Distribution Flashcards
What is Distribution?
Process of reversible transfer of the drug from the bloodstream to other areas of the body
If the drug does not return to the blood, it has been eliminated
How is the rate and extent of distribution by?
How well perfused the organs/tissues are
Binding of the drug to plasma proteins and tissue components
Permeability of tissue membranes to the drug
Ion trapping
P- glycoproteins
pKa
What patient characteristics affect drug distribution?
Oedema –Dehydration
Weight loss-Obesity
Gender
Ethnicity
Pregnancy
Age
Health status
What environments do basic and acidic drugs accumulate in?
Basic drugs accumulate in acidic environments
Acidic drugs accumulate in basic environments
What does apparent volume of distribution mean?
The apparent volume of distribution is
the amount of fluid that would be required to contain the drug in the body at the same concentration as in the blood or plasma.
The Vd is a convenient method for describing how well a drug is removed from the plasma and distributed to the tissues.
DOES not provide information om where a drug is or whether it is concentrated in a particular organ.
What is a large volume distrubution
A large volume of distribution implies wide distribution, or extensive tissue binding, or both e.g warfarin, gentamicin, theophylline mainly stays in plasma little in tissues
Example of small volumes of distribution?
protein bound drugs that are trapped in plasma, will have small volumes of distribution
e.g diazepam
Medium volume distrubution examples
Cimetidine (140) , Digoxin (510) they are similar to concentrations in plasma and tissues (in litres for average 70kg adult)
Examples of large volume distribution
Mianserin (910) and quinacrine (50000) mainly in tissues, little in plasma.
A dose of analgesic (50mg) is administered i.v. and a blood sample is taken shortly afterwards. The initial concentration of analgesic in the blood sample is 0.85 µg.ml-1.
Calculate the Vd of the analgesic (in litres).
Vd = F xD/C
= 1 x 50mg / 0.85 µg.ml-1
= 50,000 µg / 0.85 µg.ml-1
= 58,824 ml
= 59 Litres
.IV is 1 bc 100% bioavailability
What are factors which effect distribution?
DEC blood flow DEC distribution vice versa
Capillary permeability - Sinusoids and fenestrated (liver) capillaries (kidneys) blood/drug can leak in pores INC distribution of drug
BBB or continuous capillaries (muscles) no intracellular clefs tight junctions for blood/drug to leave. You need transporters or super hydrophobic drug into capillary space to tissue DEC distribution. eg brain
e.g Septic shock extreme inc capillary permeability - conc of drug inside drug dec conc of drug inc distribution of drug. HIGH DOSE bc a lot is leaking out of tissues.
Protein binding plasma protein bindings
Liver produces albumin and kidneys make sure a lot of albumin is excreted in urine.
High protein bound drug there is a decrease in free drug DEC distribution. Highly protein bound drugs will concentrate in plasma bc it cant move into blood only free drug after time as drug is metabolised and excreted the albumin will release some drug small amounts of time to ensure a continue supply of drug is made.
Very little drug is protein bound so more free drug available in blood so INC distribution
chronic kidney dec cant maintain albumin so loss of albumin
Cerossis liver failure - cant produce albumin more free drug high distribution TOXIC SIDE EFFECTS
Solubility
Free drug is small, non polar, hydrophobic, lipid soluble, easily pass through in tissues therefore HIGH distribution. conc into tissues
Large, charge, hydrophilic, polar cant easily pass so conc in blood.
Volume distribution
drugs hydrophilic, polar, protein bound less free drug, whatever is free wont pass through so DECREASE Vd - FOUND IN BLOOD PLASMA
Some protein bound, lower molecular weight, hydrophilic (some charged), smaller. DRUG CAN BE FOUND IN BLOOD PLASMA AND INTERSPATIAL FLUID.
Vd is equal
Some hydrophobic, lipophilic, no protein bound, small drug, non polar, inc blood flow
DRUG FOUND IN BLOOD PLASMA, INTERSPATIAL FLUID and TISSUE CELLS
INC Vd
Warfarin low Vd bc you want it in Blood plama to reduce blood clotts
Patient received 2000mg IV. The conc was 28.5mg/L, What is the apparent volume of distribution in L/kg?
vd = F x dose/ conc
1 x 2000 / 28.5
= 70.1L
therefore to get in l/kg 70.1/70 = 1 L/kg
