PHA 337- Special Populations L13

What special patient populations are emphasized in this lecture?

Obesity, Critical Illness, Pregnancy, Pediatrics, and Geriatrics

Why are special patient populations important in pharmacokinetics?

They have altered pharmacokinetics compared with the normal population, requiring individualized drug therapy.

Can a patient belong to more than one special population?

Yes. Patients may have multiple conditions that alter pharmacokinetics.

What does TDM stand for?

Therapeutic Drug Monitoring.

Why is therapeutic drug monitoring important?

To ensure drug efficacy while minimizing toxicity, especially for drugs with narrow therapeutic windows.

What is the definition of obesity?

Body mass index (BMI) greater than 25 kg/m².

What body composition changes occur in obesity?

Increased body fat, decreased total body water per kilogram, and increased lean body mass.

How is drug absorption affected in obesity?

Absorption is generally unchanged.

How are lipophilic drugs affected in obesity?

Volume of distribution (Vd) increases because more adipose tissue is available for distribution.

How are hydrophilic drugs affected in obesity?

Usually little or no significant change in Vd, although drugs with a naturally small Vd may have clinically significant increases.

Why does digoxin have a large increase in Vd in obese patients?

Digoxin already has a large population Vd, so obesity substantially increases its total volume of distribution.

Why can aminoglycosides have an increased Vd in obesity?

Although hydrophilic, even a modest increase in Vd is clinically significant because their normal Vd is small.

How is hepatic metabolism affected in obesity?

Variable and drug dependent.

Can one dosing recommendation be applied to all obese patients?

No. Drug dosing must be individualized because clearance changes vary by medication.

How does obesity affect glomerular filtration rate (GFR)?

GFR generally increases.

How does obesity affect renal clearance?

Renal clearance generally increases.

Which types of drugs are most affected by increased renal clearance in obesity?

Hydrophilic drugs.

How are aminoglycosides affected by obesity?

Increased clearance, increased Vd, and generally unchanged half-life.

How is carbamazepine affected by obesity?

Clearance remains relatively unchanged, Vd increases, and half-life increases.

How is methylprednisolone affected by obesity?

Clearance decreases, Vd remains unchanged, and half-life decreases.

Why can half-life remain unchanged even when clearance and Vd increase?

Half-life depends on both clearance and volume of distribution.

What equation relates half-life to elimination rate constant?

t½ = 0.693/K.

What equation relates clearance, elimination rate constant, and volume of distribution?

Cl = V × K.

What factors contribute to obesity?

Environmental factors, genetics, disease states, and medication side effects.

What medication class is commonly associated with weight loss?

GLP-1 receptor agonists.

What is the pharmacist's role when dosing obese patients?

Use evidence, clinical judgment, and pharmacokinetic principles to individualize therapy.

What defines a critically ill patient?

A patient in the intensive care unit (ICU) with a life-threatening acute illness.

What are examples of critically ill patients?

Trauma, medical, surgical, neurologic, and transplant patients.

What metabolic state is common during critical illness?

Hypermetabolic state.

Why does a hypermetabolic state occur?

Activation of the sympathetic nervous system and systemic inflammation in response to severe stress.

What medication characteristics are preferred in ICU patients?

Predictable bioavailability, rapid onset, titratable dosing, short duration of action, and a wide therapeutic window.

Which medication routes are commonly used in the ICU?

IV, subcutaneous, intramuscular, and enteral.

Why is IV administration preferred in critically ill patients?

It provides rapid and predictable drug delivery.

How is enteral drug absorption affected in critical illness?

It is generally decreased.

What causes decreased oral drug absorption in critically ill patients?

Reduced gastrointestinal perfusion, delayed gastric emptying, altered motility, and edema.

How does critical illness affect volume of distribution?

Volume of distribution often increases due to fluid resuscitation, edema, capillary leak, and hypoalbuminemia.

How does hypoalbuminemia affect acidic drugs?

It decreases protein binding, increasing the free drug concentration.

How does increased alpha-1 acid glycoprotein affect basic drugs?

It increases protein binding, decreasing the free drug concentration.

How does critical illness affect hepatic metabolism?

It is often decreased because of reduced hepatic blood flow and altered enzyme activity.

How does critical illness affect renal clearance?

Renal clearance may increase early due to augmented renal clearance or decrease later due to organ dysfunction.

What is augmented renal clearance (ARC)?

Increased renal elimination that can result in subtherapeutic drug concentrations.

Which critically ill patients are most likely to have augmented renal clearance?

Younger patients with trauma, burns, or sepsis.

How does critical illness affect half-life?

Half-life may increase because of increased volume of distribution and decreased clearance.

Why is TDM especially important in critically ill patients?

Pharmacokinetic parameters change rapidly, making standard dosing unreliable.

How does pregnancy affect drug absorption?

Absorption is variable due to delayed gastric emptying, decreased GI motility, nausea, vomiting, and increased gastric pH.

How does increased gastric pH during pregnancy affect weak acids?

Absorption may decrease.

How does increased gastric pH during pregnancy affect weak bases?

Absorption may increase.

How does pregnancy affect volume of distribution?

Volume of distribution increases because of increased plasma volume, total body water, and body fat.

