Drug distribution ( Pharmacokinetics)

Define Pharmacokinetics vs Pharmacodynamics

Pharmacokinetics :effect of the body on the drug

Pharmacodynamic: effect of the drug on the body

Types of Pharmacokinetics

Drug absorption (administration)

Drug distribution

Drug metabolism

Drug excretion

Where are drugs are distributed first

Drugs are rapidly distributed to blood rich organs (heart, liver, kidney, brain)

then to muscles fat skin (which have poor blood supply)

Which drugs have selective accumulation in certain tissue

1. Iodide → thyroid tissue

2. Tetracyclines → bone

3. Chloroquine → eye, liver

4. Some body areas (eg brain) protected from drugs → special barrier (eg BBB)

The use of drug redistribution

Termination of action of some drugs

Drug redistributed from action site to other tissues where still active but not produce any action

How is Thiopental used in drug redistribution

IV injection acts on CNS → Anesthesia →Redistributed from CNS to storage sites in muscles & fat → action termination within 10-15 mins.

Thiopental characteristics

1. Ultrashort

2. active

3. Highly lipid soluble Barbiturate

Repeated injection Thiopental leads to

Repeated Thiopental injection (eg: 3/4)

→ storage site saturation→ ↑plasma conc → Return again to CNS → prolonged action (termination of action depends on metabolism and excretion)

2 characteristic of plasma protein bound drugs

1. Inactive (no diffuse from vasc space = no effect produced , metabolised or excretion)

2. acts as a reservoir (when free drug conc ↓ by metabolism or excretion unbounding occurs = Reversible)

Binding in plasma protein binding

non selective and competition of many drugs/subst for same binding site leads to ↑ free form of one drug

Sulfonamide vs bilirubin

Sulfonamides displace bilirubin from albumin binding → ↑.free bilirubin → ↑ risk of bilirubin encephalopathy/ Kernicterus in neonates

If there is high plasma protein binding and example

Bolus injection (Very rapid IV)

Eg: diazoxide in hypertension

If there is decrease in plasma proteins (hypoproteinemia) due to liver/renal disease or malnutrition

 Reduce drug dose of drugs with high plasma protein binding

Eg: Warafrin

Example of tissue protein binding replacement

Quinidine displaces digoxin from plasma protein and tissue protein binding & ↓ renal excretion of digoxin —> ↑ free digoxin —> precipitate digoxin toxicity

Volume of distribution meaning

Apparent vol req to contain all drug in body at same conc as in plasma provided body acts as single homogenous compartment for drug.

Volume of distribution formula

Vd = amount drug given to body / Plasma conc

(after distribution equilibrium (0.5-1 hr))

What does High Volume distribution mean

High Vd as plasma conc is low means most drug distributed to diff organs in high conc

Factors affecting Vd (Favouring)

1. Highly unionized

2. Highly lipid soluble

3. Low binding to plasma protein

4. Highly binding to tissue protein

= High Vd

Drugs with high Vd vs low Vd on haemodialysis

Drugs with high Vd (eg:digoxin) if toxicity occur no adv of haemodialysis to remove drug as plasma level low and most of drug conc in tissue

Drugs with low Vd (eg: aspirin) in case of toxicity haemodialysis remove most drug as it is conc in blood.

Why does drugs with high Vd have minimal fluctuations in blood conc

high Vd drugs minimum fluctuations in blood conc as tissues act as reservoir for the drug and provide the blood by the drug when its concentration in the blood ↓.

Define steady state concentration (Css)

Rate of drug elimination = Rate of administration

Site of distribution Compartment theory levels

Vd 3-5 = Plasma

Vd 5-15 = Interstitial

Vd 20+ = Intracellular