Pharmacokinetics Absorption and Distribution

Drug disposition is divided into four stages designated by the acronym?

• ADME

What does AD in ADME stand for?

• A = Absorption of Drug from Site of Administration

• D = Distribution within the Body

What does ME in ADME stand for?

• M = Metabolism

• E = Excretion

Pharmacokinetics is the study of?

• Absorption, Distribution

• Metabolism & Excretion

Cell membranes are selectively?

• Selectively permeable membranes responsible for regulating cell volume.

• intracellular pH and the correct concentration of intracellular ions and molecules.

Molecules such as glucose and amino acids are taken up from?

• Extracellular Fluid

Molecules and ions move across the plasma membrane by?

• Passive, Facilitated Diffusion

• Active Transport Or

• Endocytosis/Exocytosis

When does Lipid Diffusion occur?

• Molecule is Small

• Molecule is Uncharged

• Molecule is Lipid Soluble

Lipid diffusion also depends on ?

• Concentration of the molecule on either side of the Membrane.

What Lipid Molecules will not pass efficiently through Diffusion?

• Charged Lipids

• Large Lipids

• Water Soluble

What is Facilitated Transport?

• Type of Passive Transport

• It allows specific molecules or ions to move across the cell membrane with the help of transport proteins.

• The process does not require energy (no ATP)

• High Concentration → Low Concentration

• No net buildup within the cell = Equilibrium.

• Uses Carrier Proteins.

Facilitated Transport allows for what Vital Movement?

• helps control the movement of vital molecules like glucose, amino acids, and ions into and out of cells.

What is Active Transport?

• Uses Specific Transporters

• Uses ATP

• Allows accumulation of specific molecules against a concentration gradient.

• Generally referred to as Pumps

 Macromolecules and some metabolites require?

• Specific Transporters to Cross the Lipid BiLayer.

What is Endocytosis?

• process whereby material at the cell surface is brought into the cell.

•  It allows large polar molecules to cross the plasma membrane into the cell.

• The plasma membrane forms a pocket around the material in the extracellular environment.

• then forms a vesicle that separates from the plasma membrane and migrates to the cell interior.

Exocytosis is?

• The Opposite of Endocytosis

• Describes the movement of material enclosed in membrane-bound vesicles from the interior of the cell to the plasma membrane where the contents are released to the exterior.

drugs must often move across?

• Membrane Barriers to be Absorbed, and Distributed. To reach Site of Action

Passive diffusion through lipid cell membrane, facilitated transport and active transport are the?

• Important Mechanisms

The lipid solubility and ionisation of the drug is a?

• Major Determining factors in the permeability of the cell membrane to the compound.

Drugs which resemble endogenous substrates for transporter…?

• Transporter Proteins can move across the Cell Membrane.

Endocytosis is important for?

• Large Molecules.

Absorption is the?

• passage of a drug from the site of administration into the plasma.

What is the only route where Passage is not as important?

• IV/IO

For some drugs absorption to the plasma is not required, such as?

• Topical / Inhalation

Absorption & Distribution Diagram

Drugs need to be stable at acidic…?

• Acid pH to pass through the Stomach

Absorption may begin in the mouth and stomach but most drugs are usually absorbed from?

• The Small Intestine

Orally administrated drugs must pass through the?

• Gut Wall

• Transported To Liver

• Before entering the Bloodstream

Most drugs administered orally are susceptible to?

• First Pass Metabolism

• Or Pesystemic metabolism in the gastrointestinal tract and the liver

Describe First Pass Metabolism?

1. Most drugs are usually absorbed from the small intestine. 

2. A proportion of the drug will undergo metabolism in the cells of the gut wall.

3. The drug is transferred from the intestine to the liver via the portal vein.

4. A proportion of the drug will undergo metabolism in the liver.

If the Drug is Rapidly Metabolized in 1st Pass Metabolism then?

• The amount of unchanged drug entering the systemic circulation is decreased. 

What is Bioavailability?

• The fraction of an administered dose of unchanged drug that reaches the systemic circulation

What is the Bioavailability of Gtn and Naloxone?

• GTN = 1%

• Naloxone = 2%

Drugs with high first-pass metabolism are generally administered by?

• By routes Such as

• Sublingual, Nasal, Injection (Paranetral)

Up to ….% of a drug can be absorbed within 1-3 hours.

• 75%

What are the 4 Main Factors affecting GI Absorption?

• GI Motility

• Sphlachnic Blood Flow

• Particle Size

• Physiochemical Factors

The sublingual route results in?

• Rapid Absorption

• And Enters Bloodstream Immediately.

• E.G GTN

Drugs administered as nasal spray must be transformed into?

• Tiny Droplets in Air (Atomized)

Nasal Administration is absorbed through?

• through the thin mucous membrane that lines the nasal passages.

• Once absorbed, the drug enters the bloodstream and avoids first-pass metabolism.

• Works Quickly

Lipid-soluble drugs can be administered through stick?

• Stick on patches.

• Causing Systemic Effects.

Inhalation administration, The Lungs serve as both…?

• Absorption & Excretion

Inhalation is used to administer?

• This method is used for gaseous and volatile drugs

Administration of drugs by injection is used for drugs that are?

• Poorly absorbed in the GI Tract, Or unstable.

• 4 Types of Injection

IV Can be administered either?

• The drug can be administered by a bolus injection

• or by slow infusion (by gravity or infusion pump). 

The addition of adrenaline to a local anaesthetic reduces the?

• the absorption of the aesthetic into the general circulation

• , thus prolonging the anaesthetic affect locally. 

IM is the preferred Route for?

• Drugs with a large volume

• Rate of Absorption is dependent on Blood Volume.

IO provides a non?

• Non Collapsable Entry Point To the Venous System