Pharmacokinetics
The physiological movement of drugs within the body and includes the mechanisms by which drugs move into, through, and out of the body
Four steps in pharmacokinetics:
- Absorption
- Distribution
- Metabolism or biotransformation
- Excretion
Four basic mechanisms allow drugs to move across cell membranes:
- Passive diffusion
- Facilitated diffusion
- Active transportation
- Pinocytosis/phagocytosis
Passive Diffusion
- The movement of drug molecules (particles) from an area of high concentration to an area of low concentration until equilibrium is reached
- Does not require energy, nor does it expend energy
- The porse in the cell membrane are small, therefore, drugs
Lipophilic
- Means fat loving
- Lipophilic drugs are chemicals that dissolve in fats or oils
- Are able to dissolve in the phospholipid cell membrane because like molecules dissolve in like molecules
Hydrophilic
- Means water loving
- Hydrophilic drugs are chemicals that dissolve in water
- Hydrophilic drugs do not pass through the lipid-rich cell membranes as easily as lipophilic drugs
Drug Ionization
- Affects the movement of the drug
- The ionization or charge of a drug depends on the pH of the liquid in which it is immersed and the pH of the drug
Ionized Drugs
- Have either a positive or a negative charge
- Nonionized drugs have no charge or are considered neutral
- Ionization or neutrality also affects the hydrophilic and lipophilic properties of a drug
- Nonionized drugs tend to be lipophilic
- Ionized drugs
Facilitated Diffusion
- Passive diffusion that utilizes a special carrier moleculre
- This carrier molecule helps the drug across the cell membrane
- No energy is needed
Active Transport
- Involves both a carrier molecule and energy
- Energy is needed in active transport because drug molecules move against the concentration gradient
- Active transport allows drugs to accumulate in high concentration within a cell or body compartment (ex.
Pinocytosis/Phagocytosis (General Information)
- Pinocytosis and phagocytosis are mechanisms of molecule movemnet in which molecules are physically taken in or engulfed by a cell
- Engulfing liquid or solid particles into the cell require energy
- Pinocytosis and phagocytosis are important for the mov
Pinocytosis
Cell drinking" occurs when the cell membrane surrounds and engulfs liquid particles (ex. insulin)
Phagocytosis
- "Cell eating" occurs when the cell membrane surrounds and engulfs solid particles
- Animal cells acquire nutrients by phagocytosis
Drug Absorption
- The movement of drug from the site of administration into the fluids of the body that will carry it to its site(s) of action
- Absorption is the first step in the pasasge of a drug through the body, unless it is introduced directly into the blood via IV
Factors affecting drug absorption
- Drug factors such as:
- Solubility
- Drug pH
- Molecular size
- Patient factors are:
- Animal's age
- Health status
Bioavailability
- The percent of drug administered that actually enters the systemic circulation
- IV and Intra-arterial drugs immediately enter the systemic blood circulation; therefore, are 100% available
Factors that Affect Bioavailability
- Blood supply to the area (muscles have a better blood supply than subcutaneous areas)
- Surface area of absorption (increased surface area means better absorption)
- Mechanism of drug absorption (diffusion versus active transport, etc...)
