Spinella Midterm Material Flashcards
pharmacology
study of the action of chemicals on biological systems; study the drugs
pharmacy
provide info about medications; dispense the drugs safely
pharmacokinetics
what the body does to a drug - how it distributes, metabolizes, eliminates, or absorbs the drug
pharmacodynamics
what the drug does to the body - how it elicits an effect
3 “Steps” of Pharmacology
Drug Dose –> Plasma Concentration –> Effect
Combination of which “steps” make up pharmacokinetics?
drug dose and plasma concentration
Combination of which “steps” make pharmacodynamics?
plasma concentration and effect
What explains how to achieve target concentration - pharmacokinetics or pharmacodynamics?
pharmacokinetics
What explains the optimal target concentration - pharmacokinetics or pharmacodynamics?
pharmacodynamics
drugs
substances which act on biological systems, usually by binding a receptor
receptor
molecule that selectively binds a ligand (drug) and undergoes a modification
biologics
produced from a living organism
pharmaceuticals
implies that there is a manufacturing process involved
inactive ingredients
make medication into final form for administration - can include coating, fillers, binders, solubilizers and disintegrants
active ingredients
those which elicit the desired pharmacologic effects
How is a drug named?
chemical name upon discovery –> code name for development –> nonproprietary generic name –> brand name upon patent and marketing
Are brand and generic drugs the same?
yes, they are bioequivalent - same ingredients, strength, dosage form, and route of administration
supplement
supplement taken orally that contains micronutrients like vitamins, probiotics, minerals, AAs, enzymes
Are supplements drugs?
no
What kind of claims can supplements make - health or disease?
health - cannot be marketed as alleviating the effects of a disease
Are supplements regulated by the FDA?
yes, but only post-marketing
Does efficacy and safety have to be proven before the sale of drugs? Supplements?
Drugs = YES
Supplements = NO
nutraceuticals
made from food or part of a food (ex: glucosamine, chondroitin)
Problems with Supplements and Nutraceuticals
can be ineffective, make false claims, contain unlisted ingredients, interact with drugs, contain toxic contaminants, adverse effects
Is there scientific data behind supplements?
not very much if any at all
Examples of nutraceuticals?
garlic, green tea, ginseng, glucosamine, etc
Efficacy
the ability of a drug to bind to a receptor and generate an effect; how well a drug works; the MAXIMUM effect a drug can produce
Which drug is the most effective?
A
Potency
relative concentration of a drug required to produce a given effect; how STRONG is a drug
Which is the most potent?
A (EC50 is at the lowest concentration)
Therapeutic Index Equation
What does a small therapeutic index mean?
harm is more likely at therapeutic doses
Therapeutic Window
space between the minimum effective concentration and the minimum toxic concentration
What therapeutic index is better - larger or smaller?
LARGER, ideally greater than 10 but better be greater than 1
What is the therapeutic index of this drug?
10
What is the therapeutic index of this drug?
100 (95 divided by .95)
Margin of Safety Equation
Agonist
drug that binds to receptor and activates it
Antagonist
drug that binds to receptor but does not activate it and prevents activation by an agonist
Competitive Antagonist
antagonist that can be overcome by increasing the concentration of the agonist
Irreversible Antagonist
cannot be overcome no matter what the concentration of the agonist
Full Agonists
produces the same effect as the endogenous ligand
Can full agonists differ in potency or efficacy?
POTENCY (efficacy will be the same)
Does a competitive agonist have an effect on efficacy or potency of the endogenous ligand?
Potency
Are competitive antagonists reversible?
yes
Are non-competitive agonists reversible?
NO, they are irreversible
Does a non-competitive (irreversible) agonist have an effect on efficacy or potency of the endogenous ligand?
Efficacy (because fewer receptors are available for binding)
What kind of antagonist is at work here?
Competitive Antagonist (decreasing potency)
What kind of antagonist is at work here?
Non-competitive (irreversible) antagonist (decreasing efficacy)
What does ADME stand for? (the big 4 of pharamacokinetics)
Absorption
Distribution
Metabolism
Elimination
Goal of pharmacokinetics?
obtain a drug concentration in the therapeutic range for your patient
Absorption
movement of a drug from its site of administration into the bloodstream
Distribution
movement of a drug from the blood into other body fluids and tissues
Metabolism
chemical transformation of a drug within the tissues, generally to enhance elimination of the drug and its metabolites
Elimination
excretion of a drug out of the body by various pathways
Major excretory organ?
kidney
Does a drug have to be lipid soluble to move across a cell membrane (be absorbed)?
yes (non-ionized) (hydrophobic)
To eliminate a drug in the urine, should it be charged or uncharged?
charged (ionized) (hydrophilic)
5 Ways to Cross a Biological Membrane
- Filtration
- Passive Diffusion
- Facilitated Diffusion
- Active transport
- Endocytosis
The major route of entry for most drugs is what?