How does increased plasma volume affect hydrophilic drugs?

Volume of distribution increases.

How does increased body fat affect lipophilic drugs?

Volume of distribution increases.

How does pregnancy affect plasma albumin?

Albumin decreases because of hemodilution.

How does decreased albumin affect protein binding?

Protein binding decreases, increasing free drug concentrations.

How does pregnancy affect hepatic metabolism?

It may increase or decrease depending on the CYP enzyme involved.

Does pregnancy affect all CYP enzymes the same way?

No. The effect depends on the specific enzyme.

How does pregnancy affect renal blood flow?

Renal blood flow increases.

How does pregnancy affect glomerular filtration rate (GFR)?

GFR increases.

How does pregnancy affect renal clearance?

Renal clearance increases.

How does increased renal clearance affect renally eliminated drugs?

Drug concentrations may decrease, requiring higher or more frequent doses.

Why is TDM important during pregnancy?

Physiologic changes can significantly alter drug concentrations and therapeutic response.

What is the primary goal of medication use during pregnancy?

Maximize maternal benefit while minimizing fetal risk.

What must always be considered before prescribing medications during pregnancy?

The benefits versus the risks to both the mother and fetus.

What physiologic changes occur during pregnancy that affect pharmacokinetics?

Changes in absorption, distribution, metabolism, and elimination.

How does lactation affect medication therapy?

Some medications pass into breast milk and may affect the infant.

What factors determine whether a drug enters breast milk?

Molecular weight, protein binding, lipid solubility, ionization, and maternal drug concentration.

Which drugs enter breast milk more easily?

Small, lipophilic, poorly protein-bound drugs.

How does high protein binding affect drug passage into breast milk?

It decreases drug transfer into breast milk.

How does high molecular weight affect passage into breast milk?

It decreases passage into breast milk.

How does lipid solubility affect passage into breast milk?

Highly lipophilic drugs enter breast milk more readily.

Why should unnecessary medications be avoided during breastfeeding?

To reduce infant drug exposure.

What is the preferred characteristic of medications used during breastfeeding?

Low infant exposure with established safety.

How can infant drug exposure during breastfeeding be minimized?

Administer the medication immediately after breastfeeding or before the infant's longest sleep period.

Why is infant monitoring important during breastfeeding?

To detect adverse drug effects such as sedation, irritability, or poor feeding.

What should be assessed before recommending a medication during lactation?

The risk to the infant, maternal benefit, and available safety data.

Why are newborns at greater risk from medications in breast milk?

They have immature hepatic metabolism and renal elimination.

How does premature birth affect medication risk during breastfeeding?

Premature infants are at greater risk because drug elimination is less developed.

What is the pharmacist's role in pregnancy and lactation?

Optimize maternal therapy while minimizing fetal or infant drug exposure through individualized recommendations.

How does body composition differ in neonates compared with adults?

Neonates have higher total body water, lower body fat, and lower protein binding.

How does increased total body water in neonates affect hydrophilic drugs?

Volume of distribution increases.

How does lower body fat in neonates affect lipophilic drugs?

Volume of distribution decreases.

How does decreased plasma protein binding affect free drug concentrations?

Free drug concentrations increase.

How does neonatal gastric pH differ from adults?

Gastric pH is higher (less acidic).

How does delayed gastric emptying affect oral drug absorption in neonates?

It delays and makes absorption less predictable.

How does immature hepatic metabolism affect neonates?

Drug metabolism is decreased, prolonging drug effects.

How does immature renal function affect neonates?

Drug elimination decreases and half-life increases.

Why do neonates often require longer dosing intervals?

Because clearance is reduced and drugs remain in the body longer.

How does maturation affect drug clearance in infants and children?

Clearance increases as organ function matures.

How do children generally eliminate drugs compared with adults?

Many children eliminate drugs faster than adults.

Why may children require larger mg/kg maintenance doses than adults?

Because drug clearance is often higher.

How does puberty affect pharmacokinetics?

Body composition and organ function gradually become similar to adults.

Why is age alone not enough to determine pediatric dosing?

Weight, organ maturation, and developmental stage must also be considered.

What is the most common method of pediatric dosing?

Weight-based dosing (mg/kg).

When is body surface area (BSA) dosing commonly used?

Chemotherapy and certain high-risk medications.

Why should adult doses not simply be scaled down for children?

Children have different pharmacokinetics, not just smaller body size.

Why is therapeutic drug monitoring important in pediatric patients?

Rapid developmental changes can significantly alter drug concentrations.

Which organ systems mature after birth and significantly affect pharmacokinetics?

The liver and kidneys.

How does decreased albumin in neonates affect acidic drugs?

Protein binding decreases, increasing free drug concentrations.

What is the pharmacist's role in pediatric pharmacokinetics?

Individualize therapy based on age, weight, organ maturation, and clinical response.

What physiologic factors should always be considered when dosing pediatric patients?

Age, weight, developmental stage, hepatic function, renal function, and body composition.

Why are neonates more susceptible to drug toxicity?

They have immature metabolism, immature renal elimination, and decreased protein binding.

Why are medication errors more common in pediatric patients?

Most medications require individualized weight-based dosing calculations.