Renal Pharmacology Flashcards
Acetazolamide
Diuretic
How does acetazolamide work
Inhibiting carbonic anhydride, halting the production of bicarbonate from water and CO2..leads to sodium bicarbonate diuretic, acidifying the blood and alkalyzing the urine
Indication for acetazolamideglaucoma,
altitude sickness, pseudotumor cerebri, CHF, metabolic alkalosis
Side effects acetazolamide
Hyperchloremic metabolic acidosis and paresthesias
Glaucoma and acetazolamide
Decreases aqueous humor , reducing intraocular pressure
Inhibits formation of bicarbonate int he eye, which draws in sodium, which is followed by water
Acetazolamide reduces bicarbonate, leading to decreased aqueous humor in the eye
Altitude sickness and acetazolamide
Decreasing bicarbonate stores, acidifying the blood pH. Facilitates the renal compensation for respiratory alkalosis, allowing ventilation to increase without having respiratory alkalosis
Acetazolamide and pseudotumor cerebri/idiopathic intracranial hypertension
Carbonic anhydride inhibitors may be able to reduce the rate of CSF production to lower pressure
Acetazolamide and DHF
Diuretic when treating CHF associated edema
Metabolic alkalosis and acetazolamide
Reduces total body stores of HCO3, i
MOA acetazolamide
Carbonic anhydride inhibitors (interfering its bicarbonate absorption into e kidneys so blood is acidified and urine is alkalyzed)
Sodium bicarbonate diuresis(reduces body stores of HCO3
Side effects of acetazolamide
Metabolic acidosis (reduce HCO3) Paresthesia
Mannitol
Osmotic diuretic which works to increase urine flow
Indications for mannitol
Acute treatment
Increased intracranial pressure
Glaucoma
Drug overdose
Mannitol is acute treatment
Intracranial hypertension, primary open angle glaucoma, drug overdose
Side effects mannitol
Use is dehydration, and patients should be monitored for this
Mannitol contradiction
Anuria and CHF
Indications mannitol
Increased intracranial pressure
Glaucoma
Drug overdose
Mannitol and increased intracranial pressure
Bolus0osmotic properties
Glaucoma and mannitol
Acute treatment of open angle
Until a more definitive treatment can be used
Decreased IOP by decreasing vitreous humor volume
Does not cross blood ocular barrier and thus exerts oncotic pressure which dehydrates the vitreous
Drug overdose and mannitol
Promote excretion of substances such as asprin and barbiturates
MOA mannitol
Osmotic diuretic, increased urine flow
How is mannitol and osmotic diuretic
Filtered by kidney glomeruli, but is incapable of being reabsorbed from the renal tubules. This results in water and Na reabsorption via its osmotic effect. Consequently mannitol increases water and Na excretion, thereby decreasing extracellular fluid volume
How does mannitol increase urine flow
Increases tubular fluid osmolarity which leads to increased Na and water flow through the collecting duct, resulting in increased urine flow
Side effects mannitol
Dehydration
Why no give mannitol to anuria
Is anuric is secondary to renal disease
Mannitol does not influence urine production, only enhances existing urine output. If there is no production (as in ARF) you would have hyperosmotic plasma due to mannitol since it would be trapped in that compartment (and thus be of no benefit and possible harm)
Why no mannitol in CHF
Causes retention of fluid in the plasma. It extracts water from the intracellular compartment and increases blood volume, which can worsen CHF and pulmonary edema
Loop diuretics
Class of diuretics that inhibit nak2cl symporter in the thick ascending limb or the loop of Henley
Most common loop diuretic
Furosemide (lasix)
Allergies to loop diuretics
Yea they are sulfa drugs, they contain a sulfonamide group and can cause allergic reactions in patients with sulfa allergies
Side effects loop diuretics
Electrolyte abnormalities (hypokalemia, hypokalemia)
Reduce irate excretion, leading to hyperuricemia, and gout
Ototoxicity
MOA loop diuretic
Inhibit NaK2CL at thick ascending loop (impermeable to water here-for diluting urine)
Prevent generation of a hypertonic renal medulla.
Prevents urine from being concentrated and leads to increased urine production, thus reducing intravascular volume
Why should we not give furosemide to patients with sulfa allergies
It is a sulfa drug
Gout and loop diuretics
High uric acid
Diuretics reduce rate of excretion by directly and indirectly increasing rate reabsorption and decreasing irate secretion.