Passive Diffusion
pH-partition theory
pKa and the lipid water partition coefficient of the compound determine passage of a drug
Is diffusion first order or zero order?
first order
Saturable
carrier/receptor involved in transport
Which of the five transport mechanisms are saturable/selective?
facilitated diffusion, active transport, and endocytosis
Which of the five transport mechanisms require energy (ATP)?
active transport and endocytosis
Which of the five transport mechanisms work with a concentration gradient?
passive and facilitated diffusion
Which of the five transport mechanisms work via a pressure gradient?
Filtration
Can ionized compounds enter via filtration?
no
Are most pharmaceutical drugs strong or weak acids/bases?
weak acids and bases (so that they only partly ionize in solution)
Henderson-Hasselbach Equation for Weak Acid
Henderson-Hasselbach Equation for Weak Base
In the stomach, are weak acids IONIZED or UNIONIZED?
unionized (think acids in an acidic solution are not charged)
In the stomach, are weak bases IONIZED or UNIONIZED?
ionized
In the intestine, are weak acids IONIZED or UNIONIZED?
ionized
In the intestine, are weak bases IONIZED or UNIONIZED?
unionized
How do you get rid of a basic drug in the urine?
acidify it (ex: with ammonium chloride)
How do you get rid of an acidic drug in the urine?
alkalize it (ex: with sodium bicarbonate)
To excrete a drug in the urine, should it be in its ionized or unionized form?
ionized (charged)
First pass effect
the loss of a drug as it passes for the first time through the absorption process (pre-systemic circulation/elimination)
Which drugs are susceptible to the first pass effect?
oral drugs
Based on these Henderson-Hasselbach equations, would you expect to be in the stomach or the small intestine?
stomach
First Order Half Life
eliminates a constant FRACTION of the drug per unit time
Zero Order Half Life
eliminates a constant QUANTITY of the drug per unit time
Definition of Biologic Half Life
the time required for the plasma drug concentration to decrease by one half
Approximately how many half lives to reach steady state concentration?
5 (five)
Factors that influence Drug Absorption
lipid solubility, particle size, route of administration, stability of drug, blood flow, concentration gradient, surface area, species, etc
Bioavailability
the fraction of the dosed parent drug that reaches the systemic circulation unchanged
Bioavailability of a drug administered IV?
100%
Acidify; BH+
Equation for Half-Life
T 1/2 = 0.693 x (Vd/Clp)
Vd = volume of distribution in L
Clp = plasma clearance in liters per hour
Equation for Volume of Distribution
Vd = D / Co
D = dose given
Co = concentration in the plasma
Equation for Plasma Clearance
Clp = Kel x Vd
Kel = elimination constant
Vd = volume of distribution
Effect of drugs with high water solubility on Vd and Clp?
small Vd and high blood plasma conc.
Effect of drugs with high lipid solubility on Vd and Clp?
large Vd and low blood plasma conc.
Will a drug with a higher volume of distribution have a longer or shorter half life?
Longer
Would a drug with a faster/higher plasma clearance have a longer or shorter half life?
shorter
Approximately how many half-lives to reach steady state concentration?
5 (five)
Process of Drug Metabolism
convert a lipid-soluble pharmacologically active drug into a water-soluble inactive metabolite
2 Primary Ways Drugs are Excreted
- Renal excretion (urine)
- Hepatic Elimination (bile, feces)
Less Common Pathways by which Drugs can be Eliminated
milk, sweat, saliva, tears, lung respiration
pro-drug
the initially inactive form of a drug
Phase 1 Metabolism
drugs which either add polar groups or remove non-polar groups
Phase 2 Metabolism
functional group on drug or Phase 1 metabolite is combined with an endogenous substrate to get a more water soluble compound
Major Phase 1 Metabolism Reactions (3)
- Oxidation
- Reduction
- Hydrolysis
Major Phase 2 Metabolism [Conjugation] Reactions (6)
- Glucuronidation
- Acetylation
- Glutathione Conjugation
- Glycine Conjugation
- Sulfate Conjugation
- Methylation
oxidation
adding oxygen or removing hydrogen from a drug
reduction
adding hydrogen to the drug
Hydrolysis
addition of water molecule to the drug (commonly with esters and amides)
Main Goal of Drug Metabolism?
increase water solubility for drug excretion
Enterohepatic Circulation
metabolite in the liver is conjugated with glucuronide, then goes from bile duct into GI tract, and some bacteria in GI tract can deconjugate and go back through portal vein back to liver –> increases drug exposure
Most common usage of NSAIDs?
mild to moderate pain management and musculoskeletal disorders
Are NSAIDs appropriate for visceral pain and broken bones?
