Unit 2 pharmacokinetics and pharmacodynamics

Question 1

4 components of pharmacokinetics:

Answer 1

Absorption
How does drug get into the plasma; routes of administration; bioavailability
Distribution
The movement of drug in plasma to the “target tissue” and other tissues.
Metabolism
Biotransformation. 1st pass effect
Elimination
How drug gets out of the body; renal elimination; enterohepatic recycling

Question 2

Pharmacokinetics is

Answer 2

the movement of drugs into, through and out of the body

Question 3

Pharmacodynamics involves

Answer 3

how drugs interact with tissues to exert physiological changes

Question 4

Movement of drug molecules across lipid membranes

Answer 4

With the exception of IV routes, all other administration routes require that the drug molecule crosses at least one layer of vascular endothelium. Drugs given per os, must also cross GI barriers

Question 5

Four mechanisms by which drugs cross lipid membranes:

Answer 5

Passive diffusion
Facilitated diffusion
Active transport
Pinocytosis and phagocytosis

Question 6

Passive diffusion is

Answer 6

Most common; most important
Random movement
From high to low concentration
Across a semipermeable membrane
Unlimited
Drug must be:
Lipid soluble (lipophilic, hydrophobic)
Non-ionic
Small

Question 7

Facilitated diffusion is

Answer 7

Larger molecular weight drugs
Very similar to passive diffusion, except that diffusion occurs across pores/channels located in the lipid bilayer
Some selectively because specific pores may only let certain types of molecules through
Still required a high to low concentration gradient’

Question 8

Active transport is

Answer 8

Active movement of a drug molecule across a lipid membrane via a pump or transporter
Use of energy allows movement from low to high concentration; allows high drug accumulation in tissues
transporter/pump will only bind to specific drugs
Ex. P-glycoprotein pump

Question 9

Phagocytosis and pinocytosis is

Answer 9

Active “swallowing” or “drinking” of drug molecules by the cell
May be through “random sampling” of molecules in the extracellular environment OR, may result from drugs binding to receptors in the cell surface

Question 10

Factors that affect rate of drug molecule movement

Answer 10

Drug form
Smaller sized drug diffuse more readily across membrane
Carrier molecule ability, for those drugs dependent on a carrier
How quick does it reset
How many carriers available
Speed of transport
Saturation limit
Concentration gradient difference
Temp
Thickness of the membrane
Lipophilic nature of the drug molecule

Question 11

Lipophilic is

Answer 11

dissolves readily in fat but not readily dissolve in water
To move across membrane, drug molecules must be lipophilic (fat loving)

Question 12

Hydrophilic is

Answer 12

dissolves readily in water but not in fat

Question 13

Absorption is

Answer 13

Describes movement of drug from site of administration until it enters the plasma (i.e., what happens during the absorption period)

Question 14

Absorption is affected by

Answer 14

Chemical nature of the drug
How it is formulated
Route of administration
The patient
Absorption also influences how much of the initial dose ends up in the plasma (this is measured as “bioavailability”)

Question 15

Bioavailability is

Answer 15

A measure of drug absorption
% of drug administered into the body that enters the systemic circulation

Question 16

How bioavalible are IV drugs

Answer 16

100% bioavailability
Fastest onset of action greatest bioavailability
#1 choice for emergency drug delivery
Be aware of increased risk of entering toxic range with rapid bolus administration

Question 17

How bioavalible are IM drugs

Answer 17

have close to 100% bioavailability
Active muscle has increased blood flow compared to inactive muscle

Question 18

How bioavalible are PO drugs

Answer 18

Bioavailability quite variable when given PO
May be affected by “first pass effect”

Question 19

Drug formulation is and determines what

Answer 19

Formulation includes anything added to the pharmaceutically active ingredient
Syrups, other liquids, flavours, color, gel coats for tablets, sustained-action coatings, creams and ointment bases, saline, alcohols….
Formulation determines which route(s) of administration can be used
Drugs formulated for oral dosing cannot be given IM,etc…

