Lecture 11/12: Drugs for Shock/Hypertension and Hypertensive Emergencies Flashcards
What is the initial treatment for Shock that is NOT cardiogenic in nature?
FLUID REPLACEMENT!
- give 20-40 mL/kg
Goal: to increase Jugular Venous Pressure slightly above normal (< 8 cm H2O)
What is the treatment for Anaphylactic Shock?
- immediately give EPINEPHRINE
- can also give antihistamine and inhaled albuterol
What is the treatment for Hypovolemic Shock?
- FLUIDS (usually do not need drugs)
Blood Loss < 15 - 30% –> give crystalloid
Blood Loss 30 - 40%+ –> give crystalloid AND blood
What receptors do these Vasopressors/Inotropes for Shock activate:
- Dopamine
- Norepinephrine
- Epinephrine
- Dobutamine
- Phenylephrine
- Vasopressor
- stimulates Beta at low doses, stimulates Alpha at high
- stimulates Alpha and Beta 1 receptors, NOT Beta 2
- stimulates Alpha, Beta 1, and Beta 2 receptors
- stimulates B1 receptors, vasodilates periphery
- stimulates Alpha receptors, reflexively dec. HR
- from posterior pituitary: V1 vasoconstrictor
What is the treatment for Cardiogenic Shock?
- can use either norepinephrine OR dopamine, but NOREPINEPHRINE is SUPERIOR
- can give dobutamine for refractory shock when low cardiac output despite adequate filling pressure
What is the treatment for Septic Shock?
- start with BROAD SPECTRUM ANTIBIOTICS
Vasopressors:
- NE is FIRST LINE CHOICE (can sub. EPI)
- Dopamine if bradycardia occurs
Inotropic: DOBUTAMINE IS FIRST LINE CHOICE
low dose corticosteroid use improves shock reversal but NOT beneficial in absence of shock
Hydrochlorothiazide
What is its MOA, what is it used to treat, and what are 3 common toxicities of use? (H/H/S)
MOA: thiazide diuretic that blocks the NA/Cl cotransporter in the distal convoluted tubule and is used for hypertension (not effective in pts with low GFR)
Toxicities: hypokalemia (K-losing), hypomagnesemia, sulfonamide (not for hypersensitive pts)
What are chlorothiazide, chlorthalidone, and metolazone?
- all are Thiazide diuretics
Chlorthalidone: prolonged (40-60 hr life) response preferred by some hypertension specialists
Metolazone: favorite of cardiologists as adjunct diuretic in congestive heart failure treatment
Furosemide
What is its MOA, what is it used for, and what are 4 common toxicities of use? (H/H/O/S)
What can it be used in that thiazides cannot?
MOA: loop diuretic that blocks Na/K/2Cl cotransporter in thick ascending limb of Henle causing massive fluid removal
use: heart failure edema (dec. preload) and hypertension (works in pts with LOW GFR)
Toxicities: hypokalemia, hypocalcemia (inc. kidney stone risk), ototoxicity (reversible), and sulfonamide
What are 3 other Loop Diuretic options? (T/B/EA)
- torsemide = longer half life, better absorption
- some evidence that it works better in heart failure
- bumetanide = more predictable oral absorption
- ethacrynic acid = NON-sulfonamide (for pts. with sulfa allergy)
Amiloride
What is its MOA, what is it used for, and what is its major boxed warning?
What is Triamterene?
MOA: blocks epithelial sodium (ENaC) channels in the collecting duct, blocking the major pathway for K elimination
use: counteracts K loss induced by other diuretics in hypertension and heart failure
Toxicity: hyperkalemia (also hyperchloremic metabolic acidosis)
T: similar to amiloride (for edema and hypertension)
Spironolactone
What is its MOA, what are its two primary uses, and what are 3 common toxicities of use? (H/AH/GI)
What is eplerenone?
MOA: competitive antagonist of aldosterone receptors that blocks aldosterone promoting Na/K exchange in collecting duct and antagonizes pro-fibrotic effects
uses: K-sparing diuretic, reduced fibrosis in HFrEF and post-MI heart failure
Toxicities: hyperkalemia, amenorrhea/hirsutism, gynecomastia/impotence
E: more selective aldosterone antagonist
What are 4 ACE inhibitors that can be used to treat hypertension? (C/E/B/L)
What are two major toxicities they cause?
captopril
- also enalapril (prodrug; enalaprilat is active), benazepril, lisonopril
Toxicities: cough (number one reason why they are NOT tolerated) and angioedema (swollen tongue = choking so stop ASAP)
What are 3 Angiotensin II Receptor blockers that can be used to treat hypertension? (L/V/C)
Losartan
- also: valsartan (not prodrug; excreted in feces) and candesartan (irreversible binding)
What drug binds DIRECTLY to renin and what is it used for?
Why is it not commonly used?
