Veterinary Pharmacology - Midterm

Front 1

in pharmacology terms, what is a 1% solution?

Back 1

1 g/100 mL

Front 2

what is the conversion factor between kg and lbs?

Back 2

1 kg = 2.2 lbs

Front 3

what is the conversion factor between fl oz and mL?

Back 3

1 fl oz ~ 30 mL

Front 4

what is the conversion between pints and fl oz?

Back 4

1 pint = 16 fl oz

Front 5

what is the conversion between pints and quarts?

Back 5

2 pints = 1 quart

Front 6

how many pints are in one gallon?

Back 6

8 pints = 1 gallon

Front 7

what information must be on a veterinary prescription for a CIII - CV drug?

Back 7

- Clinic/DVM name, address, phone number
- date
- Patient ID (name/animal number)
- species
- client name and address
- drug name & strength
- number
- directions for use
- refill instructions
- DEA registration number
- DVM signature
- DVM printed name

Front 8

what are the four main uses for a drug?

Back 8

1. prevent disease
2. cure disease
3. treat disease
4. diagnose disease

Front 9

what is an "Approved Drug?"

Back 9

drug that meets FDA requirements for safety and effacacy

Front 10

what is an "Unapproved Drug?"

Back 10

drug with health claims but no FDA approval

Front 11

how are food supplements / nutraceuticals treated by the FDA?

Back 11

there is no FDA oversight; however, they can make no health claims

Front 12

how are food additives regulated by the FDA?

Back 12

they must meet the FDA requirement for safety

Front 13

what are the three basic processes studied by pharmacokinetics?

Back 13

1. absorption (into bloodstream)
2. distribution (from blood to tissue)
3. elimination (metabolism to inactive drug & excretion)

Front 14

comment on if there is a species relation to:
- pharmacodynamics
- pharmacokinetics

Back 14

pharmacodynamics: no species differences

pharmacokinetics: species differences

Front 15

the study of the mechanism of drug action on the body

Back 15

pharmacodynamics

Front 16

the study of what the body does to a drug, in terms of absorption, distribution, and elimination

Back 16

pharmacokinetics

Front 17

applied use of drugs in disease states

Back 17

therapeutics

Front 18

individualized drug therapy

Back 18

clinical pharmacology

Front 19

use of a specific drug for a specific disease

Back 19

chemotherapy

Front 20

the study of adverse effects of drugs

Back 20

toxicology

Front 21

standardization and dispensing of drugs

Back 21

pharmacy

Front 22

science of formulating drugs

Back 22

biopharmaceutics

Front 23

study of drugs from plant sources

Back 23

pharmacognosy

Front 24

what are the four basic ways in which drugs are classified?

Back 24

1. chemical structure
2. mechanism of action
3. indication
4. system the drug affects

Front 25

what are the four basic goals of rational therapeutics?

Back 25

understanding
1. the disease process and its cause
2. how the drug produces its pharmacodynamic/chemotherapeutic properties
3. pharmacokinetics of the drug, especially how the disease process impacts their fate in the body
4. drug interactions (beneficial and detrimental)

Front 26

term used to describe how the chemical makeup of a drug affects its pharmacodynamic properties

Back 26

structure-activity relationship

Front 27

what four major pharmacodynamic properties does chemical structure affect?

Back 27

1. effectiveness
2. potency
3. dosage
4. toxicity

Front 28

what four major chemical properties of a drug affect its pharmacokinetics?

Back 28

1. molecular weight
2. acid/base properties
3. lipophilicity/hydrophilicity
4. functional groups

Front 29

what are four general physiological and pathological factors that can alter drug effectiveness?

Back 29

1. the disease itself influencing drug action

the use of multiple drugs can result in...
2. addition
3. synergism/potentiation
4. antagonism
... of drug effects

Front 30

for a properly prescribed drug, what is the veterinarian's foremost concern to achieve the desired effect?

Back 30

owner compliance

Front 31

how do youth and old age influence drug effectiveness and why?

Back 31

both groups tend to be more sensitive to a drug.

- youth: unable to metabolize a drug as fast as an adult

- old: decreased renal clearance

Front 32

what are six major medical-ethical responsibilities of a veterinarian prescribing drugs?

Back 32

1. proper Dx
2. knowledge of drug actions (efficacy, mechanisms/kinetics, safety, interactions) so they are ordered correctly
3. a VCPR
4. proper supervision
5. consideration of the client for recommended regimen and cost
6. adverse drug reaction reporting

Front 33

tendency for a drug to bind to a receptor

Back 33

affinity

Front 34

what does an agonist do?

Back 34

initiates the propagation of a message in a cell, thereby causing a biological response

Front 35

what does an antagonist do?

Back 35

it has affinity for a site, but does not initiate a biological response

Front 36

what two pharmacodynamic terms have to do with a drug's binding to a site, and therefore its affect on the body?

Back 36

affinity and specificity

Front 37

what are the three basic sites of drug action?

Back 37

1. outside the cells, not involving receptors (e.g. laxatives, antacids, osmotic diuretics)
2. in or on cells without specific molecular receptors, but rather cause a whole-organelle or whole-cell effect
3. drug action involving receptors

Front 38

how are target specificity and side-effects related?

Back 38

increased target specificity tends to decrease side effects

Front 39

what are the four general pharmacodynamic properties of receptors?

Back 39

1. specific or not
2. bind to normal body components
3. may have subtypes that can be exploited in therapeutics
4. can be desensitized

Front 40

what are the two types of dose-response curves and what do they represent?

Back 40

1. graded (quantitative) - represents the efficacy of a drug with respect to dosage amount
2. quantal - represents the number of individuals that will exhibit a response as a function of dosage

Front 41

graded (quantitative) dose-response curve:

- axes
- shape of curve
- points on the curve that represent pharmacodynamic properties

Back 41

Front 42

ability to bind to a receptor

Back 42

affinity

Front 43

the property of effecting a response when a drug is bound to a receptor
- or -
magnitude of response obtained from drug-receptor binding

Back 43

efficacy or intrinsic activity

Front 44

a drug that does not cause a maximal response

Back 44

partial agonist

Front 45

concentration of drug at a receptor needed to initiate a response

Back 45

threshold

Front 46

comparative term to describe the position of two or more agonists on a dose-response graph

Back 46

potency

Front 47

what is surmountable antagonism and how does it change the dose-response curve?

Back 47

when two drugs bind to the same receptor the more potent drug requires a higher dosage to have its effect. This will shift the curve to the right (including threshold), but not change its shape.

Front 48

what is insurmountable antagonism and how does it change the dose-response curve?

Back 48

1. when one drug binds to a receptor, but not at the target site, it changes the shape of the target site, thus making the other drug less potent.
- or -
2. when the drug has no agonist activity, but decreases the pool of receptors
- or -
3. with a partial agonist competitively binding

This will change the shape of the curve, lower the maximum efficacy, and possibly raise the threshold.

Front 49

what are the axes of the two types of quantal dose-response curves?

Back 49

1. number responding versus log dose (bell-shaped curve) - less common
2. cumulative number responding versus log dose (integral of #1) - most common

Front 50

how is the therapeutic index calculated? What do greater values mean? What is required of the dose-response curves for this data to be meaningful?

Back 50

LD50/ED50 or TD50/ED50

LD50 = lethal dose 50%, ED50 = effective dose 50%, TD50 = toxic dose 50%

greater numbers mean a safer drug. The curves must be parallel in shape

Front 51

how is the margin of safety calculated? What do the values mean?

Back 51

TD01/ED99

TD01 = toxic dose 1%, ED99 = effective dose 99%

It represents how much one can overdose a patient before toxic effects set in. It must be greater than 1 to be considered safe.

Front 52

how do the following effects affect the ability of drug translocation

- higher molecular weight?
- bound to a plasma protein?
- lipophilicity?
- charge state (degree of ionization)?
- body pH?
- drug pKa?

