Renal Pharmacology Flashcards
Ace Inhibitors (2) and effect
- Ramipril, lisinopril
- Inhibits conversion of Ang I to Ang II
- Ang II constricts efferent artery to preserve glomerular filtration
- Also stimulates aldosterone release from the adrenal glands
ARBS (2) and effect
- Losartan, candesartan
- Blocks the effect of Ang II at the receptor
What drugs act on the Proximal convoluted tubule (2, 2 )
- SGLT2 inhibitors like Canagliflozin, Dapagliflozin
- Designed for diabetes, reduce absorption of glucose at PCT
- Increase urinary excretion of glucose
- Second or third line after Metformin
- Patients with chronic heart failure and renal failure do better when treated with it
Uricosuric drugs
- sulfinpyrazone, febuxostat
- PCT also site of uric acid absorption, these drugs block reabsorption of urea → indicated for long term prevention of gout
- Make more uric acid excreted at PCT
What drugs have negative effect on renal perfusion
ACEI, ARBS => If artherosclerosis is already present especially in older patients, can have important effect on renal function
NSAIDs => PGE2 and PGI2 inhibit Na K+ Cl- transporter at LOH
What drugs are toxic to kidney ( 3 kinds)
- Acute tubular necrosis
- DIrect injury to renal tubules resulting in dysfunction and death to cells
- Gentamicin, radiocontrast media, chemotherapeutic agnets
- DIrect injury to renal tubules resulting in dysfunction and death to cells
- Acute intersitial nephritis
- Inflammation in interstitial spaces around renal tubules
- Antibiotics like cephalosporins, NSIADs and PPis
- Tubular dysfunction
- ALter tubular function without acute tubular necrosis
- Lithium, heavy metals like lead, mercury, arsenic, cadmium
How do diuretics affect blood pressure
Urine is unusually salty at the distal tubule, so macula densa will stop producing renin
What proteins do loop diuretics work on
Work on Na+ K+ Cl- cotransporter at the loop of henle => stops salt from being moved back into the interstitium and the medulla does not become hypertonic
How do loop diuretics affect Na+, K+, Cl-
Explain effect on K+
Loss of all due to loss of reuptake in TAL
More K+ lost at collecting duct since Na+ taken up by ASC => risk of hypokalemia
does loop diuretics cause metabolic alklosis or acidosis
Alkalosis => remember type A cells at CD
Effects of LD on Cl, Mg
Hypo
Effect of LD on calcium
HYPO due to less pull for calcium recovery
Effect of LD and thiazides on urea and creatinine
Increases => also leads to incontinence especially in the elderly and gout
What drug leads to otoxtoxicity
Dose related hearing loss from LD
Where do thiazide diuretics act on - what are they
On first part of distal tubule, Na+ Cl- symporter
bendroflumethiazide and hydrochlorothiazide, indapamide
what diuretics are used for BP and why
Thiazides due to vasodilating effects
Indication of thiazides
Mainly Hypertension rather than diuresis
Effect of thiazides on K+, Na+, Mg2+ and H+
Loss of all
Effect of thiazides on calcium
Hypercalcaemia
What diuretic causes hyperglycaemia and why
thiazides due to effects on ATP sensitive K+ channels involved in B cell secretion of insulin
What drug causes erectile dysfunction
Thiazide
What channels do K+ sparing diuretics and Spironolactone block the action of
ASC on the collecting duct . K+ diuretics like amiloride block the ASC directly, while spironlactone blocks aldosterone receptros to reduce synthesis of ASC and Na+K+ exchanger
Indications of Amiloride and spironolactone
- Increased circ. concentrations of aldosterone causing Na+ and water overload
- Chronic heart failure
- Liver failure
- Primary hyperaldosteronism
- block effects of na retention
- Hypertension that is resistant to standard treatment has relative excess of aldosterone, benefits from treatment
- Liddle’s Syndrome
Effect of K sparing and Spironolactone on K+ lol
Hyperkalaemia
What is a main side effect of spironolactone
Gynaecomastia
How do CA inhibitors work and where
At PCT, prevents formation of H2CO3 from HCO3- so it resists egress of water osmotically
Also,
- Prevent reabsorption of HCO3- ions with Na+ and Cl- ions in PCT by inhibiting the enzyme CA
- Reduces availability of H+ ions at the luminal membrane for exchange with sodium since CA cannot catalyse production of H+ and HCO3- in the cell
- Reduces availability of HCO3- to for co transport with Na+ into basolateral membrane
Indications for CA inhibitors
- Prevent altitude sickness due to effect on brain stem and hypoxia
- Counteracts respiratory alkalosis and sickness
- Glaucoma
Effect of osmotic agents and where?
Resist water egress at PCT, descending limb of LOH, CD
Indications of mannitol
Emergency treatment of acutely raised intracranial or intra-ocular pressure as it rapidly offloads fluid
Adverse effects of mannitol
Potential adverse effects after IV administration include transient expansion of the ECF (to reduce threat to brain function)
What drugs build up in patients with renal impairment
Digoxin, gentamicin, amox, cipro., cephas.- ALL highly toxic
Morphine also builds up
Adverse effect of carbonic anhydrase inhibitor
Metabolic acidosis because of reduced reabsorption of bicarbonate ions
