EXAM I Flashcards
1
Q
T/F. Drugs that enter the GI system may interact with material in GIT, get into intestinal juice, be carried through the GI tract, interact with GI microbes, reach systemic circulation.
A
True
2
Q
T/F. Ionization depends on the pKa of the drug and the pH of the medium.
A
True
2
Q
What are the factors related to drug that affect drug absorption? What are the factor related to animals that affect drug absorption?
A
Drug: molecular size (small moves easily), disintegration and dissolution (lipid, powder, tab), lipid solubility, degree of ionization, concentration at absorptive site, route of administration
MUCOSAL IS THE FASTEST AND ORAL IS THE SLOWEST
Animals: blood flow (great absorption with greater blood flow), absorbing SA, CT, species, individual variation, fasted vs fed.
3
Q
How is drug response quantified? What are the seven factors involved in this?
A
Measured and will typically give a curve (sigmoidal curve, straight portion between 20%-80% > therapeutic range)
Efficacy, Potency, Effective Concentration 50%, Effective Dose 50%, Therapeutic index is the LD50:ED50, Onset of action, Duration of action
4
Q
What are the four common routes to undergo absorption to get from the site of administration to the bloodstream?
A
Enteral, Parenteral, Transdermal, and respiratory absorption
5
Q
What are the FOUR mechanisms of “Transport across cell membrane”?
A
Simple/passive diffusion, facilitated diffusion, active transport, pinocytosis
5
Q
T/F. Membranes are more permeable to ionized forms of drugs than non-ionized forms.
A
False. More permeable to non-ionized forms.
6
Q
What is NOT a characteristic of BBB?
A. Right junctions between capillary endothelial cells and glial cell (force drugs to cross cell membrane to enter).
B. CSF is produced once in lifetime.
C. Active transport (P-gp) is responsbile for drug efflux out of the CNS.
D. If a drug crosses BBB, it can cross placental barriers.
A
B. CSF is produced once in lifetime.
Constantly produced and drains out of venous circulation (diluting things that do come through)
6
Q
What is bioinactivation? What is bioactivation and what are the components?
A
Bioinactivation: not biologically active format
Bioactivation: can be inactive drug (prodrug) to active metabolite or active drug (parent drug) to active metabolite or nontoxic to toxic metabolites (lethal synthesis > oragnophosphate insecticide)
7
Q
What are the five factors related to animal species?
A
Anatomical, Physiological, Biochemical, Behavior, Pharmacodynamic, Ectotherms (cold-blodded animals) vs mammals
8
Q
Match the correct terms.
A. Summation B. Synergism C. Antagonism
- Additive effect: Drug A + Drug B > A+B
- Drug A + Drug B
- Additive effect: Drug A + Drug B = A+B
A
1 - B
2 -C
3 - A
9
Q
What are the two outcomes of metabolism?
A
Physiocochmecial properties and phamacological activity
9
Q
T/F. Large Vd indicates that the drug is not being distributed to all tissues of the body (drugs remain mostly in the plasma). Small Vd indicates that the drug is distributed somewhere or sequestered.
A
False.
Small Vd: stays in plasma
Large Vd: distributed to peripheral tissues/sequestered
11
Q
Which drug are collies sensitive to?
A
ivermectin
11
Q
Which of the following is NOT a characteristic of simple/passive diffusion?
A. Paracellular movement (intercellular aqueous channels; specialized intercellular junctions).
B. Transmembrane movement (diffusion through lipid membrane and aqueous protein channels; bulk flow due to osmotic or hydrostatic differences)
C. Movement with a concentration gradient (from high to low).
D. Lipid/water partition coefficient: relative solubility of a drug in lipis compared to water.
E. Diffusion coefficient: Carrier and channel mediated.
A
E. Diffusion coefficient: Carrier and channel mediated.
Diffusion coefficient: diffusional mobility of a partical molecule (molecular size, molecular conformation, degree of ionization).
12
Q
T/F. Ion trapping: weak acids are absorbed form an acidic environment and sequestered in an alkaline medium. Weak bases are absorbed from an alkaline environment and sequestered in an acid medium.
A
TRUE
13
Q
Why do you have to consider using a lower dose of lipophilic drugs in obese patients?