Back 52

- higher molecular weight: lower
- bound to a plasma protein: lower
- lipophilicity: the more lipophilic, the easier it is to cross the membrane
- charge state (degree of ionization): charged molecules don't cross; uncharged molecules can cross
- body pH: lower pH will increase the ability of weak acids to cross; higher pH will increase the ability of weak bases to cross. ***This is assuming that the conjugate base of the weak acid is an anion and that the conjugate acid of the weak base is a cation.
- drug pKa: lower pKa favors lower pH; higher pKa favors higher pH

Front 53

what is the main "goal" of the body metabolizing a drug?

Back 53

to make it more water soluble for elimination

Front 54

a drug designed to become more potent after it has been metabolized

Back 54

prodrug

Front 55

what properties of a drug are changed by biotransformation?

Back 55

- water solubility
- activation/inactivation
- potency
- affinity and specificity
- duration of drug action
- side effects and/or toxicity

Front 56

the passage of a drug through a cellular membrane

Back 56

translocation

Front 57

in what organs does drug biotransformation occur?

Back 57

- LIVER (main site)
- intestine
- kidney
- plasma
- others

Front 58

in what organelles does drug biotransformation occur?

Back 58

- microsomes (SER) - major
- mitochondria
- cytosol

Front 59

why do neonates and elderly animals have less efficient biotransformation of drugs?

Back 59

because they have lower liver function

Front 60

generally, what organic functional groups are most susceptible to biotransformation?

Back 60

hydroxyl, carboxyl, amino

Front 61

what are the phases of drug metabolism and what is each phase's general purpose?

Back 61

Phase I: transformation
Phase II: conjugation

Front 62

what are the three most common Phase I biotransformation reactions in order of prominence?

Back 62

1. oxidation
2. reduction
3. hydrolysis

Front 63

which Phase I biotransformation is most rapid and what are the most common organic functional groups associated with this reaction?

Back 63

hydrolysis is fastest.

- esters, amides, glucuronides, glycosides

Front 64

why is oxidation a more prominent biotransformation pathway than reduction?

Back 64

because reduction requires a relatively oxygen-free environment

Front 65

which phase of drug metabolism has the most species differences and why?

Back 65

Phase II, because different species have different amounts of the transferase enzymes required for the conjugation reactions.

Front 66

what general type of reaction is in a Phase II biotransformation, and what is required to catalyze these reactions?

Back 66

these are conjugation reactions and require transferase enzymes

Front 67

what are the five predominant Phase II biotransformation reactions, in order of most important to least important? note species differences.

Back 67

1. Glucuronic acid conjugation (cats and neonates are deficient in the transferase enzyme)
2. Sulfate conjugation (pigs have limited capability)
3. Mercapturic acid conjugation (primates and guinea pigs are deficient in the transferase enzyme)
4. Acetylation (dogs are deficient)
5. Methylation

Front 68

which species is/are deficient in the Phase II biotransformation enzyme for

- glucuronic acid conjugation?
- sulfate conjugation?
- mercapturic acid conjugation?
- acetylation?
- methylation?

Back 68

- glucuronic acid conjugation: cats and neonates
- sulfate conjugation: pigs
- mercapturic acid conjugation: primates and guinea pigs
- acetylation: dogs
- methylation: none noted

Front 69

glucuronic acid conjugation:

- organ and organelle
- reversibility
- product
- functional groups
- mechanism
- species specific comments

Back 69

- organ and organelle: this is a steroid hormone pathway found in the liver that is affected by age and health; microsome (SER)
- reversibility: reversible (GI flora can do this)
- product: organic acid for tubular secretion
- functional groups: hydroxyl, carboxyl, amino, also sulfhydryl
- mechanism: UDPGA + drug + transferase --> product
- species specific comments: cats and neonates are deficient in the transferase enzyme

Front 70

sulfate conjugation

- organ and organelle
- reversibility
- product
- functional groups
- mechanism
- species specific comments

Back 70

- organ and organelle: takes place primarily in liver; cytosol
- reversibility: irreversible
- product: sulfate ester
- functional groups: aromatic hydroxyl, aromatic amino, sometimes aromatic carboxyl
- mechanism: PAPS + drug + transferase enzyme --> conjugate;
- species specific comments: pigs are deficient in the transferase enzyme

Front 71

mercapturic acid formation

- organelle
- reversibility
- product
- functional groups
- mechanism
- species specific comments

Back 71

- organelle: cytosol; a reserve pathway for many of the same functional groups that under glucuronidation/sulfation
- reversibility: irreversible
- product: a mercapturic acid
- functional groups: carboxyl, hydroxyl, amino, halogen, sulfhydryl
- mechanism: drug + glutathione (GSH) + 4 enzymes --> product
- species specific comments: primate and guinea pig are limited

Front 72

acetylation in a Phase II biotransformation:

- organelle
- reversibility
- product
- functional groups
- mechanism
- species specific comments

Back 72

- organelle: cytosol
- reversibility: irreversible
- product: amide
- functional groups: amino group only (including sulfa drugs)
- mechanism: AcCoA + drug + transferase enzyme
- species specific comments: dogs are deficient

Front 73

methylation in a Phase II biotransformation

- organelle
- reversibility
- product
- functional groups
- mechanism
- species specific comments

Back 73

- organelle: cytosol
- reversibility: reversible
- product: methylated product
- functional groups: endogenous alcohols, amino, sulfhydryl
- mechanism: SAM + drug
- species specific comments: none noted

Front 74

how many Phase II biotransformation reactions are reversible and which ones are they?

Back 74

two: glucuronidation and methylation

Front 75

what are the main irreversible Phase II biotransformation reactions?

Back 75

- sulfation
- metcapturic acid formation (glutathione)
- acetylation

Front 76

which biotransformation reactions take place in microsomes (SER)?

Back 76

only two: oxidation and glucuronidation

Front 77

what is the main organ in which microsomal biotransformation takes place?

Back 77

liver

Front 78

what are traits and conditions that affect microsomal enzyme activity?

Back 78

- age
- sex
- disease state
- genetics (e.g. breed)
- environment
- nutritional status

Front 79

testing of biotransformation enzyme isoforms in the DNA for pharmacokinetic properties such as safety and efficacy

Back 79

pharmacogenetics

Front 80

what is the predominant enzyme involved with microsomal oxidative biotransformation? What type of molecule is it?

Back 80

Cytochrome P450, which is an iron-containing protein

Front 81

what is induction, with regards to pharmacokinetics? what are its pharmacological effects?

Back 81

- up-regulation of the production of microsomal CP450 due to increased demand for drug oxidation (e.g. increased amount to drug intake)

- can result in shorter duration and/or lower drug concentrations

Front 82

what is the major reason that the body will decrease protein synthesis associated with inhibition of microsomal enzymes?

Back 82

disease

Front 83

with regards to pharmacokinetics, what is inhibition, what are the two ways in which this can occur, and how does this change the body's response to a drug?

Back 83

- decreased activity of microsomal enzymes due to

1. decreased protein synthesis (delayed effect)
2. competitive inhibition (immediate effect)

this can cause hypersensitivity to a drug

Front 84

in what four major ways can the veterinarian apply the knowledge of drug chemical structure, reactions they may undergo, and species uniqueness?

Back 84

1. increase drug effectiveness (e.g. species, age)
2. help establish dosages and regimens, especially in extralabel drug use
3. avoid drug toxicities
4. consider special situations (such as sensitivity of cats and Greyhounds, aged animals, animals with liver disease)

Front 85

what probable biotransformation pathway(s) exist for esters and amides?

Back 85

hydrolysis

Front 86

what probable biotransformation pathway(s) exist for aromatic rings (the ring itself, not its functional groups)?

Back 86

oxidation (hydroxylation)

Front 87

what probable biotransformation pathway(s) exist for aliphatic hydroxyl groups?

Back 87

glucuronidation > sulfate conjugation

Front 88

what probable biotransformation pathway(s) exist for aromatic hydroxyl groups?

Back 88

glucuronic acid conjugation, sulfation, mercapturic acid (glutathione) conjugation, methylation

Front 89

what probable biotransformation pathway(s) exist for aliphatic carboxyl groups?

Back 89

glucuronidation >> sulfation, mercapturic acid (glutathione) conjugation

Front 90

what probable biotransformation pathway(s) exist for aromatic carboxyl groups?

Back 90

glucuronidation >> sulfation, mercapturic acid (gultathione) conjugation

Front 91

what probable biotransformation pathway(s) exist for aliphatic amines?