Ototixicity of loop diuretics
Vertigo, tinnitus
Hypocalcemia and loop diuretics
Inhibit calcium reabsorption in the kidney and can lead to hypocalcemia. Occurs bc calcium reabsorption in the thick ascending limb is dependent on an electrochemical potential difference which is normally maintained by nak2cl symporter. When this symporter is inhibited there is decreased calcium resorption
Hypokalemia and loop diuretics
Prevent reabsorption of na and cl in loop of Henley, increased sodium and water passes through collecting tubules in the kidney. Increases distal tubular sodium concentration stimulates the aldosterone sensitive sodium pump to increase sodium reabsorption in exchange for k and h Ions which are lost to the urine. Also volume depletion due to increased urine output causes further increased secretion of aldosterone which further increases the secretion of k into the collecting duct and into the urine. It
Ethacrynic acid
Phenoxyacetic acid derivative and is not a sulfonamide. Loop diuretic, and works to decrease blood volume, treating hypertension and edema
MOA ethacrynic acid
Loop diuretic
Inhibits nak2cl
Side effects ethacrynic acid
Hypokalemia, ototoxicity, and gout
Large doses lead to hepatotoxicity
MOA erthacrynic acid
Non sulfa drug (can give to people with sulfa allergies)
Is a phenoxyacetic acid derivative and is composed of a ketone group and methylene group
Loop diuretic
Inhibits nak2cl
Indications for ethacrynic acid
Diuresis
Decreasing blood volume (hypertension or edema)
Side effects ethacrynic acid
Hypokalemia
Ototoxicity
Gout
Thiazides diuretics
First line treatments for hypertensionsulfa drugs (allergic)
Thiazides diuretics MOA
Inhibit NaCL reabsorption by blocking the NaCl cotransporter int he early distal tubule. Increased sodium excretion can lead to hyponatremia and increased delivery of sodium to the collecting ducts can lead to hypokalemia metabolic alkalosis
Side effects thiazides diuretics
Hyperglycemia Hyperlipidemia Hypercalcemia Hyperuricemia Hyponatremia Hypokalemia metabolic alkalosis
Thiazides and hyperglycemia
Decrease insulin
Hyperlipidemia and thiazides
Decrease insulin
Hypercalcemia and thiazides
Inhibit nacl transport, na concentration in the cell drops , causing increased activity of the basolateral na ca exchanged which brings na from the blood into the cell, while extruding ca into the blood, leading to hypercalcemia
Also induce hypovolemia which increases na and water absorption in the proximal tubula, which passively increases ca reabsorption as well
Hyperuricemia and thiazide
Reduce irate excretion by directly and indirectly increasing irate reabsorption and decreasing irate secretion. May lead to gout
Hyponatremia and thiazide
Block reabsorption of na in the distal convoluted tubule
Thiazide and hypokalemic metabolic alkalosis
Increased delivery of na to the collecting ducts causes increased cellular uptake of na from the lumen by apical. Epithelial na channels which causes the basolateral na k exchanger to more actively exchange na for k, resulting in k loss. The increased delivery of k to the collecting ducts also facilitates the exchange of k for h by the h/k exchanger on the intercalated alpha cells resulting in loss of h causing a metabolic alkalosis. Further loss of k is also stimulated by activation of renin-angiotensin-aldosterone system
Hydrochlorothiazide (HCTZ0
Most commonly used thiazide diuretic due to its function int reating high bp and fluid retention
Indications for HCTZ
Essential hypertension, edema, diabetes insipidus
First line in African Americans
MAO HCTZ
Inhibits reabsorption NaCl (in early segment of distal convoluted tubule)and H20
Promoting urine production
Indications HTCZ
Edema, mild to moderate hypertension
Edema HCTZ
Moderate heart failure to decrease excess fluid in the system
Need proper renal function for meds to work
Mild to moderate hypertension HCTZ
Lower bp by reducing blood volume and reducing arterial resistance. Along or in combo with hypertensive meds.
