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Pharmacokinetics - SL22108 > Lecture 6 > Flashcards

Lecture 6 Flashcards

1
Q

Define neonate

A

birth to 1 month

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2
Q

Define infant

A

1 month to 2 years

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3
Q

Define children

A

2-12 years

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4
Q

Define adolescent

A

12 years

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5
Q

Name the absorption changes that occur

A

Gastric acidity
Rates of gastric and intestinal emptying
Surface area of the absorption site
GI enzyme systems
Gastrointestinal permeability
Biliary function - bile acids, surfactants affect the solubility of drugs

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6
Q

What happens with a high gastric pH?

A

Enhanced BA of basic compounds
Reduced BA of acidic compounds
Deficiency of bile salts and pancreatic enzymes
Reduced BA of drugs that require solubilisation or intraluminal hydrolysis for adequate absorption (pro-drug esters)

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7
Q

How is BA affected in neonates?

A

Interaction with anatomical and physiological factors of the GI tract - may have differences in the BA

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8
Q

How is the Vd affected in neonates?

A

Neonates have a higher relative proportion of total body water and low proportion of fat relative to adults
Increase in Vd for water-soluble compounds
Lower Vd for fat-soluble drugs

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9
Q

How is plasma protein binding affected in neonates?

A

In a paediatric population you would expect the free fraction of the drug to be higher because the proteins will be less there
lower total plasma protein levels
Lower binding affinities to albumin and a1-acid-glycoprotein

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10
Q

How is metabolism and elimination affected in neonates?

A

Rates of metabolite formation can be different
Underdeveloped and inefficient hepatic and/or renal elimination pathways
Reduced CYP450 enzyme activity

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11
Q

How is renal clearance affected in neonates?

A

Incompletely developed
Renal functions reach adult levels before 1 years of age
Renal blood flow, GFR, tubular secretion reduced

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12
Q

Name the anatomical changes in the elderly

A

Increase pigmentation
endocardial thickening
increase in collagen
increase in elastic fibres

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13
Q

Name the physiologic parameter changes in the elderly

A

Decreased CO
Decreased SV
Lengthening of recovery time after exercise
Increased BP
Increased peripheral vascular resistance
Greater rise in systolic than diastolic BP
Increased circulation transit time

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14
Q

Name the changes in the stomach and duodenum in the elderly

A

Decreased secretion of HCl and pepsin
Atrophy of gastric mucosa
Gastric emptying similar to that of young subjects - delayed transfer to the small intestine

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15
Q

Name the changes in the small intestine in the elderly

A

Reduced absorption of several substances
Digestion and motility remain relatively unchanged
Reduced mixing of intestinal contents
Atrophy of intestinal micro and macro-villi - reduced absorbing SA
Possible bacterial overgrowth in the intestine

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16
Q

Name the changes in the pancreas in the elderly

A

Amylase remains constant - need to consider how some drugs will be affected by the decrease in enzymes
Lipase, trypsin decrease dramatically
Secretin-stimulated pancreatic juice and bicarbonate conc remains unchanged

17
Q

Name the changes in renal system in the elderly

A

Decreased RBF, GFR and tubular secretion
Decreased renal mass
Plasma creatinine - no concomitant increase - not a reliable indicator of GFR
Acid-base balance maintained
Reduced response to stress - inability to deal with acid loads

18
Q

Is the absorption of vitamin B12, iron and calcium increased or decreased in the elderly?

A

Decreased

19
Q

Give examples of drugs that have increased absorption in the elderly

A

Clomethiazone, cimetidine, propranolol
levodopa

20
Q

Give examples of drugs that have decreased absorption in the elderly

A

Digoxin
Quinidine
Chlordiazepoxide

21
Q

Is there an increase or decrease in the first-pass metabolism in the elderly?

A

Reduction in first pass metabolism

22
Q

How are polar compounds distributed in the elderly?

A

smaller Vd
higher serum levels
little net effect in the elimination half-life

23
Q

How are non-polar compounds distributed in the elderly?

A

Increased Vd
Prolongation of half-life

24
Q

How is hepatic clearance different in the elderly?

A

Reduction in liver blood flow - affects the clearance of drugs with a high extraction ratio
Enzyme inhibition, pathways of conjugation - no major effects of ageing

25
Q

How is renal clearance affected in the elderly?

A

Reduction in renal function - water soluble antibiotics, diuretics, digoxin, soluble beta-adrenoceptor blockers, lithium, and non-steroidal anti-inflammatory drugs - can have serious side effects

Drugs with narrow therapeutic index - likely serious side effects, accumulation

Pharmacokinetics - SL22108 (7 decks)

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