Pharmacokinetics and Drug Design and Delivery

Question 1

What are the 6 common causes of kidney failure?

Answer 1

• Pyelonephritis
• Hypertension: chronic overloading with fluid and electrolytes
• Diabetes: disturbance of sugar metabolism and acid-base balance
• Nephrotoxic drugs
• Hypovolemia: reduction of renal blood flow
• Nephroallergens

Question 2

What are the 4 functions of the kidney?

Answer 2

Regulate body fluids
Electrolyte balance
Remove metabolic waste
Drug excretion

Question 3

What is uremia?

Answer 3

Glomerular filtration impaired or reduced, causes accumulation of waste products in the blood caused by acute diseases and trauma

Question 4

What are the 5 PK consideration in renal failure?

Answer 4

• oral bioavailability
• apparent volume of distribution
• elimination
• total body clearance
• drug dosage regimen

Question 5

What are the 3 common asssumptions for PK in renal impairment?

Answer 5

• Clcr is an accurate measurement of renal impairment
• drug has a dose-dependent PK
• non-renal drug elimination remains constant

Question 6

What is the word equation for adjusting the dose dependent on renal clearance?

Answer 6

dose = (normal dose x impaired clearance)/
normal clearance

Question 7

What are the 7 properties of markers of GFR?

Answer 7

• freely filtered at glomerulus
• not reabsorbed or actively secreted by renal tubules
• not metabolised
• not bind significantly to plasma proteins
• not have an effect on filtration rate or renal
• be non-toxic
• may be infused in sufficient dose

Question 8

What are the top 3 markers of GFR?

Answer 8

• Inulin
• Creatinine
• BUN

Question 9

What are the 5 assumptions for Clcr?

Answer 9

• daily anabolic production of creatinine in liver is constant
• daily anabolic conversion in stratial muscle is constant and other non-constant sources don’t exist
• creatinine is filtered freely by the kidney and is not secreted or reabsorbed
• measurement of creatinine in serum and urine is accurate
• urine collection is complete

Question 10

What are the 5 stages of renal function with Crcl?

Answer 10

Normal - 80 ml/min
Mild impairment - 50-80 ml/min
Moderate impairment - 30-50 ml/min
Severe impairment - <30 ml/min
ESRF - requires dialysis

Question 11

What are pro-drugs?

Answer 11

compounds that are inactive until metabolised

Question 12

What are soft drugs?

Answer 12

active drugs quickly inactivated by metabolism

Question 13

What are the 3 uses of soft-drugs?

Answer 13

• reduce the duration of action
• reduce side fx and toxicity by limiting drug distribution
• by having predictable metabolism, preventing multiple metabolites with lots of different biological activities

Question 14

What are the 2 limits of soft-drugs?

Answer 14

• cannot modify the known active molecule too much
• introduction of metabolic sensitive group shouldn’t change the properties of the lead

Question 15

What is the most ideal compound for a soft drug?

Answer 15

• ideally a metabolic isostere
• most often used are esters and carbamates

Question 16

What are IV fluids?

Answer 16

• water, glucose and major electrolytes
• required when oral route in unavailable
• maintains. hydration and metabolic activity

Question 17

Why aren’t IV fluids the solution?

Answer 17

Does not contain sufficient calories (only 400)
- increasing volume = fluid overload
- increase glucose conc = damage to blood vessels

Question 18

What the 6 reasons to give enteral nutrition?

Answer 18

• functional GI tract, but unable to chew/swallow
• anoxic encephalopathy
• neurological disorders
• oropharyngeal-esophageal disease
• tumours
• trauma

Question 19

What are the 4 enteral nutrition routes?

Answer 19

• nasogastric
• nasojejunal
• gastrostomy
• jejunostomy

Question 20

Why would PN be given?

Answer 20

• long-term treatment
• unable to utilise enteral route
• have severe gut dysfunction

Question 21

What is the EN vs PN debate?

Answer 21

EN results in fewer infectious complications
EN can be cheaper
PN is associated with higher incidence of hyperglycaemia

Question 22

Why must the volume of fluid in PN be considered?

Answer 22

• 2-3L will be required if no other water source
• more water required if
  
  • fever, fistulas, v+d, burns, stomas etc
• less required if
  
  • renal failure, CHF, cirrhotic ascites etc

Question 23

What are the energy requirements for people of different ages?

Answer 23

Infants: 90-100kcal/kg/day
Children: 70-100kcal/kg/day
Adolescents: 40-55kcal/kg/day
Adults: 25-35kcal/kg/day

Question 24

Why is dextrose used in PN?

Answer 24

• usually 4-5mg/kg/min
• can replace energy need from glucose
• can reduce incidence of hyperglycaemia

Question 25

Why are lipids needed in PN?

Answer 25

• provide essential fatty acids
• carrier for fat-soluble vitamins
• reduces need for excessive volumes

Question 26

Why is nitrogen included in PN?

Answer 26

• for protein supply
• under metabolic stress amino acids can be used for energy
• 0.2mg/kg/day

Question 27

Why are amino acids included in TPN?

Answer 27

• indispensible for vital body functions
  
  • metabolic dysfunction
  • insufficient reabsorption
  • increased nutritional demands after surgical trauma

Question 28

What are the two concepts of AIO mixtures?

Answer 28

1: individually formulated
2: multiple chamber bags

Question 29

What are the limitations of individually formulated PN bags?

Answer 29

must be used within 2 hours
only made as needed to prevent destabilisation

Question 30

What are the limitations of muliple chamber PN bags?

Answer 30

only lasts 20hrs once seals broken

Question 31

How stable are AAs and carbs?

Answer 31

AA loss in presence of reducing sugar by production of imines

Question 32

How stable are AAs and lipids?

Answer 32

• acidity of AAs can decrease pH and destabilise emulsion
• lipid peroxidation of polyunsaturated acids by radical auto-oxidation, the formed lipid peroxides reacts with AAs giving degradation and oxidation products

Question 33

How stable are AAs and vitamins?

Answer 33

Vitamin C (ascorbic acid) is least stable, readily oxidised in presence of AAs