Back 91

oxidation (deamination)

Front 92

what probable biotransformation pathway(s) exist for aromatic amines?

Back 92

glucuronidation, sulfation, mercapturic acid (glutathione) conjugation, acetylation

methylation (natural substrates)

Front 93

what probable biotransformation pathway(s) exist for thiols?

Back 93

glucuronidation and mercapturic acid (glutathione) conjugation

Front 94

name three common types of reductive biotransformation reactions

Back 94

1. azo reaction (azo --> amino)
2. nitro reaction (nitro --> amino)
3. alcohol (geminal diol --> primary alcohol)

Front 95

name five common drug functional groups subject to hydrolysis.

Back 95

1. ester
2. phosphate ester
3. amide
4. glucuronide conjugate
5. glycoside

Front 96

where must a drug first go to be considered "in the body"?

Back 96

bloodstream

Front 97

what are advantages and disadvantages of oral administration?

Back 97

advantages:
- convenient, cheap, no sterility needed, variety of dose forms
- can get the dose back if you act quickly
disadvantages:
- variability due to physiology, feeding, Dz, etc
- intractable patients
- first-pass effect (goes to liver first)

Front 98

what patient and pharmaceutical differences increase variability of absorption from oral administration?

Back 98

- pill compression, coatings, suspending agents, etc.
- GI transit time, inflammation, malabsorption syndromes

Front 99

what aspects of the stomach (abomasum) can affect oral administration of drugs?

Back 99

- mechanical preparation
- "flat" absorptive surface
- pH extremes

Front 100

what aspects of the rumenoreticulum can affect oral administration of drugs?

Back 100

- stratified squamous epithelium
- pH varies with diet
- metabolism by bacterial flora
- large amount of volume compared to body water

Front 101

what aspects of the small intestine can affect oral administration of drugs?

Back 101

- large absorptive surface
- specialized absorptive functions
- relatively neutral pH

Front 102

what are advantages and disadvantages of IM administration of drug?

Back 102

advantages:
- more consistent absorption (IM ~ IV)
- certainty of administration
- depot or sustained effect possible
- viable route for patients that can't be easily given other routes (e.g. unconscious, intractable, dehydrated)
disadvantages:
- more difficult for owners of small animals
- pain
- muscle damage
- cannot recover dose

Front 103

what is the three-step process of drug absorption?

Back 103

1. dissolve (lipid/suspension) into or mix (aqueous) with tissue fluid
2. diffuse into capillaries
3. carried to circulatory system

Front 104

what does it mean when a drug "falls" out of solution?

Back 104

the vehicle carrying the drug is absorbed more quickly than the drug, leaving a residue in the tissue

Front 105

how does absorption of a spherical lipid bolus vary with time?

Back 105

it slows (less surface area)

Front 106

what are advantages and disadvantages of SQ administration?

Back 106

advantages:
- can be given by owner
- vasoconstrictor can be added to prolong effect at site of interest
disadvantages:
- variability

Front 107

how do heat, cold, and hydration status effect drug absorption from a SQ injection?

Back 107

- heat: increases blood flow; more rapid absorption
- cold and dehydration: decreases blood flow; slower absorption

Front 108

what are the two main pathways in which topical drugs enter the body?

Back 108

1. diffusion through the stratified squamous epithelium
2. "passage" through adnexal structures

Front 109

what are four patient and pharmaceutical factors affecting topical drug absorption?

Back 109

1. lipid solubility and molecule size
2. skin hydration and abrasion
3. area of application
4. ambient and patient temperature

Front 110

how does the vehicle affect topical drug absorption

Back 110

- drugs in "like" vehicles are retained on skin surface (aqueous/water of lipid/lipid)
- drugs in "unlike" vehicles are absorbed (suspensions)

Front 111

what are advantages and disadvantages of intraperitoneal drug administration?

Back 111

advantages:
- larger absorptive surface than IM/SQ
disadvantages:
- drugs/vehicles may cause peritonitis
- damage to organs by needles
- injection into organs

Front 112

what are advantages and disadvantages to intrathecal drug administration?

Back 112

advantages:
- direct delivery to CSF
disadvantages:
- difficult to calculate because CSF volume is not proportional to body weight
- toxicity is likely and may be unusual
- risk of introducing infection
- very slow absorption because it is diffusion-limited

Front 113

what comprises the vascular space?

Back 113

plasma volume + RBC volume + WBC volume

Front 114

what percentage of body weight is the vascular space?

Back 114

7%

Front 115

what three important equilibria exist in the vascular space?

Back 115

1. solution and plasma proteins
2. ionized and unionized drug
3. plasma and cells

Front 116

what comprises the tissue space

Back 116

= the body space - vascular space - structural protein - bone

Front 117

what three important equilibria exist in the tissue space?

Back 117

1. water and tissue proteins
2. ionized and unionized drug
3. intracellular fluid and extracellular fluid

Front 118

what comprises the extracellular space and what percentage of of the body weight is it?

Back 118

plasma + extracellular tissue space
15-20% of body weight

Front 119

how does extracellular space vary with age?

Back 119

babies have more

Front 120

what comprises the intracellular space and what percentage body weight is it?

Back 120

intracellular vascular space + intracellular tissue space
35-45% of body weight

Front 121

what two important equilibria exist in the extracellular space?

Back 121

1. water and proteins
2. ionized and unionized drugs

Front 122

what important equilibrium exists in the intracellular space?

Back 122

ionized and unionized drug

Front 123

how long after administration is drug distributed in the
- vascular space?
- tissue space?
- extracellular space?
intracellular space?

Back 123

- vascular space: 10-30 minutes
- tissue space: hours/days/weeks
- extracellular space: 30-90 minutes
- intracellular space: 30 minutes to 12+ hours

Front 124

what are the "reserved" spaces in the body, which have special barriers between plasma and tissue fluid?

Back 124

1. CSF
2. aqueous humor
3. prostatic fluid

Front 125

in what four ways do drugs move from extracellular vascular space to extracellular tissue space?

Back 125

1. transcytotic
2. endothelial junctions (during inflammation)
3. diffusion through endothelial membranes
4. carried in cells or on proteins (very special circumstances)

Front 126

in what two ways can drug move between extracellular space and intracellular space?

Back 126

1. diffusion through lipid bylayer
2. active uptake (esp. WBCs)

Front 127

the process of drug being reabsorbed from the bile in the intestines

Back 127

enterohepatic circulation

Front 128

what is the process of enterohepatic circulation? how does it affect volume of distribution? elimination rate? how can this circulation be interrupted clinically?

Back 128

- drug or its Phase II conjugate excreted in bile
- drug reabsorbed or its conjugate cleaved by flora and reabsorbed
- increases Vz
- slows elimination rate
- can interrupt via activated charcoal or other substances that will prevent reabsorption or unconjugation

Front 129

mammary excretion:
- how does it get into the milk?
- what properties of the drug affect this process?
- how does mastitis affect this process?
- why does drug stay in the milk?

Back 129

- non-ionic diffusion
- lipid solubility and molecular size
- inflammation reduces barrier to penetration
- milk is lower pH, so it ion-traps the drug

Front 130

why is mammary excretion important?

Back 130

- may affect treatment of mastitis
- nursing animals may be exposed to drug

Front 131

what are two reasons why salivary excretion can be important pharmacokinetically?

Back 131

1. recycles certain drugs like enterohepatic circulation (Vz goes up)
2. trap in rumen based on pH

Front 132

what are the two general processes of drug elimination?

Back 132

1. biotransformation
2. excretion

Front 133

what is the major route of elimination of a drug that is
- lipid soluble?
- aqueous?
- protein-bound?

Back 133

- lipid soluble: metabolism
- aqueous: direct excretion
- protein-bound: metabolism

Front 134

what four factors contribute to the rate of drug metabolism?

Back 134

1. metabolic activity for a drug
2. blood flow to the metabolizing organ
3. health of the metabolizing organ
4. health of the circulatory system

Front 135

what organ is most important for metabolizing autacoids?

Back 135

lungs

Front 136

what is secreted via active biliary excretion?

Back 136

- drugs with MW > 300
- mostly conjugates

Front 137

what is excreted by passive biliary excretion?

