Linger CIS Clinical Pharm of Antihypertensives Flashcards
Benefits of antihypertensive therapy relative risk reduction
Heart Failure
Stroke
MI
50%
30-40%
20-25%
Carbonic anhydrase Inhibitors prototype
acetazolamide
Carbonic anhydrase Inhibitors MOA
inhibits the membrane-bound and cytoplasmic forms of carbonic anhydrase
Carbonic anhydrase Inhibitors Results in
↓ H+formation inside PCT cell
↓ Na+/H+antiport
↑ Na+and HCO3-in lumen
↑ diuresis
Carbonic anhydrase Inhibitors PH results
Urine pH is increased and body pH is decreased
Loop Diuretics prototypes
furosemideand ethacrynicacid
Loop Diuretics moa
inhibit the luminal Na+/K+/2Cl-cotransporter(NKCC2) in the TAL of the loop of Henle
Loop Diuretics results in
↓ intracellular Na+, K+, Cl-in TAL
↓ back diffusion of K+ and positive potential
↓ reabsorption of Ca2+and Mg2+
↑ diuresis
Loop Diuretics facts
- Ion transport is virtually nonexistent
* Among the most efficacious diuretics available
Thiazide Diuretics prototype
hctz/chlorthalidone
Thiazide Diuretics moa
cause inhibition of the Na+/Cl-cotransporter(NCC) and block NaClreabsorption in the DCT
Thiazide Diuretics results in
↑ luminal Na+and Cl-in DCT
↑ diuresis
Thiazide Diuretics facts
- Enhance the reabsorption of Ca2+in both DCT and PCT
- Largest class of diuretic agents
- More hyponatremiceffects than loop diuretics
- Use with caution in patients with diabetes mellitus
K+ sparing diuretics
Mineralocorticoid receptor (MR) antagonists
- Spironolactoneand eplerenone
- Uses include hyperaldosteronism, adjunct to K+-wasting diuretics, antiandrogenicuses (female hirsutism), heart failure (reduces mortality)
- Do not require access to the tubular lumen to induce diuresis
- Adverse effects include hyperkalemia, acidosis, and antiandrogeniceffects
K+ sparing diuretics
Na+channel (ENaC) inhibitors
- Amilorideand triamterene
- Uses include adjunct to K+-wasting diuretics and lithium-induced nephrogenicdiabetes insipidus (amiloride)
- Adverse effects include hyperkalemia and acidosis
Thiazide Diuretics used for
hypertension, mild heart failure, nephrolithiasis (calcium stones), nephrogenicdiabetes insipidus
Thiazide Diuretics adverse effects
hypokalemia, alkalosis, hypercalcemia, hyperuricemia, hyperglycemia, hyperlipidemia, sulfonamide hypersensitivity
Beside thiazide diuretics what other class of diuretics can be used to treat calcium stones
loop bc they flush everything out
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?
Chlorthalidone–thiazide-like diuretic, increase ca reabsorption
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 GFRand proteinuria. Which drug is indicated for additional blood pressure control at this time?
Enalapril–ACE inhibitor, renoprotective by dialating the efferent arteriole
Which finding, if present, would contraindicate the use of angiotensin converting enzyme inhibitors?
Bilateral renal artery stenosis
Renal Considerations with ACEIs
- ACEIs prevent/delay the progression of renal disease in type 1 diabetics and in patients with nondiabeticnephropathies (results mixed in type 2 diabetics)
- ACEIs vasodilateefferent arterioles > afferent arterioles
- Reduces back pressure on the glomerulus and reduces protein excretion
- ACEIs usually improve renal blood flow and Na+excretion rates in CHF
- In rare cases, ACEIs can cause a rapid decrease in GFR, leading to acute renal failure (ARF)
- Can occur anytime during therapy, even after months or years of uneventful ACEI treatment
Risk Factors for ACEI-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, cyclosporinA)
- Diffuse atherosclerosis in smaller renal vessels
- Vasoconstrictor agents (NSAIDs, cyclosporine)
- All cause renal hypoperfusion
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?
you dont want to block b2 bc you will bronchoconstrict and exacerbate asthma
nondihyropyridine ccb, dont effect bronchoconstriction
β-Blocker Use in Hypertension
- No longer 1stline treatment for hypertension, except when concomitant with a compelling indication
- Heart failure with reduced left ventricular function
- Rate control in atrial fibrillation
- Ischemic heart disease or recent MI
- Predispose to diabetes, particularly when combined with thiazide
- Relative contraindication: 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?
Carvedilol
Labetalol
- Selective 1blocker
- Nonselective 1& 2blocker
- Partial agonist at 2
- Clinical Uses:
- IV for severe hypertension
- Acceptable option for hypertension during pregnancy
Carvedilol
- Nonselective -blocker + 1-blocker
* Also has antioxidant properties
A patient presents to the ED with acute hypotension that requires treatment. Hypovolemiais 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?