A
Redistribution into fat (stays longer in the system, therefore, overdose may occur)
13
Q
Which of the following is NOT a characteristic of active transport?
A. Carrier-mediated transport.
B. Saturable and movement against a concentration gradient.
C. Requires energy.
D. Primary active transport uses energy directly from ATP and consists of symporters and antiporters.
E. Secondary active transport uses stored energy (Na+ electrochemical gradient).
A
D. Primary active transport uses energy directly from ATP and consists of symporters and antiporters.
Uses energy directly from ATP BUT symporters and antiporters are Secondary Active Transport characteristics.
13
Q
What are the three ways to administer drugs for parenteral route?
A
IM, SC, IP
13
Q
Which of the following is INCORRECT about Effective Dose 50%?
A. Dose that produces a result (maximal effect) in 50% of the animals
B. in VIVO, observed effect
C. LD50 is the dose which kills 50% of animals (effect is death)
A
A. Dose that produces a result (maximal effect) in 50% of the animals
DESIRED EFFECT, not maximal effect!
14
Q
What is drug displacement?
A
Knocking off of from its binding site on albumin space (phenylbutazone and warfarin in horses)
15
Q
T/F. Proteins that are embedded on cell membrane will sink or float, depending on theri characteristics. Tachyphylaxis may happen due to proteins sinking, leaving with a few receptors to being to drugs.
A
True.
15
Q
T/F. Only the free drug is active and the normal dosing and disposition are predicted based on the expected degree of protein binding.
A
True
16
Q
What is NOT a correct statement about tubular reabosorption for excretion?
A. Involves proximal and distal convoluted tubules.
B. Active diffusion in distal tubules and time dependent of pinocytosis.
C. Reabsorption of lipid-soluble and non-ionized drugs.
D. Fluids and diuretics enhance drug renal excretion by reducing the time for reabsorption.
A
B. Active diffusion in distal tubules and time dependent of pinocytosis.
Passive diffusion in distal tubules and concentration dependent of pinocytosis
16
What is the difference between **side effects and adverse effects**?
**Side effects:** effects secondary to the one intended (good or bad)
**Adverse effects:** unintended and uninvited; failure to produce the expected clinical effect
18
Which drug are boxers sensitive to? What is the adverse effect of the drug?
**Phenothiazines**
Adverse cardiovascular effects.
18
Which of the following is NOT a characterstic of transdermal absorption?
A. Impermeable to aqueous solutions
B. Stratum corneum is the rate limiting barrier
C. available in "spots-on" and "pour on"
D. As temperature increases, drugs have a lower effect on the body
E. **Fentanyl formulation** does not use a patch
D. As temperature increases, drugs have a lower effect on the body
As temperature increases, drugs have a higher effect on the body
18
State percentage up to 5 half-lives. What does 5 half-life indicate?
1 half life: 50% gone
2 half life: 75% gone
3.3 half life: 90% gone
5 half life: 97% (**unlikely to have any more effect**)
19
What is **steady state concentration**? What is the difference between **interval dosing and loading dose**?
Plasma drug concentration at steady state (concentration has reached equilibrium); drug going in=drug going out.
**Interval dosing:** peak - highest concentration at each dose; trough - lowest concentration at each dose; measure levels of **therapeutic drug monitoring (TDM)**
**Loading dose:** single dose to get the plasma concentration to a certain level and start repeated dosing at maintenance rate.
20
Which of the statement is INCORRECT?
A. Oral cavity: sublingual absorption, bypasses portal vein.
B. Esophagus and agandular stomach: minimal absorption.
C. Glandular stomach: some absorption (Gastric emptying time determines rate of absorption)
D. Small intestine: primary site of absorption.
E. No drugs should be activated in colon to retain lower GI tract microflora.
E. No drugs should be activated in colon to retain lower GI tract microflora.
Some drugs cna be activated (antibiotics) so then drugs are not exposed to lower GI tract microflora.
20
T/F. High hepatice extraction rati with oral medication will work well in the body (high first pass metabolism).
False.
WILL NOT work well because drugs cannot get to where it needs to go (metabolized already in the liver)
22
What is an example of biochemical differences for species differences?
