Pharmacology - Kidneys Flashcards
What are the driving and opposing forces in ultrafiltration?
Driving Forces –> Glomerular capillary hydrostatic pressure
Oncotic pressure in the bowmans space (normally negligible)
Opposing Factors –> Oncotic pressure of the blood plasma
Pressure in the bowmans space
Rank the parts of the nephron from first to last in terms of their Na+/Cl- reabsorption
PCT
Thick Ascending Limb (TAL)
Distal Tubule
Collecting duct/tubule
Which group of diuretics has the greatest effect?
And why has the least?
Greatest –> Loop diuretics
Least –> Carbonic Anhydrase
How do Carbonic Anhydrase Inhibitors, like Acetazolamide, work?
By inhibiting Carbonic Anhydrase…..
This prevents bicarbonate from being reabsorbed in the PCT, and so less Na+ is reabsorbed….leading to diuresis
Can cause slight urine alkalosis, and mild plasma acidosis (due to less H+ being secreted)
How do Osmotic Diuretics, like Mannitol, work?
Freely filtered into the nephron, and acts on parts that are freely permeable to water (eg, PCT, decending limb of the loop of henle, collecting tubule/duct in the presence of ADH)
Increases the osmolarity of the tubular filtrate by decreasing the water absorption
It also reduces the amount of Na+ reabsorption
How do Loop Diuretics, like furosemide, work?
By the inhibition of the luminal Na+/K+/2Cl-co-transporter
This decreases Na+/Cl- reabsorption –> causing diuresis
Also an increase in K+/Ca2+/Mg2+ secretion
State some of the PKs of Furosemide
Absorbed in the gut
Strongly bound to albumin in the plasma
Secreted into the tubular filtrate by OAT in the PCT
Excreted in the urine
How do Thiazide drugs, like bendroflumathiazide, work?
By inhibiting the luminal Na+/Cl- Co-transporter in the distal tubule
This reduces Na/Cl- reabsorption –> diuresis
Also increases K+ excretion, and Ca2+ reabsorption
How do K+ sparing diuretics, like spironolactone, work?
And what effects does aldosterone usually have?
Aldosterone activates Na+ channels and increases the synthesis of the Na+/K+/ATPase…..all of which increase Na+ reabsorption
Na+ reabsorption is coupled with K+ excretion/secretion….. so the following drugs will decrease K+ excretion
Aldosterone Antagonists –> Spironolactone/Eplerenone
Na+ Channel Blockers –> Amiloride/Triamterene
What does ADH/Vasopressin do?
Increases the expression of Aquaporin 2 on the luminal membrane in the collecting tubule, via the Gs GPCR
This increases water reabsorption
What is the role in Atrial Natiuretic Peptide (ANP) in diuresis?
Causes a decrease in…..
Aldosterone
Na reabsorption
Renin release
Also causes vasodialation
These all cause blood volume to decrease
How/where is renin secreted specifically?
From the Juxtaglomerular cells
Secretion is stimulated by…..
Decrease in blood pressure
Decrease in tubular Na+ –> Release of PGE2 (via COX2)
Increase in sympathetic stimulation via B1 adrenoceptors
What’s the mechanism in ACEi that can cause a persistant dry cough?
And how will using ARBs stop this?
ACEi prevents ACE from breaking down bradykinin
This causes the levels of bradykinin to increase –> which stimulates coughing
ARBs selectively inhibit Angiotensin Receptor 1, so they have no effect on bradykinin
What is known as the “Triple Whammy” Effect?
Use of an ACEi, Diuretic and an NSAID causing very low GFR
The diuretics decrease blood volume, activating the RAAS system….however….
ACEi prevents the efferent arteriole from constricting….so GFR goes down further
The afferent arteriole can’t relax more due to NSAID inhibition of COX-2, which causes GFR to decrease even more…..
Which has the longest duration of action….. loop diuretics or thiazides?
Thiazides and thiazide-like drugs