Prazosin–alpha1-selective antagonist
extra - phenylephrine is an a1 agonist so it constricts vessels
α1-Selective Receptor Blockers clinical use
3rdor 4thline treatment of essential hypertension; added to other agents from different classes in refractory cases; also used in men with concurrent HTN and BPH
α1-Selective Receptor Blockers pharmacodynamics effects
- Prevent vasoconstriction of both arteries and veins
- ↓TPR, ↓venous return, ↓ preload
- Usually do not ↑ heart rate or cardiac output
- Do not ↑ NE release (no 2block)
- Favorable effects on lipids (↓LDL & triglycerides; ↑HDL)
- Relaxes smooth muscle in the prostate
α1-Selective Receptor Blockers adverse effects
- Postural hypotension & syncope, especially with initial doses
- Usually given at bedtime to minimize hypotensive effects
A 28-year old 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?
any raas drug
A 28-year old 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? Which drug is she most likely taking now?
A methyldopa
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
- Many side effects –sedation, dry mouth, sexual dysfunction, postural hypotension, anemia
- Now only used to treat hypertension in pregnancy because of its safety
clonidine
- An 2-adrenergic receptor agonist
- IV-increase BP (peripheral 2B) followed by decreased BP (central 2A)
- Oral -decreased BP (decreased C.O., preload)
- Patch -same as oral
- Clinical Use
- Essential hypertension (rarely used)
- Adjunct for narcotic, alcohol, & tobacco withdrawal (unlabeled)
- Side Effects
- Dry mouth, sedation, impotence, depression
- Sudden withdrawal causes hypertensive crisis
Hypertension in Pregnancy overview
Maternal benefit is well-established for treatment of severe hypertension (systolic pressure ≥ 160 mmHg and/or diastolic pressure ≥ 110) in reduction of stroke risk
Hypertension in Pregnancy long-term oral therapy options
- Methyldopa
- Beta-blockers: labetalol, pindolol, metoprolol
- Calcium channel blockers: nifedipine, nicardipine
- Hydralazine: monotherapycarries risk of reflex tachycardia, can be used as add-on therapy with methyldopa or labetalol
Hypertension in Pregnancy drugs to avoid
- ACE inhibitors, ARBs, direct renin inhibitors
* Nitroprusside
A 45 y/o male is brought to the ED with signs of delirium. His blood pressure is 220/160 and he has retinal hemorrhages. A short-acting agent that binds to voltage-gated ion channels is administered by intravenous infusion in an effort to lower his blood pressure. Which drug best fits this description?
clevidipine
Drugs for Hypertensive Emergencies goals
Controlled and gradual lowering of blood pressure without excessive hypotension that could lead to MI, stroke, or loss of vision
Drugs for Hypertensive Emergencies Vasodilators
- Sodium nitroprusside
- Nitroglycerin
- Nicardipine
- Clevidipine
- Fenoldopam
- Hydralazine
- Enalaprilat
Drugs for Hypertensive Emergencies Adrenergic antagonists
- Labetalol
- Metoprolol
- Esmolol
- Phentolamine
Initial Monotherapy
- Thiazide diuretic
- ACE inhibitor or ARB
- Renoprotective(always use first in CKD +/-diabetes)
- Less effective antihypertensive in individuals of African descent
- Do not combine direct RAS inhibitors (ACEIs, ARBs, or renin inhibitors)
- Calcium channel blocker
- β-blockers are not typically used in the absence of a specific indication
Polypharmacy
•Two or three drugs at half standard doses might have greater efficacy and less toxicity than one drug at standard or twice standard dose
African Heritage
Most preferred drugs - CCB, thiazide diuretic
Least preferred drugs -
Pregnancy
Most preferred drugs - methyldopa, hydralazine
Least preferred drugs - acei arb
Physically active
Most preferred drugs - acei ccb alpha blocker
Least preferred drugs - beta blocker
noncompliance
Most preferred drugs - drug with once daily dosage regimen, transdermal or clonidine (transdermal
Least preferred drugs - oral centrally acting a adrenoceptor agonist
Angina pectoris
Most preferred drugs - beta blocker, diltiazem verapamil
Least preferred drugs - hydralazine minoxidil
asthma copd
Most preferred drugs - ccb acei
Least preferred drugs - beta blocker
bph
Most preferred drugs - alpha blocker
Least preferred drugs -
collagen disease
Most preferred drugs - acei (but not captopril) ccb
Least preferred drugs - hydralazine methyldopa
depression
Most preferred drugs - acei ccb
Least preferred drugs - centrally actin a adrenoceptor agonist beta blocker reserpine
diabetes mellitus
Most preferred drugs - acei ccb angiotensin receptor antagonist
Least preferred drugs - beta blocker, diuretic
gout
Most preferred drugs -
Least preferred drugs - diuretic
heart failure
Most preferred drugs - acei diuretic hydralazine
Least preferred drugs - ccb
hypercholesterolemia
Most preferred drugs - alpha blocker acei ccb
Least preferred drugs - beta blocker thiazie
migraine
Most preferred drugs - beta blocker ccb
Least preferred drugs -
MI
Most preferred drugs - beta blocker acei arb
Least preferred drugs -
Osteoporosis
Most preferred drugs - thiazide
Least preferred drugs -
Peripheral Vascular disease
Most preferred drugs - acei ccb alpha blocker
Least preferred drugs - beta blocker
