Pharmacokinetics and Drug Design and Delivery Flashcards
What are the 6 common causes of kidney failure?
- 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
What are the 4 functions of the kidney?
Regulate body fluids
Electrolyte balance
Remove metabolic waste
Drug excretion
What is uremia?
Glomerular filtration impaired or reduced, causes accumulation of waste products in the blood caused by acute diseases and trauma
What are the 5 PK consideration in renal failure?
- oral bioavailability
- apparent volume of distribution
- elimination
- total body clearance
- drug dosage regimen
What are the 3 common asssumptions for PK in renal impairment?
- Clcr is an accurate measurement of renal impairment
- drug has a dose-dependent PK
- non-renal drug elimination remains constant
What is the word equation for adjusting the dose dependent on renal clearance?
dose = (normal dose x impaired clearance)/
normal clearance
What are the 7 properties of markers of GFR?
- 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
What are the top 3 markers of GFR?
- Inulin
- Creatinine
- BUN
What are the 5 assumptions for Clcr?
- 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
What are the 5 stages of renal function with Crcl?
Normal - 80 ml/min
Mild impairment - 50-80 ml/min
Moderate impairment - 30-50 ml/min
Severe impairment - <30 ml/min
ESRF - requires dialysis
What are pro-drugs?
compounds that are inactive until metabolised
What are soft drugs?
active drugs quickly inactivated by metabolism
What are the 3 uses of soft-drugs?
- 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
What are the 2 limits of soft-drugs?
- cannot modify the known active molecule too much
- introduction of metabolic sensitive group shouldn’t change the properties of the lead
What is the most ideal compound for a soft drug?
- ideally a metabolic isostere
- most often used are esters and carbamates
What are IV fluids?
- water, glucose and major electrolytes
- required when oral route in unavailable
- maintains. hydration and metabolic activity
Why aren’t IV fluids the solution?
Does not contain sufficient calories (only 400)
- increasing volume = fluid overload
- increase glucose conc = damage to blood vessels
What the 6 reasons to give enteral nutrition?
- functional GI tract, but unable to chew/swallow
- anoxic encephalopathy
- neurological disorders
- oropharyngeal-esophageal disease
- tumours
- trauma
What are the 4 enteral nutrition routes?
- nasogastric
- nasojejunal
- gastrostomy
- jejunostomy
Why would PN be given?
- long-term treatment
- unable to utilise enteral route
- have severe gut dysfunction
What is the EN vs PN debate?
EN results in fewer infectious complications
EN can be cheaper
PN is associated with higher incidence of hyperglycaemia
Why must the volume of fluid in PN be considered?
- 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
What are the energy requirements for people of different ages?
Infants: 90-100kcal/kg/day
Children: 70-100kcal/kg/day
Adolescents: 40-55kcal/kg/day
Adults: 25-35kcal/kg/day
Why is dextrose used in PN?
- usually 4-5mg/kg/min
- can replace energy need from glucose
- can reduce incidence of hyperglycaemia
Why are lipids needed in PN?
- provide essential fatty acids
- carrier for fat-soluble vitamins
- reduces need for excessive volumes
Why is nitrogen included in PN?
- for protein supply
- under metabolic stress amino acids can be used for energy
- 0.2mg/kg/day
Why are amino acids included in TPN?
- indispensible for vital body functions
- metabolic dysfunction
- insufficient reabsorption
- increased nutritional demands after surgical trauma
What are the two concepts of AIO mixtures?
1: individually formulated
2: multiple chamber bags
What are the limitations of individually formulated PN bags?
must be used within 2 hours
only made as needed to prevent destabilisation
What are the limitations of muliple chamber PN bags?
only lasts 20hrs once seals broken
How stable are AAs and carbs?
AA loss in presence of reducing sugar by production of imines
How stable are AAs and lipids?
- 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
How stable are AAs and vitamins?
Vitamin C (ascorbic acid) is least stable, readily oxidised in presence of AAs
