Pharm Principles Flashcards
What is the effect of gastric acid production on drug absorption in neonates?
Gastric acid production affects drug solubility and ionization, with acidic pH favoring absorption of acidic drugs and alkaline pH enhancing absorption of basic drugs.
At birth, gastric pH is neutral, dropping to low pH in the first 1-10 days and reaching adult values around 3 months.
What is the primary site of drug absorption in neonates?
The proximal small intestine.
It has the greatest absorptive surface area.
How does gastric emptying affect drug absorption in neonates?
Decreased motility slows intestinal drug absorption, while increased motility may decrease absorption due to reduced contact time with absorptive surfaces.
What factors influence gastric emptying in neonates?
- Type of formula
- Presence of food
- Gestational age
- Intestinal motility
What is the impact of pancreatic enzyme activity on drug absorption in neonates?
Low pancreatic enzyme activity can decrease the breakdown of fats and carbohydrates, affecting the absorption of fat-soluble drugs.
Lipase activity increases significantly in the first week of life.
What role do cytochrome P-450 enzymes play in drug metabolism in neonates?
CYPs are expressed in the intestinal wall and can alter the oral bioavailability of drugs.
Oral midazolam bioavailability is higher in preterm infants due to limited intestinal drug metabolism.
What are the effects of disease states on drug absorption in neonates?
- Decreased surface area (e.g., short bowel syndrome)
- Delayed gastric emptying (e.g., pyloric stenosis)
- Bile salt excretion issues (e.g., cholestatic liver disease)
- Intestinal transit time variations
What factors affect non-oral drug absorption in neonates?
- Lipophilicity of the drug
- Blood flow to injection site
- Muscle activity
- Total surface area of the muscle in contact with the injected solution
What is the predominant mechanism of rectal drug absorption in neonates?
Passive diffusion.
Faster absorption occurs from aqueous or alcoholic solutions than from suppositories.
What is the significance of the volume of distribution (Vd) in drug pharmacokinetics?
Vd describes the relationship between the total amount of drug in the body and its plasma concentration, influencing how much drug is circulating versus stored in tissues.
What factors affect protein binding of drugs in neonates?
- Concentration of available binding proteins
- Affinity of the drug to the protein
- Number of available binding sites
- Presence of pathophysiological conditions
What is the significance of bilirubin in relation to drug binding in neonates?
Bilirubin binds to albumin, and decreased albumin levels can lead to higher amounts of free drug, increasing the risk of kernicterus.
What is the effect of total body water on drug distribution in neonates?
Higher doses per kg must be given to neonates for water-soluble drugs to achieve comparable plasma and tissue concentrations.
What is the primary organ for drug metabolism in neonates?
The liver.
Drug metabolism is carried out by phase 1 and phase 2 enzymes.
What are the two phases of drug metabolism?
- Phase 1: microsomal reactions (oxidation, reduction, hydrolysis)
- Phase 2: conjugation reactions (adding molecules to increase solubility)
What is the significance of renal excretion in drug elimination for neonates?
Renal excretion involves GFR, active tubular secretion, and passive tubular secretion, with GFR rates being significantly lower in preterm neonates compared to adults.
What factors can affect the glomerular filtration rate (GFR) in neonates?
- Asphyxia
- Severe RDS
- Renal failure
- PDA
- Sepsis
What are ACE inhibitors?
A class of drugs used primarily for the treatment of hypertension and heart failure.
What is the role of angiotensin II receptor inhibitors?
They block the action of angiotensin II, helping to lower blood pressure.
What are NSAIDs?
Nonsteroidal anti-inflammatory drugs, used to reduce inflammation and relieve pain.
How is GFR measured?
Using creatinine clearance from a 24-hour urine collection.
What is creatinine’s role in assessing kidney function?
It is largely filtered at the glomerulus and partly secreted at the proximal tubular level.
Which drugs can competitively increase creatinine levels without truly decreasing GFR?
Trimethoprim
Ranitidine
What is a pitfall when measuring creatinine clearance?
First 24 hours reflects maternal levels.