Question 20

Generics equivalents may have different bioavailability because

Answer 20

Generic equivalents have the same active drug molecule. They do not necessarily have the same formulation
Formulation affects absorption and drug stability
Therefore, generic equivalents may have different absorptions and different bioavailability
Formulation is specific to a DIN
Important when comparing equivalents; not all generic equivalents act the same (mostly because they are absorbed differently)

Question 21

Effect of lipophilic or hydrophilic nature of drug on absorption

Answer 21

Whether a drug exist in a hydrophilic or lipophilic form when administered, will affect the ability for the drug molecule to dissolve or pass through the cellular membrane
The drug has to be proper ionization for the route of administration

Question 22

Where is a hydrophilic drug form more rapidly abosrbed

Answer 22

IM or SQ route

Question 23

Where is a lipophilic drug form more rabidly absorbed

Answer 23

PO

Question 24

Drug pH and environment pH effect on absorption

Answer 24

Drug act as either weak acids or weak bases
RULE: “like is non-ionized in like”

Question 24

What does “like is non-ionized in like” mean

Answer 24

Ex. a drug that is a weak acid, will be non-ionized in an acid environment. Because it ti nonionized it will be more lipid soluble
The same drug in a basic enviro will be less ionized (less lipid soluble)
Non-ionized = HCl vs ionized = H+ Cl-

Question 25

Aspirin works how

Answer 25

Aspirin (Acetylsalicyclic acid) is a weak acid
Aspirin is given by mouth and enters the stomach (also acidic)
If you apply the rule that “like drug in a like environment is non ionized”, then aspirin (which is a weak acid)→ in stomach acid →is non-ionized
Non-ionized molecules are lipophilic; therefore, aspirin is more likely to cross cellular membranes in the stomach
In fact, aspirin is absorbed from the stomach (compared to the intestines)

Question 26

Ion trapping is

Answer 26

Movement of a drug into a compartment where it changes from a hydrophobic state to a hydrophilic state, and stays in that compartment

Question 27

How does aspirin doe ion trapping

Answer 27

Aspirin in the stomach is non-ionized (lipophilic)
This allows aspirin to move across the stomach wall, across blood vessels walls into the circulation
Blood has a higher relative pH than the stomach.
Once the aspirin molecule enters the plasma, it is in a “less similar environment”. As a result, aspirin in blood becomes more ionized (more hydrophilic).
Result is aspirin tends to be “trapped” in plasma

Question 28

P-Glycoprotein and MDR1 gene is and does what

Answer 28

P-glycoprotein is encoded by the MDR1 gene
It is an active transport pump found in cells of the intestinal epithelium and BBB.

Question 29

P-Glycoprotein and MDR1 gene mutation does what

Answer 29

A genetic mutation of the MDR1 gene can lead to a lack of functional P-glycoprotein which leads to increased susceptibility to drug toxicosis.
Drug levels build up in CNS as pumps not pumping it out.

Question 30

MDR1 gene deficiency can be in what animals

Answer 30

Many herding dog breeds (e.g. Collies, Shelties, Border Collie, Australian Shepherds) and very young kittens
Can test via Washington State University

Question 31

MDR1 gene deficiency is what

Answer 31

Heterozygous mutation produces some functional pumps; are less affected
Homozygous mutation more severely affected
Pump can also be inhibited by certain drugs

Question 32

Cytochrome P450 (CYP enzymes). is what

Answer 32

Enzyme located in cells of the intestinal wall
Metabolizes the same drugs that P glycoprotein removes from the cell.
Need to keep in mind if drugs or disease or other drugs inhibit the function of these enzymes a correct dose will deliver a larger than expected quantity of drug
Alternatively some drugs with long term use may induce these enzymes therefore dose may need to increase over time e.g. phenobarbital

Question 33

Why does PO have the lowest bioavailability

Answer 33

Degradation in saliva
Degradation in stomach acid
Digestion in small intestine
Degradation by GI flora
-Per os is not commonly used in ruminants due to the large number of microbes in the rumen that will degrade most medications before they can be absorbed
If peristalsis is too fast, drug will pass through without a chance to absorb
-Note that GI transit times in dogs/cats much faster than humans; will affect bioavailability of human formulations
-Transit time is faster if there is diarrhea
-Oral drugs may be absorbed MORE if constipation
1st Pass Effect
-Drugs that are absorbed through the small intestine enter the portal vein and are transported to the liver, where they may be metabolized (partially or completely) before entering the systemic circulation