Back 137

- drugs with MW < 300
- biliary concentrations similar to plasma water

Front 138

what three factors sum up renal elimination?

Back 138

renal elimination = glomerular filtration + tubular secretion - passive reabsorption

Front 139

what happens to an unionized drug when concentrated in the nephron? why?

Back 139

it gets reabsorbed because concentration in nephron > concentration in blood

Front 140

how are protein-bound drugs eliminated by the kidney?

Back 140

by active tubular secretion

Front 141

what two things most commonly reduce renal passive reabsorption? how does this affect elimination rate of the drug?

Back 141

1. disease (accidental)
2. therapy (intentional)
- increases the elimination rate of the drug

Front 142

when does reducing the passive reabsorption of a drug not work?

Back 142

- if reabsorption is not an important part of renal elimination

Front 143

by what two ways can renal passive reabsorption be reduced therapeutically?

Back 143

1. high urine production (less contact time with epithelium for drug to be reabsorbed)
2. urine pH (ionized drug will not be reabsorbed)

Front 144

what ratio does the volume of distribution, Vz represent at any given time? How is it determined experimentally?

Back 144

Vz = amount of drug in the body / plasma concentration

experimentally:
Vz = dose/Cp0, where Cp0 is the y-intercept of a plot of log(plasma conc) versus time

Front 145

normally, how much of blood volume is comprised of plasma water?

Back 145

55%

Front 146

if clearance was 100% efficient, what would determine clearance rate?

Back 146

blood flow

Front 147

how is organ clearance calculated?

Back 147

Clearance = Q x E

where Q is blood flow to the organ and E is efficiency of extraction

Front 148

what are the three major components of total body clearance?

Back 148

Cl_total = Cl_hepatic + Cl_renal + Cl_pulmonary

Front 149

how is clearance measured experimentally?

Back 149

Clearance = Vz x λz

where λz is the SLOPE of a plot of ln(drug plasma concentration) versus time

Front 150

after how many half-lives has a drug been "effectively eliminated?" what percentage of drug is this?

Back 150

5 half-lives, 97%

Front 151

what is a loading dose?

Back 151

an initial high dose of a drug given to shorten the time to reach steady-state concentrations

Front 152

what is the absorption rate constant? How is this number applied clinically?

Back 152

- ka describes the rate of drug movement to the site of administration to the circulatory system
- ka will determine the time required to reach a peak concentration of the drug

Front 153

what is bioavailability?

Back 153

the fraction of the dose of a drug that gets into the bloodstream

Front 154

what are two major factors that affect bioequivalence between two drugs or dose forms?

Back 154

1. bioavailability
2. rate of absorption

Front 155

miosis:
- branch of ANS?
- receptors?

Back 155

(pupil constrition)
- parasympathetic
- M3, M2

Front 156

visual accommodation:
- branch of ANS?
- receptors?

Back 156

- parasympathetic
- M3, M2

Front 157

lacrimation:
- branch of ANS?
- receptors?

Back 157

- parasympathetic
- M3, M2

Front 158

pharyngeal mucus secretion:
- branch of ANS?
- receptors?

Back 158

- parasympathetic
- M3, M2

Front 159

salivation:
- branch of ANS?
- receptors?

Back 159

- parasympathetic and sympathetic
- M3, M2, α1

Front 160

bronchoconstriction:
- branch of ANS?
- receptors?

Back 160

- parasympathetic
- M3 = M2

Front 161

pulmonary mucus secretion:
- branch of ANS?
- receptors?

Back 161

- parasympathetic
- M3, M2

Front 162

lower heart rate:
- branch of ANS?
- receptors?

Back 162

- parasympathetic
- M2

Front 163

↓ atrioventricular conduction:
- branch of ANS?
- receptors?

Back 163

- parasympathetic
- M2

Front 164

higher gastric acid secretion:
- branch of ANS?
- receptors?

Back 164

- parasympathetic
- M3, M2

Front 165

increased GI motility:
- branch of ANS?
- receptors?

Back 165

- parasympathetic
- M3, M2

Front 166

micturition:
- branch of ANS?
- receptors?

Back 166

- parasympathetic
- M3

Front 167

erection (male):
- branch of ANS?
- receptors?

Back 167

- parasympathetic
- M3

Front 168

mydriasis:
- branch of ANS?
- receptors?

Back 168

(pupil dilation)
- sympathetic
- α1

Front 169

vasoconstriction:
- branch of ANS?
- receptors?

Back 169

- sympathetic
- α1

Front 170

sweating:
- branch of ANS?
- receptors?

Back 170

- sympathetic
- M3, M2

Front 171

bronchodilation:
- branch of ANS?
- receptors?

Back 171

- sympathetic
- β2

Front 172

increased heart rate:
- branch of ANS?
- receptors?

Back 172

- sympathetic
- β1

Front 173

increased atrioventricular conduction:
- branch of ANS?
- receptors?

Back 173

- sympathetic
- β1

Front 174

increased heart contractility:
- branch of ANS?
- receptors?

Back 174

- sympathetic
- β1

Front 175

decreased GI motility:
- branch of ANS?
- receptors?

Back 175

- sympathetic
- α and β

Front 176

renin secretion:
- branch of the ANS?
- receptors?

Back 176

- sympathetic
- β1

Front 177

increased hepatic glycogenolysis:
- branch of ANS?
- receptors?

Back 177

- sympathetic
- β2

Front 178

uterine relaxation:
- branch of ANS?
- receptors?

Back 178

- sympathetic
- β1

Front 179

urinary retention:
- branch of ANS?
- receptors?

Back 179

- sympathetic
- α1

Front 180

ejaculation:
- branch of ANS?
- receptors?

Back 180

- sympathetic
- α1

Front 181

for the parasympathetic and sympathetic branches of the ANS
- what is the preganglionic receptor?
- length of preganglionic fiber
- length of postganglionic fiber

Back 181

PARASYMPATHETIC
- nicotinic preganglionic receptor
- long preganglionic fiber
- short postganglionic fiber
SYMPATHETIC
- nicotinic preganglionic receptor
- short preganaglionic fiber
- long postganglionic fiber

Front 182

what are the postganglionic receptors for
- parasympathetic?
- sympathetic?
- somatic?

Back 182

- parasympathetic: muscarinic
- sympathetic: α and β
- somatic: nicotinic (there is no ganglion)

Front 183

what are the primary neurotransmitters that are agonists for the following receptors:
- nicotinic?
- muscarinic?
- α and β?

Back 183

- nicotinic: acetylcholine
- muscarinic: acetylcholine
- α and β: norepinephrine (α), epinephrine (α and β)

Front 184

which nerve endings are the primary targets of drugs?

Back 184

post-ganglionic

Front 185

what differentiates the different autonomic nervous system receptor sub-types?

Back 185

the type of second-messenger

Front 186

which enzyme
- produces acetylcholine in the neuron?
- breaks down acetylcholine in the synapse?

Back 186

- choline acetyltransferase produces acetylcholine
- acetylcholinesterase breaks down AcCh in the synapse

Front 187

which enzymes are involved in the breakdown of norepinephrine, epinephrine, and dopamine in the synapse?

Back 187

- monoamine oxidase (MAO)
- catecholamine O-methyltransferase (COMT)

Front 188

which enzyme is required to synthesize epinephrine from norepinephrine?

Back 188

N-methyltransferase

Front 189

what is the basic synthetic pathway from amino acid to epinephrine?

Back 189

tyrosine --> DOPA --> dopamine --> norepinephrine --> epinephrine

Front 190

what are major target organs for:
- α1
- α2
- β1
- β2
- dopamine

Back 190

- α1: blood vessels, eye, uterus, urinary sphincter, CNS
- α2: CNS
- β1: heart
- β2: bronchi, muscle blood vessels, pancreas, bladder wall, uterus, liver
- dopamine: CNS, kidney, vasculature

Front 191

what is the meaning of the suffixes "mimetic" and "lytic"?

Back 191

- mimetic = agonist
- lytic = antagonist

Front 192

what are the effects of the SNS and PNS on the eye?

Back 192

- SNS dilates (α1)
- PNS constricts

Front 193

what are the effects of the SNS and PNS on the heart?

