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Rinderpest, Anthrax, F&D

What are the Epizootics in the early 1700s

1790-1854

Establishment year of Veterinary medicine in the US and UK

Drug was derived from the French word

Drogue / dried herbs

crude drug

is any naturally occurring unrefined substance derived from biological or mineral sources intended for use in the diagnosis, cure, mitigation, and prevention of diseases

crude drug

contains pharmacologically active ingredients and requires no additional processing for use

plants (botanicals/herbs), biologicals (bacteria/fungi), minerals, animals and animal by-products, recombination

what are the drug sources

The entire plant, plant parts, secretion, and exudate of plants

sources of plant drugs

alkaloids, glycosides, gums, resins, and oils

Active components in plants

Alkaloids

usually end in –ine (eg. atropine, caffeine, and nicotine)

Glycosides

end in –in (eg. Digoxin and digitoxin)

Bacteria and molds

produce many of the antibiotics (penicillin, erythromycin)

Sodium, potassium, and chloride

Electrolytes in the mineral sources of drugs

metallic and non-metallic substances

Drugs from mineral source include both

whole animals, glandular products (thyroid organ), liver extract, polypeptide venoms, non-peptide toxins, etc .

what are the drugs obtained from animals sources

insulin

examples of hormones from animals

heparin

example of anticoagulants from animals

Advances in recombinant DNA technology.

What technological advancement has enabled the production of animal and human products like insulin in bacteria?

Hepatitis-B vaccine, recombinant DNA engineered insulin, interferon-α-2a.

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Give examples of genetically engineered drugs.

Diagnostic, Empirical, and Symptomatic methods.

What are the three broadly defined methods for selecting a drug in pharmacotherapeutics?

The regimen includes the route of administration, the total dose, frequency of administration, and the duration of treatment.

What elements are included in the drug administration plan, also known as a regimen?

Such drugs are classified as prescription drugs, and they require the supervision of a veterinarian.

What is the classification of a drug that has potential toxic effects or requires administration by trained personnel for animal use?

No, these labels do not designate prescription drugs. Prescription drugs are specifically approved by the FDA for certain species or conditions.

Do labels stating "For veterinary use only" or "Sold to veterinarians only" necessarily indicate prescription drugs?

Extra-label drug use in veterinary medicine involves administering a drug in a way that differs from the FDA-approved label. It's also known as "off-label" use.

What is the definition of extra-label drug use in veterinary medicine, and what is another term for it?

These drugs are called over-the-counter drugs (OTC) because they can be bought without a prescription.

What are drugs called that do not have significant toxicity, do not require special administration, and can be purchased without a prescription?

Drugs with the potential for abuse or dependence are classified as controlled substances.

How are drugs classified if they have the potential for abuse or dependence?

1. Ensuring the correct drug is administered.
2. Administering the drug through the correct route and at the designated time.
3. Vigilantly observing the animal's response to the drug.
4. Clarifying any unclear medication orders.
5. Accurately labeling medication containers.
6. Providing clear administration instructions to clients.


1. Thoroughly documenting relevant information in the medical record.

What are the key responsibilities of veterinary clinicians when administering drugs based on verbal or written orders?

Pharmacokinetics is concerned with "what the body does to the medication." It involves the movement and modification of drugs within the body.

What is pharmacokinetics concerned with in relation to medications?

1. Absorption - “ How will it get in”
2. Distribution - “Where will it go?” *Transporters*
3. Metabolism (or biotransformation) - “How is it broken down?“ *Liveer*
4. Excretion - “How does it leave?“

What are the four main steps involved in pharmacokinetics?

In pharmacokinetics, "pharmaco-" means "drug," and "kine-" means "motion."

What do the prefixes "pharmaco-" and "kine-" mean in the context of pharmacokinetics?

Drug absorption in pharmacokinetics refers to the movement of a drug from the site of administration into the body's fluids, which will transport it to its intended site(s) of action.

What does drug absorption involve in pharmacokinetics?

Absorption is usually the first step in the journey of a drug through the body unless the drug is directly introduced into the bloodstream through intravenous administration.

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When does drug absorption typically occur in the process of a drug passing through the body?

The majority of drugs are absorbed through passive or simple diffusion.

How do the majority of drugs get absorbed in the body?

The driving force for passive absorption is the concentration gradient.

What drives the passive absorption of a drug in the body?

Passive diffusion does not involve a carrier, and it does not require energy.

Does passive diffusion of drugs involve a carrier, and does it require energy?

Lipid-soluble drugs can readily move across most biologic membranes because they are soluble in the membrane's lipid bilayers.

Why do lipid-soluble drugs easily cross biologic membranes?

