Pharmacokinetics & Pharmacodynamics Flashcards
The study of what happens to the drug(s) in the animal’s body after it is administered. It covers absorption, distribution, metabolism, and excretion (ADME).
Pharmacokinetics
The process by which a drug crosses various barriers to reach the bloodstream.
Absorption
What is Bioavailability?
The degree to which a drug is absorbed and becomes available via the general circulation
What are the two main methods of crossing cellular membranes?
Passive (no energy required) and Active Processes (energy required)
What are the two processes of Passive Process?
Simple Diffusion and Facilitated Diffusion
What are the two processes of Active Process?
Active Transport and Phagocytosis/Pinocytosis
What are the factors affecting the oral absorption of drugs?
- Gut fill and the rate of pyloric emptying may delay transit of drugs into the lower intestinal tract where the majority are absorbed.
- Some drugs may bind to gut contents, which may delay or prevent absorption.
- Low gastric pH may destroy or inactivate some drugs.
- The presence of gastrointestinal disease is an important factor in altering the absorption of drugs
What are some issues of absorption for Ruminants?
- Large capacity of rumen dilutes drugs.
- pH 5.5–6.5 tends to cause ion trapping of basic drugs (more on this later).
- Microbial activity - affects the stability of many drugs.
- Rate of passage of feed out of the rumen depends on the amount of feed the ruminant is eating and the digestible level of the feed.
What are the factors affecting the absorption of parenteral drugs?
Parenteral drugs must be formulated to be:
- pyrogen-free (i.e. not causing a fever);
- sterile;
- adjusted to body pH;
- adjusted to body osmolality.
What are the factors affecting the absorption of topical drugs?
- Increased absorption occurs if the skin is broken.
- Also, increased circulation to the skin allows for increased absorption.
- The rate of absorption may be increased by placing the drug in a vehicle such as dimethyl sulfoxide (DMSO)
(T or F) Lipid-soluble (fat-soluble) drugs cross cell membranes more readily than water-soluble drugs
True
The _____ the drug molecule, the easier it can be absorbed
Smaller
(T or F) Non-ionized drugs diffuse through cell membranes harder than drug molecules with a charge
False
What are factors that affect absorption rate?
The higher the drug concentration at a site, the faster the absorption.
The greater the blood supply to the absorptive area, the faster the absorption.
What are the 6 factors that affect drug distribution?
- Concentration gradient.
- Protein binding.
- Storage in various tissues. * Dilution in luminal fluids. * Specialized barriers.
- Disease processes.
Drugs tend to move from an area of high concentration to one of low concentration.
Concentration Gradient
Drug in plasma is exposed to plasma proteins
Protein Binding
Once the drug has left the plasma compartment, it may be ______ in tissue.
Stored
What is the Blood Brain Barrier?
- Exists between plasma and the extracellular fluid of brain.
- Endothelial cells of capillaries have tight junctions instead of pores (gaps).
- Neonatal animals have a less efficient BBB
- Not as effective a barrier as the BBB to many drugs (e.g. fetal effects from administered drugs).
- Lipid-soluble drugs diffuse across easily.
- Therefore, it is important in a C-section to choose a drug that does not cross as readily.
Placenta
Tight capillary endothelium junctions limit absorption and distribution of drugs.
Eye and Joint Synovia
(T or F) Antibiotics do not enter exudates, abscesses, or necrotic tissue very well due
True
Biotransformation
This is the body’s ability to change a drug chemically from the form in which it was administered into a form that can be eliminated from the body.
(T or F) Some drugs require metabolism before achieving active form
True
Where does metabolism/biotransformation occur?
Mainly occurs in liver, but also kidney
Amount of enzymes available depends on what factors?
- Species
- Age
- Sex
- Stress
- Nutritional status
- Disease
- Enzyme induction
What is the First Pass Effect?
When orally administered drugs are absorbed from the gut, they then enter the portal circulation. The blood in the portal veins is filtered by the liver before entering the systemic circulation. These drugs are exposed to metabolic enzymes before they enter the systemic circulation, so some of the drug may be metabolized before it reaches the systemic circulation.
What are the 5 Routes of Excretion?
Renal, Biliary Excretion, Intestinal Excretion, Glandular Secretions, Lungs
The major route for drug excretion. The drug must be water soluble. Metabolism of the drugs usually makes them water-soluble. If the metabolite is lipophilic, it tends to get reabsorbed back into the circulation system through the kidney tubules.
Renal
The liver excretes drugs into bile (the highly lipid-soluble drugs may be excreted this way).
Biliary Excretion
- Some drugs are secreted across the GIT mucosa by active transport.
- Drugs can also be excreted in gut secretions, especially ruminant saliva.
- Ruminants produce large amounts of alkaline saliva, which traps acidic drugs or metabolites.
Intestinal Excretion
Salivary, mammary, and sweat glands, also male genitalia
Glandular Secretions
Gas anesthetics eliminated in expired air
Lungs
What is a Half Life?
The time required for the amount of drug in the blood to be reduced by one half (i.e. the time required to excrete half of the administered dose from the blood).
How many Half Life’s does it take for the body to eliminate 99.9% of the drugs from the plasma?
Ten T1/2s
