I. Introduction
● Pharmacology: the study of the properties of chemicals used as drugs for therapeutic
purposes
○ Pharmacokinetics: the study of drug absorption, distribution,
biotransformation (metabolism), and excretion
○ Pharmacodynamics: the study of cell/tissue responses and selective receptor
effects
II. Drug Absorption and Disposition
A. General Principles
How do drugs reach their site of action?
● Passive diffusion → through membranes
○ Weak acids and weak bases
■ Degree to which drugs are
fat-soluble → regulated by their
pKa and the pH of the medium
containing the drug
■ pKa = pH at which 50% of the drug
is ionized and 50% is nonionized
○ Henderson-Hasselbalch equation
𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑜𝑓 𝑛𝑜𝑛𝑖𝑜𝑛𝑖𝑧𝑒𝑑 𝑎𝑐𝑖𝑑
■ Weak acid: 𝑝𝐾𝑎 = 𝑝𝐻 + 𝑙𝑜𝑔 𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑜𝑓 𝑖𝑜𝑛𝑖𝑧𝑒𝑑 𝑎𝑐𝑖𝑑
𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑜𝑓 𝑖𝑜𝑛𝑖𝑧𝑒𝑑 𝑏𝑎𝑠𝑒
■ Weak base: 𝑝𝐾𝑎 = 𝑝𝐻 + 𝑙𝑜𝑔 𝐶𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑜𝑓 𝑛𝑜𝑛𝑖𝑜𝑛𝑖𝑧𝑒𝑑 𝑏𝑎𝑠𝑒
● Filtration → through pores
● Facilitated diffusion → attached to a carrier
○ No cellular energy needed + not against a concentration gradient
● Active transport → attached to a carrier
○ Cellular energy needed + against a concentration gradient
● Pinocytosis
B. Routes of Administration
● Alimentary routes
○ Oral
■ Advantages
● Safest, convenient, economical
● Drugs can be mixed in the food to facilitate
, ● Food stimulates bile secretion → helps dissolve lipophilic
drugs
■ Disadvantages
● Acidic environment of stomach and digestive enzymes →
destroy drug
● May irritate GI mucosa
● Drugs may be metabolized by GI mucosa and liver before they
reach the systemic circulation
○ First-pass effect
○ Rectal
■ Advantages
● Can be used in unconscious or vomiting animal
● Slower absorption
● Reduces first-pass effect
● Parental routes
○ Examples
■ Intravenous (IV)
■ Intramuscular (IM)
■ Subcutaneous (SC)
■ Intraperitoneal (IP)
■ Spinal and subdural
○ Advantages
■ Rapid onset → absorption is more uniform and predictable
■ Absorption from IM and SC injection sites → determined by the
amount of blood flow
○ Disadvantages
■ Asepsis is necessary
■ Causes pain
■ May penetrate blood vessel during IM injection
■ Rapid onset → cardiovascular responses may occur
■ Food animals → devalues the carcass
● Other routes
○ Dermal or topical
■ Degree of absorption → dependent on lipid solubility
■ Abraded or damaged skin may be expected to absorb more drug than
intact skin
■ Animals with thin skin → absorb drugs readily if applied topically
■ Convenient + allows non-skilled operators to administer the drugs
○ Inhalation
■ Used for volatile or gas anesthetics
■ Rapid response → large surface area of lungs + large blood flow to
lungs
■ Reversible
C. Drug Distribution
● Distribution: the reversible transfer of drug from one site in the body to another site
● Junction between capillary endothelial cells → not tight
, ○ Permits free drug to rapidly reach equilibrium on both sites of the vessel wall
● Distribution into the CNS and CSF is restricted → blood-brain barrier (BBB)
○ Processes that contribute to keeping drug concentration in CNS low
■ Capillary endothelial junctions are tight + glial cells surround the
precapillaries
● Reduces filtration → requires drug to diffuse across cell
membranes to enter CSF
■ CSF production circulates through the ventricles + over the surface of
the brain + spinal cord to flow into the venous drainage system
● Dilutes out the drug’s concentration in the CSF
■ Active transport mechanisms → found for organic acids and bases in
the choroid plexus → transports drug from CSF into the blood
● Plasma protein binding → drug + protein (free) ⇌ drug - protein (bound)
○ Acidic drugs → bound to albumin
○ Basic drugs → bound to ⍺1-acid glycoprotein
○ Steroid + thyroid hormones → bound by globulins
○ Drug-protein binding reaction → reversible
○ Binding slows the rate at which it reaches a concentration sufficient to
produce a pharmacological effect
○ Limits glomerular filtration → bound drugs cannot be filtered
○ Binding to albumin → lowers the free drug concentration
○ Drug interactions may occur when 2 drugs are used that bind at the same site
