Renal Pharmacology

Question 1

Ace Inhibitors (2) and effect

Answer 1

• 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

Question 2

ARBS (2) and effect

Answer 2

• Losartan, candesartan
  
  • Blocks the effect of Ang II at the receptor

Question 3

What drugs act on the Proximal convoluted tubule (2, 2 )

Answer 3

• 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

Question 4

What drugs have negative effect on renal perfusion

Answer 4

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

Question 5

What drugs are toxic to kidney ( 3 kinds)

Answer 5

• Acute tubular necrosis
  
  • DIrect injury to renal tubules resulting in dysfunction and death to cells
    
    • Gentamicin, radiocontrast media, chemotherapeutic agnets
• 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

Question 6

How do diuretics affect blood pressure

Answer 6

Urine is unusually salty at the distal tubule, so macula densa will stop producing renin

Question 7

What proteins do loop diuretics work on

Answer 7

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

Question 8

How do loop diuretics affect Na+, K+, Cl-
Explain effect on K+

Answer 8

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

Question 9

does loop diuretics cause metabolic alklosis or acidosis

Answer 9

Alkalosis => remember type A cells at CD

Question 10

Effects of LD on Cl, Mg

Answer 10

Hypo

Question 11

Effect of LD on calcium

Answer 11

HYPO due to less pull for calcium recovery

Question 12

Effect of LD and thiazides on urea and creatinine

Answer 12

Increases => also leads to incontinence especially in the elderly and gout

Question 13

What drug leads to otoxtoxicity

Answer 13

Dose related hearing loss from LD

Question 14

Where do thiazide diuretics act on - what are they

Answer 14

On first part of distal tubule, Na+ Cl- symporter
bendroflumethiazide and hydrochlorothiazide, indapamide

Question 15

what diuretics are used for BP and why

Answer 15

Thiazides due to vasodilating effects

Question 16

Indication of thiazides

Answer 16

Mainly Hypertension rather than diuresis

Question 17

Effect of thiazides on K+, Na+, Mg2+ and H+

Answer 17

Loss of all

Question 18

Effect of thiazides on calcium

Answer 18

Hypercalcaemia

Question 19

What diuretic causes hyperglycaemia and why

Answer 19

thiazides due to effects on ATP sensitive K+ channels involved in B cell secretion of insulin

Question 20

What drug causes erectile dysfunction

Answer 20

Thiazide

Question 21

What channels do K+ sparing diuretics and Spironolactone block the action of

Answer 21

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

Question 22

Indications of Amiloride and spironolactone

Answer 22

• 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

Question 23

Effect of K sparing and Spironolactone on K+ lol

Answer 23

Hyperkalaemia

Question 24

What is a main side effect of spironolactone

Answer 24

Gynaecomastia

Question 25

How do CA inhibitors work and where

Answer 25

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

Question 26

Indications for CA inhibitors

Answer 26

• Prevent altitude sickness due to effect on brain stem and hypoxia
• Counteracts respiratory alkalosis and sickness
• Glaucoma

Question 27

Effect of osmotic agents and where?

Answer 27

Resist water egress at PCT, descending limb of LOH, CD

Question 28

Indications of mannitol

Answer 28

Emergency treatment of acutely raised intracranial or intra-ocular pressure as it rapidly offloads fluid

Question 29

Adverse effects of mannitol

Answer 29

Potential adverse effects after IV administration include transient expansion of the ECF (to reduce threat to brain function)

Question 30

What drugs build up in patients with renal impairment

Answer 30

Digoxin, gentamicin, amox, cipro., cephas.- ALL highly toxic
Morphine also builds up

Question 31

Adverse effect of carbonic anhydrase inhibitor

Answer 31

Metabolic acidosis because of reduced reabsorption of bicarbonate ions