**Metabolic enzymes: cats**
Deficient in glucuronyl transferase, therefore, alter metabolism of drugs.
22
Which of the following is NOT a characteristic of **plasma protein binding**? (Choose 2)
A. Basic drugs bind primarily to albumin (alpha drug to other proteins)
B. Binding is generally reversible and a satruable process
C. Bound drug is generally inactive
D. Species differences can occur
E. May be a concentration depedent dose
F. disease may modify protein binding
G. The more highly protein bound a drug is, the less significant changes in protein binding
A. Basic drugs bind primarily to albumin (alpha drug to other proteins)
Acidic drugs bind to albumin; basic drugs to other proteins.
G. The more highly protein bound a drug is, the less significant changes in protein binding
the MORE significant minor changes
23
What are the main routes to excrete drugs? What are other routes?
**Renal (most) and hepatic**
Feces (bile, non-absorbed drugs given orally, plasma to GIT), Milk/Egg (weak basic drugs ion trapped in milk, drug residues, suckling animal effects), Expired air, sweat, saliva, hair/feathers
24
T/F. **Two compartment open model** has central compartment (plasma/blood) and peripheral compartment (other tissues).
True
25
What are the characteristics of **idiosyncratic drug reactions**? Give two examples.
**Unpredictable**, **Genetic, Uncommon, NOT** dependent on dose, **drug withdrawal,** caused by reactive drug metabolites
**Griseofulvin:** liver damage in cats (acute hepatitis)
**Methimazole:** facial itching in cats
26
What is **total renal excretion of a drug?**
**Filtration rate + secretion + reabsorption**
27
What is **drug disposition**? What are the FOUR processes that are involved in this?
Study of movement of drugs across biological membrane in the body from the time of absroption until elimination.
ADME (absorption, distribution, metabolism, excretion)
29
T/F. **Lidocaine**
Given perineurally induces antiarrhythmic. Given IV induces local anesthesia.
False.
Perineurally: local anesthesia
IV: antiarrhythmic
30
What is INCORRECT about drugs targeting for **enzymes** through **non-receptors**?
A. Drugs compete with the real substrate for binding to the enzyme (acetylcholinesterase inhibitors by binding to the active site of acetylcholinesterase)
B. Drugs act as false substrates that will lead to the formation of abnormal metabolites instead of active products.
C. Prodrugs where the drug nees to be metaolized to its active form.
D. None of the above.
D. None of the above.
31
Which of the following is CORRECT for older animals?
A. Increased metabolism and excretion
B. Increased cardiac output & hepatic blood flow
C. Increased lean body mass and decreased body fat.
D. Increased total body water.
E. Reduced plasma proteins
E. Reduced plasma proteins **related to kidney or liver disease**
Everything else is the opposite.
33
What is **glycoprotein efflux pump (p-gp)**? Which drug/species is this deficient in?
Drug transporter; removes drugs after being absorbed into specific cells or tissues.
**Ivermectin in Collies** (CNS toxicity): p-gp is deficient, therefore, cannot pump out drug.
34
What are the two phases of live metabolism of drugs?
Phase I: Nonsynthetic and Phase II: Synthetic
35
Which of the following is INCORRECT about **Effective Concentration 50%**?
A. The concentration at which a drug produces 50% of its maximal effect
B. Only applies in vivo preparations (we want to see the effect in animals)
C. Useful to compare the efficacy of different ligands (full agonists vs. partial agonists)
B. Only applies in vivo preparations (we want to see the effect in animals)
in VITRO (cannot get this kind of measurement in an animal!)
36
What is **bioequivalence?**
Different **formulation of the same drug** that are absrobed to a **similar extend and rate**
## Footnote
**Similar AUC, Cmax, Tmax**
37
What does it mean by **cumulation**? What is **dissolution**?
The rate of elimination is slower than the rate of absorption (digitalis, phenylbutazone, thiopental)
**Dissolution:** oral (absorbed in the body); IV (dissolving before giving it to the patient)
38
What is a **ligand**? What are the two outcomes of this?
**Ligand:** anything that binds to a recognition site (endogenous ligand); prevents other ligands to bind to that site.
**Agonist:** mimics the effect of the endogneous ligand.
**Antagonist (neutral agonist):** binds to the receptor but does nothing on its own (sits there and prevents anything else from binding, therefore, blocking the receptor).
