Anti-Hypertensives CIS Flashcards
A 53 y/o female presents with BP of 155/90. She has a history of diabetes with hypertension currently treated with insulin and hydrochlorothiazide. Laboratory results indicate reduced GFR and proteinuria. Which drug is indicated for additional blood pressure control at this time?
A. Enalapril B. Metoprolol C. Nifedipine D. Prazosin E. Torsemide
A- renal protective effects– selectivity of efferent vs afferent (RIGHT ANSWER)
b- cardio selective beta blocker
c- dihydropyridine CA channel blocker
d- alpha one selective blocker
e- loop diuretic
A 53 y/o female presents with BP of 155/90. She has a history of diabetes with hypertension currently treated with insulin and hydrochlorothiazide. Laboratory results indicate reduced GFR and proteinuria. Which finding, if present, would contraindicate the use of angiotensin-converting enzyme inhibitors?
A. Bilateral renal artery stenosis B. Congestive heart failure C. Gastroesophageal reflux disease D. Hypokalemia E. Peripheral edema
A- bilateral renal artery stenosis
Renal Considerations with ACE Inhibitors
ACE inhibitors prevent/delay the progression of renal disease in type 1 diabetics and in patients with nondiabetic nephropathies (results mixed in type 2 diabetics)
ACE inhibitors vasodilate efferent arterioles > afferent arterioles
- Reduces back pressure on the glomerulus and reduces protein excretion
ACE inhibitors usually improve renal blood flow and Na+ excretion rates in CHF
In rare cases, ACE inhibitors can cause a rapid decrease in GFR, leading to acute renal failure (ARF)
- Can occur anytime during therapy, even after months/years of uneventful treatment
Risk Factors for ACE Inhibitor-Induced ARF
MAP insufficient for adequate renal perfusion
- Poor cardiac output
- Low systemic vascular resistance
Volume depletion (diuretic use)
Renal vascular disease
- Bilateral renal artery stenosis
- Stenosis of dominant or single kidney
- Afferent arteriolar narrowing (HTN, cyclosporin A)
- Diffuse atherosclerosis in smaller renal vessels
Vasoconstrictor agents
- NSAIDs
- Cyclosporine
All cause renal hypoperfusion
Benefits of antihypertensive therapy
Reduced risk of heart failure, stroke, MI (in that order)
The degree of blood pressure reduction, not the choice of antihypertensive medication, determines risk reduction.
Changes in Urinary Electrolytes and Body pH in response to different classes of diuretics
Carbonic Anydrase inhibitors –> highest level of NaHCO3 in urine
Potassium sparing –> decreased potassium in urine
Loop diuretics–> greatest amount of NaCl excreted
Thiazide diuretics–> NaCl, NaHCo3 and K+ to urine
Carbonic Anhydrase Inhibitors
Prototype: acetazolamide MOA: inhibits the membrane-bound and cytoplasmic forms of carbonic anhydrase Results in: ↓ H+ formation inside PCT cell ↓ Na+/H+ antiport ↑ Na+ and HCO3- in lumen ↑ diuresis Urine pH is increased and body pH is decreased
Loop Diuretics
Prototypes: furosemide and ethacrynic acid
MOA: inhibit the luminal Na+/K+/2Cl- cotransporter (NKCC2) in the TAL of the loop of Henle
Results in: ↓ intracellular Na+, K+, Cl- in TAL ↓ back diffusion of K+ and positive potential ↓ reabsorption of Ca2+ and Mg2+ ↑ diuresis
Ion transport is virtually nonexistent
Among the most efficacious diuretics
Thiazide Diuretics
Prototype: hydrochlorothiazide (HCTZ)
MOA: cause inhibition of the Na+/Cl- cotransporter (NCC) and block NaCl reabsorption in the DCT
Results in:
↑ luminal Na+ and Cl- in DCT
↑ diuresis
Enhance the reabsorption of Ca2+ in both DCT and PCT
Largest class of diuretic agents
Potassium-Sparing Diuretics: 2 classes
Mineralocorticoid receptor Antagonists
ENaC Inhibitors
Mineralocorticoid Receptor (MR) Antagonists
Spironolactone and eplerenone
Therapeutic Use: hyperaldosteronism, adjunct to K+-wasting diuretics, antiandrogenic uses (female hirsutism), heart failure (reduces mortality)
Do not require access to the tubular lumen to induce diuresis
ADRs: hyperkalemia, acidosis, antiandrogenic
Na+ Channel (ENaC) Inhibitors
Amiloride and triamterene
Therapeutic Use: adjunct to K+-wasting diuretics and lithium-induced nephrogenic diabetes insipidus (amiloride)
ADRs: hyperkalemia and acidosis
A 42 y/o male presents to the ED complaining of sharp flank pain radiating to the groin, gross hematuria, and dysuria. A urine sample is obtained. Microscopy identifies a large amount of calcium oxalate crystals in the urinary sediment. He has a history of untreated hypertension and previous episodes of nephrolithiasis. Which agent would be most appropriate in this setting?
A. Acetazolamide B. Benazepril C. Chlorthalidone D. Spironolactone E. Valsartan
We are looking for thiazide diuretic because it increases Ca+ absorption, so the answer is
C.