Question 34

Patient factors affecting absorption

Answer 34

Young animals may have poor oral absorption
Vomit and diarrhea decrease oral absorption
Constipation may increase oral absorption
Fever and heating sources increase rate of absorption for IM, ID, SQ, transdermal routes
Cold causes vasoconstriction and disease ID, SQ absorption
BCS- fat has poor perfusion; decrease SQ absorption
Ruminants -PO absorption typically poor

Question 35

Drug distubution describes what

Answer 35

Describes the movement of drug from the plasma into the tissues
A drug is only effective if it makes it to the target tissue
There is constant movement of drug between plasma and the different tissues

Question 36

Drug factors affecting distribution

Answer 36

Chemical nature of the drug; especially its solubility in aqueous solution versus fat- solubility
Degree to which the drug binds to albumin and other plasma proteins
“Volume of distribution”–a pharmacological measure of how much of a drug leaves or stays in the plasma….more to follow

Question 37

Size and ionization matters because

Answer 37

Small molecules have increased ability to cross semi-permeable membranes by passive diffusion
Large molecules cannot pass through fenestrations of blood capillaries
Non-ionized (lipophilic) molecules will diffuse across lipid membranes. Ionized (hydrophilic) molecules will not.

Question 38

Plasma protein binding is done by

Answer 38

Many drugs bind to plasma proteins, such as albumin and globulins, as soon as they reach the circulation

Protein bound drugs are not active- they are too big to leave the circulation; only unbound drugs are active and can leave the circulation into tissues
Plasma protein binding is a dynamic equilibrium
I.e., constantly binding and detaching

Dosage take into account plasma protein binding by drugs

Question 39

Concurrent drug use:

Answer 39

If two highly protein bound drugs are given at the same time but one has more affinity for protein binding (e.g. phenylbutazone) it makes preferentially bind to protein leaving more of the drug “free” to be active, therefore see increased effects from the other drug

Question 40

Volume of distribution (VD) is

Answer 40

Property of the drug determined in testing phase
Measure of how much drug leaves the circulation and enters the extracellular fluid

Question 41

What does a high and low VD mean

Answer 41

Drugs with a high VD leave the plasma more readily and enter the tissues
Drugs with a low VD have a harder time leaving the circulation
Used to determine drug dosage

Question 42

Patient factors affecting distribution

Answer 42

Blood flow
%body water
Tissue barriers and membrane permeability

Question 43

How does % body water affect drug distribution

Answer 43

Degree of hydration affects the total concentration of dissolved drug in plasma, other extracellular fluids and intracellular fluids
Dehydrated and older animals have lower %BW therefore may require lower doses of drugs to achieve a given plasma concentration

Question 44

How does tissue barriers and membrane permeability affect drug distribution

Answer 44

Some tissues are easier for drugs to get into than others

Question 45

Membrane permeability affects drugs by

Answer 45

Drugs pass out of the capillaries, into most tissues by passive diffusion through small gaps between vascular endothelial cells
The vascular endothelium has different degrees of “leakiness” in different tissues

Question 46

What are vascular endothelium different degrees of “leakiness” in different tissues

Answer 46

Capillaries in the liver are very permeable
Neonatal blood vessels are more permeable
Inflammation causes increased vascular permeability
Contraction of vascular endothelial cells that allows WBC to exit the capillaries and enter the damaged tissue also allows more drug to exit

Question 47

Tissue perfusion affects drugs by

Answer 47

A tissue with poor blood flow is less likely to receive drug from systemic circulation
Highest perfusion: brain, heart, liver, kidney
Lowest perfusion: fat

Question 48

How does fat affect drug absorption

Answer 48

Drugs must be lipophilic to a degree to cross out of the blood vessels
Drugs that are very lipophilic have increased ability to leave the blood vessels and only those drugs that are very lipophilic tend to be able to enter the BBB, choroid (vascular layer of the eye) and prostate
Body fat acts as a drug depot for lipophilic drugs
Drugs act very differently in thin versus fat animals