39
What is **pharmacokinetics**? What is **pharmacodynamics**?
**Pharmacokinetics:** what the body does to the drug (mathematical models of quantitate the time course of drug disposition in man and animals).
**Pharmacodynamics:** What the drug does to the body (Effects of drugs and their mechanism of action in the body).
40
What is NOT a characteristic of topical usage?
A. Local use but can happen in number of places (can be systemic)
B. Minimal absorption into systemic circulation
C. Inflammation can increase the amount of drug absorbed
D. Steroids, antibiotics, chemoterapy are related to topical usage.
E. Do not need to worry about overdose since it is non-invasie.
E. Do not need to worry about overdose since it is non-invasie.
May overdose.
42
T/F. Gender, neuter/spay status, pregnancy can change drug disposition.
True
43
What is **Distribution**?
Transfer of drugs from the bloodstream to tissues around the body.
43
What is **total body clearance (CLB)**?
Volume of distribution of drug in the body cleared of the drug per unit of time (ml/min/kg)
43
T/F. Endogenous neurotransmitters bind to **more than one type receptor**. Same signal can cause different effects or have different affinity in different tissues/species. Ex: **adrenergic receptors** have different **subtypes**.
True
44
What is the difference between **onset of action (LATENT PERIOD) and duration of action**?
**Onset of action:** time required after drug administration for a **response to be observed.**
**Duration of action:** the **length of time** that a drug is effective (from onset of action until terminaiton of action).
45
T/F. **Penicillin** concentrations in the CNs are kept low by an active organic anion transporter.
True
46
Match the following.
A. Chemical antagonism B. Pharmacokinetic antagonism C. Physiologic antagonism
1. A drug alters ADME of another drug and reduces its effect.
2. Drugs have opposite effects that cancel each other out.
3. Two drug chemically inactivate each other.
1 - B
2 - C
3 - A
47
How do drugs affect **carrier proteins** through non-receptor mechanism?
Drugs may alter movement of molecules either **preventing re-uptake (serotonin)** to increase its level or **preventing output (hydrogen ions** pumped out of gastric parietal cells) to decrease its level.
48
Which of the following is NOT a characteristic of **Parental route?**
A. The barrier to absorption is generally less than oral and topical delivery
B. Invasive procedure so need to use aseptic technique
C. Generally SC absorption is faster than IM
D. Characteristics of the drug can alter absorption (insulin: some are slow/fast)
E. Local environment: increased inflammation increases drug absorption and fibrosis slows absorption.
C. Generally SC absorption is faster than IM
IM is faster than SC
(IV is the fastest)
49
What is **chemical** antagonism (give an example)? What is **physiolgical** antagonism? What is **pharmacokinetic** antagonism? What is **receptor** antagonism?
**Chemical:** drugs react chemically to inactivate each other (**tetracycline and Ca2+)**
**Physiological:** drugs work in different ways and have opposing effects (Cancel each other out)
**Pharmacokinetic:** one drug reduces the concentration of the other by interfering with ADME process (increasing duration of one drug).
**Receptor:** one drug binds to a receptor and prevents the other drug from having its normal activity at that receptor.
50
What is the difference amongst **full agonist, partial agonist, and reverse agonist**?
**Full agonist:** binds to the receptor to clicit a maxiamal response.
**Partial agonist:** bind to the receptor but not cause as much effect as a full agonist (lower efficacy: **ceiling effect**).
**Reverse agonist:** bind to the receptor and cause the opposite effect as the endogenous ligand would.
51
What are some **nonspecific drug effects of physical interactions**?
**Osmotic diuretics:** mannitol moves through the body, dragging water with them by osmosis.
**Antacids (direct neuralizers):** oral will interact with acid in GI tract (physiologic antagonism)
**Radioactive iodine:** Iodine is actively concentrated in the thyroid and the radiation will destroy all tissues within 2-3mm.
53
T/F. Calm animals may need lower doses of CNS depressants than aggressive or excited animals.
True.
54
What are the characteristics of hypersensitivity?
