Pharmacology Flashcards
List the main drugs that act on the kidney
Diuretics Vasopressin agonists/antagonists SGLT2 inhibitors Renal failure drugs pH-altering drugs
What effect do diuretics have on volume of urine? What are the indications for diuretic use?
Increase urine volume by inhibiting reabsorption of salt which causes decreased reabsorption of water Hypertension Congestive HF Hepatic cirrhosis with ascites Nephrotic syndrome
How does oedema arise?
Imbalance between rate of formation and absorption of interstitial fluid
Which forces are involved in formation of interstitial fluid?
Pc = capillary pressure πp = capillary oncotic pressure Pi = interstitial fluid pressure πI = interstitial fluid oncotic pressure
Disease states that increase/decrease Pc or increase/decrease πp produce oedema
Disease states that increase Pc or decrease πp produce oedema
What (simply) happens in nephrotic syndrome?
Disorder of glomerular filtration where plasma protein appears in filtrate, resulting in proteinuria
Once plasma protein is in the urine, it can’t be reabsorbed. True/False?
True
Thus voided in urine; urine appears frothy
What effect does the presence of plasma protein in the filtrate have on πp? What is the result of this?
Body loses plasma protein in urine so πp decreases; this leads to oedema
What effect does decreased πp have on blood volume and cardiac output? What is the result of this?
Decreased πp causes decreased blood volume and cardiac output, activating RAAS to cause sodium and water retention
What effect does sodium and water retention have on Pc and πp? What is the result of this?
Pc increases and πp decreases, causing oedema
when this happens in nephrotic syndrome, you ultimately get worsening oedema
List the major sites of diuretic action in the nephron
Proximal convoluted tubule
Ascending limb of loop of Henle
Distal convoluted tubule
Collecting tubule
Which class of diuretic works in the proximal convoluted tubule? How does it work?
Carbonic anhydrase inhibitor
Blocks production of H+, thus inhibiting Na-H+ exchanger (H+ drive sodium reabsorption)
Which class of diuretic works in the ascending limb of loop of Henle? How does it work?
Loop diuretic
Blocks Na-K-2Cl triple cotransporter
Which class of diuretic works in the distal convoluted tubule? How does it work?
Thiazide diuretic
Blocks Na-Cl cotransporter
Which class of diuretic works in the collecting tubule? How does it work?
Potassium-sparing diuretic
Blocks Na-K antiporter
Diuretics must be in the filtrate to reach site of action. Why?
Site of action is the apical membrane (near the lumen)
List the ways diuretic can enter the filtrate
Glomerular filtration (if not bound to plasma protein)
Secretion via transport processes in proximal tubule
Organic anion transporter (OAT)
Organic cation transporter (OCT)
Which type of drug - acid or alkali - is transported by organic anion transporter (OAT)?
Acidic drugs e.g. thiazide, loop diuretics
Which type of drug - acid or alkali - is transported by organic cation transporter (OCT)?
Basic drugs e.g. triamterene, amiloride
How do acidic drugs reach the lumen of the tubule?
Enter cell via OAT on basolateral membrane in exchange for alpha-ketoglutarate
Exit cell/enter lumen via MRP2 or via OAT
How do basic drugs reach the lumen of the tubule?
Enter cell via OCT on basolateral membrane
Exit cell/enter lumen via MRP1 or OC-H+ antiporter
What competes with thiazide diuretic for the OAT? What is the consequence of this?
Uric acid competes with thiazide diuretic for the OAT
Predisposes to gout
Name the main loop diuretics
Furosemide
Bumetanide
Loop diuretics inhibit the Na-K-Cl triple cotransporter by binding to what site? What effect does this have on Na, K, Ca and Mg levels?
Chlorine site
This increases the load of Na in the distal tubules
Less K, Mg and Ca reabsorbed, resulting in hypokalaemia, hypocalcaemia, hypomagnesia
List clinical conditions where loop diuretics are used
Acute pulmonary oedema (secondary to HF) Chronic heart/kidney failure Nephrotic syndrome Hepatic cirrhosis with ascites AKI
Name the main thiazide diuretics
Bendroflumethiazide
Hydrochlorothiazide
Thiazide diuretics block the Na-Cl cotransporter by binding to what site? What effect does this have on Na, K and Ca levels?
Chlorine site
This increases Na delivered to the collecting tubule
Less K absorption, resulting in hypokalaemia
Interestingly, for no solid reason, increased Ca absorption
List clinical conditions where thiazide diuretics are used
Hypertension
Mild heart failure
Renal stone disease
Nephrogenic diabetes insipidus
Name the main potassium-sparing diuretics
Amiloride
Triamterene
Spironolactone
Epleronone
How do amiloride and triamterene work?
Block apical Na channel to decrease Na reabsorption in late distal and collecting tubules, ultimately reduce K excretion
How do spironolactone and epleronone work?
