SIGNIFICANCE OF PROTEIN BINDING

SIGNIFICANCE OF PROTEIN BINDING OF DRUGS : 

SIGNIFICANCE OF PROTEIN BINDING OF DRUGS Presented by: Patel Riteshkumar K. Department of Pharmaceutics Srinivas College Of Pharmacy

Basic Consideration of Protein Binding of Drugs: 

Basic Consideration of Protein Binding of Drugs Bound Drug is Pharmaodynamicaly inert. Binding: Half life of drug. Bonding : Hydrogen bond, Hydrophilic bond, ionic bond, Vander Walls bond. Irreversible bonding : Covalent bonding : responsible for the Carcinogenicity or Tissue toxicity.

Significance : 

Significance ABSORPTON SYSTEMIC SOLUBILITY OF DRUGS DISTRIBUTION ELIMINATION KERNICTERUS THERAPY AND DRUG TARGETING APPARENT VOLUME OF DIRTIBUTION AND DRUG STORAGE DIAGNOSIS

ABSORPTON : 

ABSORPTON The absorption equilibrium is attained by transfer of free drug from the site of administration into the systemic circulation and when the concentration in these two compartments become equal. However ,binding of the absorbed drug to plasma proteins decreases free drug concentration and disturbs such an equilibrium . Thus , sink conditions and the concentration gradient are reestablished which now act as the driving force for further absorption. This is particularly useful incase of ionized drugs which are transported with difficulty.

SYSTEMIC SOLUBILITY OF DRUGS : 

SYSTEMIC SOLUBILITY OF DRUGS Water insoluble drugs ,neutral endogenous macromolecules such as Heparin , several steroids . Oil soluble vitamins are circulated and distributed to tissues by binding especially to lipoproteins which act as a vehicle for such hydrophobic compounds.

DISTRIBUTION: 

DISTRIBUTION Plasma protein binding restricts the entry of drugs that have specific affinity for certain tissues . This prevents accumulation of large fraction of drugs in such tissues and thus , subsequent toxic reactions. Plasma protein binding thus favors uniform distribution of drugs throughout the body by its buffer function. A protein bound drug in particular does not cross the BBB ,the placental barrier and the glomerulus.

APPARENT VOLUME OF DIRTIBUTION AND DRUG STORAGE : 

APPARENT VOLUME OF DIRTIBUTION AND DRUG STORAGE Drug bound to the blood components means intracellular and remain confined in blood , such drugs has small volume of distribution. On other side drugs who shows the extra vascular tissue binding that show large volume of distribution A tissue /blood also provide a great affinity for a particular drugs who act as a “Depot” or “Storage Site” for eg :- RBC is a storage site for drug like tetrahydrocannabinol

ELIMINATION : 

ELIMINATION Only the unbound drug is capable of being eliminated. This is because the drug protein complex cannot penetrate into the liver . The large molecular size of the complex also prevents it from getting filtered through the glomerulus . Thus, drugs which are more than 95% bound are eliminated slowly i.e they have long elimination half lives ;for eg tetracycline ,which is only 65% bound ,has an elimination half life of 8.5 hours in comparison to 15.1 hours of doxycycline which is 93% bound to plasma proteins .

PowerPoint Presentation: 

However penicillin have short have –lives despite being extensively bound to plasma proteins. This is because rapid equilibration occurs between the free and the bound drug and the free drug is equally rapidly excreted by active secretion in renal tubules.

Diagnosis: 

Diagnosis The chorine atom of choroquine when replaced with radiolabelled I-131 can be used to visualize melanomas of the eye since choroquine has a tendency to interact with the melanin of eyes. the thyroid gland has great affinity for iodine contaning containing compound. Hence any disorder of the same can be detected by tagging such a compound with a radioisotope of iodine.

THERAPY AND DRUG TARGETING: 

THERAPY AND DRUG TARGETING The binding of drugs to lipoproteins can be used for site specific delivery of hydrophilic moieties. This is particularly useful in certain cancer therapy because certain tumor cells have greater affinity to for LDL then normal cells. Thus binding a suitable antineoplastic to it can be used as therapeutic tool. Estradiol binds selectively and strongly to prostrate and thus prostate cancer can be treated by attaching nitrogen mustered to estradiol for targeting of prostate glands.

REFRENCES : 

REFRENCES D. M. Brahmankar , Biopharmaceutics and Pharmacokinetics. Page no. 130-133. www.google.com/image