Act as **antigens or haptens,** **prior exposure, cross sensitivity, Type I hypersensitivity**
55
What are the factors that glomerular filtration depend on?
**GFR:** depends on BP, blood flow; passive process
**Molecular size:**
**Electric charge:** large, negative charged drugs repelled by cell membrane proteins
**Plasma protein binding:** unbound molecules filtered
57
What are the factors that are affecting **distribution**?
Physiochemical properties of drugs, concentration gradient between blood and tissue, ratio of blood flow to tissue mass, affinity of the drug for tissue constituents, blood flow, tissue barriers, and plasma protein binding, stereochemistry, changes in metabolism and excretion, redistribution.
58
What are the four factors related to the **drug?**
Route of administration, Timing of administration, Cumulation, Drug drug interactions
59
What is **Bioavailability (F)**?
The sense of kinetics of a drug (Tmax: time to get to the highest concentration and rate of absorption; Cmax: highest concentration)
Fraction of dose given which finds its way into the systemic circulation.
**Area under the plasma concentration-time curve (AUC)**
60
What is the difference between **Elimination half-life and Elimination Rate Constant?**
**Elimination half-life: time** required for drug concentration to **decrease by 50%** (predict time to steady state, adjust withdrawal times, determine best dosing interval)
**Elimination Rate Constant:** **Fraction/proportion** of the drug that would be eliminated **per unit time.**
60
What are the three factors involved in targeting for **non-receptors** (pharmacodynamics)?
Voltage gated ion channels, Enzymes, and carrier proteins
61
What is **excretion**?
Removal of the drug and metabolites out of the body.
62
T/F. **Zero order kinetics:** **Amount** of drug eliminated per unit time is fixed (**dependent on the concentration**). **First order kinetics:** **Proportion** of drug eliminated per unit time is fixed (**not dependent on the concentration**).
True.
63
What is the difference between **ionotropic receptors and metabotropic receptors**?
**Ionotropic receptors:** composed of several proteins embedded in the cell membrane, creating a pore/channel; change in shape to allow a large influx of ions; fast neurotransmitters (msec).
**Metabotropic receptors:** G-protein coupled receptors or 7TM receptors; extracellular signal to intracellular signal, activating G-protein second messenger; seretory and smooth muscle functions (sec).
65
T/F. Respiratory administration of a drug is usually used for upper respiratory tract.
False. lower respiratory tract.
66
What is an example of physiogical differences in species differences?
**Urinary pH: carnivores vs. herbivores**
Carnivores more acidic, therefore, alter elimination of some drug.
67
What is NOT a characteristic of Phase I (nonsynthetic)?
A. More reactive molecules then can conjugate with polar molecules in phase II (turning into hydrolytic substance)
B. May be toxic intermediates
C. Addition or loss of an electron \> free radical formation
D. Phase I will never undergo Phase II reactions
D. Phase I will never undergo Phase II reactions
May undergo phase II reactions
68
What is the difference between **up-regulation and down-regulation**?
**Up-regulation:** an increase in the number of receptors resulting in an increase in the effect of the drug.
**Down regulation:** decrease in number of receptors (reductiong in effect) - Internalization, lysosomes, recycle, sequester, degrade; **tolerance vs tachyphylaxis**
70
What is **enterohepatic recylcing**? What do you need to do in order to reduce this effect?
Drug \> systemic circulation \> bile \> SI \> bile (continuous intestinal absorption)
Drugs with a meal to stimulate bile secretion and associated miecelle formation.
72
Which drug do Australian Terriers not respond well to?
**Droperidol/fentanyl**
Exhibit little sedation; have salivation, tachycardia, muscle tremors and convulsion.
73
What is the difference between disintegration and dissolution?
**Disintegration:** physical dispersion of a solid dosage form (affected by excipients, compaction pressure, enteric coatings, capsules, homogeneity).
**Dissolution:** drug molescules enter the solution (affected by particle size, binding, local pH, buffers, boundary layers).
74
What is an example of pharmacodynamic difference for species differences?
**Sensitivity to certain drugs: cattle vs. horses**
Xylazine doses lower for cattle
75
Name FOUR characteristics of **facilitated diffusion.**
Movement with a **concentration gradient.**
**No energy required.**
**Carrier mediated:** may or may not be specific; saturable
**Channel mediated:** involves opening of ion channel proteins.
76
Which of the following is INCORRECT regarding young animals?
