01) Drug absorption is affected by several factors. What is the best factor that can affect the drug absorption? (SBR) a) Plasma electrolyte level. b) pH at the absorption. c) Blood urea level. d) Serum amylase level. e) Plasma protein concentration. 02) WOF T/F regarding principles of pharmacokinetics? a) b) c) d) e) Conjugation of a drug is seen in phase I metabolic reactions. Free form of a drug is the inactive form. Drug distribution occurs from periphery to central. Volume of distribution is low in highly plasma protein bound drugs. Drugs which has zero order kinetics has lower clearance. 03) T/F regarding pharmacokinetics of paediatric patients a) Absorption via skin is high. b) Absorption through stomach is high. c) Urinary excretion is high. d) Metabolism is high. 04) Regarding drug distribution a) Ketamine prefers to propofol during the labour as it does not cross the placenta readily. b) c) d) e) Redistribution of thiopentone reduces therapeutic effect. Hydrophilic drugs resist to cross the placenta. Levodopa does not cross the blood brain barrier. Drugs excessively bind to plasma protein show apparently high distribution. 05) Volume of distribution a) It is used to calculate loading dose. b) Cannot be higher than total body water. c) Of heparin similar to the plasma volume. d) More in hydrophilic drugs than hydrophobic drugs. e) Assess liters per body surface area.
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pharmacokinetics absorption pH distribution volume of distribution plasma protein binding reliable source
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Drug absorption
- Factors controlling absorption
- Importance of pH and drug ionization
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Core pharmacokinetics
- Phase I vs Phase II metabolism
- Free vs protein-bound drug
- Direction of distribution
- First-order and zero-order kinetics
- Clearance
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Paediatric pharmacokinetics
- Skin, gastrointestinal, hepatic, and renal differences from adults
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Drug distribution and barriers
- Placental transfer
- Blood-brain barrier
- Protein binding
- Redistribution, including thiopentone
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Volume of distribution
- Definition and clinical applications
- Relationship to loading dose, plasma binding, hydrophilicity, and heparin
High-level overview: pharmacokinetics describes what the body does to a drug: absorption, distribution, metabolism, and excretion. Drug pH and ionization strongly affect absorption, while the free, unbound fraction is the pharmacologically active fraction that can cross most membranes.
In infants and children, pharmacokinetics varies with developmental changes in skin permeability, gastric physiology, liver enzyme function, body-water composition, and renal elimination. Volume of distribution is an apparent volume, can exceed total body water, and is central to calculating a loading dose.
Please select the topic you want explained in detail next.
Explain the correct answers for each pharmacokinetics item
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pediatric pharmacokinetics
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NCBI pharmacokinetics volume distribution loading dose zero order clearance protein binding
1. Drug absorption
Correct answer: b) pH at the absorption site
Drug absorption depends greatly on the proportion of drug that is unionized. The unionized form crosses lipid cell membranes most easily.
- Weak acids are more unionized in an acidic environment.
- Weak bases are more unionized in an alkaline environment.
- Therefore, pH at the absorption site changes drug solubility and membrane permeability.
Why others are incorrect:
- a. Plasma electrolyte level: not a main determinant of ordinary drug absorption.
- c. Blood urea and d. serum amylase: do not directly determine absorption.
- e. Plasma protein concentration: mainly influences distribution of drug after it has entered the circulation, not absorption.
2. Principles of pharmacokinetics: True/False
a) Conjugation of a drug is seen in phase I metabolic reactions.
False.
- Phase I reactions: oxidation, reduction, hydrolysis. Often mediated by cytochrome P450 enzymes.
- Phase II reactions: conjugation, for example glucuronidation, acetylation, sulfation, glutathione conjugation.
- Conjugation generally makes a drug more water-soluble and easier to excrete.
b) Free form of a drug is the inactive form.
False.
The free or unbound drug is the pharmacologically active fraction. It can:
- Cross membranes
- Bind to receptors
- Produce therapeutic or toxic effects
- Be filtered at the glomerulus
- Undergo metabolism
Protein-bound drug is usually temporarily inactive while bound, acting as a reservoir.
c) Drug distribution occurs from periphery to central.
False.
Distribution usually occurs from the central compartment (blood/plasma) to the peripheral tissues.
For an intravenous drug:
- Drug enters blood.
- It is delivered first to highly perfused organs such as brain, heart, liver, and kidney.
- It then distributes into muscle, skin, and fat.
d) Volume of distribution is low in highly plasma protein-bound drugs.
True.
A drug that binds extensively to plasma proteins remains in the intravascular compartment. Less drug is free to enter tissues, so its apparent volume of distribution, Vd, tends to be low.
Example: warfarin is highly protein-bound and has a relatively low Vd.
e) Drugs which have zero-order kinetics have lower clearance.
True, in the usual exam sense.
In zero-order elimination, metabolic or transport pathways are saturated. A constant amount of drug is eliminated per unit time, rather than a constant fraction.