Question 49

How does sighthounds body fat affect drugs given to them

Answer 49

Sighthounds have low % body fat; have less body fat to bind very lipophilic drugs. Drugs will go to other tissues (especially those with high lipid content)

Question 50

Why would you dose to lean body weight

Answer 50

Animals should ALWAYS be dosed to lean body weight
assumed/estimated weight if animal were to have a BCS ⅗ or 5/9 (their “ideal weight”)
Decreased risk of toxicity
Fat has low extracellular fluid content; does not influence body water content
Drugs are designed to move in and around body water
Dosing to “fat” weight increase concentration of drug in both plasma and tissues

Question 51

Two compartments for bodies

Answer 51

tissues+blood
If more drug is in the tissue then the blood, VD is high
If more drug stays in the plasma and less enters the tissues, VD is low

Question 52

How to dose an obese animal and why

Answer 52

The amount of body water in the circulation and extracellular fluid compartments stay the same
Even though the animal weighs more, it has the same distribution volume as an animal with a BCS of ⅗ (5/9) that weighs less
Therefore, dose to lean body weight-reduce risk of relative OD

Question 53

Receptor drug theory is

Answer 53

Generally, most drugs work by altering the function of specific cells through binding to specific receptors on or in cells and turning the receptor on or off thereby altering their activity
Drugs can also bind to specific enzymes and turn them on or off
The drug must reach the correct cells in the “target tissue” that has receptor we want to influence in order to cause the desired effect
Not all cells have the same receptors/enzymes
Unfortunately drugs cannot be directed to only affect the target tissues
The same receptors we want to influence may also exist in other tissues in the body which when influenced may cause undesirable effects aka “side effects”
Side effects may be mild to severe
More drugs→ more receptor binding→ more activity
If there is enough drug to occupy ALL the receptors, giving any more drug will not have an effect. At this point, the receptors are saturated

Question 54

Affinity of drug def

Answer 54

Ability of drug to bind or fit with the receptor
One drug may have “more affinity” for a given receptor than another

Question 55

Affinity of drugs and receptors

Answer 55

Drugs do not bind to a receptor, produce an effect and then just sit there
They combine, pop off, recombine multiple times
Each time they combine they stimulate the cell to react

Question 56

Intrinsic activity is

Answer 56

The ability of a drug molecule to produce a cellular effect when it combines with the cells receptor

Question 57

Agonist is

Answer 57

Drug with both a good affinity for the receptor and ability to produce intrinsic activity

Question 58

Antagonist is

Answer 58

Drug a good affinity but little or no intrinsic activity
Can be either a reversal agent or blocker

Question 59

Types of antagonists

Answer 59

Reversal agent (inhibitor)
Blocker
Competitive antagonist
Noncompetitive antagonist

Question 60

Reversal agent works by

Answer 60

(inhibitor)
Combine with receptors to block the site from exogenous agonist drugs

Question 61

Naloxone works by

Answer 61

reversal agent for opioid analgesics
Occupies the receptor on cells preventing opioids such as hydromorphone from attaching to the receptor. Inhibiting or “reversing” the effect of the hydromorphone

Question 62

Blocker antagonist works by

Answer 62

Combine with receptors to prevent endogenous agonist compounds such as hormones or neurotransmitters from combining with receptor and stimulating the cell

Question 63

How does the blocker propranolol work

Answer 63

“Beta blocker” as it occupies the beta receptor on the heart and prevents norepinephrine from combining with the receptor which would cause an increase in the heart rate

Question 64

Competitive antagonist works by

Answer 64

Competes with another drug for attachment to the receptor
Determination as to whether drug A or B will successfully occupying receptor depends on which of these 2 drugs is the most abundant in the system

Question 65

Noncompetitive antagonist works by

Answer 65

Drug has a high affinity for the receptor site so other drugs can’t access the receptor or
Drug that modifies the receptor so other drug cannot attach
Not determined by amount of drug in system

Question 66

Nonreceptor mediated reactions

Answer 66

Some drugs produce an effect without attaching to a receptor
Ex
mannitol is an “osmotic” diuretic
Chelators- combine with ions e.g. penicillamine chelates (therefore removes) lead in lead toxicity
Antacids- reduce gastric acidity by binding with HCl therefore reduce stomach irritation/ulcers

