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Clinical Significance of Drug-Protein Binding: A Comprehensive Overview, Schemes and Mind Maps of Biopharmaceutics and Pharmacokinetics

A detailed explanation of the clinical significance of drug-protein binding, covering its impact on absorption, distribution, elimination, and therapeutic applications. It explores the role of protein binding in drug targeting, sustained release, and the influence on drug action and metabolism. The document also discusses the relationship between protein binding and pharmacokinetic parameters, highlighting its importance in antimicrobial therapy.

Typology: Schemes and Mind Maps

2022/2023

Available from 02/16/2025

amlodipine-losartan
amlodipine-losartan 🇵🇭

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Good morning once again, I’m Nurhana s kalbi, and I will be presenting this topic
which is
G. Clinical significance of drug-protein binding
SLIDES
Drugs are widely used in clinical psychopharmacology, with few exceptions, that
are hepatically eliminated and circulate in the blood bound to plasma proteins. Often,
the degree of binding is high which is >90%. And This fact has led to a widespread
belief that such drugs may frequently participate in drug-binding interactions.
Coadministration of drugs can result in a highly bound drug displacing a less avidly
bound drug from its binding sites. And This reasoning simplifies a complex situation
where compensatory changes occur in the body to buffer the impact of drug-binding
interactions.
Stated here are the
SIGNIFICANCE OF DRUG PROTEIN BINDING
Absorption
Systemic solubility of drug
Distribution
Elimination
Therapy and drug targeting
Apparent volume of distribution and drug storage
Diagnosis
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. As we know the conventional dosage
form follow first order kinetics. So, when there is more protein binding then it disturbs
the absorption equilibrium. Therefore, the sink conditions and the concentration gradient
are re-established which now act as the driving force for further absorption. this is
particularly useful in case of ionized drugs which are transported with difficulty.
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Good morning once again, I’m Nurhana s kalbi, and I will be presenting this topic which is G. Clinical significance of drug-protein binding SLIDES Drugs are widely used in clinical psychopharmacology, with few exceptions, that are hepatically eliminated and circulate in the blood bound to plasma proteins. Often, the degree of binding is high which is >90%. And This fact has led to a widespread belief that such drugs may frequently participate in drug-binding interactions. Coadministration of drugs can result in a highly bound drug displacing a less avidly bound drug from its binding sites. And This reasoning simplifies a complex situation where compensatory changes occur in the body to buffer the impact of drug-binding interactions. Stated here are the SIGNIFICANCE OF DRUG PROTEIN BINDING  Absorption  Systemic solubility of drug  Distribution  Elimination  Therapy and drug targeting  Apparent volume of distribution and drug storage  Diagnosis  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. As we know the conventional dosage form follow first order kinetics. So, when there is more protein binding then it disturbs the absorption equilibrium. Therefore, the sink conditions and the concentration gradient are re-established which now act as the driving force for further absorption. this is particularly useful in case of ionized drugs which are transported with difficulty.

Systemic solubility of drug Like for example, Lipoprotein acts as a vehicle for hydrophobic drugs like steroids, heparin, oil soluble vit. Since they are water insoluble drugs, they are circulated and distributed to tissues by binding especially to lipoproteins which act as a compound.  Distribution A protein bound drug in particular does not cross the BBB (blood-brain barrier ) , the placental barrier, which is the glomerulus. Plasma protein binding restricts the entry of drugs that have specific affinity for certain tissues. basically, This prevents accumulation of large fraction of drugs in such tissues and subsequent toxic reactions. Plasma protein binding favors uniform distribution of drugs throughout the body by buffer function.  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. e.g., Tetracycline is eliminated mainly by glomerular filtration. 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. hence, drugs which are more than 95% bound are eliminated slowly, that they have long elimination half-lives like the tetracycline, which has a 65% bound and has an elimination half-life of 8.5 hours in comparison to 15.1 hours of doxycycline which is 93% 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.  Therapy and drug targeting The binding of drugs to lipoproteins can be used for site specific delivery of hydrophilic moieties. SO, This is particularly useful in certain cancer therapy because certain tumor cells have greater affinity for LDL then normal cells. therefore, binding a suitable anti neoplastic to it can be used as a therapeutic tool.

So basically, this means that Protein binding is most clinically significant for antimicrobial therapy , where a high degree of protein binding serves as a drug DEEPOW “depot,” allowing for increased duration of the time the drug concentration remains above the bacterial minimum inhibitory concentration, adding to antimicrobial efficacy. E. Protein binding of Drugs

  1. Pharmacokinetic importance of protein-binding
  2. Factors that influence drug-protein binding
  3. Effects of protein binding on apparent Vd
  4. Effects of changing plasma protein
  5. Displacement from plasma protein binding sites F. Relationship of plasma drug protein binding to distribution and elimination
  6. Relationship between Vd, drug elimination half-life and clearance G. Clinical significance of drug-protein binding H. Relationship of Drug distribution and Pharmacodynamics  Absorption  Distribution  Metabolism  Elimination  Systemic solubility of drug  Drug action  Sustain release  Diagnosis  Drug action Protein binding inactivates the drugs because of sufficient concentration of drug cannot be built up in the receptor site for action.

e.g., Naphthoquinone Protein-binding may affect drug activity in one of two ways: either by changing the effective concentration of the drug at its site of action or by changing the rate at which the drug is eliminated, thus affecting the length of time for which effective concentrations are maintained.  Sustain release The complex of drug proteins in the blood act as a reservoir & continuously supply the free drug. e.g., Suramin sodium-protein binding for antitrypanosomal action.  Drug Targeting The binding of drugs to lipoproteins can be used for site-specific delivery of hydrophilic drugs.