Veterinary Pharmacology Questions

Pharmacokinetics

• It is the complex sequence of events that occurs after a drug is administered, specifically focusing on the effects of the body on the drug.
• A drug must reach the desired area and accumulate in the required concentration to be effective.
• Repeated drug administrations at fixed intervals are necessary to maintain the desired concentration, counteracting breakdown and excretion.
• Initial high dose administration rapidly achieves an effective concentration.
• Reduced dose that maintains concentration by replacing the amount lost through elimination.
• A steady state is achieved when drug accumulation equals drug elimination.
• The therapeutic drug level is the effective drug level that avoids toxicity and ineffectiveness.
• The therapeutic index is the difference between the minimum effective dose and the maximum effective dose; a narrow index indicates closely spaced doses.
• Therapeutic drug monitoring involves measuring drug levels in blood, urine or CSF.
• Factors influencing drug concentrations include absorption rate along with its amount, distribution, drug metabolism/biotransformation and excretion rate/route.

Routes of Administration

• Influenced by: available form, drug properties (irritation), desired speed of onset and animal behavior/condition being treated
• Drugs can be administered directly into the mouth, via nasogastric or orogastric tube.
• Oral drugs are usually absorbed more slowly than injections.
• Absorption may vary by species or depend on stomach pH, fill % and GI motility/drug solubility.
• Oral drugs generally produce a longer-lasting effect than injected drugs.
• Any drug given by injection is considered parenteral.
• Parenteral routes include intravenous (IV), intramuscular (IM), subcutaneous (SQ/SC), intradermal (ID), intraperitoneal (IP), intraarterial (IA), intraarticular, intracardiac (IC), intramedullary and epidural/subdural.
• IV drugs have the fastest effect.
• Irritating drugs are often given IV due to bloodstream dilution.
• Most IV drugs should be given slowly to avoid adverse reactions.
• Do not administer cloudy/thick fluids or fluids with particles IV, with exceptions for propofol, euthanasia solutions and Legend.
• Drugs meant for IV injection can cause tissue necrosis if injected outside the vein.
• IM drugs typically have a slower onset but longer duration.
• Water-based IM drugs can have a fast onset.
• Depot-form IM drugs have a long duration, sometimes in oil suspension.
• Aspiration before IM injection prevents inadvertent IV injection.
• SQ drugs have a slower onset but a slightly longer duration.
• Avoid irritating or hypertonic SQ solutions.
• Limit SQ volumes to avoid dissection between skin and underlying tissues.
• Hyaluronidase can speed up drug absorption.
• ID injections are used for tuberculosis and allergy testing.
• IP injections deliver drugs to the abdominal cavity and are used when other routes are unavailable.
• IA injections are usually inadvertent.
• In horses, accidental IA injection of sedatives into the carotid artery can cause seizures/death.
• Intraarticular injections treat inflammatory joint conditions.
• Use sterile technique for intraarticular injections of antibiotics, corticosteroids, hyaluronic acid or stem cells.
• The IC route is infrequently used for cardiopulmonary resuscitation/euthanasia.
• Intramedullary injections involve injecting a substance into the medullary cavity of a long bone, most often in exotics/pediatrics for rehydration when IV access is unavailable.
• Epidural/subdural (intrathecal) injections are used for anesthesia/pain control, requiring hyperextension of the lumbosacral space.

Inhalation & Topical Drug Adminstration

• Medications administered through inhalation are converted from a liquid to a gaseous form via nebulizers/vaporizers and include inhaled anesthetics, bronchodilators and antibiotics.
• Skin-transdermal is topical
• Mucosa-topical includes sublingual, rectal, mammary glands, uterus, eyes, ears

Drug Absorption

• The degree to which a drug is absorbed and then reaches the general circulation is called bioavailability.
• Bioavailability is depicted using a blood level curve that is influenced by: manufacturing/coating, absorption mechanism, pH/ionization/solubility and absorptive surface area.
• Drugs are absorbed through passive transport with simple diffusion from high to low concentration.
• Passive transport requires no energy use.
• Drugs absorbed through active transport use energy to move drugs from lower to a higher concentration.
• Pinocytosis, a form of passive transport, involves drug invagination into a vesicle that separates within the cell.
• Absorption rate depends on fat/water solubility, size/shape and degree of ionization.
• Nonionized are more readily absorbed
• Acidic drugs are readily absorbed in an acidic environment, where they do not ionize well.
• Alkaline drugs are more likely trapped/not absorbed in acidic environments, where they ionize.
• Absorption rate increases with absorptive surface area, as with intestinal villi.
• Drugs given IM absorb faster than SQ due to higher blood flow.
• Solubility affects absorption; lipid solubility is proportional to nonionization.
• Lipid-soluble/nonionized drugs are absorbed more quickly since they can cross the cell membrane.
• Lipid partition coefficient: degree of lipid solubility, influencing absorption.
• Absorption rate may depend on formulation via depot- or spansule-binding agents for sustained release.
• Oral drug absorption depends on GI tract condition.
• Combining certain drugs/foods can alter absorption.
• Milk/dairy products reduce tetracycline absorption.
• Substances absorbed by the GI tract enter the hepatic portal venous system and go to the liver before entering general circulation.
• This allows liver enzymes to remove toxins.
• Liver may metabolize drugs into altered forms that can be more/less active + inactive.
• Drugs with extensive first-pass effect not recommended orally.

