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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

BLOOD

PP-D

Pharm. effect Vd

D Liver

Kidney

Excretion

Met.


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 Drug

Warfarin Drug Warfarin Albumin

 Kernictrus


When displacement is significant? 1. Both displacing and displaced drugs are of 2. 3.

4. 5.

high PPB affinity. Concentrations Narrow therapeutic index If displacement is accompanied by enzyme inhibition. 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 ‍Ř&#x;‏ 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.


Distribution drug interaction