CARDIO FINAL ELSAID: SNS/HTN

Adrenergic Receptor Subtypes

alpha-1

• in blood vessels

• excitatory

• vasoconstriction of arteries/arterioles

• increases BP and SVR

alpha-2

• in autonomic ganglia and CNS

• inhibitory autoreceptor

• inhibits release further release of NE, Ach, and insulin to prevent overstimulation

beta-1

• in heart

• excitatory

• inotropic (contractility) + chronotropic (HR)

• increases renin

beta-2

• in lungs/muscles

• inhibitory/excitatory

• vasodilation + bronchodilation

• increases glucagon

Adrenergic Agonists

Phenylephrine

• alpha 1 >

• nasal decongestant, vasopressor

Clonidine

• alpha 2 >

• centrally acting antihypertensive, alcohol/BZD withdrawal, chronic pain

• inhibitory effect

dexmedetomidine

• alpha 2 >

• ICU sedation

NE

• predominantly alpha 1 (some beta-1)

• vasopressor (vasoconstricts + increases HR)

epinephrine low dose

• 0.01 - 0.05: beta effect (increase CO, decrease SVR)

• vasopressor, anaphylaxis, asthma

epinephrine high dose

• 0.05+: alpha-1 > (increase SVR)

• vasopressor, anaphylaxis, asthma

dobutamine

• beta 1 >

• inotrope (increases contractility)

isoproterenol

• beta 1 = beta 2 > alpha

• inotrope (increases contractility)

albuterol

• beta-2 >

• bronchodilator for acute asthma

dopamine low dose

• 2 - 5

• D1 receptor

• renal vasodilation

• improve urine output

dopamine medium dose

• 5 - 10

• beta 1 + D1 (inotropic, chronotropic + renal vasodilation, improve urine output)

dopamine high dose

• 1 - 20

• alpha-1 (vasoconstriction, increase BP, SVR)

Adrenergic Antagonists

Prazosin, Terazosin, Doxazosin

• alpha 1 >

• antihypertensives

• lowe BP by relaxing blood vessels

Tamsulosin

• alpha 1 >

• manages BPH

Yohimbine

• alpha 2 >

• supplement for ED/stimulant

• blocks alpha-2 → no inhibitory effect → continued NE release → increases BP

Labetalol and Carvedilol

• beta 1 = beta 2 >/= alpha 1 > alpha 2

• non selective beta blocker w/ alpha 1 blocking

• decreases BP (decrease HR + vasodilation)

which drug improves heart failure survival?

Carvedilol

Metoprolol and Atenolol

• beta 1 >

• selective

• treats HTN and arrhythmia (reduces HR)

Propranolol

• beta 1 = beta 2

• nonselective

• HTN and arrhythmia

• used for migraines because it it lipophilic and crosses BBB easily

renin

• protect against hypotension

• low BP → activate RAAS → increase BP

renin released as

pro-renin

actions of angiotensin II

• vasoconstriction

  • increases PVR and BP

• aldosterone release

• ADH release

• increase sympathetic activity

actions of aldosterone

• promote sodium reabsorption in exchange for potassium excretion

• water reabsorption → increase blood volume → BP increase

• release ADH

Captopril, Lisinopril, Enalapril

• class

• MOA

• ACEis

• MOA

  • inhibit ACE = prevent conersion to Ang II

    • vasodilation, decreased aldosterone, less Na/water retention

• 1st line

• “prils”

ACEi also inhibits

breakdown of bradykinin

• more bradykinin → cough side effect

Enalaprilat

• IV

• metabolite of oral Enalapril (prodrug)

Azilartan, Candesartan, Olmesartan, etc

• class

• MOA

• angiotensin II receptor blockers (ARBs)

• MOA

  • prevent Ang II from binding

    • no aldosterone release → no vasoconstrictor effect

• “sartans”

Aliskiren

• class

• MOA

• renin inhibitor

• directly inhibit renin activity (not pro-renin)

• not 100% effective

Spironolactone

• class

• MOA

• type of diuretic

• aldosterone antagonist

• block aldosterone receptor in kidney → prevent Na reabsorption

• K+ sparing diuretic

hyperkalemia

• which drugs cause?

• high risk in?

• high potassium

• ACEis, ARBs, aldosterone antagonists

  • low aldosterone → less Na/K exchange → conserves K+

• HF and CKD

ACEi specific ADEs

• dry cough

• angioedema = allergic swelling of soft tissues

• both due to increase of bradykinin

HTN: Diuretics

what do diuretics do?