Aliskiren –> direct renin inhibitor that can be used for hypertension (can block renin inc. that could possibly offset ACEi/ARB therapy)
- NOT COMMONLY USED because it is new/expensive, has no obvious benefits, and might have evidence of inc. risk of adverse events
What are 2 dihydropyridine and 2 non-dihydropyridine Calcium Channel Blockers that can be used in pts. with hypertension?
Which drug will show inc. HR and contractility?
D: nifedipine (prototype) and amlodipine (very widely used due to long half life of 30-50 hrs)
- Nifedipine has inc. HR/contractility due to primarily affecting vasculature (SNS reflex occurs)
ND: verapamil and diltiazem
CCBs are important first line therapy drugs for hypertension
What are the 4 front line oral drug classes used to treat hypertension? (TD/Ai/A/C)
- Thiazide or thiazide-type diuretics
- ACE inhibitors
- ARBs
- CCBs - dihydropyridines AND non-dihydropyridines
What are the alpha 1, alpha 2, beta 1, and beta 2 adrenergic receptors responsible for in the Sympathetic Baroreceptor Reflex?
a1: on blood vessels = vasoconstriction
a2: brain/periphery = dec. sympathetic tone
B1: inc. HR and contractility, stimulate renin secretion by kidneys
B2: dilate skeletal muscle vasculature
What Prazosin used to treat and what are two of its major toxicities? (OH/RE)
What is tamsulosin/terazosin/doxazosin used to treat?
P: blocks a1 receptors to vasodilate veins/arterioles in pts. with hypertension but has many adverse effects
TE: orthostatic hypotension, retrograde ejaculation
T/T/D: similar to prazosin but marketed for BPH and to help kidney stones pass
- one drug solution for old man in wheelchair with BPH and hypertension
What are Clonidine and a-methyldopa used for?
What are 2 toxicities found with each drug?
C: alpha-2 receptor agonist that causes reduced sympathetic outflow once in brainstem (transient inc. in BP after IV though)
- TE: drowsiness, xerostomia, REBOUND HTN if missed a dose
aM: selective a2 receptor agonist for moderate-severe HTN and is a drug of choice for GESTATIONAL HTN (along with labetalol and nifedipine)
- TE: positive Coombs test, SLE-like syndromes
What Beta Blocker used for hypertension is nonselective and why is it contraindicated with Peripheral Vascular Disease?
What are 3 competitive B1-selective blockers (A/M/B) and what are they used for?
beta 1 receptor antagonists block both cardiac and juxtaglomerular cells (no renin release)
Propranolol - nonselective antagonist that slows HR/contractility but blunts vascular vasodilation
CI: can cause cold extremities, especially in infants
- also causes bronchospasm and bradycardia
Atenolol, metoprolol, bisoprolol (has highest beta-1 selectivity) –> treat HTN and angina pectoris (dec. HR)
What happens if a2-agonists or Beta-blockers are stopped abruptly?
- cause REBOUND HYPERTENSION
B1 blockers –> cardiac stimulation to normal SNS tone
a2 agonists –> excessive SNS tone
Hydralazine and Hypertension
What is its MOA and what 3 things is it used for?
What is a major toxicity it can cause?
MOA: direct arteriole vasodilator that decreases systemic resistance
use: HFrEF intolerant to ARB/ACEi, HFrEF in African Americans, HTN emergency in pregnancy
T: drug-induced lupus-like syndrome
Nitroprusside and Hypertension
What is its MOA and what is it used for?
What is a major toxicity it can cause?
MOA: peripheral vasodilation by direct action on venous AND arteriolar SM that reduced peripheral resistance and inc. CO by decreasing afterload
use: hypertensive crises and acute decompensated HF
T: metabolic acidosis due to CYANIDE TOXICITY
Minoxidil and Hypertension
What is its MOA and what is it used for?
MOA: direct vasodilation by directly relaxing arteriolar SM and can stimulate HAIR GROWTH; lowers arteriolar vascular resistance
use: treatment of HTN that is symptomatic and NOT manageable with maximum therapeutic doses of diuretic plus 2 other antihypertensives
What are 3 conditions that suggest bilateral renovascular hypertension rather than primary hypertension? (FPE/RF/RCCF)
- Flash Pulmonary Edema
- Progressive Renal Failure
- Refractory Congestive Cardiac Failure
What drugs would be used for each of these classes in a Hypertensive Emergency:
- CCB - dihydropyridines (N/C)
- Vasodilators - NO dependent (N/N)
- Vasodilators - direct (H)
- Beta-1 selective blocker (E)
- nicardipine and clevidipine
- sodium nitroprusside and nitroglycerin
- hydralazine
- esmolol
What drugs would be used for each of these classes in a Hypertensive Emergency:
- alpha-1/nonselective Beta blocker (L)
- nonselective alpha blocker (P)
- D1 receptor agonist (F)
- ACE Inhibitor (E)
- labetalol
- phentolamine
- fenoldopam
- enalaprilat
