diuretics Flashcards
what are diuretics commonly used for
HTN
heart failure
diuretics sit of action
upstream of the collecting duct. =hyponatremia, hypokalemia and metabolic alkalosis.
in collecting duct result in hyperkalemia and metabolic acidosis
what class of drugs is Acetazolamide
prototype of a class of sulfonamide drugs that- avidly bind to the enzyme carbonic anhydrase
what type of inhibition does acetazolamide produce
noncompetitive inhibition of the enzyme activity
in normal circumstances- what is the carbonic anhydrase enzyme responsible for in the renal tubule
NA+/H+ exchanger- allowing absorption of NA in exchange for secretion of H+ into the renal tubule
in normal circumstances what happens to bicarb and H in the proximal renal tubule
they combine to form carbonic acid
what does the carbonic anhydrase enzyme do to H2C03
catalyzes it into C02 and water
c02 diffuses readily into the tubular cells where cytoplasmic carbonic anhydrase catalyses the reverse reaction leading to
Hc03- and absorption of HC03
carbonic anhydrase inhibitors do what
inhibit carbonic anhydrase in the proximal renal tubule by this class of diuretics results in decreased reabsorption of Na, HC03, an water
who do we adjust acetazolamide dosing for
renal patients and the elderly
acetazolamide blocks what in the proximal tubule
membrane bound and cytoplasmic carbonic anhydrase in the proximal tubule-preventing na and HC03 absorption
***acetazolamide acid base imbalance
alkaline urine and metabolic acidosis
***acetazolamide increase in delivery of sodium to the distal tubules leads to
k loss
how is acetazolamide effective in the treatment of glaucoma
high concentration of carbonic anhydrase enzyme in the ciliary processes, inhibition of the enzyme activity by acetazolamide results in decreased formation of aqueous humor and consequently a decrease in intraocular pressure.
acetazolamide what does it do to ICP
cerebral spinal fluid formation is inhibited by acetazolamide- treatment for idiopathic intracranial hypertension.
if acetazolamide does not decrease ICP-what treatment should occur
placement of ventriculoperitoneal shunt to reduce elevated ICP
acetazolamide produces metabolic acidosis- what might it do to the respiratory drive
it may stimulate the respiratory drive in patients who are hyperventilating in a compensatory response to respiratory alkalosis- such as in altitude sickness
hypoxia at high altitudes is counteracted by hyperventilating which results in respiratory alkalosis resulting in ventilation depression. what can we give to reverse this hypoventilaiton
acetazolamide induced metabolic acidosis can reverse hypoventilation.
***The loss of bicarbonate ions necessary to buffer carbon dioxide may result in the exacerbation of respiratory acidosis in patients with COPD leading to CNS depression
.
Side Effects of Acetazolamide:
Fatigue
Decreased appetite
Depression
Paresthesia (could be secondary to metabolic acidosis)
LOOP DIURETICS
Furosemide, Torasemide, Azosemide, Bumetanide and Ethacrynic acid
loop diuretics Inhibit reabsorption of
NA, K, CL
where do loop diuretics work in the nephron
thick ascending limb of the loop of henle
the thick ascending limb of the loop of henle- is impermeable to water and accounts for the reabsorption of how much filtered na
20-30%
Diuretics in general and loop diuretics in particular are 1st line therapy for what patients
patients with fluid retention resulting form heart failure
what is a common side effect of all loop diuretics
ototoxicity
why dont we use ethacrynic acid
no longer in use due to increased incidence of ototoxicity and nausea and vomiting
furosemide % protein bound to albumin
90%
furosemide PO absorption varies 10-100% with average bioavailability of what %
50%
glomerular filtration and renal tubular secretion account for what percent of furosemide excretion
50-60%
furosemide remaining 40-50% is
conjugated to glucuronide in the kidneys
elimination furosemide half life
1-2 hours resulting in short duration of action
furosemide rapid onset producing diuresis is within
5-10 minutes of administration
peak effect of furosemide
30 minutes
duration of furosemide
2-6hrs
normal renal function furomsedie dose
40mgIV
what happens to the furosemide dose in renal insufficiency patients
increase dose
max diuresis can be achieved with IV bolus of furosemide- what mg?
push slow d/t?
160-200mg
give slowly to avoid tinnitus
will doses larger than 200 of furosemide increase natriuresis
no
bumetanide bioavailability
80-100% after PO administration
bumetanide administration routes
IV, PO, IM
bumetanide how many more times potent than furosemide
40 x more potent
torasemide metabolism
mostly by liver
patients with liver failure receiving torsemide will have an increase drug delivery to which organ
kidneys
torasemide is how much more potent as furosemide
2x
torsemide duration of action
longer duration of action with plasma 1/2 life 3-4 hours thus once a day dosing
comparing furosemide to torsemide which is better for heart failure
Treatment with torasemide was found to decrease readmissions related to heart failure when compared to furosemide.1
what diuretic lowers calcium.