Question 67

Drug metabolism is

Answer 67

Aka Biotransformation
When drugs in the body are chemically altered
Usually a chemical reaction that is carried out by enzymes. Different enzymes mediate different types of reactions
Oxidation, reduction or hydrolysis of drug molecules
May add or remove different functional groups to/from the drug molecule
Biotransformation can turn drugs on or can inactivate drugs prior to elimination

Question 68

What is prodrug and what do they do

Answer 68

Biotransformation can activate pro-drugs
Prodrugs is the precursor form of a drug
No biological activity
Must be activated through some enzymatic reaction to turn into the “active” form of the drug

Question 69

Activation of a prodrug

Answer 69

Hydroxysteroid dehydrogenase
Required for activation or prednisolone
Prednisone → prednisolone
“Prodrug” active drug
No activity
Cats, horses have very low levels of this enzyme and cannot effectively transform prednisone into prednisolone
Must give prednisolone ($$$) or use a different steroid
Dogs, bovids have normal levels of enzyme; can dose with prednisone (cheap)

Question 70

How are drugs metabolized before eliminaiton

Answer 70

Enzymatic alteration of a drug can change its molecular structure so that it is no longer biologically active
Often this same enzymatic reaction will alter the drug so it becomes less lipid soluble
Less lipid soluble drugs are more likely to stay trapped in the plasma
The drug can then be eliminated from the plasma via the kidneys
The resulting chemical is called a metabolite

Question 71

Where does drug metabolism occur?

Answer 71

> 90% occurs in the liver
Next important are Gi tract >lungs, skin, kidney > other tissues
Most tissues have some ability to metabolize drugs

Question 72

Cytochrome P450 (CYP) enzymes are found in

Answer 72

Found in liver
Group of related enzymes; among most important for drug detoxification (also activates some drugs)

Question 73

Increasing cytochrome P450 is because

Answer 73

Liver induction= more cytochrome P450 activity
Increased enzyme activity→ drugs breakdown faster (i.e., drug is less effective)
May need higher dose or more frequent dosing
Certain drugs can increase the levels of cytochrome P450 activity
Chronic phenobarbital (epilepsy drug) turns up cytochrome P450→ same dose becomes less effective
Chronic opioids

Question 74

Decreasing cytochrome P450 is

Answer 74

If enzyme activity is decreased → drug is metabolised slower→ can result in drug accumulation→ increased risk of toxicity

Question 75

Cause of decreased cytochrome P450

Answer 75

Grapefruit specifically inhibits cytochrome P450
Ketoconazole (antifungal drug)
Liver disease
Very old patients
Patients taking steroids
Any other cause of hepatopathy
Some species produce less cytochrome P450 than others- dogs have less than cats

Question 76

Glucuronyl transferase is

Answer 76

Drug metabolism enzyme in liver
Adds a glucuronic acid molecule to the drug
Causes drug to be inactivated and increases renal elimination
Cats cannot produce glucuronic acid and have very low levels of glucuronyl transferase; therefore, are susceptible to toxicity from drugs that are metabolized by this enzyme
Ex. tylenol, aspirin, meloxicam (Metacam@)

Question 77

Concurrent drug use reduces metabolism by

Answer 77

If the patient is taking multiple drugs at the same time that require metabolism by the same enzyme
There will be competition for binding of drugs to enzymes. One drug will be metabolized first; the drug that does not bind as strongly to the enzyme will be metabolized slower

Question 78

1st pass effect (1st pass metabolism) is

Answer 78

PO route
Drug is absorbed via capillaries in the SI→ portal vein→ liver→ liver metabolism→ systemic circulation
Some drugs are unaffected by liver metabolism
Some drugs are metabolised into their active form
Many drugs are inactivated through liver metabolism
In most mases, 1st pass metabolism decreases bioavailability due to lower metabolism of the drug before it reaches the systemic circulation
Some drugs may be 100% inactivated on 1st pass
E.g. lidocaine- therefore not given PO