• promote Na and H2O excretion

  • decrease blood volume → decrease BP

water needs —— to be reabsorbed

• aquaporin channels

Acetazolamide

• class

• MOA

• effect

• use

• carbonic anhydrase inhibitors

• inhibit carbonic anhydrase in PCT

  • prevent bicarbonate and Na+ reabsorption

• weak diuretic

  • loss of bicarbonate → lead to acidic blood (acidosis)

• patients w/ metabolic alkalosis

Furosemide, Bumetanide, Torsemide

• class

• MOA

• effect

• side effects

• loop diuretics

• inhibit Na/K/Cl symporter in thick ascending loop

  • lose Na (no reabsorption) → diuretic effect

• most powerful diuretic

  • major loss of Na, K, Ca, Mg

• hypokalemia, hypocalcemia, hypomagnesia

Hydrochlorothiazide, Chlorthalidone

• class

• MOA

• preferred in…

• side effects

• thiazide and thiazide-like diuretic

• inhibit Na/Cl symporter in DCT

• HTN

• hypokalemia, hypercalcemia, hyperuricemia

what to use instead of thiazides if pt has sulfa allergy?

ethacrynic acid

2 types of potassium sparing diuretics

• Na channel antagonist

• aldosterone antagonist

potassium sparing diuretics

• what it increases?

• target?

• combined?

• increase K levels

• targets collecting tubule

• combined w/ loop and thiazide

Amiloridine, Triamterene

• class

• MOA

• effect

• Na channel antagonists

• block Na channel → no Na reabsorption → no exchange w/ K

• weak diuretic effect

• Spironolactone

• Aldosterone

  • MOA

  • side effects

• aldosterone antagonists

• block aldosterone receptor → No Na/K exchange

• Spironolactone

  • gynecomastia > >

• epelerenone

  • hyperkalemia > >

• hyperkalemia, hyperuricemia

Mannitol

• class

• MOA

• osmotic diuretic

• prevent water reabsorption

non-DHPs

• drugs

• target

• for what?

• Verapamil, Diltiazem

• affects heart

  • slows HR and contractility

• for arrythmias

DHP

• drugs

• target

• for what?

• Amlodipine, Nifedipine (“pines”)

• vasodilation of arteries/arterioles

• for HTN

DHP selectivity

• in smooth muscle

• vasodilation → lower BP

• can cause reflex tachycardia

reflex tachycardia

• sudden drop in BP from vasodilation sensed by baroreceptors → trigger compensatory increase in HR

• use Amlodipine to reduce this effect

non-DHP selectivity

• equipotent for cardiac tissue and vasculature

• SA node

  • block Ca entry → decreased HR

• cardiac myocytes

  • block Ca entry → decreased contractility

non-DHP ADEs

• bradycardia

• AV block

• worsening of systolic HF

Precautions/CIs of CCBs

• avoid in HFrEF

• avoid non-DHPs in pts w/ 2nd or 3rd degree AV block

• avoid short-acting DHPs due to risk of profound hypotension and reflex tachycardia

Beta Blockers

Labetalol

• non-selective beta-blocker and alpha blocker

• added vasodilatory effect

• IV in hypertensive emergencies

Carvedilol

• non-selective beta-blocker and alpha blocker

• for HF

• oral

Atenolol and Metoprolol

• beta-1 selective (cardioselective)

• widely used for HTN and HF

cautions of beta blockers

• avoid abrupt discontinuation

  • rebound HTN

  • tachycardia

• renal dysfunction

  • reduce dose

DDI of beta blockers

• non-DHP (Verapamil, Diltiazem)

  • cause heart block and hypotension

avoid beta blockers in

• sinus bradycardia

• heart block

• asthma

ADE of beta blockers

• bradycardia/conduction abnormalities

• bronchospasm (non-selective)

• fatigue, dizziness

Alpha blockers

• MOA

• example

• vasodilation of arteries

• “zosin” — Prazosin, Doxazosin, Terazosin

which patients benefit from alpha blockers?

BPH — benign prostatic hyperplasia

ADE of alpha blockers

• 1st dose phenomenon

  • significant drop in BP (hypotension) and reflex tachy after 1st dose

• orthostatic hypotension

  • take at bedtime to minimize risk

• edema

DDI of alpha blockers

• phosphodiesterase-5 inhibitors

  • additive hypotensive effect

centrally acting antihypertensives

• alpha-2 receptor agonists in CNS

• clonidine, methyldopa

• inhibit NE release → reduce sympathetic outflow → vasodilation → reduce BP

centrally acting antihypertensives Place in therapy

• clonidine

  • resistant HTN

• methyldopa

  • pregnancy-induced HTN

ADE of centrally acting antihypertensives

• edema (worse in methyldopa)

• orthostatic hypotension

direct vasodilators

• MOA

act directly on smooth muscle of blood vessels → vasodilation by

• hyperpolarization → open K+ channels

• - release nitric oxide (NO)

hydralazine

• vasodilator

• preferred in CKD or renal failure → increases renal blood flow

Minoxidil is

• not 1st line

ADE of vasodilators

• reflex tachycardia

• edema

• drug induced lupus (hydralazine) but reversible

• hirsutism (minoxidil) (hair growth)