Thiazide Diuretics
Prototype: hydrochlorothiazide (HCTZ)
Therapeutic Use:
- Hypertension, mild heart failure, nephrolithiasis (calcium stones), nephrogenic diabetes insipidus
ADRs: hypokalemia, alkalosis, hypercalcemia, hyperuricemia, hyperglycemia, hyperlipidemia, sulfonamide hypersensitivity
- More hyponatremic effects than loop diuretics
- Use with caution in patients with diabetes mellitus
Besides Thiazide diuretics,
What other class of diuretics can be used to treat calcium stones?
Potentially loop because of increased volume of urine, but not a firstline option becuase it increases Ca+ in the urine
A 51 y/o male presents with difficulty breathing. The patient is afebrile and normotensive, but tachypneic. Auscultation of the chest reveals diffuse wheezes. The physician provisionally makes the diagnosis of bronchial asthma and administers epinephrine by intramuscular injection, improving the patient’s breathing over several minutes. A normal chest X-ray is subsequently obtained, and the medical history is remarkable only for mild hypertension that was recently treated with propranolol. The physician instructs the patient to discontinue use of propranolol, and change the patient’s antihypertensive medication to verapamil.
Why is the physician correct to discontinue propranolol?
Why is verapamil a better choice for managing hypertension in this patient?
Propanalol is contraindicated in wheezing due to its bronchocontrictive effects from Beta receptor blocking effects.
Verapamil acts specifically at cardiac receptors
β-Blocker Use in Hypertension
No longer 1st line treatment for hypertension, except when concomitant with a compelling indication:
- Heart failure
- Recent MI
- Reduced left ventricular function
Caution in diabetes, particularly when combined with thiazide
Relative CI: asthma
Less stroke protection than other antihypertensives
A patient has essential hypertension, and lab tests show that their circulating catecholamine and plasma renin levels are unusually high. The chosen therapeutic approach for this patient is to give a single drug that blocks both α- and β-adrenergic receptors, thereby reducing BP by reducing both CO and TPR. Which drug is most likely prescribed?
A. Carvedilol B. Metoprolol C. Nadolol D. Pindolol E. Timolol
A. Carvedilol
B-E beta selective blockers
β-Blockers with α-Blocking Activity
Labetalol Selective alpha 1 blocker Nonselective beta 1 & beta 2 blocker Partial agonist at b2 Therapeutic Use: - IV for severe hypertension - Acceptable option for hypertension during pregnancy
Carvedilol
Nonselective b-blocker + a1-blocker
Also has antioxidant properties
A patient presents to the ED with acute hypotension that requires treatment. Hypovolemia is ruled-out as a cause or contributor, and information gathered from the patient and family indicates that the cause is overdose of an antihypertensive drug. One approach to treatment is to administer a pharmacologic (ordinarily effective) dose of phenylephrine. You do just that, and BP fails to rise at all—and a second dose doesn’t work either. On which drug did the patient most likely overdose?
A. Atenolol B. Nicardipine C. Prazosin D. Propranolol E. Verapamil
C. Prazosin, alpha 1 selective
phenylephrine is an alpha 1 agonist
atenolol- beta blocker
nicardipine- dihydropyridine CCB
Propanalol- beta blocker
Verapamil- non-dihydropyridine CCB
alpha 1-Selective Receptor Blockers
MOA: prevent vasoconstriction of both arteries and veins
↓ total peripheral resistance, ↓ venous return, ↓ preload
Usually do not ↑ heart rate or cardiac output
Do not ↑ NE release (no 2 block)
Favorable effects on lipids (↓ LDL & triglycerides; ↑ HDL)
Relaxes smooth muscle in the prostate
Therapeutic Use: 3rd or 4th line treatment of essential hypertension; added to other agents from different classes in refractory cases; also used in men with concurrent HTN and BPH
ADRs: postural hypotension & syncope, especially with initial doses; usually given at bedtime to minimize hypotensive effects
selectiity of alpha blockers
alpha 2 receptors are on the cell releasing the NE, alpha 1 receptors on the receiving cell
Phentolamine blocks both (leads to release of more NE), prazosin just the alpha 1 receptors
A 28 y/o woman is receiving drug therapy for essential hypertension. She subsequently becomes pregnant. You realize that the drug she’s been taking for her high blood pressure can have serious, if not fatal, effects on the fetus. As a result, you stop the current antihypertensive drug and substitute another that is deemed to be equally effective in terms of her blood pressure, and safer for the fetus. Which drug was she most likely taking before she became pregnant?
A. α-Methyldopa B. Captopril C. Furosemide D. Labetalol E. Verapamil
B. Captopril is an ACE inhibitor, teratogenic
Now we’ve probably switched her to methyldopa. labetalol could also be ok.
Methyldopa
False neurotransmitter concept:
- Converted to methyl-NE
- Stored in vesicles instead of NE
- Released & acts as a centrally acting α2-agonist
- Decreases central sympathetic outflow & decreases blood pressure
Therapeutic Use: only used to treat hypertension in pregnancy because of its safety
ADRs (many): sedation, dry mouth, sexual dysfunction, postural hypotension, anemia