Back 193

- SNS increases hr (β1)
- PNS decreases hr

Front 194

what are the effects of the SNS on blood vessels?

Back 194

- α1 constricts blood vessels and raises bp
- β2 increases blood flow to skeletal muscles

Front 195

what are the effects of the SNS on the bronchi?

Back 195

- β2 dilates bronchi

Front 196

what are the effects of the PNS on the GI tract and urination

Back 196

- PNS increases peristalsis and urination

Front 197

what are the effects of the PNS on exocrine glands?

Back 197

- PNS increases secretions

Front 198

how do endogenous substances of the autonomic nervous system tend to differ from synthetics?

Back 198

endogenous substances tend to be more potent and shorter acting

Front 199

what is the chemical structure of direct acting sympathomimetics?

Back 199

phenylethylamines

Front 200

if a sympathomimetic is modified at the alkyl group, how is it affected?

Back 200

kinetics change; e.g. the drug lasts longer

Front 201

if the nitrogen group on a sympathomimetic is modified, how does affect its action?

Back 201

- affects pharmacodynamics
- preference of β over α receptors

Front 202

if the substitution on the aromatic ring of a sympathomimetic is changed, how does that affect its action?

Back 202

- dynamics and kinetics
- β > α
- affects duration of action

Front 203

how does removing a hydroxyl group from a catechol based sympathomimetic affect its activity?

Back 203

- increases stability because COMT enzyme no longer works on this substrate
- increases its α activity

Front 204

how does substituting an OH group on the aliphatic carbons of a sympathomimetic affect its activity?

Back 204

makes it more polar

Front 205

how does substituting a methyl group on the aliphatic carbons of a sympathomimetic affect its activity?

Back 205

increases stability because MAO will not work on this substrate

Front 206

how does substitution of a methyl or larger group onto a sympathomimetic affect its activity?

Back 206

increases its β activity

Front 207

how does rearranging and/or substituting the OH groups on a sympathomimetic affect its activity?

Back 207

makes it more β2 selective

Front 208

what is the receptor selectivity of the following catecholamines:
- norepinephrine?
- epinephrine?
- isoproterenol?

Back 208

- norepinepherine: α
- epinepherine: α and β
- isoproterenol: β

Front 209

how are sympathomimetics used to affect the cardiovascular system?

Back 209

- α1 drugs: decrease hemorrhage; nasal decongestant; localize drugs; increase BP; shock treatment
- α2 drugs: lower BP
- β1 drugs: raise HR and contractility

Front 210

how are sympathomimetics used to affect the respiratory system?

Back 210

β2 drugs are bronchodilators

Front 211

how are sympathomimetics used to affect the eyes?

Back 211

α1 drugs are mydriatics

Front 212

how are sympathomimetics used to affect the urethra and uterus?

Back 212

α1 drugs cause smooth muscle contraction

Front 213

how are sympathomimetics used to affect the CNS?

Back 213

- α1 and dopaminergic drugs are stimulants
- α2 drugs are tranquilizers and analgesics

Front 214

what is tachyphylaxis?

Back 214

diminished response to a drug as repeated doses are given

Front 215

what are four general side-effects/toxic effects of sympathomimetics

Back 215

1. action at non-selective sites (e.g. β2 pancreas receptors)
2. overstimulation (especially heart, BP, CNS; notable for α1 drugs)
3. tolerance and/or tachyphylaxis
4. drug interactions (e.g. arrhythmias with anesthetics)

Front 216

α1 drugs:
- examples
- indications
- side effects

Back 216

- epinephrine (more β than α), norepinephrine (more α than β)
- vasoconstrictors, mydriatics, increase smooth muscle tone (e.g. bladder, uterus)

Front 217

α2 drugs:
- examples
- indications
- action
- side-effects

Back 217

- xylazine, (detomidine, dexmedetomidine) - tranquilizers; (clondine) - antihypertensive (amitraz) - insecticide
- CNS effects: tranquilization, lower BP, analgesia
- decreases presynaptic outflow

Front 218

β receptor agonists:
- examples
- indications

Back 218

- isoproterenol (β2 bronchodilator; β1 cardiostimulatory effects)
- epinephrine (same effects, but also affects α)

Front 219

what are the five types of sympathomimetics that act by indirect mechanisms?

Back 219

1. phosphodiesterase inhibitors - especially methylxanthines (THEOPHYLLINE, caffeine, theobromine)
2. MAO inhibitors
3. monoamine reuptake inhibitors
4. CNS stimulants that increase the effects of norepinephrine or dopamine (e.g. amphetamine or methylphenidate)
5. COMT (catechol-O-methyltransferase) inhibitors

Front 220

what is the basic reaction pathway of glucuronidation?

Back 220

UDP-glucose --> UDP-glucuronic acid --(drug + transferase) --> drug conjugate

Front 221

which drug conjugate is especially labile to intestinal flora?

Back 221

glucuronic acid conjugates

Front 222

why can certain substances such as acetaminophen, furosemide (Lasix), and bromobenzene, which undergo mercapturic acid conjugation, cause toxicities

Back 222

because in high doses, the mercapturic acid pathway becomes saturated

Front 223

in which type of conjugation is the moiety directly added to the drug?

Back 223

acetylation

Front 224

name three types of reductions

Back 224

1. azo reaction
2. nitro reaction
3. alcohol reaction

Front 225

what specifically is the reason for species differences in the ability to oxidize drugs?

Back 225

the quantity and quality of the various Cytochrome P450 (CYP) enzymes

Front 226

are Cytrochrome P450 enzymes required for all oxidation biotransformations? Why?

Back 226

no, because CYP enzymes are only in the microsomes. Some oxidation can occur outside of the microsomes

Front 227

what biochemicals must be present for microsomal drug oxidation?

Back 227

NADPH, oxygen, Mg2+, flavoprotein, Cytrochrome P450

Front 228

what is necessary for microsomal enzyme induction?

Back 228

exposure to a chemical that increases protein synthesis, especially CYP450

Front 229

what are the two major concerns arising as a result of enzyme induction?

Back 229

1. drug tolerance
2. drug interactions

Front 230

in which organelle is monoamine oxidase found?

Back 230

mitochondria

Front 231

list four areas outside the microsomes where drug metabolism can occur?

Back 231

1. cytosol
2. blood
3. microflora
4. mitochondria

Front 232

what are the three body compartments and their constituents?

Back 232

1. central compartment - blood volume and organs of elimination
2. peripheral compartment - muscle, SQ, lung
3. deep compartment - fat, kidneys

Front 233

how is elimination rate constant calculated?

Back 233

λz = Clearance Time / Vz

Front 234

what are four major uses of sympatholytics? Three common side-effects?

Back 234

USES
1. lower BP
2. lower ocular pressure
3. depress CNS function
4. lower HR
SIDE-EFFECTS
1. increased peristalsis
2. decreased ejaculation
3. increased sodium retention

Front 235

what is one major use for
- α1 blockade?
- α2 blockade?

Back 235

- α1 blockade: lower blood pressure
- α2 blockade: antidotes to α2 agonists

Front 236

what are three examples of uses of direct β antagonists?

Back 236

1. arrhythmias
2. lower heart rate and cardiac output
3. lower ocular pressure (topical)

Front 237

why should you not suddenly take a patient off of a β-antagonist that has been using the drug PO for a long time?

Back 237

can cause cardiac arrhythmias and heart failure

Front 238

what are two common side-effects of direct β antagonists

Back 238

1. arrhythmia
2. increased airway resistance

Front 239

why don't we use selective β2 blockers?

Back 239

becuase they would cause severe side effects such as bronchoconstriction

Front 240

give an example of a non-selective β blocker and its effects

Back 240

propanolol
- lowers HR (competitive antagonist for β1 at heart)
- bronchoconstriction (competitive antagonist for β2 in bronchioles)

Front 241

what are the three general mechanisms of action of indirect-acting sympatholytics?

Back 241

1. antidopaminergic
2. reduces NE by synaptic action
3. decrease sympathetic outflow

Front 242

an AGONIST of which receptor will cause indirect-acting sympathoLYTIC properties? What is a common drug that does this?