- Dosage form
pH
- The pH of the drug and the pH of the environment where the drug is administered both play a role in drug absorption
- pH is the measurement of the acidity of alkalinity of a substance
- pH is based on a scale of 0-14 with the lower numbers indicating ac
Acidic vs. Alkaline
The acidic or alkaline nature of the drug itself also helps determine whether a drug is predominately in lipophilic or hydrophilic form
Drug: Weak Acid
Environment: Alkaline
Form: Hydrophilic
Drug: Acid
Environment: Alkaline
Form: Ionized
Drug: Weak Alkaline
Environment: Acid
Form: Hydrophilic
Drug: Alkaline
Environment: Acid
Form: Ionized
Ion Trapping
- Occurs when a drug molecule changes from ionized to nonionized form as it moves from one body compartment to another
- When the drug changes compartments, it may change its ionization and become trapped in that new environment
Oral vs. Parenteral Drug Forms
- Absorption is further affected by the choice of oral or parenteral route of administration
- Solid drugs administered orally must first be broken down and then dissolved in gastric or intestinal fluids before they can be dissolved
- Parenterally adminis
Patient factors affecting drug absorption:
- Blood Flow
- Pain
- Stress
- Hunger
- Fasting
- Food consumption
- pH
Drug Distribution
- The physiological movement of drugs from the systemic circulation to the tissues
- the goal of drug distribution is for the drug to reach the target tissue or intended site of action
Factors that affect drug distribution:
- Membrane permeability
- Tissue perfusion
- Protein binding
- Volume of distribution
Membrane Permeability (Drug Distribution)
- Has a great effect on drug distribution
- Blood capillaries are only one cell layer thick and have fenestrations or small holes between cells to allow drug molecules to move in and out of the capillaries
- Exceptions: Blood-brain barrier (no fenestratio
Tissue Perfusion (Drug Distribution)
- Tissue perfusions affects how rapidly drugs will be distributed
- Tissue perfusion is the relative amount of blood supply to an area or body system
- Fast perfusion - brain, heart, liver, kidneys
- Slow perfusion - fat, skin
Protein Binding (Drug Distribution)
- Some drugs bind to proteins in the blood (particularly albumin)
- Proteins are large and cannot leave the capillaries, so the drug-protein complexes become trapped in the circulation
- Free or unbound drugs are able to leave the capillaries
- Liver dise
Volume of Distribution (Drug Distribution)
- How well a drug is distributed throughout the body based on the concentration of drug in the blood
- Drug concentration in blood will be lower if the drug has a large volume to distribute itself through
Biotransformation (aka Drug Metabolism)
- The chemical alteration of drug molecules by the body cells of patients to a metabolite that is in an activated from an inactivated form, and/or a toxic form
- The goal of biotransformation is to make drugs more water soluble so that they can be more ea
Primary site of biotransformation
- The Liver
- Other sites of biotransformation include
- Kidneys
- Small intestines
- Brain and neurological tissue
- Lungs
- Skin
Ways drugs interact with each other include:
- Altered absorption
- Competition for plasma proteins
- Altered excretion
- Altered metabolism
Altered absorption
One drug may alter the absorption of other drugs (ex. Antacids)
Competition for Plasma Proteins
Drug A and Drug B may both bind to plasma proteins
Altered Excretion
Some drugs may act directly on the kidney and decrease the excretion of other drugs (ex. Diuretics)
Altered Metabolism
The same enzymes may be needed for biotransformation of both drugs
Tolerance
The decrease response to a drug resulting from repeated use
An animal that develops tolerance requires a larger dose of drug to achieve the effect originally obtained by a smaller dose
Drug Elimination (Excretion)
Removal of a drug from the body
Routes of drug elimination include:
- Kidneys
- Liver
- Intestine
- Lungs
- Milk
- Saliva
- Sweat
Renal Elimination
- Glomerular filtration occurs at the level of the nephron and works by pushing water and small molecules through a tuft of capillaries called the glomerulus, similar to pushing things through a sieve
Tubular Secretion
- Active transport across the convoluted tubule membrane that moves certain molecules from blood into the urine filtrate
- Is generally a more rapid process of elimination than glomerular filtration
Hepatic Elimination
- Drugs excreted by the liver usually move by passive diffusion from the blood into the liver
- Once in the liver, they are secreted into the bile
- The bile is then secreted into the duodenum
- If lipophilic drug -- goes back to the liver
- If hydrophili
Drug Action
- Drugs can form a chemical bond with specific cell components on target cells within the animal's body
- These specific cell components are called receptors
- Receptors are three-dimensional proteins that are usually located on the cell membrane, but may
Affinity
- The strength of binding between a drug and its receptor
- The better the drug fits at the receptor site, the more biologically active it is
Agonist
A drug that binds to a cell receptor and causes action
Antagonist
A drug that inhibits or blocks the respose of a cell when the drug is bound to the receptors