A. Increased metabolism and excretion of drugs
B. Increased permeability of BBB
C. Decreased plasma protein binding
D. Increased total body water
A. Increased metabolism and excretion of drugs
## Footnote
**Decreased!**
76
What are factors related to the patient regarding renal excretion? What are factors related to the drug regarding renal excretion?
**Patient:** age (
**Drug:** size, protein binding, dose, lipid solubility, pKa of drug
77
What is NOT a characteristic of **active tubular secretion** regarding excretion?
A. Involves proximal convoluted tubules and movement against electrochemical gradient
B. Ioninized molecules can be transported
C. Sensitive to protein binding
D. Saturability and inhibition
E. Primary active transport (Na+-K+ pump) and secondary active transport (Na+ electrochemical gradient) involved
C. Sensitive to protein binding
INSENSITIVE to protein binding (more bound drug will become unbound)
78
What is the difference between **microsomal and non-microsomal**?
**Microsomal:** SER; cytochrome P450 system; mixed function oxidase/mono-oxygenase system (non-specific enzymes)
**Nonmicrosomal:** Cytoplasm or mitochondria
79
T/F. **Liver disease** decreases drug metabolism. **Renal disease** decreases drug excretion. **Congestive heart failure** decreases drug metabolism & excretion.
False. **Congestive heart failure** decreases drug **distribution** & excretion.
80
What is **Non-competitive antagonism**?
A ligand that interacts somewhere other than the receptor but causes a change in the receptor that blocks its ability to bind to the normal ligand.
82
Which statement is INCORRECT (General)?
A. pKa = pH of the medium at which the dissolved drug is 50% ionized and 50% nonionized.
B. Most drugs are weak acids or weak bases (pKa= 3-11).
C. Acidic drugs ionize in acidic environments and basic drugs ionize in basic environments.
C. Acidic drugs ionize in acidic environments and basic drugs ionize in basic environments.
**Acidic** drugs ionize in **basic** and **basic** drugs ionize in **acidic**
84
T/F. Plasma drug concentration may depend in part upon its apparent volume of distribution.
True.
84
What is NOT a characteristic of Changes in drug **physicochemical properties?**
A. Most drugs are eliminated by the kidney (lipophilic drugs will not eliminated easily)
B. Drugs are usually converted to metabolites that are less water soluble, polar, ionized than parent drugs (facilitates drug excretion from the body).
C. Some polar drugs are eliminated unchanged (penicillin).
D. Metabolite: the product that the drug has undergone.
B. Drugs are usually converted to metabolites that are less water soluble, polar, ionized than parent drugs (facilitates drug excretion from the body).
MORE water soluble, poalr, ionized than parent drug \> facilitates excretion.
85
What is an example of anatomical difference for species differences?
**GI anatomy: Ruminants vs nonruminants**
Rumen capacity is HUGE, therfore, will affect distribution of drugs.
86
What is the difference between **efficacy and potency**?
**Efficacy:** the maximal effect a drug can have (e=1: full effect); a partial agonist may never be able to achieve full effect.
**Potency:** comparsion of the concentration of two drugs needed to induce the same manitude effect; a partial agnoist could be more potent.
88
What is the difference between **rate and extent**? What are the components of **elimination**? What is **dosage regimen**?
**Rate:** how FAST the mass (dose) of a drug changes per unit time.
**Extent:** how MUCH the mass (dose) of a drug changes in total.
**Elimination: Metabolism + Excretion**
**Dosage regimen:** dosage and route of administration, frequency of administration, duration of administration.
89
T/F. A high therapeutic index indicates a safe drug (LD50 to ED50). A narrow or low therapeutic index indicates a more dangerous drug.
True
90
T/F. The **liver** is the main organ for drug biotransoformation. But smaller amounts of drugs can be metabolized plasma, lungs, kidneys, skin and GI tract.
True
91
What are the five factors that are related to environment? What is an example of each factor?