Back 242

- α2 receptor
- xylazine

Front 243

what are two examples of antidopaminergic indirect-acting sympatholytics

Back 243

acepromazine and metoclopramide

Front 244

what are the two main uses for antidopaminergic indirect-acting sympatholytics?

Back 244

1. tranquilizer
2. antiemetics (DA causes emesis)

Front 245

how do indirect-acting sympatholytics decrease available NE at the synapse? what are some of their therapeutic uses? what is a common side-effect?

Back 245

- they are Calcium channel blockers (Ca influx into the neuron is required to release NE)

TREATS
- cardiovascular hypertrophy
- arrhythmias
- hypertension
SIDE-EFFECT: microsomial enzyme induction

Front 246

what are four common uses for α2-agonists?

Back 246

1. tranquilizers
2. antihypertensives
3. analgesics
4. emetics

Front 247

examples of direct-acting parasympathomimetics?

Back 247

1. acetylcholine
2. metoclopramide
3. pilocarpine

Front 248

what are seven uses for parasympathomimetics

Back 248

1. miotics
2. glaucoma
3. smooth muscle atony
4. urine retention
5. neuromuscular disease
6. anthelmintics and insecticides
7. antidotes

Front 249

what are five contraindications for parasympathomimetics?

Back 249

1. low heart rate
2. hypotension
3. asthma
4. hyperthyroidism
5. ulcers

Front 250

what are the two binding sites of the acetylcholinesterase enzyme? what binds to each of these components?

Back 250

1. anionic site - binds to quarternary ammonium ions
2. esteratic site - binds to esters and amides

Front 251

what are the two common types of direct acting parasympathomimetics?

Back 251

1. ester and amide acetylcholine-like structures
2. plant alkaloids

Front 252

what is one example of a synthetic acetylcholine-like drug

Back 252

metoclopramide

Front 253

what is an example of a plant alkaolid that acts as a direct acting parasympathomimetnic?

Back 253

pilocarpine

Front 254

what is the major advantage of using a direct versus an indirect parasympathomimetic?

Back 254

fewer side-effects

Front 255

what is the mechanism of an indirect parasympathomimetic?

Back 255

cholinesterase inhibitor

Front 256

what are the two types of cholinesterase enzymes and where are they located?

Back 256

- true: neural tissue, RBC
- pseudo: plasma, liver

Front 257

which type of cholinesterase enzyme do indirect parasympathomimetics target?

Back 257

"true" cholinesterase enzymes in neural tissue

Front 258

how does cholinesterase inhibition cause a parasympathomimetic effect? is this a reversible or irreversible process? what is a specific example of a cholinesterase inhibitor?

Back 258

- it increases the amount of AcCh in the synapse
- reversible
- neostigmine

Front 259

what are short acting indirect cholinesterase inhibitors used for?

Back 259

1. diagnostics
2. antidote for NM blocking agents (recovery from anesthesia)

Front 260

what five examples of what long acting indirect cholinesterase inhibitors may used for?

Back 260

1. neuromuscular diseases
2. miotics (glaucoma treatment)
3. myasthenia gravis
4. insecticides, antiprotozoal
5. Alzheimer's in people

Front 261

what are the two chemical classes of cholinesterase inhibitors?

Back 261

1. quarternary ammonium salts
2. carbamates

Front 262

what is the only indication for therapeutic use of an irreversible cholinesterase inhibitor? where on cholinesterase do they bind? what type of drugs are they? what other non-therapeutic uses do this type of drug they have?

Back 262

- glaucoma meds (miotics)
- they are organophosphates
- they bind to the esteratic site of cholinesterase
- also used as anthelminthics, antiprotozoals, insecticides

Front 263

why are antidopaminergic compounds classified as indirect-acting sympatholytics?

Back 263

because dopamine is the precursor to norepinephrine

Front 264

what is the general chemistry profile of a parasympatholytic?

Back 264

quarternary or tertiary amines, polar (many are esters), affinity for peripheral muscarinic sites, don't cross BBB well

Front 265

name two examples of direct-acting parasympatholytics

Back 265

1. atropine
2. acepromazine

Front 266

name seven uses of parasympatholytics

Back 266

1. cardiovascular: increase heart rate and cardiac output
2. lowers GI peristalsis
3. decrease exocrine secretions
4. mydriatics
5. decrease respiratory secretions; mild bronchodilation
6. CNS: motion sickness, antitremornergic, sedative, tricyclic antidepressants
7. antidotes, especially to carbamate and organophosphate poisoning

Front 267

what is the common reason why a parasympatholytic has side-effects?

Back 267

overdose

Front 268

what are three common types of parasympatholytics?

Back 268

1. Belladonna alkaloids (atropine)
2. Synthetics
3. Non-selective compounds (acepromazine)

Front 269

what two sites in the body are the most common targets for agents acting at nicotinic sites?

Back 269

1. autonomic ganglia
2. neuromuscular junction

Front 270

what are the two classes of drugs that cause blockade at nicotinic receptors and what is their mechanism of action?

Back 270

1. nondepolarizing blockade - surmountable antagonism
2. depolarizing blockade - stimulation, then block of receptor

Front 271

what is an example of a non-specific nicotinic stimulator?

Back 271

acetylcholine

Front 272

in what circumstances would a direct ganglionic blocking agent be used?

Back 272

- lower BP in emergencies or surgery
- paralyze muscles in surgery

Front 273

heart rate:
- primary tone
- effects of stimulation
- effects of ganglionic blockade

Back 273

- primary tone: PNS
- effects of stimulation: bradycardia
- effects of ganglionic blockade: tachycardia, arrhythmias

Front 274

blood pressure:
- primary tone
- effects of stimulation
- effects of ganglionic blockade

Back 274

- primary tone: SNS (α1)
- effects of stimulation: increased BP
- effects of ganglionic blockade: vasodilation, venous pooling, decreased venous return, decreased cardiac output, **orthostatic hypotension (hypotension when standing up)

Front 275

bronchial smooth muscle:
- primary tone
- effects of stimulation
- effects of ganglionic blockade

Back 275

- primary tone: SNS (β2)
- effects of stimulation: relaxation
- effects of ganglionic blockade: bronchoconstriction

Front 276

urinary bladder:
- primary tone
- effects of stimulation
- effects of ganglionic blockade

Back 276

- primary tone: PNS
- effects of stimulation: micturition
- effects of ganglionic blockade: urine retention

Front 277

eye
- primary tone
- effects of stimulation
- effects of ganglionic blockade

Back 277

- primary tone: PNS
- effects of ganglionic stimulation: miosis
- effects of blockade: mydriasis and cycloplegia (paralysis of the ciliary muscle of the eye)

Front 278

salivary glands:
- primary tone
- effects of stimulation
- effects of ganglionic blockade

Back 278

- primary tone: PNS
- effects of stimulation: secretions
- effects of ganglionic blockade: reduced secretion, dry mouth

Front 279

what is the mechanism of neuromuscular blocking agents? what are they used for? what is a major adverse effect of overdose? what is an example of a drug?

Back 279

- they block the pseudocholinesterases in the NM junctions
- they increase muscle relaxation, especially at surgery
- overdose can lead to respiratory muscles being paralyzed (without loss of consciousness)
- neostigmine

Front 280

what are the four classes of CNS neurotransmitters of clinical importance and the specific natural neurotransmitters that are classified under these types?

