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1
Q

What breed of dog is particularly sensitive to the cardiovascular effects of the phenothiazine sedative, acepromazine?

A

Boxers

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2
Q

A dog with GI disease is on antiacid therapy which raises his stomach pH. This dog is inadvertenly exposed to a toxin that requires a very acidic environment to be absorbed, but because of the antacid the dog absorbs very little of the toxin. What is the best description of this drug-drug interaction?

A

Pharmacokinetic antagonism- because it is affected the absorption

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3
Q

The antibiotic chloramphenicol is known to cause aplastic anemia(complete shutdown of RBC production) that has a 50% mortality rate. This reaction occurs in about 1:524,000 people. It is an unpredictable response and does not require previous exposure to the drug. What best describes this type of reaction

A

Idiosyncratic reaction

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4
Q

Which form of cellular transport directly utilizes ATP?

A

Primary active transport

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5
Q

Define Drug disposition

A

the study of the movement of drugs across biological membranes in the body from the time of absorption until elimination. Can be broken down into four stages called the ADME process. The time in the body until the time it leaves

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6
Q

Passive Diffussion

A

Movement with a concentration gradient; can be paracelluar or via specialized intercellular junctions

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7
Q

Ionization

A

The pka of a weak acid or base determines in what pH the substance will be ionized

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8
Q

When the pKa= pH

A

the drug is 50% ionized and 50% non-ionized

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9
Q

Acidic drugs are ionized in _______, while basic drugs are ionized in_____

A

Acidic drugs are ionized in basic environments, while basic drugs are ionized in acidic environments

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10
Q

What determines ionization?

A
  1. Acid or base 2. pKa 3. environment of drug
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11
Q

Formula for pKa of an acidic drug

A

pka= pH + log [AH- non-ionized]/ [A-ionized]

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12
Q

Formula for pKa of a basic drug

A

pka= pH + log [BH+ionized]/ [B non-ionized]

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13
Q

Ion-trapping

A

Because of the properties of ionization a drug will be more likely to cross membranes from a certain pH environment, but it then may ionize and be unable to cross back over the membrane

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14
Q

Weak acids are absorbed from an acidic environment and will become trapped in a ______ environment.

A

basic

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15
Q

Weak bases are absorbed from a basic environment and will become trapped in a more _______ enviroment.

A

Acidic

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16
Q

Faciliatated diffusion

A

This is a carrier mediated form of transport to move substances across lipid membranes. THIS IS SATURABLE!
This moves with passive diffusion and does NOT require energy to work.

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17
Q

Active Transport

A

Carrier mediated(like facilitated diffusion) and it can also be saturated. It is also selective, meaning that only certain molecules can be moved by a specific transporter) Substances are being moved AGAINST the concentration gradient, thus it REQUIRES ENGERY

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18
Q

Primary active transport

A

A form of active transport that requires that energy is supplied directly i.e. Na/ K ATPase

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19
Q

secondary active transport

A

A form of active transport where the energy is supplied indirectly i.e. ATP is used to make an electrochemical gradient and this is used to move substances

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20
Q

antiporter

A

A type of transport where one substance is exchanged for another

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21
Q

symporter

A

A type of transport where two substances are brought into the cell together

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22
Q

P-glycoprotein system

A

This is a specific form of active transport in which the transporter is an efflux pump. This protein expresses ABCB-1(MDR 1 gene) and will remove substances from specific cells.

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23
Q

Efflux Pump

A

before the drugs can move through the cell, it moves to the other side of the membrane. This is a form of ACTIVE TRANSPORT. i.e. BBB- keeps drugs out- however, ivermectin in collies messes with this

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24
Q

pinocytosis

A

A specific type of endocytosis. Drugs bind to the surface of the cell, then the cell membrane invaginates and interiorizes the drug. REQUIRES ENGERY
i.e. aminoglycosides being taken up this way by renal tubular cells