In the presence of symptomatic hypercalcemia, furosemide may be used to lower the plasma concentration of calcium by stimulating urine output
what combination decreases ICP most effectively.
A combination of furosemide and mannitol is more effective in decreasing ICP than either drug alone
Side Effects: loop diuretics
Normally manifest as abnormalities of fluid and electrolyte balance
Hypokalemia; Digitalis Toxicity
Hyperuricemia: rarely clinically significant
Potential hyperglycemia not as likely as thiazides
braking phenomenon
Acute or chronic treatment of patients with diuretics, including loop diuretics, may result in tolerance to the diuretic effect
Side Effects: look diuretics relating to aminoglycosides
enhances he possible nephrotoxic effects of these antibotics
side effects - loop diuretics and non depolarizing neuromuscular blockers
potentiate non depolarizing neuromuscular blockade
loop diuretics cephalosporin
Cephalosporin nephrotoxicity may also be increased by furosemide
furosemide cross sensitivity
Cross sensitivity may exist when allergic to sulfonamides
furosemide and lithium reaction
An acute increase in lithium plasma concentrations with IV administration of furosemide in perioperative period
furosemide- ototoxicity
Ototoxicity is either transient or permanent; is a rare reaction and is dose dependent.
HCTZ and thiazide drugs
chlorthalidone and indapamide
thiazide diuretics what are they used for
most often used for long term treatment of hypertension in which the combination of diuresis, natriuresis, and vasodilation are synergistic
what is the second most frequently prescribed antihypertensive med with other antihypertensives
HCTZ
thiazide diuretics may be used to mobilize edema associated with what three organ dysfunction
renal
hepatic
cardiac dysfunction
thiazide diuretics less common use is
management of DI and hypercalcemia
are thiazide diuretics readily absorbed PO?
yes
HCTZ bioavailability and protein bound
60-70% bioavailability extensively protein bound.
thiazides are eliminated unchanged by the kidneys- except indapamide which is metabolized how
by the liver
thiazide diuretics half life
8-12 hours
thiazide diuretic with the longest elimination half life of 50-60 hrs
chlorthalidone
how effective is thiazide diuretics in renal patients
markedly decrease effectiveness
with the exception of metolazone. thiazide diuretics have what effect on severe renal insufficiency
ineffective in renal insufficiency- use loop diuretics
electrolyte excretion with thiazide diuretics
kaliuresis may accompany sodium and magnesium ion loss
with the loss of potassium and magnesium- thiazide diuretics may present with cardiac
dysrhythmias
side effects of thiazide diuretics
Hypercalcemia especially if on supplements
Potentiate NDMB by producing hypokalemia
Effectiveness is decreased when patient is taking NSAIDS
Potentiates lithium toxicity
May cause glucose intolerance and aggravate glucose control in diabetics
May aggravate hyperlipidemia
Patients with sulfa allergy may demonstrate cross-reactivity to these classes of diuretics
preop orthostatic hypotension suggest
low circulation of fluid volume
what is the only osmotic diuretic in use
mannitol
where does mannitol work
proximal real tubule and loop of henle are the principle site of action
how is osmotic diuretics cleared
from plasma by glomerular filtration
mannitol is a scavenger of free radicals which may prevent?
Is a scavenger of oxygen-free radicals, which may prevent cellular injury
Mannitol Clinical Uses:
Primarily used in the acute management of elevated ICP and in treatment of glaucoma
Exerts effect within 10-15 minutes
Peak effect at 30-45 minutes
Duration of 6 hours
Mannitol Clinical Uses:
Effect on ICP is dose dependent: larger dose may last longer
Large doses up to 2g/kg and repeated administration can result in metabolic derangements
Intact blood-brain barrier is necessary for cerebral effects of Mannitol
Non-intact blood-brain barrier may enter the brain, drawing fluid with it and causing worsening cerebral edema
Rebound increase in ICP may occur following mannitol use
in the setting of acute tubular necrosis- what can mannitol be used to prevent
Can be used to prevent perioperative kidney failure in the setting of acute tubular necrosis
patients with LV dysfunction may not tolerated mannitol leading to
pulmonary edema
what medication is a better choice to treat high ICP in patients with LV dysfunction
furosemide
in renal dysfunction mannitol is not filtered and will cause
In renal dysfunction mannitol is not filtered and will cause increase in the intravascular volume
Prolonged use of Mannitol may cause:
Hypovolemia
Electrolyte disturbances
Hypokalemic hypochloremic alkalosis
Plasma hyperosmolarity due to excessive excretion of water and Na+
NOT INCLUDED_potassium sparing diuretics
potassium sparing diuretics