Since:
[
\text{Clearance} = \frac{\text{rate of elimination}}{\text{plasma concentration}}
]
when concentration rises during saturation, clearance falls. Thus clearance is not constant and becomes lower at higher concentrations.
Examples of drugs that may show zero-order kinetics include:
- Ethanol
- Phenytoin at higher concentrations
- Aspirin at high doses
3. Pharmacokinetics in paediatric patients
These statements are most accurate for neonates and young infants, rather than all paediatric age groups.
a) Absorption via skin is high.
True.
Neonates have:
- Thin skin
- Higher skin hydration
- A relatively larger body-surface-area-to-weight ratio
Therefore, they can absorb topical drugs more readily and are more prone to systemic toxicity from topical preparations.
b) Absorption through stomach is high.
False.
In neonates:
- Gastric emptying is slower and variable.
- Gastric acidity is lower, so gastric pH is higher than in older children and adults.
Therefore, oral absorption is often unpredictable, not simply high. Absorption may rise or fall depending on the drug.
c) Urinary excretion is high.
False.
Neonatal renal function is immature:
- Reduced glomerular filtration rate
- Reduced tubular secretion
- Reduced tubular reabsorption
Therefore, renal elimination of many drugs is reduced and drug half-life may be prolonged.
d) Metabolism is high.
False.
Hepatic enzymes are immature at birth, so metabolism of many drugs is reduced. However, metabolism matures with age and for some drugs may eventually be faster in children than in adults. The broad neonatal statement is false.
4. Drug distribution
a) Ketamine is preferred to propofol during labour as it does not cross the placenta readily.
False.
Ketamine is lipid-soluble and does cross the placenta. Propofol also crosses the placenta. Placental transfer is not an appropriate reason to say ketamine is preferred in labour.
b) Redistribution of thiopentone reduces therapeutic effect.
True.
Thiopentone is highly lipid-soluble. After IV administration, it rapidly enters the brain and induces anaesthesia. It then redistributes from brain to muscle and fat.
This lowers its brain concentration and terminates the anaesthetic effect after a single dose, even though the drug has not yet been fully metabolized. This is why thiopentone has a short duration of action after a bolus dose.
c) Hydrophilic drugs resist crossing the placenta.
True.
Placental transfer is easier for drugs that are:
- Lipid-soluble
- Nonionized
- Small molecular weight
- Not highly protein-bound
Hydrophilic and strongly ionized drugs cross lipid membranes poorly, so placental transfer is relatively limited.
d) Levodopa does not cross the blood-brain barrier.
False.
Levodopa does cross the blood-brain barrier using the large neutral amino-acid transporter.
In contrast, dopamine itself does not cross the blood-brain barrier. This is why levodopa is used in Parkinson disease.
e) Drugs excessively bound to plasma protein show apparently high distribution.
False.
Extensive plasma protein binding keeps drug within the vascular compartment and generally produces a low Vd, not a high Vd.
A high Vd is more likely with:
- High lipid solubility
- Extensive tissue binding
- Low plasma protein binding
The role of protein binding, pH, and tissue permeability in distribution is summarized in this NCBI pharmacokinetics review.
5. Volume of distribution, Vd
[
V_d = \frac{\text{Amount of drug in the body}}{\text{Plasma drug concentration}}
]
It is an apparent volume, not necessarily a real anatomical fluid volume.
a) It is used to calculate loading dose.
True.
[
\text{Loading dose} = \frac{V_d \times \text{target plasma concentration}}{\text{bioavailability}}
]
A drug with a large Vd requires a larger loading dose to reach a specified plasma concentration. See the loading-dose formula.
b) Cannot be higher than total body water.
False.
Vd can be much greater than total body water because it is an apparent volume.
A very high Vd indicates that much of the drug has left plasma and is extensively distributed or bound within tissues. For example, some lipophilic drugs may have Vd values of hundreds of litres.
c) Vd of heparin is similar to plasma volume.
True.
Heparin is large, highly charged, and hydrophilic. It remains largely confined to the intravascular compartment, giving it a small Vd close to plasma volume.
d) Vd is more in hydrophilic drugs than hydrophobic drugs.
False.
Hydrophobic or lipid-soluble drugs cross cell membranes readily and distribute into tissues and fat. They tend to have a higher Vd.
Hydrophilic drugs remain mainly in plasma or extracellular fluid and tend to have a lower Vd.
e) Vd is assessed as litres per body surface area.
False.
Vd is usually expressed as:
- Litres (L), or
- Litres per kilogram body weight (L/kg)
It is not routinely expressed as litres per body surface area.
Answer key
| Question | Correct answers |
|---|---|
| 1 | b |
| 2 | a F, b F, c F, d T, e T |
| 3 | a T, b F, c F, d F |
| 4 | a F, b T, c T, d F, e F |
| 5 | a T, b F, c T, d F, e F |
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