Water-soluble drugs penetrate cell membranes through aqueous channels or pores.

How do water-soluble drugs penetrate cell membranes?

Facilitated diffusion in drug absorption involves drugs entering cells through specialized transmembrane carrier proteins that assist in the passage of large molecules.

What is facilitated diffusion in drug absorption?

Facilitated diffusion relies on the concentration gradient, with drugs moving from an area of high concentration to an area of low concentration.

What is the driving force for facilitated diffusion of drugs?

No, facilitated diffusion in drug absorption does not require energy.

Does facilitated diffusion in drug absorption require energy?

The function of carrier proteins in facilitated diffusion can be inhibited by compounds that compete for the same carrier.

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How can the function of carrier proteins in facilitated diffusion be affected?

Active transport in drug absorption involves specific carrier proteins and is energy-dependent, driven by the hydrolysis of Adenosine Tri-phosphate (ATP) into Adenosine Di-phosphate (ADP).

What characterizes active transport in drug absorption?

Yes, active transport is capable of moving drugs against a concentration gradient, meaning it can transport drugs from a region of low drug concentration to one of higher drug concentration.

Can active transport move drugs against a concentration gradient, and if so, how?

The function of carrier proteins in active transport can be inhibited by compounds that compete for the same carrier.

How can the function of carrier proteins in active transport be affected?

Pinocytosis, also known as "cell drinking," is a process in which the cell membrane surrounds and engulfs liquid particles.

What is pinocytosis in the context of drug absorption?

Phagocytosis, also known as "cell eating," is a process in which the cell membrane surrounds and engulfs solid particles.

What is phagocytosis in the context of drug absorption?

Greater blood flow to a specific absorption site, such as the intestine, favors absorption from that site over sites with lower blood flow, like the stomach.

How does blood flow to the absorption site influence drug absorption?

The intestine has a much larger surface area than the stomach due to brush borders with microvilli, making drug absorption across the intestine more efficient.

What role does the total surface area available for absorption play in drug absorption?

If a drug moves too quickly through the gastrointestinal tract, such as in cases of severe diarrhea, it is not well absorbed. Conversely, anything that delays the transport of the drug from the stomach to the intestine also delays the rate of drug absorption.

How does contact time at the absorption surface impact drug absorption?

Bioavailability refers to the fraction of an administered drug that reaches the systemic circulation in its active form.

What does the term "bioavailability" refer to in pharmacology?

Determining bioavailability is crucial for calculating drug dosages, especially for non-intravenous routes of administration.

Why is determining bioavailability important in pharmacology?

The route of administration, as well as the chemical and physical properties of the drug, can affect its bioavailability.

What factors can influence the bioavailability of a drug?

Bioavailability is determined by comparing the plasma drug levels achieved after a specific route of administration (e.g., oral) with the plasma drug levels achieved by intravenous (IV) injection. A common method involves plotting drug concentration in plasma over time to measure the area under the curve (AUC), which reflects the extent of drug absorption.

How is bioavailability determined in practice?

Bioavailability

is the fraction or % of a drug that reaches systemic circulation

The first-pass effect, also known as hepatic first pass, is the process in which some drugs, after being absorbed from the intestinal lumen, pass first through the liver via the portal vein before entering the systemic circulation. In the liver, many drugs are metabolized into inactive forms before reaching the general circulation. This reduces the amount of active drug available in the systemic circulation.

What is the first-pass effect in pharmacology?

Drug in Circulation / Drug Administered

Format for Bioavailability

Both weak acidic drugs and weak basic drugs can exist in two forms: the un-ionized (nonpolar) form and the ionized (charged) form.

What are the two forms in which weak acidic drugs and weak basic drugs can exist?

"HA" represents the un-ionized (nonpolar) form of a weak acidic drug, and "A" represents the ionized (charged) form.

What is represented by "HA" and "A" in the context of weak acidic drugs?

"HB" represents the un-ionized (nonpolar) form of a weak basic drug, and "B" represents the ionized (charged) form.

What is represented by "HB" and "B" in the context of weak basic drugs?

The unionized (nonionized) form of a drug is lipid-soluble and is readily absorbable.

What are the characteristics of the unionized (nonionized) form of a drug in terms of solubility and absorbability?

The ionized (charged) form of a drug is water-soluble and is poorly absorbed.

What are the characteristics of the ionized (charged) form of a drug in terms of solubility and absorbability?

Acidic drugs are unionized (uncharged) in an acidic medium. As a result, they are typically absorbed from the stomach, which has an acidic pH (approximately 1.5 to 3.5).

How do acidic drugs behave in an acidic medium, and where are they mainly absorbed?