Back 280

1. ester: acetylcholine
2. monoamines: NE, DA, serotonin (5-HT)
3. amino acids: GABA, Glutamate
4. Neuropeptides: enkephalins (natural opoids)

Front 281

CNS acetylcholine:
- putative role
- receptors
- degradative pathway(s)

Back 281

- putative role: cognition, neural development
- receptors: muscarinic, nicotinic, other
- degradative pathway(s): acetylcholinesterase

Front 282

CNS norepinephrine:
- putative role
- receptors
- degradative pathway(s)

Back 282

- putative role: multipurpose
- receptors: α2 for tranquilization, stimulatory CNS receptors
- degradative pathway(s): reuptake, MAO, COMT

Front 283

CNS dopamine:
- putative role
- receptors
- degradative pathway(s)

Back 283

- putative role: multi-purpose (mustly stimulatory)
- receptors: D1, D1, D3, D4, D5
- degradative pathway(s): reuptake, MAO, COMT

Front 284

CNS serotonin:
- putative role
- receptors
- degradative pathway(s)

Back 284

- putative role: behavior
- receptors: 5-HT1, 5-HT2, etc.
- degradative pathway(s): reuptake, MAO; (note no COMT because serotonin has only one hydroxyl group)

Front 285

CNS GABA:
- putative role
- receptors

Back 285

- putative role: inhibitory NT
- receptors: GABA-A, GABA-B

Front 286

CNS glutamate:
- putative role
- receptors

Back 286

- putative role: excitatory NT
- receptors: NMDA, many others

Front 287

CNS enkephalins:
- putative role
- receptors

Back 287

- putative role: pain perception and pain tolerance
- receptors: mu, kappa, delta opoid receptors

Front 288

what are the five main uses for CNS drugs in veterinary medicine?

Back 288

1. tranquilizers (neuroleptics, anxiolytics, sedatives)
2. anticonvulsants
3. stimulants (antidepressants)
4. opoid analgesics
5. general anesthetics

Front 289

what are the three most commonly used types of therapeutic GABA agonists?

Back 289

1. benzodiazepine tranquilizers (diazepam)
2. barbiturates (thiopental, pentobarbital, phenobarbital)
3. general anesthetics

Front 290

why can GABA-A agonists have an additive or synergistic effect?

Back 290

because they bind to different sites on the GABA-A receptor

Front 291

benzodiazepines:
- mechanism of action
- example of a generic
- uses
- analgesic potency
- advantages with respect to drug interaction
- legal classifications

Back 291

- GABA agonist
- diazepam (Valium)
- tranquilizer, chemical restraint, anxiolytic, muscle relaxer, anticonvulsant
- no analgesic effect
- does not affect respiration, so it is good to use with general anesthesia
- C-IV drug

Front 292

barbiturates:
- mechanism of action
- examples of generics
- uses
- legal classifications

Back 292

- mechanism of action: GABA agonist
- examples of generics: thiopental, pentobarbital, phenobarbital
- uses: CNS, respiratory, and CV depressants; sedative-hypnotic-anesthetics; euthanasia; anticonvulsant
- legal classifications: C-II - C-IV

Front 293

of the three common barbiturates that we are learning about, classify them according to duration of action and their most common usage in veterinary medicine

Back 293

- thiopental: short-acting; anesthesia
- pentobarbital: medium-acting; euthanasia
- phenobarbital: long-acting; anticonvulsant

Front 294

what are the two main mechanisms of action for the lipophilic general anesthetics such as isoflurane, propofol, etc?

Back 294

- GABA agonists
- solvent-like to cell membranes, so they slow down cell function as a result

Front 295

for barbiturates, what are the four dose-dependent effects?

Back 295

sedation --> hypnosis --> anesthesia --> euthanasia

Front 296

what are the major pharmacokinetic differences between inhalant and IV general anesthetics?

Back 296

- inhalant: quick onset, quick recovery
- IV: needs to redistribute (longer onset), longer recovery

Front 297

comment on antagonists/antidotes for the main classes of GABA agonists.

Back 297

only the benzodiazepines have an antagoinst; barbiturates and general anesthetics do not

Front 298

what are the three major uses for CNS GABA receptor inhibitors. Why aren't they more commonly used?

Back 298

1. benzodiazepine antidote
2. pesticides
3. analeptics

- they tend to cause convulsions, which is kind of a bad thing for a drug to do

Front 299

comment on the usage of CNS glutamate agonists

Back 299

they are not used because they cause convulsions, which have a tendency to make pet owners upset

Front 300

give an example of a CNS glutamate antagonist and its uses and side-effects

Back 300

ketamine
- dissociative anesthetic: catalepsy (immobilization), no respiratory side-effects
- causes amnesia and hallucinations (but animal can't move to "freak out" at hallucinations)
- restricted C-III due to it being a date rape drug

Front 301

name the main CNS opioid receptors and the receptor function

Back 301

- Mu (μ) - supraspinal analgesia, respiratory depression, euphoria, physical dependence
- Kappa (κ) - receptor for spinal analgesia, sedation, and miosis
Delta (δ) - unknown

Front 302

what binding must an opioid have to be considered a full agonist? partial agonist?

Back 302

full agonist: both μ and κ
partial agonist: either μ or κ

Front 303

what are two examples of drugs that are full CNS opioid agonists?

Back 303

morphine, codeine

Front 304

what is an example of a drug that is a partial CNS opioid agonist?

Back 304

butorphanol

Front 305

what are six therapeutic uses for CNS opioid agonists? side-effects?

Back 305

1. antitussive (codeine)
2. analgesic (morphine, codeine)
3. antidotes for opioid poisoning
4. emetics
5. sedation
6. miosis
side effects: respiratory depression, GI effects, euphoria, psychological dependence

Front 306

what are the three main monoamine neurotransmitters in the CNS?

Back 306

norepinephrine, dopamine, serotinin (5-hydroxytryptophan)

Front 307

in general what three things are CNS MAO inhibitors used for in dogs?

Back 307

1. behavioral modification (e.g. separation anxiety)
2. cognitive dysfunction
3. hyperadrenocorticism

Front 308

what are the three types of drugs used in the CNS that have non-specific actions on monoamines?

Back 308

1. MAO inhibitors
2. monoamine reuptake inhibitors
3. COMT inhibitors

Front 309

what type of drug is a tricyclic antidepressant? what are they indicated for in dogs? what are side-effects? In general, why do some of these side-effects occur?

Back 309

- monoamine reuptake inhibitor (SSRI)
- used for separation anxiety
- side-effects include confusion, twitching, and others
- side-effects occur because of non-specific action at other CNS sites and also SSRIs have cholinergic side-effects

Front 310

in the CNS, what effects are seen with
- α1 agonists?
- α2 agonists?

Back 310

- α1 agonists: stimulatory effects
- α2 agonists: tranquilizing; analgesic

Front 311

what are MAO-B selective inhibitors indicated for in humans? dogs?

Back 311

humans: Parkinson's
dogs: cognitive dysfunction; hyperadrenocorticism

Front 312

which of the main CNS monoamine neurotransmitters will be affected by COMT inhibitors? unaffected? what are these drugs indicated for in humans?

Back 312

- affected: norepinephrine and dopamine (they are catacholamines)
- not affected: serotonin (not a catechol)
- indicated for treatment of Parkinson's

Front 313

what is an example of a CNS specific adrenergic drug? What are its pharmacodynamics? What are its indications?

Back 313

- xylazine
- agonist of pre-synaptic α2 receptors, which blocks the release of norepinephrine
- indications: tranquilizer, analgesia, emesis

Front 314

what type of drug would be used as a xylazine antidote

Back 314

α2 blocker (e.g. yohimbine) because xylazine is an α2 agonist

Front 315

why would IV dopamine administration have very limited affect in the CNS?

Back 315

because it is too polar to cross the BBB

Front 316

what are two effects of agonists of the CNS dopamine receptors D1 and D2?

Back 316

1. emesis
2. lower prolactin secretion

Front 317

what are two examples of dopamine antagonists that have antiemetic properties? which have tranquilizing effects and which do not?

Back 317

1. acepromazine - tranquilizer
2. metoclopramide - not a tranquilizer

Front 318

phenothiazine tranquilizers are what type of drug? what is an example of one? besides tranquilizing, what other effects does this drug have? side-effects?

Back 318

- dopamine receptor blocker
- acepromazine
- antiemetic, antihistamine, antiadrenergic, anticholinergic
- seizures, Parkinson-like disorders with long-term use

Front 319

why are *specific* CNS serotonin drugs necessary to be useful pharmaceuticals?

Back 319

because there are so many receptors with widespread action that many side-effects would occur

Front 320

what is the most common use for a specific serotonin agonist?

Back 320

antianxiety

Front 321

what are the three common serotinergic drug types?

Back 321

1. direct agonists
2. specific serotonin reuptake inhibitors (SSRI)
3. 5-HT receptor blockers

Front 322

in what ways are specific serotonin reuptake inhibitors (SSRIs) used in veterinary medicine?