Compete with aldosterone for binding to intracellular cytoplasmic receptors, to decrease Na reabsorption, ultimately reduce K excretion
Potassium-sparing diuretics are usually used alone. True/False?
False
Usually used in conjunction with loop/thiazide where there is hypokalaema
Used alone, can cause hyperkalaemia
Name an osmotic diuretic
Mannitol
How do osmotic diuretics work?
Become trapped in filtrate (cannot be reabsorbed) and exert osmotic pressure to retain water, which in turn retains sodium due to dilution
Net effect: decrease water and sodium reabsorption
What are the indications for using osmotic diuretic? What is the main side effect?
Prevent acute hypovolaemic renal failure
Increase ICP and IOP
Hyponatraemic headache
Name a carbonic anhydrase inhibitor
Acetazolamide
What is the effect of carbonic anhydrase inhibitor? List some side effects
Increase excretion of HCO3, Na, K and H20 (alkaline diuresis), resulting in metabolic acidosis
Glaucoma, acute mountain sickness, alkalinise urine (UTI), infantile epilepsy
How do aquaretics work?
Vasopressin competitve antagonists
Block vasopressin receptors to cause excretion of water without Na loss, resulting in hypernatraemia
Name some aquaretics and give their main indication and side effect
Conivaptan (V1a, V2)
Tolvaptan (V2)
SIADH
Polydipsia
Where do SGLT2 inhibitors act?
Block SGLT2 (Na glucose cotransporter) in the proximal tubule to prevent glucose reabsorption
SGLT1 is present in the intestine only, SGLT2 in the kidney only. True/False?
False
SGLT1 = intestine + kidney
SGLT2 = kidney only
SGLT2 have low/high affinity for glucose; SGLT1 have low/high affinity for glucose
SGLT2 have low affinity for glucose; SGLT1 have high affinity for glucose
Name some SGLT2 inhibitors. What is their main indication and side effect?
Dapagliflozin
Canagliflozin
Type 2 diabetes
Increase genital bacterial and fungal infections
Which enzymes catalyse the formation of prostaglandins?
Cyclo-oxygenases
COX 1 and 2
State the major prostaglandins synthesised by the kidney
PGE2 (medulla)
PGI2 (glomeruli)
What is the effect of prostaglandins on vasculature and GFR?
Vasodilation of afferent arteriole
Increase GFR by constricting efferent arteriole
How might NSAIDs cause acute renal failure?
Inhibit COX, thus inhibit prostaglandin formation, so GFR decreases
List side effects of loop diuretics
Hypokalaemia Metabolic alkalosis Hypovolaemia/ hypotension (especially in elderly) Hypocalcaemia and hypomagnesia Hyperglycaemia and hyperuricaemia (gout)
List side effects of thiazide diuretics
Postural hypotension (especially in elderly)
Metabolic alkalosis
Hypokalaemia, hypomagnesia, hyponatraemia
Hypercalcaemia, hyperglycaemia, hyperuricaemia (gout)
Impotence/ sexual function
Pancreatitis, cholestasis, pneumonitis
Outline the mechanism behind loop and thiazide diuretic induced hypokalaemia
Increased sodium in filtrate leads to increased reabsorption of sodium in distal and collecting duct, increasing the secretion of potassium and hydrogen via action of Na/K ATPase (activated by aldosterone)
List symptoms of diuretic-induced hypokalaemia
Weakness
Myalgia
Fatigue
Arrhythmia
Outline management of diuretic-induced hypokalaemia
Potassium supplements
Potassium-sparing diuretics
List some side effects of spirinolactone, potassium-sparing diuretic
Harmonal disturbance - gynaecomastia, impotence, menstrual irregularities
List indications for potassium-sparing diuretics
Mod-severe CHF
Secondary hyperaldosteronism (hepatic cirrhosis with ascites or nephrotic oedema)
Primary hyperaldosteronism (Conns)
Resistant hypertension
What is the ‘triple whammy combo’ leading to reduced renal function?
ACEi/ARB
Diuretic
NSAID
What is the mechanism of action of uricosurics? What is their main indication?
Block active transport of organic acids, reducing net reabsorption of urate
LT gout control (1-3 weeks after acute attack)
Name the main uricosuric. Uricosurics are contraindicated in…
Allopurinol
Renal impairment
History of renal stones
Name the main vasopressin agonists. What are their main indications?
Terlipressin Desmopressin Neurogenic diabetes insipidus Nocturnal enuresis Variceal bleeding in portal hypertension
What is the mechanism of action of vasopressin agonists?
Increase aldosterone
Increase salt and sodium absorption by increasing activity of sodium channel and synthesis of NA+K+
Action of vasopressin on kidney inhibited by…
Lithium
Democlocycline
Tumours
Vaptans