Basic drugs are primarily in their unionized (uncharged) form in a basic (alkaline) medium. Consequently, basic drugs are mainly absorbed from the intestine, which has a slightly basic pH (approximately 6 to 7.4).

How do basic drugs behave in a basic (alkaline) medium, and where are they mainly absorbed?

The effective concentration of the permeable form of a drug at its absorption site is determined by the ratio between the ionized and unionized forms of the drug.

What determines the effective concentration of the permeable form of a drug at its absorption site?

The pH at the site of absorption and the ionization constant (pKa) of the drug are the factors that influence the ratio between the ionized and unionized forms of a drug. The pKa represents the acid dissociation constant of the drug.

What factors influence the ratio between the ionized and unionized forms of a drug?

Ion trapping refers to the phenomenon where a drug molecule changes from its ionized (charged) form to its nonionized (uncharged) form as it moves from one body compartment to another, typically due to differences in pH between the compartments. This change in ionization state can affect the drug's distribution and pharmacological activity within the body.

What is ion trapping in pharmacology?

Henderson–Hasselbalch

What is the equation used to calculate the percent ionized of a drug?

Drug distribution in pharmacology refers to the physiological movement of drugs from the systemic circulation to the various tissues in the body. The primary goal of drug distribution is to enable the drug to reach its target tissue or the intended site of action.

What is drug distribution in pharmacology?

1. Membrane permeability
2. Tissue perfusion (blood flow to tissues)
3. Protein binding
4. Volume of distribution

What are some factors that can influence drug distribution in the body?

Drug distribution is essential to ensure that the drug reaches its target tissue or site of action, where it can exert its therapeutic effect. The distribution process is critical for achieving the desired pharmacological outcome.

Why is it important for drugs to undergo distribution within the body?

When thiopental is administered intravenously in dogs, well-perfused tissues like the brain rapidly receive high concentrations of the drug. At the same time, thiopental is also being distributed to poorly perfused fat tissue.

What happens when thiopental is administered intravenously in dogs with regard to its distribution in the body?

The concentration of thiopental in the blood decreases as the drug moves from the blood to the fat tissue.

How does the concentration of thiopental change as it moves from the blood to the fat tissue?

At a certain point in the distribution process, the concentration of thiopental in the blood becomes lower than its concentration in the brain. This is a critical point in drug distribution and can affect the drug's pharmacological activity.

What critical point is reached during the distribution of thiopental in the body?

Biotransformation in pharmacology is also known as drug metabolism. It involves the chemical alteration of drug molecules by the body's cells, resulting in the formation of metabolites that can be in an activated, inactivated, and/or toxic form.

What is another term for biotransformation in pharmacology, and what does it involve?

1. Oxidation - involving the loss of electrons from the drug molecule.
2. Reduction - involving the gain of electrons by the drug molecule.
3. Hydrolysis - where the drug molecule is split, and a water molecule is added to each of the split portions.
4. Conjugation - where compounds like glucuronic acid or similar substances are added to the drug molecule, significantly increasing its water solubility.

What are the four main pathways by which drugs undergo biotransformation in the body?

species, age, nutritional status, tissue storage, health status

What are some of the factors that can influence drug metabolism in the body?

The primary organ where Phase I biotransformation enzymes are located, including cytochrome P450 (CyP450), is the liver. These enzymes, particularly CyP450, are primarily found in hepatocytes, which are liver cells.

Where is the primary location of Phase I biotransformation enzymes, particularly the microsomal enzyme cytochrome P450 (CyP450)?

Cytochrome P450 (CyP450) is a family of detoxifying enzymes in the liver that play a crucial role in altering the structure of drug molecules. They are involved in various oxidative reactions that transform drugs, making them more water-soluble and easier for the body to eliminate.

What is the role of cytochrome P450 (CyP450) in drug metabolism?

(a) Side chain and aromatic hydroxylation

(b) O-dealkylation

(c) N-oxidation

(d) S-oxidation

(e) Deamination or N-dealkylation

(f) Desulfuration

What are some examples of microsomal oxidation reactions catalyzed by CyP450 enzymes?

Nonmicrosomal oxidation reactions utilize enzymes other than CyP450. Examples of enzymes involved in nonmicrosomal oxidation include alcohol dehydrogenase, aldehyde dehydrogenase, monoamine oxidase, and xanthine oxidase.

What distinguishes nonmicrosomal oxidation reactions from microsomal oxidation reactions in drug metabolism?

An example is alcohol metabolism, where alcohol dehydrogenase and aldehyde dehydrogenase are involved in converting ethanol (alcohol) into acetaldehyde and then into acetic acid.

Can you provide an example of a nonmicrosomal oxidation reaction involving specific enzymes?