Back 322

- behavior modification (e.g. "OCD" like behaviors in dogs, like tail chasing)
- anxiety
- dominance aggression

Front 323

for what purpose, in veterinary medicine, are 5-hydroxytryptamine (serotonin) receptor blockers used?

Back 323

- antiemetics, especially for chemotherapy patients

Front 324

what effect does acetylcholine stimulation of nicotinic and muscarinic receptors in the brain have?

Back 324

stimulatory effects

Front 325

why does neostigmine not commonly cause CNS side-effects?

Back 325

because it does not cross the BBB

Front 326

what are two uses of agents that block cholinergic receptors in the CNS?

Back 326

1. antiemetics (acepromazine)
2. anesthetics

Front 327

what is the second messenger at β receptors? what drug is a target for this system? how does it work? what are its uses

Back 327

- cAMP is the second messenger
- theophylline (a methylxanthate)
- it is a phosphodiseterase inhibitor, which inhibits the breakdown of cAMP, thus having β sympathomimetic effects
- used as a stimulant and smooth muscle relaxor (e.g. bronchi)

Front 328

acepromazine
- receptor action
- nervous system branches
- uses in veterinary medicine
- type of chemical
- side-effects

Back 328

acepromazine
- receptor action: dopamine antagonist; antimuscarinic
- nervous system branches: PNS
- uses: tranquilizer, antiemetic
- type of chemical: synthetic
- side-effects: seizures, tremors (long-term use)

Front 329

acetylcholine
- receptor action
- nervous system branches
- uses in veterinary medicine
- type of chemical
- side-effects

Back 329

acetylcholine
- receptor action: nicotinic agonist; muscarininic agonist
- nervous system branches: SNS, PNS, neuro-muscular junction, CNS
- uses: stimulation of SNS, PNS, CNS, NMJ
- type of chemical: amino-ester
- side-effects: lots of them

Front 330

atropine
- receptor action
- nervous system branches
- uses in veterinary medicine
- type of chemical
- side-effects

Back 330

atropine
- receptor action: antimuscarinic
- nervous system branches: PNS
- uses: increase HR and cardiac output, preanesthetic antisecretory
- type of chemical: alkaloid (Belladonna)
- side-effects: dry mouth, dry eye

Front 331

butorphanol
- receptor action
- nervous system branches
- uses in veterinary medicine
- type of chemical
- side-effects

Back 331

butorphanol
- receptor action: partial opioid agonist
- nervous system branches: CNS
- uses: emetic
- type of chemical: opioid
- side-effects: puking

Front 332

codeine
- receptor action
- nervous system branches
- uses in veterinary medicine
- type of chemical
- side-effects

Back 332

codeine
- receptor action: full opoid agonist
- nervous system branches: CNS
- uses: analgesic, antitussive
- type of chemical: opioid
- side-effects: respiratory depression, emesis, GI stasis

Front 333

diazepam
- receptor action
- nervous system branches
- uses in veterinary medicine
- type of chemical
- side-effects

Back 333

diazepam
- receptor action: GABA agonist
- nervous system branches: CNS
- uses: tranquilizer, anxiolytic, anticonvulsant, muscle relaxor
- type of chemical: benzodiazepine
- side-effects: generally safe

Front 334

epinephrine
- receptor action
- nervous system branches
- uses in veterinary medicine
- type of chemical
- side-effects

Back 334

epinephrine
- receptor action: α agonist; β agonist
- nervous system branches: SNS
- uses: increase HR and BP, bronchodilate
- type of chemical: catecholamine
- side-effects: tachycardia, arrhythmia, hypertension

Front 335

isoproterenol
- receptor action
- nervous system branches
- uses in veterinary medicine
- type of chemical
- side-effects

Back 335

isoproterenol
- receptor action: β agonist
- nervous system branches: SNS
- uses: increase HR, bronchodilate
- type of chemical: monoamine
- side-effects: tachycardia, arrhythmia

Front 336

ketamine
- receptor action
- nervous system branches
- uses in veterinary medicine
- type of chemical
- side-effects

Back 336

ketamine
- receptor action: glutamate receptor inhibitor
- nervous system branches: CNS
- uses: anesthetic, chemical restraint (catalepsy)
- type of chemical: dissociative anesthetic
- side-effects: amnesia, hallucinations

Front 337

metoclopramide
- receptor action
- nervous system branches
- uses in veterinary medicine
- type of chemical
- side-effects

Back 337

metoclopramide
- receptor action: dopamine antagonist; muscarinic agonist
- nervous system branches: PNS
- uses: antiemetic; GI stimulant (increases AcCh in GI tract)
- type of chemical: synthetic
- side-effects: none noted

Front 338

morphine
- receptor action
- nervous system branches
- uses in veterinary medicine
- type of chemical
- side-effects

Back 338

morphine
- receptor action: full opoid agonist
- nervous system branches: CNS
- uses: analgesic, antitussive
- type of chemical: opioid
- side-effects: respiratory depression, emesis, GI stasis

Front 339

neostigmine
- receptor action
- nervous system branches
- uses in veterinary medicine
- type of chemical
- side-effects

Back 339

neostigmine
- receptor action: cholinesterase inhibitor; non-depolarizing neuromuscular blocking agent
- nervous system branches: SNS, PNS, neuro-muscular junction
- uses: antidote to NM blockers
- type of chemical: carbamate neonicotinoid
- side-effects:overdose can lead to respiratory muscles being paralyzed (without loss of consciousness)

Front 340

norepinephrine
- receptor action
- nervous system branches
- uses in veterinary medicine
- type of chemical
- side-effects

Back 340

norepinephrine
- receptor action: α agonist
- nervous system branches: SNS
- uses: increase BP
- type of chemical: catecholamine
- side-effects: hypertension

Front 341

pentobarbital
- receptor action
- nervous system branches
- uses in veterinary medicine
- type of chemical
- side-effects

Back 341

pentobarbital
- receptor action: GABA agonist
- nervous system branches: CNS
- uses: euthanasia
- type of chemical: barbiturate
- side-effects: euthanasia

Front 342

phenobarbital
- receptor action
- nervous system branches
- uses in veterinary medicine
- type of chemical
- side-effects

Back 342

phenobarbital
- receptor action: GABA agonist
- nervous system branches: CNS
- uses: anticonvulsant
- type of chemical: barbiturate
- side-effects: sedation, respiratory depression, euthanasia

Front 343

pilocarpine
- receptor action
- nervous system branches
- uses in veterinary medicine
- type of chemical
- side-effects

Back 343

pilocarpine
- receptor action: muscarinic agonist
- nervous system branches: PNS
- uses: topical treatment of glaucoma
- type of chemical: alkaloid (plant)
- side-effects: none noted

Front 344

propanolol
- receptor action
- nervous system branches
- uses in veterinary medicine
- type of chemical
- side-effects

Back 344

propanolol
- receptor action: β blocker
- nervous system branches: SNS
- uses: slow heart rate, antiarrhythmetic, antihypertensive
- type of chemical: monoamine
- side-effects: heart failure (especially with sudden withdrawal or parenteral administration), bronchoconstriction

Front 345

theophylline
- receptor action
- nervous system branches
- uses in veterinary medicine
- type of chemical
- side-effects

Back 345

theophylline
- receptor action: phosphodiesterase inhibitor
- nervous system branches: SNS
- uses: increase BP, increase HR, bronchodilator, muscle relaxor (β2 action)
- type of chemical: methylxanthine
- side-effects: from OD

Front 346

thiopental
- receptor action
- nervous system branches
- uses in veterinary medicine
- type of chemical
- side-effects

Back 346

thiopental
- receptor action: GABA agonist
- nervous system branches: CNS
- uses: general anesthesia
- type of chemical: barbiturate
- side-effects: respiratory depression, euthanasia

Front 347

xylazine
- receptor action
- nervous system branches
- uses in veterinary medicine
- type of chemical
- side-effects

Back 347

xylazine
- receptor action: α2 agonist
- nervous system branches: SNS, CNS
- uses: tranquilizer, decrease BP, analgesic, antiarrhythmetic
- type of chemical: synthetic
- side-effects: emesis