Special Considerations

Question 1

One change about drug absorption in pediatrics?

Answer 1

• Reduced gastric acid secretion = PH neutral (high compared to adults) = more unionised

Gastric acid secretion reaches adult level at around 2-3 years old

Variation in PH can change ionisation = increase/decrease absorption of drug

Question 2

Another change about drug absorption in pediatrics?

Answer 2

Peristalsis is slower = decreased gastric emptying

Reaches adult valves at 6-8 months

Question 3

Another change about drug absorption in pediatrics (specifically neonates)?

Answer 3

Absorption of fat-soluble drugs can be affected by a decreased level of bile production in neonates.

Also, large body surface area relative to weight in neonates and infants = systemic absorption of topical agents may be increased

Question 4

How can gastric emptying affect absorption?

FACT - small intestine has greatest capacity to absorb drugs

Answer 4

Delayed gastric emptying = decreased rate in absorption

Delayed gastric emptying can be influenced by: volume of meal, composition of meal, physical state and viscosity of meal, temperature of meal, gastrointestinal PH, electrolyte and osmotic pressure, body posture, emotional state, disease state

EXAMPLE - Crohns Disease affecting absorption.

FACT - NSAIDS if have longer in GI tract then they have more time to irritate stomach lining

Question 5

Factors that alter drug absorption in elderly people?

Answer 5

Increase gastric PH (alters ionisation of the drug)

Decreased small intestine surface area

Slow gastric emptying

Question 6

Factors that alter pediatric drug distribution?

Answer 6

• Babies have a higher proportion of water (80%)
• This impacts on dose of water soluble drugs as volume of distribution is increased and increase dose on mg/kg basis
• Drugs (prescribed drugs) require increased monitoring as child gets older
• Plasma proteins (ALBUMIN) are reduced, these values reach adult level in 1 year
• Also the proteins present have less binding affinity = increased ‘free drug’ = increase risk of toxicity

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Question 7

Factors affecting drug distribution in elderly

Answer 7

• Increased Vd = prolonged half-life
• Increased Vd and half-life has been observed for drugs such as diazepam

THIS IS DUE TO DO:
increased adipose tissue
increased Vd lipid soluble drug
decreased body water
decreased muscle mass
decrease Vd water soluable drug
decreased serum albumin

Question 8

How does renal impairment impact distribution? REGARDING VOLUME OF DISTRIBUTION

Answer 8

Volume of distribution can alter

Oedema = ↑ Vd (therefore dose may need increasing)

Oedema -> ↑ Vd

Water soluble drugs , e.g. gentamicin, dose ↑

Question 9

How does renal impairment impact distribution? DRUG BINDING

Answer 9

Reduced albumin binding/availability – nephrotic syndrome

↓ albumin

Highly protein bound drugs -> ↑ free drug

So ↑ therapeutic effect

Question 10

What are the risks of supplying/administering drugs in pharmacology?

Answer 10

• Greatest risk is in 3rd and the 11th week of pregnancy

Risks in first trimester = teratogenesis (congenital malformations of foetus)

Risks in second and third trimesters = drugs can affect functional development or have toxic effects on foetal tissue

Drugs given towards end of pregnancy can have adverse effects on labour and neonate after delivery

EXAMPLE - Phenytoin and Tetracyclines can cause dose-dependant foetal abnormalities

Question 11

Who is at increased risk of CYP highly polymorphic

Answer 11

= large variation in different people/demographics

FOR EXAMPLE - increased CYP2D6 enzymes in east Africans and absent in small percentage of Caucasians

Question 12

What enzyme is codeine bioactivated by….

Answer 12

P450 CYP2D6

Question 13

What factors affect enzyme activity in relation to metabolism?

Answer 13

Paediatric – lower enzyme activity

Pregnancy - Variation in enzyme activity

Consider pro-drugs

Question 14

How does liver impairment affect metabolism?

Answer 14

Liver disease (Cirrhosis or viral Infections)

Blood flow (Heart Failure)

Toxic drugs (Paracetamol, Amiodarone)

Malnourished patients
(reduced protein levels)

Question 15

How does liver cirrhosis affect metabolism?

Answer 15

Decreased enzymatic activity (mainly phase I)

Damaged hepatocytes

Decreased metabolism – unable to form inactive or active metabolite

Drug accumulation
Increased bio availability

Decreased hepatic blood flow

Question 16

Liver function tests….

Answer 16

tell you if liver is damaged but not function of CYP enzymes

Question 17

What are the factors affecting glomerular filtration rate in excretion?

Answer 17

Newborns = GFR reduces

6-12 months = GFR > than adults GFR

EXAMPLE - Glomerular filtration at 30 years old = 100% VS 85 years old = 40%

Question 18

What are the two types of renal impairment and describe characterists?

Answer 18

ACUTE - occurs suddenly due to physical trauma, infection, inflammation, exposure to nephrotoxic chemical

CHRONIC - progressive loss of kidney function, can progress to end stage renal disease and defined into different stages based on GFR

Question 19

Medication alterations with renal impairment

Answer 19

• Renal function generally declines with age = increased half-life
• Reduce dose or prolong dosing interval e.g. palliative anticipatory medications

Avoid/cautious with drugs with narrow therapeutic range (nephrotoxic drugs)

Avoid deydration