Differences in the activity of oxidative enzymes among animal species can be attributed to various factors, including kinetic parameters. These differences can result from genetic variations, enzyme levels, and other factors.

What are some factors that lead to differences in the activity of oxidative enzymes among various animal species?

Generally, oxidation activity is higher in horses than in cattle, which, in turn, is higher than in dogs. Cats typically have the lowest oxidation activity among domestic animals.

How does the oxidation activity compare among horses, cattle, dogs, and cats?

The level of oxidative enzymes is typically lower in very young animals.

What can be said about the level of oxidative enzymes in very young animals?

The duration of pentobarbital anesthesia is much shorter in horses than in dogs.

How does the duration of pentobarbital anesthesia compare between horses and dogs?

Young calves are much more sensitive to pentobarbital and lindane than adult cattle.

What is the difference in sensitivity to pentobarbital and lindane between young calves and adult cattle?

Reduction biotransformation reactions are less frequent than oxidation-type reactions in drug metabolism.

In comparison to oxidation reactions, are reduction biotransformation reactions more or less frequent?

Enzymes for reduction biotransformation reactions can be located in both microsomal and nonmicrosomal fractions.

In which cellular fractions can enzymes for reduction biotransformation reactions be found?

Examples of drugs that undergo reduction biotransformation reactions include chloramphenicol and naloxone.

Can you provide examples of drugs that undergo reduction biotransformation reactions?

Hydrolysis reactions can occur with either ester-linked chemicals (involving esterases) or amide-linked chemicals (involving amidases).

What types of chemical bonds are subject to hydrolysis reactions in drug metabolism?

Esterases are primarily found in nonmicrosomal systems and can be found in the plasma, liver, and other tissues. Examples of drugs hydrolyzed by esterases include acetylcholine, succinylcholine, and procaine.

Where are esterases primarily found, and can you provide examples of drugs hydrolyzed by esterases?

Amidases are nonmicrosomal enzymes primarily found in the liver. Examples of drugs hydrolyzed by amidases include acetazolamide, lidocaine, procainamide, sulfacetamide, and sulfadimethoxine.

Where are amidases primarily located, and can you provide examples of drugs hydrolyzed by amidases?

Phase 2 biotransformation involves the coupling of an endogenous chemical (e.g., glucuronic acid, acetate, glutathione, glycine, sulfate, or a methyl group) to either a phase I metabolite or a parent drug/chemical.

What does Phase 2 biotransformation involve, and to what can it occur?

Endogenous chemicals used in Phase 2 biotransformation include glucuronic acid, acetate, glutathione, glycine, sulfate, and methyl groups.

Can you provide examples of endogenous chemicals used in Phase 2 biotransformation?

Yes, there are considerable species-specific variations in Phase 2 conjugation reactions. Some examples include:

(a) In cats, glucuronide synthesis for certain target functional groups (e.g., -OH, -COOH, -NH2, =NH, -SH) occurs at a low rate, leading to longer plasma half-lives for many drugs in cats compared to other species.

(b) Dogs lack acetylation of aromatic-NH2 groups, affecting the metabolism of drugs like sulfonamides.

(c) In pigs, sulfate conjugation of aromatic-OH and aromatic-NH2 groups occurs at a low extent.

Are there species-specific variations in Phase 2 conjugation reactions?

Drug elimination in pharmacology refers to the process of removing a drug from the body. It is also known as drug excretion.

What is drug elimination in pharmacology, and is it known by any other term?

Drugs can be eliminated from the body through various routes, including the kidneys, liver, intestine, lungs, milk, saliva, and sweat.

What are the various routes through which drugs can be eliminated from the body?

The kidneys and liver are the most important routes of drug elimination.

Which routes of drug elimination are considered the most important?

Renal elimination of drugs involves mechanisms associated with urine production. These mechanisms help remove drugs from the body through the urine.

What are some of the mechanisms involved in renal elimination of drugs?

1. Glomerular filtration
2. Active tubular secretion


1. Passive tubular reabsorption

What are the three main mechanisms involved in drug elimination from the body?

a. Biliary secretion, where both the parent drug and the glucuronide form of the drug can be eliminated via the bile.

b. Milk, which is important when drugs given to a dam appear in the milk, requiring withdrawal periods if the milk is intended for human consumption.

c. Saliva, which is particularly relevant in herbivores receiving parenteral antimicrobial drugs. Drugs enter the saliva through passive diffusion from the blood, and excessive salivation can affect the digestive process in animals like cattle and sheep.

d. Expired air, primarily important for volatile drugs like gas anesthetic drugs.

e. Minor routes of excretion, such as through tears and sweat.

What are some additional routes through which drugs can be eliminated from the body, aside from the primary renal mechanisms?