Question 79

How are drugs eliminated from the body

Answer 79

How drug is physically removed from the body
Can be active drug or inactivated drug (metabolites)
Kidney- most important
Urine testing in competition animals
liver/GI tract- next important
Aka biliary excretion
Lungs- important for elimination of inhalant anesthetics and gasses
Also skin, secretions (saliva, milk)
Mammary secretion is important in nursing animals and dairy cows

Question 80

Renal drug elimination is decreased by

Answer 80

Kidney disease- not able to filter drugs out
Hypotension, dehydration, blood loss, increased sympathetic tone (cause renal vasoconstriction)- anything that decreased blood flow through the kidney
Changes in urine pH

Question 81

Renal drug elimination is increased by

Answer 81

Kidney disease-reduced reabsorption
Fluids
Use of diuretics

Question 82

Biliary (hepatic) excretion is done by

Answer 82

2 most important route of drug elimination (esp for large molecular sized drugs)

Drug enters the liver via the portal vein (small intestine) or hepatic vein (systemic circulation) → may or may not undergo liver metabolism→ enters biliary ducts→ secreted in bile→ gallbladder→ bile enters the intestine→ fecal elimination
Decreased in patients with liver disease

Question 83

Entero-hepatic recirculation

Answer 83

Related to biliary excretion
Only relates to drugs that are NOT completely inactivated in the liver and some (or all) of the drug is excreted via the bile in ACTIVE FORM
When bile is secreted into the small intestines, the active drug is reabsorbed
The cycle is continuous until all drug is either metabolized, degraded or defecated
Can occur with any route of administration; related to the drug and how it is eliminated
With enterohepatic recirculation, will see the following absorption curve following a single dose

Question 84

When bile is secreted into the small intestines, the active drug is reabsorbed where

Answer 84

(Liver) → at least some drug stays active→ bile acid→ gallbladder→ bile duct→ small intestines→ absorption through SI capillaries→ portal vein→ liver→ systemic circulation→ liver,…

Question 85

Half-life of elimination (t½) is

Answer 85

More commonly used unit of measure of drug elimination
Time required for the amount of active drug in the body to be reduced by half of its original level
Takes into account all methods of elimination and metabolism
Can be minutes, hours or days depending on drug and individual patient
Usually found on the drug label

Question 86

How dose a dose increase affect half life

Answer 86

t1/2 is not affected by mg/kg dose
But if you double a single dose you add one t1/2 to the time it takes to eliminate the drug

Question 87

how does half life get affected

Answer 87

Can be affected by patient factors
Slower elimination in patients with renal disease
May be affected by the route of administration only referring to a single dose
IV drugs are eliminated faster than SQ drugs
Is used to calculate dosing frequency and WDTs

Question 88

What does steady state mean

Answer 88

Only applies to long term dosage regiments
The point when drug accumulation and drug elimination are balanced
In other words, once steady state is reached, the therapeutic range is maintained by giving a dose that is equal to the amount of drug elimination in the same time period
It takes time to reach the steady state

Question 89

peak concentration is

Answer 89

Highest plasma concentration of a drug after a single dose or while in steady state
Occurs after giving a dose of drug
Should stay below the minimum toxic concentration

Question 90

Through concentration is

Answer 90

Lowest plasma concentration of a drug in steady state
Occurs before next does
Should always be above the minimum effective concentration

Question 91

Therapeutic drug monitoring is

Answer 91

To make sure the drug is working as it should and to prevent toxicity
Measures plasma concentration of drug

Question 92

Measures plasma concentration of drug is

Answer 92

After 5 elimination half-lives (i.e., after the drug has reached steady state)
For some drugs, blood collection must be done at a certain numbers of hours after dosing
Time of peak concentration if monitoring for toxicity
Time of trough concentration if measuring for therapeutic effect
Can compare to the known therapeutic range

Question 93

When to test therapeutic drug monitoring

Answer 93

Serious toxicity
When pharmacokinetics are strongly affected by patient factors; i.e., pharmacokinetics may vary in every patient
Drugs that cause enzyme induction e.g. phenobarbital
Drugs with low therapeutic index e.g. aminoglycosides
If drug appears not to be working

Question 94

Causes of drugs not working

Answer 94

Wrong drug, wrong dose, wrong frequency, poor owner compliance
Blood sample taken at wrong time; sample not handled properly