Drug Distribution

• It is the process by which the drug is carried from the site of absorption to its site of action.
• The drugs will go from site->plasma->interstitial fluid->into cells->bind with cellular receptors->action.
• Distribution depends on: tissue perfusion, concentration gradient, protein binding and lipid solubility.
• Conditions like temperature, vasoconstriction, vasodilation can affect tissue prefusion.
• Lipid-soluble drugs move into tissue and may be bound there.
• Barriers to distribution include the placenta, prostate, eye, and brain.
• Prostrate- seminal fluid preserves sperm from immune response
• Brain barrier allows thing through barrier
• Drugs bind to plasma protein which is too large to pass through the fenestrations in the capillary’s endothelium so the bound drug remains inactive.
• Only the unbound/free from drug is capable of exerting its effect.
• Animals given highly protein bound drugs who are HYPOproteinemic may require lower doses or suffer toxicity.
• Some drugs (cefovecin) use protein binding for longer effect.
• P-glycoprotein is an active transport pump in the epithelium of the intestinal wall, liver and BBB.
• It pumps drugs back into circulation for excretion.
• P-glycoprotein defect/ MDR1 gene defect is a dysfunction where some individuals are ivermectin toxic due tp ivermectin freely passing through the BBB.
• Reptiles' renal portal system distributes toxic drug levels to the kidney if the drug is given in the posterior 1/3 of the body

Biotransformation & Drug Excretion

• Metabolism is the body's ability to change the drug chemically for elimination.
• Biotransformation occurs mostly in the liver.
• Enzymes make drugs water-soluble for urine excretion.
• Altered drugs are called metabolites, which are mostly inactive.
• Lipid-soluble drugs are eliminated in the bile.
• Four chemical reactions of liver microsomal enzymes: oxidation (loss), reduction (gain), hydrolysis (splitting), and conjugation (addition).
• Cats have limited ability to form glucuronic acid, so they have difficulty metabolizing aspirin, barbiturates and narcotics.
• Young animals do not have fully formed liver enzyme systems.
• Older/malnourished animals have decreased liver enzymes.
• Most drugs are metabolized by the live then eliminated form the body through the kidneys
• May be excreted by mammary glands, bile, lungs, intestinal tract, salivary glands and skin
• Must consider route of selection during drug excreation
• Must consider the effects of the drug in certain species by selecting the correct ROA
• For example, ketamine may accumulate to toxic levels in the CNS of cats with causes ulcers in the urinary tract because it damages cartilage
• If the product ends up in the small intestine, then the drug is excreted in feces or reabsorbed.
• Oral drugs that are not absorbed are also eliminated in the feces
• Gases are eliminated via the lungs
• Drugs may pass from blood into milk- a consideration for nursing offspring or people drinking milk

Renal Excretion

• Glomerular filtration: the glomerulus acts like a sieve to remove metabolites out of blood into the glomerular filtrate
• Tubular secretion is where the kidney tubules secrete metabolites out of capillaries into the glomerular filtrate
• If any portion of the system is not functioning well, toxic levels of the drug may accumulate

Half Life & Drug Residue

• Half-life measures the ammount of time for the ammount of drug in the body to be reduced by one half.
• This will determinine how often to administer a maintain a therapeutic range
• Drug remain in animal products
• People are allergic to certian drugs
• Prolonged exposed may result in antibiotic resistance
• Residues may cause cancel Food Animal Residue Avoidance Database (FARAD) is a repository of residue information- provides withholding times for milk and meat

Pharmacodynamics

• It is the study to the drug's effect on the body

• Drugs that interact exactly like a lock and key action

• Affinity is the tendency of the drug to bind with its receptor

• Agonist* a drug with high affinity and efficacy

• Morphine* high affinity

• Partial Agonist* is a drug with less affinity

• Buprenorphine* low affinity

• Anagonist* is a drug that blocks another drug by combining with a receptor

• Naloxone* a drug that blocks morphine

• No drug has a single effect so some doses may cause different effects

• Potency is the amount of drug needed to produce a desired repsosne

• Efficacy is the degree to which the drug produces the desired response

• Therapeutic index is is the relationship between the drug's ability to produce a desired reposnse and its tendency to produce toxic effects

• Therapeutic index = LD50/ED50*

  • LD50 is the dose at which the drug is lethal t0 50% of animals treated
  • ED50 id the dose at which the drug has the desired effect in 50% of animals treated

• Adverse drug reaction ANY underisable from drug, quality, purity or high does

  • Can include dermatitis, anaphylactic shock and photosnsitivity
  • Drug Interactions is a altered pharmacologic reposnse to a drug that si causes form a second drug

Altered Drug Responses Clssified

1. Pharmacokinestic Interaction is where the plasma or tissue level of one drug is affected by the presence of another (calcium's effect on tetracyycline absorption is and is an example of
2. Pharmacodynamic Intteraction is when the action or effect of one drug is altered by annother
3. Pharmaceutic Interaction s is when a physical or chemical reaction takes place cause of physically mixing drugs (diazepam may percipitate withh drugs when mixed in the same syringe)

Questions covering veterinary pharmacology, including drug action, metabolism, and clinical applications such as protein binding, genetic defects, biotransformation, achieving therapeutic concentrations, therapeutic index, and the impact of liver disease on drug metabolism.