Pharmacokinetics and Pharmacodynamics

Question 1

What is Pharmacokinetics (PK)?

Answer 1

What the body does to the drug (ADME: Absorption, Distribution, Metabolism, Excretion)

PK is a critical aspect of pharmacology that encompasses the processes of absorption, distribution, metabolism, and excretion of drugs.

Question 2

What is Pharmacodynamics (PD)?

Answer 2

What the drug does to the body (receptor interaction, drug response)

PD focuses on the biochemical and physiological effects of drugs and their mechanisms of action.

Question 3

What factors affect Absorption in pharmacokinetics?

Answer 3

Route of administration (oral, rectal, topical, intramuscular, inhalation)

The absorption of drugs can vary significantly based on the route through which they are administered.

Question 4

What is the gastric pH evolution in neonates?

Answer 4

Neutral gastric pH at birth → acidic within 48 hrs → neutral again for ~1 week → adult pH (~2) by 2 years

This evolution affects the absorption of drugs in neonates.

Question 5

What are the effects of slower gastric emptying in neonates?

Answer 5

Immature enzymes, decreased surface area, variable motility

These factors can lead to altered drug absorption in neonates.

Question 6

Which type of drugs has increased bioavailability in neonates?

Answer 6

Acid-labile drugs (e.g., penicillin)

The immature gastrointestinal system of neonates enhances the bioavailability of certain drugs.

Question 7

Which type of drugs has decreased bioavailability in neonates?

Answer 7

Weak acids (e.g., phenytoin)

The unique characteristics of the neonatal gastrointestinal system result in reduced bioavailability for certain drugs.

Question 8

What is the effect of rectal administration on drug bioavailability?

Answer 8

↓ First-pass effect may ↑ bioavailability

Rectal administration can enhance the bioavailability of certain drugs by bypassing some metabolic pathways.

Question 9

What increases absorption in percutaneous (topical) administration?

Answer 9

Thin stratum corneum, larger surface area:body mass, higher skin hydration and perfusion

These factors are particularly pronounced in preterm infants.

Question 10

What is a risk associated with percutaneous (topical) administration?

Answer 10

Risk of systemic effects (e.g., corticosteroids, lidocaine, iodine)

Due to enhanced absorption in neonates, certain topical medications can lead to systemic side effects.

Question 11

Why is the intramuscular (IM) route variable in absorption for neonates?

Answer 11

↓ Muscle blood flow & contraction

The unique anatomy and physiology of neonatal muscles can lead to unpredictable drug absorption via the IM route.

Question 12

What is the total body water content in preterm and term neonates?

Answer 12

85% in preterms, 75% in terms

This higher total body water content affects the distribution of hydrophilic drugs.

Question 13

What is the effect of increased volume of distribution for hydrophilic drugs?

Answer 13

Need higher doses

Due to the high total body water content in neonates, hydrophilic drugs require larger doses for therapeutic effects.

Question 14

What is the effect of decreased volume of distribution for lipophilic drugs?

Answer 14

Need lower doses

The lower fat content in neonates means that lipophilic drugs require smaller doses.

Question 15

What is the state of the blood-brain barrier in neonates?

Answer 15

Less mature → more CNS penetration

This immaturity can lead to increased susceptibility to central nervous system effects from medications.

Question 16

What is the status of liver enzyme maturity in neonates?

Answer 16

Immature liver enzyme systems (especially CYP450 system)

This immaturity impacts drug metabolism significantly in neonates.

Question 17

Which phase of metabolism is characterized by oxidation and reduction?

Answer 17

Phase I

Phase I reactions are crucial for the initial transformation of drugs in the liver.

Question 18

Which enzyme dominates in neonates under 6 months?

Answer 18

CYP3A7

This enzyme plays a significant role in drug metabolism during early infancy.

Question 19

What is the clearance of Midazolam in neonates?

Answer 19

↓ clearance in neonates

This highlights the reduced metabolic capacity of neonates for certain drugs.

Question 20

What is the maturity level of CYP2C9 and CYP2C19 at birth?

Answer 20

CYP2C9: ~30% adult level, CYP2C19: ~15% at birth

These enzymes mature at different rates, affecting drug metabolism.

Question 21

When does CYP1A2 appear in neonates?

Answer 21

Appears at 1–3 months

The appearance of this enzyme is crucial for metabolizing certain drugs, such as caffeine.

Question 22

What is the half-life of caffeine in neonates?

Answer 22

T1/2 ~100 hrs in neonates (vs 5 hrs in adults)

The prolonged half-life in neonates highlights immature metabolic pathways.

Question 23

Which phase of metabolism is characterized by conjugation?

Answer 23

Phase II

Phase II reactions involve converting drugs into more water-soluble compounds for excretion.

Question 24

What is the status of glucuronidation in neonates?

Answer 24

Delayed development

This can lead to accumulation of drugs that require glucuronidation for elimination.

Question 25

What is the GFR at birth for term and preterm infants?

Answer 25

Term: ~2–4 mL/min/1.73m², Preterm: ~0.6–0.8 mL/min/1.73m² ## Footnote GFR values indicate the immature renal function in neonates.

Question 26

What happens to GFR in neonates after birth?

Answer 26

GFR ↑ rapidly over 1–2 weeks ## Footnote This rapid increase necessitates dose interval adjustments for certain medications.

Question 27

What is the status of tubular function in neonates?

Answer 27

Immature tubular function delays elimination ## Footnote Tubular secretion and reabsorption reach adult levels at different ages, affecting drug clearance.