Intro To Hypertensives-Kruse Flashcards
What part of the nephron does acetazolamide target?
PCT
What is the prototype carbonic anydrase inhibitor and what is its MOA?
Acetazolamide
Inhibits membrane-bound and cytoplasmic forms of carbonic anhydrase
Describe what happens to the following (increase or decrease) with the administration of acetazolamide:
___ H+ formation inside PCT cell
___ Na/H antiport
___ Na and HCO3 in lumen
___ diuresis
Urine pH is ___ and body pH is ___
Decrease Decrease Increase Increase Increase Decrease
___ is rarely used as an antihypertensive due to low efficacy as single agents and development of metabolic acidosis. Instead, they are used for glaucoma, acute mountain sickness, and metabolic alkalosis
Carbonic anhydrase inhibitors
What are adverse effects of carbonic anhydrase inhibitors?
Acidosis, hypoK, renal stones, parasthesias (high doses), sulfonamide hypersensitivity
What are the prototype loop diuretics and what is their MOA?
Furosemide and ethacrynic acid
Inhibit luminal Na/K/2 Cl cotransporter
Describe what happens to the following (increase or decrease) when furosemide or ethacrynic acid are administered:
___ intracellular Na, K, Cl in TAL
___ back diffusion of K and positive potential
___ reabsorption of Ca and Mg
___ diuresis
Decrease
Decrease
Decrease
Increase
Ion transport virtually nonexistent
Among the most efficacious diuretics available
What are some clinical indications for loop diuretics?
What are some adverse effects of loop diuretics?
Used for edema, heart failure, HTN, acute renal failure, anion overdose, and hypercalcemic states
Adverse effects include hypoK, alkalosis, hypocalcemia, hypomagnesemia, hyperuricemia, ototoxicity, sulfonamide hypersensitivity
What is the prototype thiazide diuretic and its MOA?
Hydrochlorothiazide
Causes inhibition of the Na/Cl cotransporter (NCC) and blocks NaCl reabsorption in the DCT
Describe what happens to the following (increase or decrease) when given a thiazide diuretic:
___ luminal Na and Cl in DCT
___ diuresis
___ reabsorption of Ca in both DCT and PCT
Increase
Increase
Increase
What are some adverse effects of thiazide diuretics?
Thiazide diuretics should be used with caution in patients with ___
Adverse effects include hypoK, alkalosis, hypercalcemia, hyperuricemia, HYPERGLYCEMIA, HYPERLIPIDEMIA, sulfonamide hypersensitivity
DM
___ is the most important site of K secretion by the kidney and is the site at which all diuretic-induced changes in K balance occur-more Na delivered to this portion leads to more K secretion
Collecting tubule
What are the K sparing diuretics that are mineralocorticoid receptor antagonists and what are some of their uses?
Spironolactone and eplerenone
Uses include hyperaldosteronism, adjunct to K-wasting diuretics, antiandrogenic uses (female hirsutism), heart failure (REDUCES MORTALITY)
What are some K sparing diuretics that are ENaC inhibitors and what are some of their uses?
Amiloride and triamterene
Uses include adjunct to K-wasting diuretics and Lithium-induced nephrogenic diabetes insipidus (amiloride)
Describe the effects of carbonic anhydrase inhibitors on the following urinary electrolytes:
- NaCl
- NaHCO3
- K
- Body pH
NaCl-Increase (+)
NaHCO3-Increase (+++)
K-increase (+)
Body pH-decrease
Describe the effects of loop agents on the following urinary electrolytes:
- NaCl
- NaHCO3
- K
- Body pH
NaCl-increase (++++)
NaHCO3-no change
K-Increase (+)
Body pH-increase
Describe the effects of thiazides on the following urinary electrolytes:
- NaCl
- NaHCO3
- K
- Body pH
NaCl-increase (++)
NaHCO3-increase (+)
K-increase (+)
Body pH-increase
Describe the effects of loop agents plus thiazides on the following urinary electrolytes:
- NaCl
- NaHCO3
- K
- Body pH
NaCl-increase (+++++)
NaHCO3-increase (+)
K-increase (++)
Body pH-increase
Describe the effects of K-sparing agents on the following urinary electrolytes:
- NaCl
- NaHCO3
- K
- Body pH
NaCl-increase (+)
NaHCO3-slight increase (+)
K-decrease (-)
Body pH-decrease
What are the prototypical ACE inhibitor drugs and what are their MOA?
Captopril and enalapril
Inhibit the conversion of Ang I to the more active Ang II; also prevent degradation of bradykinin and other vasodilator peptides
What are some adverse effects associated with ACE inhibitors?
Hypotension
COUGH
ANGIOEDEMA
HYPERKALEMIA-avoid K-sparing diuretics
ACUTE RENAL FAILURE-particularly in pts with renal a. stenosis
Fetopathic potential (teratogen)-CONTRAINDICATED IN PREGNANCY
What are some drug interactions associated with ACE inhibitors?
Antacids Capsaicin NSAIDs K sparing diuretics Digoxin Lithium Allopurinol
What are some risk factors for ACE inhibitor-induced ARF?
- MAP insufficient for adequate renal perfusion–> poor CO, low systemic vascular resistance
- Volume depletion (diuretic use)
- Renal vascular disease –> b/l renal a. 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
What type of signal transduction pathway is associated with AT1 receptors?
Gq –> PLC –> IP3 + DAG –> smooth m. Contraction
Major subtype in adults
___ receptors cause production of NO and bradykinin, smooth m. dilation
AT2
What are the prototype ARB drugs And what are their MOA?
