PCOL of Diuretics Flashcards
Functions of Kidney (6)
- Regulate water, inorganic ion, acid-base balance and blood volume
- Remove metabolic waste products via urine
- Remove foreign chemicals via urine
- Gluconeogenesis
- Renal metabolism of substances
- Acts as secretory gland
Functional unit of a kidney
Nephron
Processes During Urine Formation (3):
- Glomerular Filtration
- Tubular Reabsorption
- Tubular Secretion
Glomerular Filtration:
- Glomerular filtrate has same ___-_______ solute concentration as plasma
- Glomerular filtration rate (GFR) definition: ______ of fluid _____ per unit ____.
~~Average adult GFR is ___ L/day - GFR subject to __________ regulation
~~Constriction of afferent arterials = ________ GFR
~~Constriction of efferent arterials = ________ GFR
~~Constriction of glomerular mesangial cells = _________ GFR
- non-protein
- volume, filtered; time
~~180 - physiological
~~decrease
~~increase
~~decrease
What is the percentage of tubular reabsorption of urea, and is it useful or waste?
- 44%
- waste
What is the percentage of tubular reabsorption of water, and is it useful or waste?
- 99%
- useful
What is the percentage of tubular reabsorption of glucose, and is it useful or waste?
- 100%
- useful
What is the percentage of tubular reabsorption of Na+, and is it useful or waste?
- 99.5%
- useful
Tubular Secretion:
- Moves substances from _________ _________ into the _____ of the nephron
- Many _______ _______ and ______ substances are also secreted
- Requires active transport across __________ (on the blood side) membrane or across ______ (on the luminal side) membrane
- __ and __ secretion usually coupled with reabsorption of ___
- Usually under ________ control
- peritubular capillaries, lumen
- organic anions (choline and creatinine) and foreign (penicillin)
- basolateral, apical
- H+ and K+, Na+
- physiologic
What are the 2 most important secreted substances?
- H+
- K+
Nephron Division of Labor:
What is the primary role of the proximal tubule?
to reabsorb most filtered water and nonwaste plasma solutes
Nephron Division of Labor:
The Loop of Henle is important in?
reabsorbing large quantities of ions (and water, to a lesser extent)
Nephron Division of Labor:
Distal segments of the tubule is where ____-______ of final urine occurs
- fine-tuning
Na+ Reabsorption
Na+ and water filter freely from __________ capillaries into _______ _______.
glomerular, Bowman’s capsule
Is Na+ reabsorption an active or passive process?
active
Na+ reabsorption occurs in all tubular segments except
descending limb of loop of Henle
Why is it important to remember that the amount of Na+ reabsorption varies down the length of the tubule?
This is linked to the MOA of our diuretics and it will reflect the efficacy of these diuretics.
The Na+/K+ ATPase is always on the _________________ side:
- __________ ___________ cells
- __________ ___________ ____ cells
basolateral
- proximal convoluted
- cortical collecting duct
Water reabsorption is by _________ and is influenced by the movement of ___.
diffusion, Na+
Water permeability varies along tubule:
- _______ _________ ______ very water permeable
- _________ ____ water permeability varies with the presence of ___________
- Proximal Convoluted Tubule (PCT)
- Collecting duct; vasopressin (antidiuretic hormone; ADH)
ADH - secreted by pituitary
Vasopressin -
- Peptide hormone secreted by _______ ________
- Stimulates insertion of __________ into luminal membrane of collecting ducts
- High plasma vasopressin concentrations _______ urine volume
- posterior pituitary
- aquaporins
- decrease
(hyperosmotic urine compared to plasma)
Dependence of Water Reabsorption on Na+
Local osmolarity is ___________ in the tubular lumen as Na+ _______
decreased, leaves
Dependence of Water Reabsorption on Na+
Local osmolarity is ___________ in the interstitial fluid as Na+ _______
increased, leaves
Diuretics in general work by (4):
- Affecting the specific renal epithelial tubular membrane transporters
- Exerting osmotic effects that prevent water reabsorption
- Inhibiting enzymes
- Interfering with hormone receptors in renal epithelial cells
Pharmacology of drug is linked to _______ ____ of renal physiology.
The efficacy of diuretics is __________ to the amount of Na+ reabsorbed at their site of action.
specific site
proportional
First practical and powerful agent available for widespread use was:
chlorothiazide
Classification of diuretics has historically been a mosaic of (5):
- site of action
- efficacy
- chemical structure
- similarity of action
- effects on K+ excretion
Sites of Action:
- PCT
- Ascending Loop of Henle
- DCT
- Collecting Duct
- Lumen
Diuretics that work in the proximal convoluted tubule:
Carbonic Anhydrase Inhibitors
CAI - Pharmacodynamics:
- ____ can be reabsorbed at other sites of nephron independent of carbonic anhydrase
- ______ decreases in a few days due to _________ enhancement of ____ reabsorption in later parts of tubule
- HCO3-
(but still have significant HCO3- loss which may cause hyperchloremic metabolic acidosis) - Efficacy; compensatory; NaCl
CAI - Pharmacokinetics:
- _______ urine pH within __ minutes of dose
- Excretion by _______ in ___ (gets drug to site of action)
- _______ dose for renal insufficiency
- Increased; 30
- secretion; PCT
- Adjust
CAI - Clinical Uses:
- Glaucoma – get decreased aqueous humor production
- Urinary alkalization
- Metabolic alkalosis
- Acute mountain sickness
CAI - Toxicity
- Hyperchloremic metabolic acidosis
- Renal stones
- Renal potassium wasting
- Other:
- Drowsiness
- NS toxicity (in renal failure patients)
- Hypersensitivity
CAI - Contraindications:
May contribute to hyperammonemia and hepatic encephalopathy for cirrhotic patients
Diuretics that work in the ascending limb of the loop of henle
Loop diuretics