First line African Americans
Side effects HCTZ
Hypokalemia Hyponatremia Dehydration Hyperglycemia Gout
HCTZ allergy
Sulfa allergy
HCTZ pregnancy and breast feeding
NO
It will be excreted in breast milk
Also category B risk during pregnancy
Diuretics may reduce overall circulating volume and reduce blood flow to the placenta leading to the risk of birth defects. For this reason , diuretics like HCTZ are often avoided as first line agents
K sparing diuretics
Diuretic which do not promote the secretion of potassium into the urine
How do k sparing diuretics work
Competing with aldosterone for binding sites or directly blocking epithelial Na channels (ENaC)
Indication or k sparing diuretics
CHF , hypertension and combined with other diuretics to Counter hypokalemia which they may cause
Spironolactone
K sparing diuretic
Treats hyperaldosteronism
Side effects k sparing diuretics
Hypercalcemia, which may lead to arrhythmias and muscle weakness, as wel as spironolactone induced gynecomastia
Indication for k sparing diuretics
CHF, hypertension
Hypokalemia
Hyperaldosteronism
What k sparing diuretic treats hyperaldosteronism
Spironolactone bc it is a competitive aldosterone receptor antagonist
MOA k sparing diuretics at the collecting tubule
Antagonize aldosterone or na channels
Amigo ride and triamterene
Block the apical sodium channel decrease na reabsorption
Spironolactone and eplerenone
Compete with aldosterone for binding to intracellular receptors causing:
- Decreased gene expression and reduced synthesis of a protein mediator that activates na channels int he apical membrane
- Decreased na/k/atpase pumps in the basolateral membrane
What is spironolactone used for
Heart failure, as cites, hypertension, hypokalemia, hyperaldosteronism
Also antiadronergic as it blocks androgen binding through various mechanisms
Competitive aldosterone receptor antagonist(competes for intracellular mineralocorticoid receptors in late distal tubule or collecting tubule decreasing reabsorption of na and water while decreasing secretion of k)
__ is a similar drug to spironolactone
Eplerenone
Amiloride and triamterene
K sparing diuretics which act in the distal tubule of collecting tubule to decrease k loss by excreting their actions on epithelial sodium channels
Block ENaC to prevent its reabsorption in collecting tubules. Na is not reabsorbed and k is not exchanged or wanted into collecting tubule lumen
Side effects k sparing diuretics
Hyperkalemia
Gynecomastia
Signs of hyperkalemia
Muscle weakness and fatal arrhythmias
Gynecomastia with spironolactone
Antiandrogen effects and weak progesterone effects
Spironolactone (aldactone)
K sparing diuretic. Opposite effects as aldosterone as it promotes k retention and na excretion
Spironolactone produces minimal ___ bc the excreted sodium is quickly reabsorbed by the nephron
Diuresis
May take 48 hours
MOA spironolactone
Na and water retention and k excretion
Blocks effect of aldosterone and increases k reabsorption and sodium excretion
Why is potassium (spironolactone) retention important for cardiac patients
Elevated potassium can lead to dysarrhythmias. To maintain an ion balance in the nephron as potassium is retained, na will be excreted
Indications for spironolactone
Hypertension, edema, heart failure
Why use spironolactone for heart failure
Blocking aldosterone receptors int he heart and blood vessels, along with decreasing fluid and retaining k.
Aldosterone has harmful effects on the heart, so blocking it provides beneficial results in HF patients
Side effects spironolactone
Hyperkalemia and endocrine effects
Why get endocrine effects with spironolactone
Structure is derived from a steroid structure bc of this spironolactone can cause menstrual irregularities, deeming of the voice and gynecomastia
Why avoid potassium supplements on spironolactone
It increases k reabsorption can lead to hyperkalemia if not watched
ACE inhibitor
Treat hypertension, CHF, and diabetic nephropathy
Worry about ACE inhibitors
Toxicities
What are toxicities of ACE inhibitors
Cough, angioedema, K changes, taste changes, hypotension, pregnancy changes, rash increased renin, lower angiotensin II, also hyperkalemia(bc lower aldosterone)
How remember ACE inhibitors toxicities
CARTOPRIL
Why cough on ACE inhibitor
Increased bradykinin
Angioedema ACE inhibitors
Increased bradykinin
Seen in patients with genetic predisposition to degrade bradykinin more slowly
ACE inhibitors and potassium changes (hyperkalemia)
Decreased angiotensin also leads to decreased aldosterone