Ambient temperature: 122F (50C) solubility of **procaine** increases in **penicillin G procaine.**
Oxygen: decreased oxygen worsens the respiratory depression induced by **pentobarbital.**
Humidity: **Amoxicilin** should be discarded after 14 days after reconstitution.
Light: **Diazepem -** reduced in efficacy in light.
Contact surfaces: **Diazepem -** adhere to react syringe (put in glass vial before use).
93
How does "drug-drug interaction" occur? What are examples of **benefical drug-drug interaction**? What are examples of **detrimental drug-drug interaction**?
Administering drugs concurrently or sequentially.
**Beneficial:** Trimethoprime and Sulfonamide; ACE inhibitor and thiazide diuretic
**Detrimental:** Aminoglycoside and muscle relaxants; Chloramphenicol and phenobarbital
94
T/F. **Acidification** (ammonium chloride/methionine) enhances excretion of **weak basic drug** (procaine, amphetamine). **Alkalinization** (sodium bicarbonate) enhances excretion of **weak acidic drug** (NSAIDs).
True
95
What is the difference between **Organic cation transporters (OCTs) and Organic anion transporter (OATs)** regarding active tubular secretion for excretion?
**OCTs:** secretion of organic **bases**
**OATs:** secretion of organic **acids**
96
What are the two factors affecting timing of administration?
**Food & absorption after oral administration**: **Absorption** delayed with food/fluid (**Mitotane** increases absorption in small animals); **Adsorption** pf phenylbuazone to hay (affects absorption in cecum)
**Circadian effects: CNS stimulatnts -** more effective daytime; **CNS depressants** - more effective at night.
98
Which of the following is NOT a characteristic of Phase II (synthetic)?
A. Combination of a molecule with a reactive group capable of attaching a substituent group.
B. Metabolites conjugates are inactive and water soluble.
C. Glucuronidation is the most common reaction.
D. Glucuronidation does not include enterohepatic recyling.
E. Acetylation is deficient in dogs; conjugation with ornithin only in birds; sulfation deficient in swine.
D. Glucuronidation does not include enterohepatic recyling.
DOES INCLUDE IT!
99
What is drug absorption? Is this pharmacokinetic or phamacodynamic?
Movement of drug from the site of administration into the blood.
PHARMACOKINETIC
100
What is the difference between tolerance and tachyphylaxis?
**Tolerance:** gradual decrease in responsiveness
**Tachyphylaxis:** an acute form of tolerance (EPHEDRINE!!!)
101
T/F. First pass metabolism occurs if drugs are absorbed in GIT (anywhere between distal to the oral cavity and proximal to rectum). Drugs include opioids and lidocaine.
True
102
What is NOT a characteristic of pinocytosis?
A. a type of endocytosis
B. Invaginates and interiorizes the drug
C. It does not require energy
D. **Aminoglycosies** in renal tubules
C. It does not require energy
IT DOES!
104
What is **non-comparmental (stochastic) modeling**? What is **Non-linear modeling**? What is **Population phamacokinetics**? What is **Allometric scaling**?
**Non-compartmental (stochastic) modeling:** involves probability, describes processes in terms of stats moments, **Mean Residence Time (MRT):** the avg time that molecule spends time in the body.
**Non-linear modeling:** Zero-order kinetics, energy-consumptive and saturable (**CLB decreases and half-life increases**).
**Population pharmacokinetics:** apply to all breeds, ages, and gender; studies in large numbers of animals.
**Allometric scaling:** Multiples species against weight to estimate in an unknown species (off label, previcox and equioxx).
105
T/F. **Buccal/sublingual** may have first-pass metabolism **reduced.** **Rectal drugs (suppository)** always avoids first pass metabolism.
False.
Buccal/sublingal: AVOIDS first-pass metabolism; Rectal drugs: first-pass metabolism may or may not be reduced.
106
Which of the statement is INCORRECT about **relative blood flow**?
A. **High:** brain, heart, kidney, endocrine organs.
B. **Intermediate:** nails, hair, nose
C. **Low:** cortical bone, fat, muscle (at rest).
D. Need to consider alterations in blood flow as well as affinity of the drug for a particular tissue.
B. Intermediate: nails, hair, nose
Intermediate: liver, skin, muscle (active).
107
What is **Mixed agonist-antagonist**?
