Drug distribution IA % + Flashcards

1
Q

Distribution

A
  • Once a drug has been absorbed it must be available for biological action and distribution to the tissues.
  • To be active a drug must then leave the blood stream and enter the inter or intracellular spaces.
  • Drug Distribution refers to the Reversible Transfer of a Drug between the Blood and the Extra Vascular Fluids and Tissues of the body (for example, fat, muscle, and brain tissue).
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2
Q

Tissue distribution terms

A
  • Plasma protein binding
  • Tissue perfusion
  • Membrane characteristics

•Blood-brain barrier, Placental, Testis►

  • Blood-testes/ovary barrier
  • Lipid soluble drugs
  • Actively transported
  • Transport mechanisms
  • Diseases and other drugs (esp renal failure, liver disease, obesity)
  • Elimination
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3
Q

Plasma protein binding

A
  • Many drugs bind to proteins in the plasma such as albumin or a1-glycoprotein & lipoproteins► (eg phenytoin).
  • Only unbound drug is biologically active.
  • Binding is reversible.

Amount of bound drug can be changed by:

  • Renal failure
  • Hypoalbuminaemia (low blood albumin)
  • Pregnancy
  • Other drugs
  • Saturability of binding
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4
Q

Volume of ditribution

A
  • The volume of plasma that would be necessary to account for the total amount of drug in a patient’s body, If that drug were present throughout the body at the same concentration as found in the plasma.
  • The result are expressed in terms of litres per kilogram.
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5
Q

Clearance

A
  • Clearance is defined as the theoretical volume from which a drug is completely removed over a period of time.
  • Measured in units of time (ml/min).
  • Measure of elimination.
  • Dependent on concentration and urine flow rate for renal clearance.
  • Dependent on metabolism and biliary excretion for hepatic clearance.
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6
Q

Half life

A
  • The time taken for the drug concentration in the blood to decline to half of the current/initial value.
  • e.g if it takes 4 hours for the concentration of a drug in the blood stream to drop from 10mg/L to 5 mg/L then the half life is 4 hours
  • Half life depends on the volume of distribution and rate of clearance.
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7
Q

Chronic administration

A
  • To have a therapeutic benefit most drugs needed to be given chronically.
  • Plasma levels of a drug take many doses before they stabilise, usually 4-5 half-lives.
  • This may necessitate a loading dose.
  • It is important to know how a particular drug will build up in the body.
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8
Q

Drug elimination

A
  • This term covers the removal of active drug and matabolites from the body.
  • This determines the length of action of the drug.

Made up of 2 parts:

  • Drug Metabolism (usually in the liver)
  • Drug Excretion (usually in the kidney but also biliary system/gut, lung, milk)
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9
Q

Excretion

A

-The kidneys are the primary organ for drug excretion.

Three principal mechanisms are used:

  • Glomerular filtration
  • Passive tubular reabsorption
  • Active tubular secretion

-Renal damage is therefore important in causing drug toxicity.

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10
Q

Glomerular filtration

A
  • The glomerulus filters 190 litres of fluid a day.
  • All unbound drugs will be filtered at the glomerulus as long as their molecular size, charge or shape are not excessively large.
  • Factors that affect the glomerular filtration rate will reduce the clearance of a drug.
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11
Q

Active Tubular Secretion

A
  • Some drugs are actively secreted into the proximal tubule (acidic and basic compounds).
  • This is the most important system for eliminating protein-bound cationic and anionic drugs.
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12
Q

Passive tubular reabsorption

A
  • As the filtrate moves down the renal tubule any drug present is concentrated.
  • Passive diffusion along the concentration gradient allows the drug to move back through the tubule into the circulation.
  • Passive diffusion occurs in the distal tubule and collecting duct.
  • Only un-ionised drugs such as weak acids are reabsorbed.
  • Can also be affected by renal failure.
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13
Q

Biliary secretion 1

A
  • The liver secretes 1 litre of bile a day.
  • Drugs may be passively or actively secreted into the bile.
  • Biliary secretion accounts for 5-95% of drug elimination for many drugs.
  • Many drugs are then reabsorbed from the bile into the circulation. This is called entero-hepatic circulation.
  • It continues until the drug is metabolised in the liver or excreted by the kidneys.
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14
Q

Biliary secretion 2 Ø

A
  • Metabolism in the liver often leads to conjugation of the drug.
  • The conjugated drug is not reabsorbed from the intestine.
  • Damage to the liver may reduce the rates of conjugation and biliary secretion and so allow the build up or reabsorption of the drug with resultant toxicity.
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15
Q

Steady state concentration graph

A
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