W26 Renal Drugs (MM)

Question 1

What are the roles of the kidneys?

Answer 1

• Filter the blood
• Kidneys add/remove substances to/from the plasma
• Regulate water concentration, inorganic ion concentration and volume of the internal environment
• Sodium ion (Na+) regulation
• Hydrogen ion (H+) regulation
• Potassium ion (K+) regulation
• Calcium ion (Ca2+) regulation
• Bicarbonate (HCO3-) regulation

Question 2

What is hyperkalaemia?
What are potassium levels maintained by?

Answer 2

• Higher than normal potassium levels
  in the blood
• sodium-potassium pump

Question 3

Why is potassium homeostasis important?
What could disruption to homeostasis be caused by?

Answer 3

• Potassium homeostasis is necessary to maintain physiological processes (neuronal, muscular, cardiac, mineralocorticoid activity…)
• Acute kidney injury (AKI) or chronic kidney disease (CKD)

Question 4

Signs and symptoms of Hyperkalaemia:
What does the acronym MURDER stand for?

Answer 4

Muscle weakness
Urine, oliguria or anuria
Respiratory distress
Decreased cardiac contractility
EKG changes (peaked T waves)
Reflexes, hyper or hypo

Question 5

Features of Sodium Zirconium Cyclosilicate (SZC):

Answer 5

AKA Lokelma powder for oral suspension
* Chemical formula Na1.5H0.5ZrSi3O9●3H2O
* Forms a 3D framework around a central 3Å pore
* Exchanges hydrogen and sodium ions for other cations (K+, Ca2+, Mg2+)
* >25-fold selectivity for potassium over calcium or magnesium
* 3Å is roughly equivalent to the diameter of an unhydrated potassium ion

Question 6

What is meant by Metal Ion Coordination?

Answer 6

• Metal ions in solution do not exist in isolation
• They coordinate with ligands (solvent molecules or simple ions) or chelating groups
• Results in a central atom (usually a metal ion) surrounded by a cluster of ions or neutral molecules

Question 7

Examples of bi and tridendate ligands?

Answer 7

• Ethylenediamine (en) (H2NCH2CH2NH2) is bidentate
• Diethylenetriamine (dien (H2NCH2CH2NHCH2CH2NH2) is tridentate
• Ligands can be monodentate, bidentate, tridentate etc
• This derives from the concept of teeth/ biting (Latin: dent = tooth)
• Chelate is derived from the Greek word chely meaning claw of the lobster/other crustaceans.

Question 8

When is a chelate ring formed?

Answer 8

• When a polydentate ligand binds to a metal ion
• In this instance, the polydentate ligand becomes a chelating agent as chelate complexes are formed
• Experimentally, it is observed that metal complexes of polydentate ligands are significantly more stable than corresponding complexes of monodentate ligands

Question 9

What is the formation constant Kf?

Answer 9

• Describes the formation of a complex ion from its central ion and attached ligands
• Also known as stability constant or
  association constant
• The larger the Kf value of an ion, the
  more stable it is
• The inverse is the dissociation constant (Kd), the larger this value is, the more unstable the complex is
  Kf=1/Kd

The formation constants of various complexes can therefore be used to determine if one type of ligand forms more stable complexes with the particular ion than another ligand

Question 10

What is the role of Phosphate binding agents?

Answer 10

• Bind to phosphate [PO4]3- in the GI
  tract forming insoluble compounds
  that cannot be absorbed into the body
• Hydrogen phosphate [HPO4]2- and
  dihydrogen phosphate [H2PO4]- ions
  may also bind to binding agents
• Examples include calcium carbonate,
  calcium acetate, aluminium salts, lanthanum carbonate
• Sevelamer polymers are also sometimes used but these also bind fat-soluble vitamins and are costly

Question 11

What are Calcimimetic agents?

Answer 11

• Mimic the action of calcium on tissues
• Used to treat hyperparathyroidism
• Over-secretion of parathyroid hormone (PTH) is prevented by binding at the calcium-sensing receptors (CaSR) which increases the
  sensitivity to calcium
• The binding happens at a secondary site of the receptor (allosteric activation).

Question 12

What is Alfacalcidol?
What is a Diol?

Answer 12

• Used to promote calcium
  homeostasis and bone metabolism
• Analogue of Vitamin D3
• Vitamin D3 undergoes 25-hydroxylation in the liver
• The product (25OHD) then undergoes
  24-hydroxylation or 1α-hydroxylation
• Those with renal failure cannot perform the 1α-hydroxylation and so alfacaldiol is given

Question 13

What are diuretics?
What are the most commonly used ? and what is their mechanism of action?

Answer 13

• Diuretics: Drugs that promote diuresis (production of urine) or water loss
• Thiazide and thiazide-like diuretics
  are among the most commonly used
• Mechanism: Block sodium/chloride
  transporter, inhibits reabsorption of
  Na+ and Cl-, increases elimination of
  water from the body
• This can also lead to increased loss of
  K+ and increased absorption of Ca2+