clopidogrel​​