Pharmacology Flashcards
Give examples of drugs which act on the kidney
Diuretics
Vasopressin (ADH) agonists/antagonists
SGLT2 inhibitors
Uricosuric drugs (promote uric acid excretion)
When does oedema occur?
When there is an imbalance between the rate of formation and absorption of interstitial fluid
What 4 forces are responsible for the constant water exchange between blood and the interstitium?
STARLING FORCES
Pc - hydrostatic pressure in capillary
Pi - hydrostatic pressure in interstitial fluid
Op - oncotic pressure of plasma
Oi - oncotic pressure of interstitial fluid
Changes in which of the 4 starling forces promotes Oedema?
Increased Hydrostatic Capillary pressure
Decreased Plasma Oncotic pressure
What diseases change the Hydrostatic capillary pressure and plasma oncotic pressure therefore leading to oedema?
- nephrotic syndrome
- congestive heart failure
- hepatic cirrhosis with ascites
How does nephrotic syndrome contribute to oedema?
- Increased production of interstitial fluid
- Decreased blood vol and cardiac output
- Activates RAAS
- Salt and water retention
- Increased Pc, Decreased Op
=> oedema
How does congestive heart failure cause oedema?
Decreased cardiac output => renal hypoperfusion => activates RAAS => Water and Na retention => blood volume and pressure increases BUT Op decreases => pulmonary and peripheral oedema
How does Hepatic cirrhosis with Ascites contribute to oedema?
- Increased pressure in the hepatic portal vein
- decreased production of albumin
=> loss of fluid into the peritoneal cavity and oedema (ascites)
Activation of RAAS occurs in response
What subtype of diuretics work in the proximal convoluted tubule?
carbonic anhydrase inhibitors
Where do LOOP diuretics complete their action?
Thick ascending limb of the LOOP of Henle
What diuretics work in the early distal convoluted tubule?
Carbonic Anhydrase inhibitors
thiazides
Where in the nephron do potassium sparing diuretics act?
Collecting duct
Why must diuretics get into the filtrate in order to act?
site of action of most diuretics is the apical membrane of tubular cells
How do diuretics get into the filtrate?
glomerular filtration (for drug not bound to large plasma protein) secretion in prox. tubule via OATs/OCTs
What are OATs and OCTs?
organic anion transporters (OATs) – transport acidic drugs
organic cation transporters (OCTs) – transport basic drugs
How does secretion of a diuretic into the filtrat contribute to pharmacological selectivity?
secretion means concentration of diuretic in the filtrate is higher than that in blood
=> more likely to act on receptors in nephrons than elsewhere in the body
How do Organic anion transporters move from the interstitium into the lumen of the nephron?
Na/K ATPase regulates low intracellular Na
=> Na outside cell moves IN via conc. gradient
=> Na moves in on transporter which also brings in α-KG
=> α-KG exchanges back out of cell for an OAT
=> Then moved into lumen via PRIMARY ACTIVE transport
Give examples of drugs that use OATs?
Diuretics (bumetanide, furosemide) Simvastatin Many penicillins NSAIDs Endogenous urate
Describe how OCTs travel from the interstitium to the tubule lumen?
- Na/K ATPase regulates membrane potential
- OC+ moves into cell due to negative membrane potential attraction
- Move into lumen via antiport with H+
OR primary active transport MDR1
What drugs are known to use OCTs?
diuretics (amiloride, triamterene => potassium sparing) atropine metformin morphine procainamide endogenous catecholamines
Describe the normal function of the Na/K/2Cl triple cotransporter
Na moves in via triple transporter and out via Na/K pump
Cl moves in via triple transporter and out via CIC-Kb/Barttin
K moves in via triple transporter and out via apical or basolateral K channels
Why is it important to have K channels on the apical membrane
So K moves back into lumen
=> can rebind to transporter
What creates the charge difference between the lumen (+ve) and interstitium (-ve)?
K moving back into lumen
=> allows Ca and Mg to move paracellulary
What genetic diseases can affect the function of the triple co-transporter?
Mutation in transporter itself
CIC-Kb/Barttin mutation
K+ channel mutation
What does Bartter syndrome cause?
Na and H2O wasting
hypokalemia, alkalosis, and normal to low blood pressure
What are the main jobs of loop diuretics?
- decrease hypertonicity of the medulla
- prevent dilution of the filtrate in the thick ascending limb
- increase the load of Na+ delivered to distal regions (=> lose K+)
- increase excretion of Ca2+ and Mg2+
How soon after IV and oral administrations does furosemide tend to take effect?
IV - within 30 mins
Oral - within an hour
What are the contra-indications to a loop diuretic?
Severe hypovolaemia, or dehydration
What are the cautions with loop diuretics?
Severe hypokalaemia and/or hyponatraemia
hepatic encephalopathy
gout
What are the main adverse effects in loop diuretics?
- hypokalaemia
- metabolic alkalosis
- hypocalcaemia, hypomagnesaemia
- Hypovolaemia and hypotension
- Hyperuricaemia
- Dose-related loss of hearing