Presented by pharmacist: Eman El-Khateeb

1. Once the drug is absorbed, there is an equilibrium between bound drug and free drug.

2. Bound drugs are involved in both pharmacodynamics and extravasation.

3. A highly protein bound drug has less potency.

4. A highly protein bound drug has less elimination.

5. protein-bound drug will not be filtered through the glomerulus.

6. protein binding completely prevents the drug from reaching its site of action.

7. If all the drug was bound to plasma protein, the

apparent Vd would be limited to intravascular compartment.

8. Basic drugs have a high affinity for albumin. 9. Glycoprotein is the most abundant plasma

protein. 10. Drug interactions concerning PPB is significant for

drugs with narrow therapeutic index.

Unbound (Free) Bound

Pharmacologically #Pharmacologically active inactive

Distributable # Not distributable

Undergoes Met. # Not prone to Met. Or elimination Or elimination

Binding either with plasma proteins or with tissue proteins outside blood.

Site of action

(receptor)

Storage tissue

Liver

Kidney

BLOOD

PP-D D

Pharm. effect

Vd

Met.

Excretion

Albumin Albumin

Displaced drug = Drug with lower affinity 96%

Displacing drug =Drug with higher affinity 99%

Unbound (Free) Bound

Pharmacologically # Pharmacologically

active inactive

Distributable # Not distributable

Undergoes Met. # Not prone to Met.

Or elimination Or elimination

Plasma protein binding

The proteins commonly involved in binding with drugs are

albumin (most common),

lipoproteins,

and a1-acid-glycoprotein (AGP).

Acidic and neutral compounds will tend to bond with albumin, which is basic,

while basic substances will primarily bind to the acidic AGP molecule. Acidic molecules may also bond with lipoproteins if the albumin is saturated.

Examples

Warfarin + chloral hydrate or phenytoin

Warfarin + Phenylbutazone

Warfarin + Aspirin

Kernictrus

Sulphonamides + Bilirubin

Albumin

Drug Warfarin

Drug Warfarin

When displacement is significant?

1. Both displacing and displaced drugs are of high PPB affinity.

2. Concentrations

3. Narrow therapeutic index

4. If displacement is accompanied by enzyme inhibition.

5. If displacement is accompanied by decreased renal elimination.

Drugs with high affinity to PP. Salicylates

Valproate, Phenytoin

OHG

OAC

Phenylbutazone, NSAID

MTX

Sulphonamides

Ethacrynic acid

Group excercise

12

Over all quiz

1- A drug M is injected IV into a laboratory subject. It is noted to have high plasma protein binding. Which of the following is most likely to be increased as a result ?

A. Drug interaction B. Distribution of the drug to tissue sites C. Renal excretion D. Liver metabolism

Over all quiz (cont.)

2- An agent is noted to have a very low calculated volume of distribution(Vd). Which of the following is the best explanation ؟ A. The agent is eliminated by the kidneys, and the patient has renal insufficiency. B. The agent is extensively bound to plasma proteins. C. The agent is extensively sequestered in tissue. D. The agent is eliminated by zero-order kinetics

Over all quiz (cont.)

3- The followings can cause possible interactions with hydrochlorothiazide:

a. Prazocine

b. Too much banana.

c. Prpranolol.

D. A &C

E. All the above

Over all quiz (cont.)

4- All of the following substances may cause digoxin induced arrhythmia except:

A. Propanthelin

B. Furosemide

C. Cholestyramine

D. None of the above

E. All of the above

Over all quiz (cont.)

5- Metoclopramide decreases absorption of the following drugs except:

A. Riboflavin.

B. L-DOPA.

C. Astemizole.

D. A&B.

E. B&C.

Over all quiz (cont.)

6- Ketoconazole absorption is increased by :

A. Alumag antacid.

B. Ranitidine.

C. A&B.

D. None of the above.