on the plasma proteins
■ Competition increases
● Drug redistribution → can terminate drug response
○ Biologic response to a drug → terminated by metabolism/biotransformation
and excretion
○ Redistribution of drug → lowers its concentration at its site of action →
terminates drug response
○ Drug exhibiting redistribution phenomenon → highly lipid soluble
● Drug distribution from dam to fetus
○ Drug transfer across the placenta → simple diffusion
○ Drugs cross placenta best if they are lipid soluble
○ Fetus → exposed to some extent to drugs with low lipid solubility when given
to dam
○ General rule: drugs with an effect on the maternal CNS have the
physical-chemical characteristics to freely cross the placenta and affect the
fetus
D. Drug metabolism/biotransformation
● Drug metabolism/biotransformation: the chemical alteration of drugs and normally
found substances in the body
● Principles
○ After filtration at renal glomerulus → most lipophilic drugs are reabsorbed
from the filtrate
○ Biotransformation of drugs to more water-soluble chemicals → reduces ability
to be reabsorbed once filtered by the kidney
, ■ Enhances excretion + reduces volume of distribution
○ Liver → most important organ for biotransformation
○ Frequently reduces the biological activity of the drug
○ Not synonymous with drug inactivation
■ Parent chemical may be transformed to a chemical with greater
activity
● 2 phases of biotransformation
○ Phase I → biotransformation
enzymes are found in the SER
of hepatic cells (microsomal
enzymes)
■ Oxidation → carried out
by cytochrome P450s
■ Mixed function oxidase
→ 1 O atom is incorporated in the drug molecule + other O atom
combines with H to form water
● Side chain and aromatic hydroxylation
● O-dealkylation
● N-oxidation
● S-oxidation
● Deamination or N-dealkylation
● Desulfuration
■ Nonmicrosomal oxidation → a few chemicals are oxidized by cytosol
or mitochondrial enzymes
● Alcohol dehydrogenase + aldehyde dehydrogenase
● Monoamine oxidase
● Xanthine oxidase
■ Oxidative metabolism
■ Reduction biotransformation reactions → less frequent than
oxidation-type reactions
■ Hydrolysis reactions → occur with ester or amide linked chemicals
● Esterases → occur in nonmicrosomal systems → found in
plasma, liver + other tissues
● Amidases → nonmicrosomal enzymes → found in liver
○ Phase II → occurs to a phase I metabolite/parent drug → involves the
coupling of an endogenous chemical → enzyme systems are present in the
microsomes, cytosol, and mitochondria
■ Products of phase II biotransformation → greater water solubility +
more readily excreted via the kidney
■ Species variation in phase II metabolism
● Cat
○ Glucuronide synthesis where the target is -OH, -COOH,
-NH2, =NH, -SH → present at a low rate
○ Cats have longer plasma t1/2 for many drugs
● Dog
○ Acetylation of aromatic -NH2 groups → absent
○ Affects the metabolism of sulfonamides and other drugs
● Pig
The benefits of buying summaries with Stuvia:
Guaranteed quality through customer reviews
Stuvia customers have reviewed more than 700,000 summaries. This how you know that you are buying the best documents.
Quick and easy check-out
You can quickly pay through credit card or Stuvia-credit for the summaries. There is no membership needed.
Focus on what matters
Your fellow students write the study notes themselves, which is why the documents are always reliable and up-to-date. This ensures you quickly get to the core!
Frequently asked questions
What do I get when I buy this document?
You get a PDF, available immediately after your purchase. The purchased document is accessible anytime, anywhere and indefinitely through your profile.
Satisfaction guarantee: how does it work?
Our satisfaction guarantee ensures that you always find a study document that suits you well. You fill out a form, and our customer service team takes care of the rest.
Who am I buying these notes from?
Stuvia is a marketplace, so you are not buying this document from us, but from seller ankejesse. Stuvia facilitates payment to the seller.
Will I be stuck with a subscription?
No, you only buy these notes for $4.34. You're not tied to anything after your purchase.
