11 - Special Populations Flashcards
How does age affect pharmacokinetics?
Young = Enzyme immaturity
Old = morbidity, co-morbidity, polypharmacy, organ failure
Describe how body composition of infants are different from adults (5 things)
- Metabolism capacity low in 1st 2 months
- Higher water percentage in 1st 6 months
- Gastrointestinal tract changes
- Renal function matures in 6-12 months
- Skin thickness is low in neonates
Describe how absorption in infants is different
Gastrointestinal
- Higher pH + gastric emptying
- Less enzymes + transporters
- Makes acid-labile products more absorbing (bases less absorbing)
Skin:
- Thinner, more perfusion
- Locally applied drugs e.g. cortciosteroids, antihistamines = more systemic absorption
Describe how distribution in infants is different
- More water, less fat = Water-soluble drugs Vd increase, Lipid-soluble drugs Vd decrease
- Less albumin = more free drug.
- Drug availability not significantly affected. May be higher due to thinner skin. CNS drugs more effect due to blood brain barrier less developed.
Describe how elimination in infants is different
- Immature enzymes affect metabolism. More or less drug required.
- Renal function developing until 8 – 12 months
Describe how prescribing in infants is different
- Under 6 months, see specialised.
- 12 years or less, use equations for body weight and SA.
- Remember that absorption may be different and clearance may be affected.
Describe how distribution in elderly is different
More fat, less water = Water soluble drugs Vd decrease, lipid-soluble drugs Vd increase
Note: Protein binding changes not clinically relevant.
Describe how clearance is different in elderly
- How to dose?
- Decreased clearance as GFR decreases with age.
- Half life longer so dosing is at longer intervals.
- Variability lots.
Consider reducing dose when patients reach 55 yrs.
- Start low, and slowly raise concentration.
- Monitory frequently, especially if Therapeutic Index (TI) is low
- Reduce drug use if possible (reduce polypharmacy)
- Provide information on drugs.
Describe what effects drugs can have on pregnancy as it progresses
- 2 weeks. Has no effect on embryo or kills it. Patient probably don’t know they pregnant to begin with.
- 12 weeks. Can have congenital abnormalities like NTDs.
- Last trimester. Can induce labour.
Can drugs cross the placenta?
Most drugs can to some extent but depends on size, charge, lipid solubility, protein binding.
How is pharmacokinetics influenced by pregnancy?
- Vd – Increases for both water and lipid soluble drugs.
– Requires more doses - Protein binding – Decrease albumin
– So adjust for drugs that are usually plasma protein bound. - Clearance increase due to increase renal/hepatic metabolism, renal blood flow, and GFR.
– Maintenance dose needs to increase.
How is prescribing different in pregnancy?
Avoid if possible, especially during 1st trimester.
- Choose drugs with proven saftey, least toxic, and most local. Use shorter courses and smallest dose.
Why is lactaction important to consider when prescribing?
How to prescribe differently?
Drugs can pass into breast milk via passive diffusion. This is transferred into baby.
- Be careful of toxic agents
- Mother takes dose immediately post-feeding (to increase time for drug elimination before feeding again)
- Bottle feed until off meds.
Why is liver disease important in prescribing?
Drugs are eliminated mainly via liver (metabolism) and kidneys (excretion). Livers metabolise drugs and that activity depends on:
- Activity of enzymes
- Protein binding amount
- Hepatic blood flow.
Phase one (for fat-soluble toxins) and phase two (for water soluble waste).
Note: Issue w/ one pathway may not affect other pathway.
1) The liver makes ____ which is stored in the ____. This comprises of _______. This stuff helps with…
2) Describe the Enterohepatic circulation.
1) The liver makes bile which is stored in the gallbladder. This comprises of bile salts, eletrolytes, bile pigments, cholesterol, and other fats. This stuff helps with digestion and eliminates waste products.
2) Liver cells transfer substances from plasma to bile. These are hydrophilic. Once in intestines, can be hydrolysed back into active form and reabsorbed. This creates drug reservoir and any damage to bile system can affect this process.