Question 95

What is drug withdrawal time dependent on

Answer 95

All drugs approved for use in food animals have mandated withdrawal times
Expressed in days
Based on half-lives
Drug movement is slower in meat or fat than in blood so withdrawal times tend to be quite long

Question 96

Why are withdrawal times important

Answer 96

Government imposes fines and penalties on producers if there are drug residues discovered
VT have important role to educate producers regarding the purpose of withdrawal times and to ensure that they are aware of the withdrawal time on any particular drug they are using

Question 97

When are withdrawal time important in competition horses

Answer 97

National and international equestrian federations publish allowable limits (most are zero) for certain medication and typical WTs needed post treatment to meet these limits if the horse is tested in competition
A drug tester will follow a competitor straight from the competition arena to the horses stall to collect a urine sample or secondarily a blood sample for testing
Wise to confirm horse is not given to a competition prior to routine treatments
This is one means of ensuring fairness in sport (performance enhancing drugs) and equine welfare( ie. disease is not masked and horse continued to be worked)

Question 98

Drug interactions can happen because

Answer 98

Can occur when two or more drugs are administered at the same time
Can alter pharmacokinetics
One drug is made more effective and/or
One drug is made less effective
Or, if both drugs have similar effects, can increase toxicity

Question 99

Interactions that affect absorption

Answer 99

One drug may alter the absorption of another
Antacids alter the pH of the stomach
GI protectants block intestinal absorbency
GI motility drugs increase or decrease rate of GI passage
Drugs that cause vasoconstriction decrease the absorption of SQ and ID administered drugs
Two solutions with different pH when mixed together will later overall pH; solutions precipitate when mixed together

Question 100

Interactions that affect distribution

Answer 100

Diuretics will decrease the volume of distribution so drug is present in both tissue and blood compartment at higher concentration
Plasma protein binding drugs compete with one another
If two drugs bind to plasma proteins (i.e., albumin), the drug with less affinity for binding to albumin will present in the plasma in “active” form at higher than expected concentration

Question 101

Interactions that affect metabolism

Answer 101

Drugs that are hepatotoxic will decrease drug metabolism
Competition for biotransformation enzymes
Cytochrome P450 liver induction
Cytochrome P450 inhibition

Question 102

How does hypoatotoxic drugs decrease drug metabolism

Answer 102

Drugs with adverse hepatic effects will affect albumin, globulins, biotransformation enzymes
Ex. steroids, methotrexate, phenobarbital, azathioprine, clomipramine

Question 103

How does competition for biotransformation enzymes decreased drug metabolisim

Answer 103

If equal binding; both drugs will have decreased metabolism
If drug A binds with greater affinity, it will be metabolised first while drug B accumulates

Question 104

How does cytochrome P450 liver induction decrease drug metabolism

Answer 104

Drugs such as phenobarbital can increase the number of cytochrome P450 enzymes; this increases rate of metabolism of the phenobarbital and other drugs

Question 105

How does cytochrome P450 inhibition decrease drug metabolism

Answer 105

Direct inhibition by grapefruit and ketoconazole

Question 106

Interaction that affect elimination

Answer 106

Certain drugs can alter excretion
Certain drugs act directly on kidneys and increase/decrease renal elimination
Ex. diuretics will increase renal elimination
Some drugs can cause renal damage and decrease function
Aminoglycoside class of antibiotics are very nephrotoxic

Question 107

Incompatible drugs are

Answer 107

Drugs that should not be used together at the same time
Some (but not all) are listed under the drug label “Drug incompatibility” or “Contraindications”

Question 108

Additive drug effects

Answer 108

If 2 drugs have the same physiological effect and are taken together, the overall physiological effect will be amplified. This could be:
Additive; 4 and 4=8 or
Synergistic; 4 and 4 = 16
Pertains to deserted effects and adverse effects

Question 109

What drugs have additive drug effects

Answer 109

Opioids +NSAIDs taken together produce an additive increase in analgesia
Steroids, NSAIDs both decrease GI mucus production and GI healing; cause GI ulcers if taken together
Acepromazine, isoflurane and dexmedetomidine all contribute to hypotension