Acts an agonist in one type of receptors and as an antagonist on other types of receptors
109
What are the factors that affect liver metabolism? Be able to explain each factor.
Age (young and old animals have less metabolic capacitiy)
Individual/breed (Genetic differences - deficiency of certain enzymes)
Body temperature (hypothermia decreases biotransformation)
Liver disease (decrease liver enzymes)
hepatic blood flow (decreased in heart disease)
Plasma protein binding (decreases metabolism)
Route of administration (first pass effect/high hepatic extraction raito)
Enzyme induction (induces excretion: **microsomal enzymes; Phenobarbital, phenytonin, rifampin are CYP inducers;** kale)
Enzyme inhibition (inhibit the liver production of certain metabolic enzymes: **Chloramphenicol, cimetidine, ketoconzol are CYP inhibitors**; grapefruit)
109
What are **biological interactions** that involve in targeting for **specific receptors?**
Inotropic receptors, metabotropic receptors, kinase coupled receptors, nuclear receptors/transcription factor receptors, receptor subtypes, receptors can undergo up/down regulation.
110
What are the factors that are related to **animals**?
Species, breed, individual factors, gender/gestation, body condition, age, disease, temperament, idiosyncratic drug reactions, hypersensitivity, tolerance
111
113
What are three drugs that increase susceptibility in adverse effects for young animals?
**Tetracyclines**: yellowing of teeth
**Fluoroquinolones:** catilage damage
**Glucocorticoids:** premature closure of epiphysis
115
What are some specialized tissue barriers? What are some trancellular fluid compartments?
BBB, ocular, prostatic, testicular, synovial, mammary, placenta.
SCF, intraocular, synovial, pericardial, pleural, peritoneal.
116
What is **metabolism?**
Chemical alteration of the drug by different body tissues (BIOTRANSFORMATION)
Specificity, saturability, drug competition, induction/inhibition can be altered.
117
T/F. Distribution is discussed in terms of **compartments**. These are groups of tissue or fluid for which the rates of uptake and clerance of a drug are similar.
True
118
What is **competitive antagonism**? What are the sub-categories of this?
**Competitive antagonism:** when the antagonist ligand binds on the site of where agonist would bind. Depends on the concentration of agonists/antagonists.
**Reversible:** Carbamate toxins to anticholinerasterase
**Irreversible (Non-competitive):** Organophosphate toxins to anticholinerasterase; receptors are never free
119
What is the mechanism of drugs to target **voltage gated ion channels** through **non-receptors**?
Blocking of ion channels by the drug molecule physically obstructing the channel to impair ion movement.
May modulate the opening/closing of the channel.
120
T/F. **One compartment open model** is distributed evenly (**single homogenous compartment**), therefore, volume of compartment is the volume of distribution.
True
121
Which of the following is INCORRECT about **hepatic excretion**?
A. Active transport of parent drugs/conjuates from sinusoids to bile.
B. Lipid insoluble drugs with MW
C. Involvement of enterohepatic circulation (free drug can be reabsorbed, which prolongs the drug's residence time in the body).
B. Lipid insoluble drugs with MW
Lipid **soluble** with MW **\>300** wih polar group attached
122
What is the difference between **kinase coupled receptors and nuclear receptors**?
**Kinase-coupled receptors:** transmembrane proteins that have extracellular receptor and intracellular receptor for enzymatic activity (Phosphorylation and activation of proteins to activate effectors: **insulin and growth promoting hormones**).
**Nuclear receptors/Transcription factor receptors:** After ligand binds to receptors in cytoplasm, translocate to the nucleus for specific gene transcription (steroids and thyroid hormones).
123
T/F. Glucuronidation is the only non-microsomal and other conjugations are all microsomal.
False.
Glucuronidation is the only MICROSOMAL and other conjugations are non-microsomal.
124
What is **oxidative reaction?** What is **reductive reaction?** What is **hydrolytic reaction?**
**Oxidative** (microsomal or non-microsomal): most common, horses and catlle have higher oxidative enzymes, lowest in cats and young animals.
**Reductive** (microsomal or non-microsomal)
**Hydrolytic** (non-microsomal): plasma esterases, hepatic amidases
