Protiene drug binding-PATEL

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WELCOME

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PROTEIN BINDING OF DRUGS & ITS IMPORTANCE Presented by ; P.Megha Raju M.Pharm(2nd sem) Pharmacology branch.

CONTENTS: 

CONTENTS INTRODUCTION PROTEIN & ITS TYPES NEEDS FOR BINDING STUDY PROTEIN BINDING & TYPES OF BONDS FACTORS AFFECTING BINDING IMPORTANCE OF PROTEIN BINDING CONCLUSION REFERENCES

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INTRODUCTION The degree of binding of drugs to proteins of plasma and other proteins has a marked effect on its distribution,elimination & pharmacological effect. This is due to the fact that unbound form of the drugs can penetrate the wall of the blood vessel , where as the bound protein cannot. Drugs bind to different proteins like H.S.A , Lipoproteins , Globulin , Alpha –1 A.A.G. Study of protein drug binding effect should be carried out effectively.

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Definition ; the phenomenon of drugs are complex formation with proteins is called as protein - drug binding. A drug in blood exists in two forms: bound and unbound. Depending on a specific drug's affinity for plasma protein, a proportion of the drug may become bound to plasma proteins, with the remainder being unbound. If the protein binding is reversible, then a chemical equilibrium will exist between the bound and unbound states, such that: Protein + drug ⇌ Protein-drug complex

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PROTEIN & ITS TYPES Complex structure made up of amino-acid linked by peptide bonds or group of C,H,O,N (S,P may also present). The great majority of drug binds to one or other of the following types of proteins Receptors Ion-Channels Enzymes Carrier molecules 5. Plasma Proteins

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A drug in the body can interact with several tissue .these are 2 major categories , 1.Blood 2.Extravascular tissue Protein binding of drugs 2 types , 1.Inracellular binding 2.Extracellilar binding

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WHY ? DRUG PROTEIN BINDING STUDY The degree of drug plasma protein binding gives significant effect on the pharmacokinetic and pharmacodynamic properties of a drug. To achieve therapeutic effectiveness. To minimize toxicity.

Protein binding: 

Protein binding Complex formation between drug & protein. TYPES OF BONDS 1.Weak chemical bonds. 2.Hydrogen bonds. 3.Ionic bonds. 4.Vanderwaals force

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BINDING SITES

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PLASMA PROTEINS Types Albumin , Prealbumin Alpha -1 A.A.G Lipoproteins Globulins Albumin > Alpha -1 A.A.G > Lipoproteins > Globulin H.S.A binding sites Acidic drugs Binds to ? Basic drugs Binds to ? Primary & Secondary binding sites

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PLASMA PROTEIN BINDING TO DRUGS PLASMA PROTEIN DRUG

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HAEMOGLOBIN BINDING SITES Binding Sites

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Main Class of Protein Subclass Drugs Human serum Albumin Site I Site II Site III Site IV Warfarin , Phenylbutozone Diazepam,ibuprofen Digitoxin Tamoxifen Alpha –1 A.A.G Basic drugs like imipramine,lidocaine,qunidine,propranolol Lipoproteins Chylomicrons V.L.D.L L.D.L H.D.L A number of acidic (diclofenac) neutral (cyclosporin) & basic drugs (chlorpromazine) bind to lipoproteins. Alpha globulins Alpha-1 globulin Alpha-2 globulin Beta –1 globulin Beta-2 globulin Gamma globulin Steroids such as cortisone,predinisone Vitamin A,D,E & K Ferrous ions Carotenoids Antigens Haemoglobin Phenytoin,pentobarbital and phenothiazines

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FACTORS AFFECTING PROTEIN DRUG BINDING Factors relating to Drug. Factors relating to Protein and other binding components. Drug interaction. 4. Patient related factors.

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THERAPEUTIC EFFECTIVENESS OF DRUG PROTEIN BINDING The Therapeutic effectiveness of a drug may either increase or decrease due to protein drug binding. The drugs are therapeutically effective in unbound forms.

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1.Binding of C-arabinoside to Alpha –1 AAG 2.Binding of H.S.A to racemic ibuprofen. 3.Digitalis affinity for H.S.A in infants. 4.Sulphonamids which have affinity for albumin increases risk in new borns. 5.Binding of lidocaine and propranolol to albumin during old age.

IMPORTANCE: 

IMPORTANCE ABSORPTION- As we know the conventional dosage form follow first order kinetics. So when there is more protein binding then it disturbs the absorption equilibrium. DISTRIBUTION - A protein bound drug in particular does not cross the BBB,the placental barrier, the glomerulus. Thus protein binding decreases the distribution of drugs.

METABOLISM-: 

METABOLISM- Protein binding decreases the metabolism of drugs & enhances the biological half life. Only unbound fraction get metabolized. egg- Phenylbutazone & Sulfonamide ELIMINATION- Only the unbound drug is capable of being eliminated. Protein binding prevent the entry of drug to the metabolizing organ (liver ) & to glomerulus filtration. egg-Tetracycline is eliminated mainly by glomerular filtration.

SYSTEMIC SOLUBIILITY OF DRUG -: 

SYSTEMIC SOLUBIILITY OF DRUG - Lipoprotein act as vehicle for hydrophobic drugs like steroids, heparin, oil soluble vit. DRUG ACTION- Protein binding inactivates the drugs because sufficient concentration of drug can not be build up in the receptor site for action. Egg- Naphthoquinone

SUSTAIN RELEASE-: 

SUSTAIN RELEASE- The complex of drug protein in the blood act as a reservoir & continuously supply the free drug. Eg- Suramin protein binding for antitrypanosomal action. DIAGNOSIS - The chlorine atom of chloroquine replaced with radiolabeled I-131 can be used to visualize- molanomas of eye & disorders of thyroid gland .

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KINETICS OF PROTEIN BINDING : P =protein, d=drug, then applying law of mass action to reversible protein drug binding p+d <=> pd (pd) ka = (p)(d) pd =ka(p)(d) P=concentration of protein Pd=concentration protein drug complex , Ka=association constant , Kd=dissociation constant

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CONCLUSION As we can conclude from above discussion that protein binding affects the pharmacokinetics and pharmacodynamics of a drug. Therefore exhaustive studies should be carried out for protein drug binding in order to minimize the protein binding as much as possible because only in this way we can achieve the goal of therapeutic effectiveness.

REFERENCES ;: 

REFERENCES ; 1.Gibaldi M, Biopharmaceutics and Pharmacokinetics , pub-pharma book syndicate, p-182-201. 2.Gilman godman, Alfred,The pharmacological basis of therapeutics,10 th edition,McGra hill,p-24. 3.Notari,Robert E, Biopharmaceutics and Clinical Pharmacokinetics pub-marcel dekker ,inc, p-48-50. 4.Brahmankar.D.M, Jaiswal,Sunil B, Biopharmaceutics and Pharmacokinetics pub-v. prakashan, p-91-109. 5. Tripathi,KD, Essentials of medical pharmacology 5 th edition,pub-jaypee brothers med pub. P-18-19. 6. WWW.Google.com.

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