Losartan and valsartan
Selectively block AT1 receptors
Describe what happens to the following (increase or decrease) when given an ARB:
___ contraction of vascular smooth m.
___ aldosterone secretion
___ pressor responses
___ cardiac cellular hypertrophy and hyperplasia
All decrease
No effect on bradykinin metabolism
What are some adverse effects of ARBs and when is it contraindicated?
Similar to ACEI’s but less cough and edema; contraindicated in pregnancy
___ is a direct renin inhibitor that that blocks the conversion of angiotensinogen to ANG I. It does not increase bradykinin
Aliskiren
Similar to ACEIs and ARBs and contraindicated in pregnancy
What are the prototypes (or the 2 that kruse wants us to know) for the non-DHP CCB’s? What are their effects?
Verapamil > Diltiazem
Promote cardiac effects, but also act at vascular tissues
What are the prototypes of DHP CCB’s and their effects?
Amlodipine and Nifedipine
Predominantly arteriolar vasodilation effects
What are some adverse effects and toxicity related to CCBs?
- GENERALLY VERY WELL TOLERATED
- Excessive vasodilation-dizziness, hypotension, headache, flushing, nausea; diminished by long-acting formulations and long half-life agents
- CONSTIPATION (Esp. VERAPAMIL), PERIPHERAL EDEMA, coughing, wheezing, pulmonary edema
- Use of verapamil/diltiazem with a B-blocker is CONTRAINDICATED b/c of potential for AV block
These CCBs should not be used in pts with ventricular dysfunction, SA or AV nodal conduction defects and systolic BP
Verapamil/Diltiazem
What are clinical uses of CCBs?
HTN –> most useful when combo with another agent to counteract the reflex CV responses
Hypertensive emergencies –> parenteral formulations
Angina–> reduction of O2 demand makes particularly useful
These drugs increase K permeability, stabilizie the smooth muscle membrane at resting potential, reducing the probability of contraction
K channel openers
Includes Diazoxide and Minoxidil
This K channel opener vasodilates arterioles but has diminishing use in HTN emergencies due to adverse effects such as excessive hypotension that can cause stroke and MI as well as hyperglycemia
Diazoxide
This K channel opener vasodilates arterioles and clinical uses include severe HTN and baldness (topical). Adverse affects include headache, sweating, hypertrichosis, and reflex tachycardia and edema (must be used with B blocker and diuretic to avoid this)
Minoxidil
___ is a D1 receptor agonist. Activation of these receptors by this drug increases blood flow to the kidneys by dilating the afferent arteriole. It is used for HTN emergencies and post-operative HTN
Fenoldopam
Adverse effects –> tachycardia, headache, and flushing
Should be avoided in pts with glaucoma due to increases in intraocular pressure
THis drug release NO from endothelium and dilates arterioles but not veins. It is first line PO therapy for HTN in pregnancy, with methyldopa.
Hydralazine
What are some adverse effects of hydralazine?
- can induce fluid and sodium retention
- headache, nausea, anorexia, flushing, palpitations
- reflex tachycardia can provoke angina in pts with ischemic heart disease
- lupus-like syndrome
Nitroprusside and organic nitrates are used to tx HTN emergencies, heart failure, and angina (nitrates). What is the prototype?
Nitroglycerin
___ dilates both arterial and venous vessels - decreases TPR and venous return. They decrease both preload and afterload. Effects are mainly relaxation of large veins –> decrease venous return –> decrease preload –> decrease O2 demand (major effect), smaller decrease in afterload
Nitroprusside
What are some adverse effects of nitroprusside? Nitrates?
Nitroprusside: excessive hypotension, cyanide poisoning
Nitrates: orthostatic hypotension, syncope, throbbing headache
Propanolol is this type of B-adrenoreceptor antagonist:
Non-selective, Non-ISA (intrinsic sympathomimetic activity)
Metoprolol and Atenolol are this type of B-adrenoreceptor antagonist:
B1-selective, Non-ISA
B blockers are no longer 1st line tx for HTN, except when concomitant with a compelling indication such as:
Heart failure
Recent MI
Reduced left ventricular function
What is a relative contraindication of usage of beta blockers for HTN?
Asthma
___ is a selective a1 blocker, nonselective B1 and B2 blocker, and partial agonist at B2. It is used for IV for severe HTN, and an acceptable option for HTN during pregnancy
Labetalol
___ is a nonselective B blocker + a1 blocker. It has antioxidant properties
Carvedilol
These drugs are non-selective vasodilating B blockers
Carvedilol and Labetalol
This B1 selective drug has a very rapid onset and short DOA. It is used as IV fusion for peri-operative tachycardia and HTN, HTN emergencies, and arrhythmias. It is also used in electroconvulsive therapy
Esmolol
These types of drugs are 3rd or 4th line tx for essential HTN; added to other agents from different classes in refractory cases; also used in men with concurrent HTN and BPH
a1 selective receptor blockers
__ is an a2 adrenergic receptor agonist. When given IV will increase BP followed by decreased BP. When PO, will decrease BP. It is used clinically for essential HTN (Rarely used). Side effects include sudden withdrawal causing HTN crisis
Clonidine
___ is a false NT concept and when released acts as a centrally acting a2 agonist and decreases central sympathetic outflow and decreases BP. It is now only used treat HTN in pregnancy because of its safety
Methyldopa
These diuretics target specific membrane transport proteins:
Loop diuretics –> Na/K/2Cl co-transporter
Thiazide diuretics –> Na/Cl co-transporter
K sparing diuretics –> Na channels
