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Protein Bond

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Muhammad Ikram
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15 views3 pages

Protein Bond

Uploaded by

Muhammad Ikram
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as TXT, PDF, TXT or read online on Scribd
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protein binding of drugs, including all the important points:

Introduction

- Drugs interact with plasma or tissue proteins or macromolecules to form a drug-


macromolecule complex
- Drug-protein binding can be reversible or irreversible

Irreversible Drug-Protein Binding

- Results from chemical activation of the drug, leading to covalent bonding with
the protein
- Accounts for certain types of drug toxicity, such as:
- Chemical carcinogenesis
- Hepatotoxicity (e.g., acetaminophen)
- Can lead to drug accumulation and prolonged toxicity
- Examples:
- Acetaminophen (hepatotoxicity)
- Chloramphenicol (bone marrow toxicity)

Reversible Drug-Protein Binding

- Most drugs bind to proteins through weaker chemical bonds (hydrogen bonds, van
der Waals forces)
- Protein-bound drug is:
- Pharmacologically inactive
- Has restricted distribution
- Free or unbound drug is:
- Therapeutically active
- Crosses cell membranes
- Reversible binding can affect drug pharmacokinetics and pharmacodynamics
- Examples:
- Warfarin (albumin binding)
- Propranolol (AAG binding)

Methods for Studying Protein Binding

- Equilibrium dialysis
- Ultrafiltration
- In vitro methods using purified proteins (e.g., albumin)
- In vivo methods using radiolabeled drugs
- Chromatographic methods (e.g., HPLC)

Experimental Factors for Measuring Protein Binding

- Cost
- Ease of measurement
- Time
- Instrumentation
- Other considerations (see Table 11-5)

Macromolecular Components in Blood

- Albumin
- α1-acid glycoprotein (AAG)
- Lipoproteins
- Immunoglobulins (IgG)
- Erythrocytes (RBC)
Albumin

- Molecular weight: 65,000-69,000 Da


- Synthesized in the liver
- Major component of plasma proteins responsible for reversible drug binding
- Distributed in:
- Plasma
- Extracellular fluids
- Elimination half-life: 17-18 days
- Normal concentration: 3.5-5.5% (weight per volume) or 4.5 mg/dL
- Binds to:
- Weak acidic drugs
- Weak basic drugs
- Fatty acids
- Bilirubin
- Albumin binding can affect drug distribution and pharmacokinetics

Alpha-1-acid Glycoprotein (AAG)

- Molecular weight: approximately 44,000 Da


- Plasma concentration: 0.4-1%
- Binds primarily basic (cationic) drugs
- Examples:
- Saquinavir
- Propranolol
- Imipramine
- Lidocaine
- AAG levels can increase in response to inflammation or tissue damage
- AAG binding can affect drug distribution and pharmacokinetics

Globulins

- α-, β-, γ-globulins


- Responsible for plasma transport of certain endogenous substances
- Low capacity but high affinity for binding
- Examples:
- Corticosteroids
- Thyroxine
- Trypothan
Here is the complete and organized data:

Drug: Dexmedetomidine hydrochloride injection (Precedex®)

Pharmacological Properties:

- α-2-adrenergic agonist
- Sedative and analgesic properties

Administration:

- Intravenous infusion using a controlled infusion device

Pharmacokinetic Study:

- Conducted in volunteers with and without severe renal impairment (De Wolf et al,
2001)
- Compared pharmacokinetics and hemodynamic responses between the two groups

Findings:
- Pharmacokinetics of dexmedetomidine differed little between the two groups
- No significant differences in hemodynamic responses
- Elimination half-life:
- Subjects with severe renal impairment: 113 ± 11 minutes
- Normal subjects: 136 ± 13 minutes (p < 0.05)
- Prolonged sedation observed in subjects with severe renal impairment
- Reduced protein binding in renal disease subjects (hypothetical explanation for
prolonged sedation)

Drug Properties:

- Mainly cleared by hepatic metabolism


- Highly protein bound (albumin and alpha-1-acid glycoprotein)
- Substrate for the efflux transporter P-glycoprotein

Questions:

- Can reduced protein binding change the concentration of the active drug in the
CNS?
- Is the drug a substrate for a transporter? (Yes, P-glycoprotein)

Please let me know if this is complete.

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