Pharmacokinetics

Def . Effect of the body on the drug .

Consist of 4 process ( ADME )

1 ) Absorption

Def . Transfer of drug from the site of administration to the systemic circulation

Mechanism of Absorption :

1 : Simple diffusion ( Lipid diffusion )

o From high conc . to low conc . ( Along concentration gradient ) .

o Depend on lipid solubility .

o Not needed energy and carrier .

o The drug must be lipid soluble and small in molecular weight ( Mwt . ) .

 Factors affecting simple diffusion :

1: Dose concentration ( Increase dose concentration Increase absorption

2:Molecular weight & size ( Increase Mwt . Decrease absorption ) .

3 : Ionization ( Water soluble drug ( Ionized ) > Decrease absorption )

4 PH at the site of absorption .

Most of drugs are weak acids or weak bases

Weak acid drugs less ionized in acidic medium---decrease ionization --- Increase Absorption

Weak base drugs less ionized in basic medium---decrease ionization--Increase Absorption

2 : Facilitate Diffusion :

- From high concentration to low concentration ( Along concentration gradient . )

- Need carrier and not need energy

3:Active transport :

-From low concentration to high concentration ( Against concentration gradient ) .

- Need carrier and need energy

4 : Pinocytosis or Endocytosis :

- Drugs of exceptionally large size .

- Engulfment of a drug molecule by the cell membrane . - Eg ( Vitamin B1 + intrinsic factor ) complex

► Factors affecting absorption of drugs :

1 : Patient - Related factors :

Route of administration IV > IM > SC > Oral > Skin .

Absorbing surface area Increase surface - Increase absorption .

Systemic circulation Shock and heart failure decrease absorption .

Presence of other drugs Adrenaline SC=Vasoconstriction( VC ) leads to decrease absorption .

Specific factors E.g. intrinsic factor for Vit . B12 .

2: Drug - Related factors:

o Lipid solubility High lipid solubility drug - High absorption .

o Ionization Non - ionized drugs High absorption .

o Valency Ferrous iron ( Fe ) absorbed more than ferric iron ( Fe ) .

o Nature Inorganic ( Small molecules ) > Organic ( Big molecules ) .

o Pharmaceutical preparation Solution > Suspension > Tablet

o PH of the drug .

2) Distribution

Def. The transfer of drug from the blood stream into interstitium(extracellular fluid) and tissue

Distribution of drug Depend on:

1-Blood flow

Increase blood flow---Increase distribution

Blood flow to the vessel-rich organs (brain, liver and kidney) is greater than that to the skeletal

muscles, adipose tissue and viscera

2-Capillary permeability:

 it depend on capillary structure and the chemical nature of the drug.

 In the liver and spleen(high capillary permeability)—large plasma proteins can pass.

 In the brain only lipid soluble drugs can pass through blood brain barrier(BBB).

3-Binding to plasma protiens:

 Albumin is the major drug-binding protein and may act as a drug reservoir.

 Bound fraction of the drug ---not active (not distributed, metabolized and excreted).

 Free fraction of the drug --- active (not distributed, metabolized and excreted)

 The concentration of free drug decrease due to elimination ---the bound drug dissociates

from the protein (to maintain equilibrium between free-drug and bound-drug).

 Amount of free drug can be increase by:

o 1-Displacement by other drugs.

o 2-Decrease in albumin or plasma proteins.

4- Volume of distribution

Def. The apparent volume of fluid into which an administrated drug is dispersed.

Vd ( Volume of distribution ) = Q ( Total amount of drug in the body ) /Cp ( Plasma concentration of the drug )

 Useful to determine the total amount of drug in the body (Q = Cp×Vd)

 Can be used to calculate the amount of drug needed to achieve a desired Cp:

- ( Vd ) ( target concentration = C1 ) = amount of drug initially in the body .

- ( Va ) ( higher conc . = C2) = amount of drug in the body needed to achieve a desired Cp

The additional dosage needed = Vd ( C2- C1 )

- If the drug has high Vd that means The drug has low affinity to binding to PP.

- If the drug has low Vd that means The drug has high affinity to binding to PP.

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