E2: Perinatal Pharm Flashcards
Describe the various disposition of drugs throguhout the compartments of the body following absorption
Absorption → Plasma Compartment
⇔Body Organs
⇔Liver
⇔Kidney
⇔Tissue Reservoir
⇔Site of Action
Describe the fluid compartment breakdown of the body
Total body vol: 30.25L (55% of BW)
→ Intracellular Fluid: 22L
→ Extracellular Fluid: 11L
→Intravascular Fluid (Plasma): 2.35L
→Extravascular Fluid: 8.65L
→Interstitial Fluid: 8.25L
→Transcellular Fluid: 0.4L
What is the Cmax?
The Cmax is the highest drug concentration observed in plasma after administration of a single Extravascular dose
What is the Tmax?
The Tmax is the time it takes to reach Cmax
What is T1/2?
T1/2 is the duration in which the plasma concentration of a drug falls by 50%
What is Vd?
Volume of Distribution (Vd) is the total space available in the body to contain the known amount of drug.
If a drug has a high Vd, it is widely distributed and attains a lower plasma concentration per the given dose.
Describe/draw the fates of a drug
What are the factors influencing the distribution of drugs in the fetus?
- Amount and type of Drug
- Membrane permeability, receptor function, & Placental enzymes
- Fetal circulation, pH, & body water compartment
- Gestational age
- Maternal Serum Binding Protein
What are the pharmacokinetic parameters of absorption?
- Intestinal Motility
- Ventilation
- Cardiac Output
- Blood flow to skin
What are the pharmacokinetic parameters of Distribution?
- Plasma Vol.
- Total Body water
- Plasma Proteins
- Body fat
What are the pharmacokinetic parameters of Metabolism?
- Hepatic Metabolism
- Extrahepatic metabolism
What are the pharmacokinetic parameters of Excretion?
- Uterine BF
- Renal BF
- Glomerular Filtration Rate
- Ventilation
How do the pharmacokinetic parameters of absorption change during pregnancy?
Intestinal Motility: Decreases
Ventilation: Increases
Cardiac Output: Increases
BF to skin: Increases
How do the pharmacokinetic parameters of Distribution change during pregnancy?
Plasma Volume: Increases
Total Body water: Increases
Plasma proteins: Decrease
Body fat: Increases
How do the pharmacokinetic parameters of Metabolism change during pregnancy?
Both Hepatic & Extrahepatic metabolism is variable
How do the pharmacokinetic parameters of excretion change during pregnancy?
Uterine BF: Increases
Renal BF: Increases
GFR: Increases
Ventilation: Increases
Describe the characteristics of a molecule most likely to pass the placental barrier in terms of;
- Solubility
- Charge
- Protein-binding
- Molecular Mass
- Fat-soluble (hydrophobic)
- Uncharged
- Low amount of protein-binding > higher free molecules
- Low molecular mass
What are the consequences of the delayed gastric emptying & increased gastric pH during pregnancy on drug disposition?
Bioavailability of drug is altered and delayed time to peak levels following oral administration
What are the consequences of the increased Cardiac Output during pregnancy on drug disposition?
Increased CO>
Increased hepatic BF > Increased elimination of SOME drugs
What are the consequences of the increased total body water (TBW)/ Extracellular Fluid during pregnancy on drug disposition?
Altered Drug disposition> increased Vd for hydrophilic drugs
What are the consequences of the Increased fat compartment during pregnancy on drug disposition?
Increased body fat >
Decreased elimination of fat-soluble drugs > increased Vd for hydrophobic drugs
What are the consequences of the Increased Renal BF & GFR during pregnancy on drug disposition?
Increased RBF & GFR>
Increased Renal Clearance
What are the consequences of the decreased plasma albumin concentration during pregnancy on drug disposition?
Decreased Plasma Albumin conc. >
Increased free fraction of drug
What are the consequences of the altered CYP450 & UGT activity during pregnancy on drug disposition?
altered oral bioavailability & hepatic elimination.