NO
Most common side effect of NSAIDs?
GI upset (ulceration due to the inhibition of the protective effects of prostaglandins)
NSAID Effect on COX
inhibit COX activity (directly binding to active site)
Steroid Effect on COX
inhibit COX levels (by preventing production)
Are NSAIDs acids or bases?
weak acids
What is the only NSAID that irreversibly inhibits COX?
aspirin (anti-thrombic)
MOA: it acetylates the COX enzyme
Flunixin Meglumine
Banamine
NSAID used for colic in horses (anti-inflammatory, analgesic, anti-endotoxic, and antipyretic)
can also be used in other large animals
PGE2
most potent prostaglandin and the principle mediator of pain/inflammation/fever
Most COX-2 selective drug in vet med?
Firocoxib
Three Main Organ Systems Most Commonly Associated with [NSAID] Toxicity
- Gastrointestinal
- Renal
- Hepatic
If NSAIDs are weak acids, then where are they absorbed?
stomach
Why are cats susceptible to acetaminophen toxicity?
lack enzyme for glucuronidation (glucuronyl transferase)
Is aspirin COX1 or COX2 selective?
COX-1
Can dogs use Advil, Motrin, or Aleve?
absolutely the fuck not
Meloxicam
COX-2 preferential that is one of cats’ only approved NSAIDs (there’s only two), and ONLY as a one time injection, according to drug label
Meloxicam Overdose in Cats?
acute renal failure and death
Besides meloxicam, what’s the only other approved NSAID for cats?
Robenacoxib (Onsior)
administered orally (also available as an injectable), also COX-2 preferential
Which COX produces the prostaglandins most associated with inflammation?
COX-2
Do NSAIDs inhibit prostaglandin production?
yes
Galliprant
new drug which targets the EP4 receptor (for PGE2) and does not inhibit COX
for OA in dogs
Why is COX-2 a main target of our anti-inflammatories?
COX-2 isn’t really commonly produced in the body, except at sites of inflammation
Who is the “good guy” - COX-1 or COX-2?
COX-1
has physiological functions GI protection, kidney function, platelet function, and regulation of blood flow
Who is the “bad guy” - COX-1 or COX-2?
COX-2
causes inflammation, pain, and fever
5 Classes of Diuretics
- Osmotic
- Carbonic Acid Inhibitors
- Loop
- Thiazides
- Potassium Sparing
What class of diuretic will cause the most increase in urine volume?
loop diuretics (highest percent sodium excretion increase (25%))
Which class of diuretics can cause hypercalciuria?
Loop diuretics (increases calcium excretion)
Which class of diuretics can cause hypocalciuria?
Thiazide diuretics
Hypokalemia is a risk of what two diuretic classes?
loop and thiazide
Metabolic alkalosis is a risk of what two diuretic classes?
loop and thiazide
Mannitol
osmotic diuretic
Acetazolamide
carbonic acid inhibitor
Furosemide
loop diuretic
Hydrochlorothiazide
thiazide diuretic
Amiloride
potassium sparing diuretic
Spironolactone
potassium sparing diuretic
Which class of diuretics has a potential side effect of metabolic acidosis?
carbonic acid inhibitors (greater increase in bicarbonate excretion)
Enzyme that produces prostaglandins?
COX
What do prostaglandins do?
many things, but help mediate (cause) pain, inflammation, and fever
What drugs are more soluble in the bloodstream - ionized or unionized?
ionized
Diuretic
a drug that increase the excretion rate of water (sodium)
Therapeutic goal of diuretics?
decrease ECF (edema) and/or excess intravascular volume (hypervolemia)
Carbonic Acid Inhibitor Site of Action
proximal convoluted tubule
Osmotic Diuretic Site of Action
proximal convoluted tubule and descending limb of Henle
Loop Diuretic Site of Action
ascending limb of Henle
Thiazide Diuretic Site of Action
distal convoluted tubule
Potassium-Sparing Diuretic Site of Action
distal convoluted tubule
If mannitol was accidentally given orally, what’s the biggest side effect?
diarrhea
Diuretic sometimes used for treatment of glaucoma?
mannitol
Diuretic Resistance/Braking Phenomenon
kidney can sense high levels of sodium further down in the renal tubule and kicks in RAAS and can even add more transporters to try and compensate
Major difference between loop and thiazide diruretics?
thiazides promote RESORPTION of calcium while loops promote EXCRETION of calcium