Taste chance ACE inhibitor
Sulfhydryl group found in ACE inhibitors
High doses of captopril
AcE inhibitors and pregnancy
Still birth, fetal renal damage, congenital malformations
Rash and ACe inhibitors
Captopril
Associated with sulfhydryl group found in ACE inhibitors
Increased renin ACE inhibitors
Due to negative feedback of angiotensin I to angiotensin II conversion
Lower angiotensin II ACE inhibitors
Inhibits angiotensin converting enzyme, which is responsible for the conversion of angiotensinI to angiostatin II
ACE inhibitors
Antihypertensive drugs that work by inhibiting the renin angiotensin aldosterone system
How do ACE inhibitors lower bp
Inhibiting angiotensin converting enzyme and decreasing the amount of angiotensin II and aldosterone
-get lowered arteriolar resistance, increased venous capacity
-decrease cardiac output and index and stroke volume
Natriuresis is increased, while there is a decreased resistance in the blood vessels of the kidney
Side effect ACE inhibitors
Bradykinin, which display as persistent dry cough
Suffix of ACE inhibitors
Pril
Indication for ACE inhibitors
Hypertension, CHF (with left ventricular systolic dysfunction), angina, cardiac ischemia, post MI patients diabetic nephropathy
MOA ACE inhibitors
Inhibit ACE
Decrease GFR-inhibits constriction of efferentarteriole
ACE
Secreted by the lungs and kidneys. Converts angiotensin I to II to activate AT1 receptors in the adrenal cortex. Leads to lowered aldosterone levels too
What happens when angiotensin II binds to AT1 receptor
Vascular NADpH oxidase, superoxide, adhesion molecules, PAI-1
CARDIOVASCULR TOXICITY
What happens when angiotensin II bindsto AT2
Increase eNOS, NO, PGI2, EDHF, t-PA, PKC, cGMP
CARDIOVASCULAR PROTECTION
What does bradykinin do
Increase eNOS, NO, PGI2, EDHF, tPA, and CARDIOVASCULAR PROTECTION
What does angiotensin 2 do
Constricts efferent arterioles increasing GFR
Why increased concentration of renin with ACE inhibitors
Bc negative feedback of angiotensin I to angiotensin II conversion
Side effects ACE inhibitors
Increased bradykinin cough
Potent vasodilator
Angiotensin receptor blockers (ARBs)
Similar in effect to ACE inhibitors but do not result in increased level of bradykinin and are not as likely to cause persistent dry cough as a side effect
Indication for ARB
Intolerant to ACE inhibitor
Suffix ARB
Sartan
What do ARBs treat
Hypertension, CHF, slow progression of ice tic nephropathy
How do ARB work
Block angiotensin II receptors
Side effect ARB
Hyperkalemia due to interference with the renin angiotensin aldosterone system
Indications ARB
Hypertension, CHF, diabetic nephropathy
Hypertension and ARB
Intolerant to ACE inhibitor
Block angiotensin II at AT! Leading to vasopressin and aldosterone reduction, reducing BP
CHF ARB
Candesartan
Diabetic nephropathy ARB
Delay the progression
MOA ARB
Block activation of angiotensin II AT1 receptors without effecting bradykinin levels
Result of angiotensin II AT1 receptors being blocked without effecting bradykinin
Vasodilation and reduction of vasopressin secretion and reduction of aldosterone production and secretion
Side effects ARB
Hyperkalemia
-
Pregnancy and ARB
Not major human. Teratogens but are generally avoided in all trimesters of pregnancy due to the risk of adverse effects
In all trimesters
Erythropoietin (epoetin Alfa, exogenous, procrit)
Recombinant growth hormone that is similar to human erythropoietin and stimulates the production of rbc in the bone marrow. This drug is indicated for patients with anemia secondary to health conditions such as chronic renal failure or chemotherapy treated cancers.
MOA epo
Stimulates RBC production from bone marrow
This increases patients hemoglobin, hematocrit and reticulocyte counts.
On epo the patient must have adequate intake of what
Iron, folic acid, and vitamin B12 in order to maximize the effectiveness of epo
Indications epo
Chronic Rena failure and anemia
Why epo with chronic renal failure
Kidneys make epo
Side effects epo
Increased risk of thrombosis
Pelvic and limb pain
Hypertension
Epo and increased risk of thrombosis ,stroke, MI
Ok
Hypertension and EPO
Increases rbc production , hemoglobin and hematocrit monitor BP
Why shouldn’t you shake a vial of epo
Denature glycoproteins and inactivate medication
Why monitor hog weekly on epo
Idk
Why may epo accelerate tumor progression
Promotes angiogenesis
Do not give to people with leukemia or other myeloid malignancies
Who should not take epo
Cancer patients not receiving radiation or chemotherapy bc of tumor acceleration