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25
Absorption
Movement of the drug from the site of admin. into the blood- Remember, there is no absorption for IV drugs!
26
Dissolution
the first part of absorption and can actually be the rate limiting step. Once dissolution has occurred, then the real absorption can start to take place
27
Solubility of a drug
Determined by it's molecular structure, ionization, and preparation.
28
Fastest-slowest routes of administration
IV> sublingual/inhaled/IP>IM>SC>PO
29
What are some factors related to the drug that can influence absorption?
- Molecular size of the drug - rate of dissolution - degree of ionization - concentration at absorptive site( higher concentration= more absorption) - Route of adminstration
30
What are some factors related to the animal that can influence absorption?
- blood flow ( more blood flow= more absorption) - Absorbing surface area( more surface area= more absorption) - presence of connective/scar tissue - species - fasted vs fed - indiviudal variation
31
Bioavailability
The fraction of a given dose that ends up in systemic circulation. IV administration is considered to represent 100% bioavailability (F=1). Topical drugs generally mean that they do not enter systemic circulation
32
enteral
anything that goes into the alimentary canal- usually oral
33
Enterohepatic Recycling
Where a drug is absorbed into portal circulation, metabolized and excreted into bile, then reabsorbed into the SI again- Drugs that do this generally have longer half lives
34
First-Pass Metabolism
where an oral drug(also rectal) is absorbed into portal circulation and a portion of that drug is metabolized by the liver before it reaches systemic circulation. A drug that undergoes first pass metabolism will have lower bioavailability
35
Most absorption takes place in ___________
in the small intestine- where there is large SA, rich blood supply, and presence of microorganism
36
Parenteral
IV, IM, SC, and IP; Generally the barrier to absorption via these routes is less than with oral and topical use and so drug levels are expected to get into systemic circulation faster.
37
Drug that has a high first pass metabolism
Propanoal if given orally. Thus, the oral dose will be much higher than the injectable
38
Distribution of drugs
The transfer of drugs from the bloodstream to tissues around the body
39
Compartments
Groups of tissues/fluids for which the rate of update/clearance of drugs are simliar
40
Volume of distribution
what compartments a drug is being distributed.
41
Tissue Barriers
Specialized barriers exist between the blood stream and certain organs, these often make use of tight junctions between cells and selective transport mechanisms to regulate movements of substances into and out of the organ/tissue
42
Blood Brain Barrier
1. tight junctions between the capilaries endothelial cells and glial cells 2. Active Transport Mechanisms 3. Constant CSF production/drainage Remember if it crosses the BBB, then it also crosses the placenta.
43
Acidic drugs bind to________
albumin
44
Basic drugs bind to________
several proteins (B-globulins and glycoprotein and sometimes a little bit to albumin)
45
Free drugs( non-bound)
are ACTIVE
46
Metabolism
the chemical alteration of the drug by different body tissues aka biotransformation
47
Bioinactivation
the process of making a drug inactive and easier to excrete
48
Bioactivation
when an inactive substance (prodrug) is converted to an active metabolite i.e. cefpodoximine proxayil to cefpodoximine
49
Lethal Synthesis
non-toxic substance can be converted to a toxic | metabolite i.e. acetaminophen to n acetol benzaoquinoimine
50
Main site of metabolism
LIVER
51
Why do we see Tyenol toxicity in cats?
cats are deficient in glycuroyl transferase which alters their metabolism of some drugs
52
Boxers are senisitve to...
phenothiamzines(acepromazine)
53
Collies are sensitive to
Ivermectin- causes CNS depression
54
Australian terriers respond differently
to droperidol/fentanylp they exhibit little sedation
55
Young animals have
lower metabolism, lower rate of excretion, increased permeabiity of the BBB
56
Specific Effects to young animals
1. tetracylines affecting tooth enamel 2. Fluroquinolones affecting cartilage 3. Glucocorticoids affecting bone physes
57
Geriatric Animals will have....
decreased metabolism, decreased excretion,
58
Hypersentivity VS Idosyncratic
Idiosyncratic reactions- NOT DOSE DEPENDENT and can occur on the first exposure where as hypersentivity occurs on second exposure
59
Tolerance
diminished response over time to a drug
60
tachyphylaxis
acute tolerance
61
Phase 1
includes oxidative( most common), reductive, and hydrolytic reactions( rare). Most of these take place in hepatocytes and are catalyzed by enzymes attached to the Smooth ER- most imporant cytochrome P450
62
Phase 2
a molecule with a reactive group conjugates with a substiutent group rendering a final metabolite that is typically inactive and water soluble (polar)
63
Glucuronidation
most common reaction and IS the ONLY microsomal- cats are deficent in this- PHASE 2 rxn
64
Enzyme Induction
drugs that increase the capacity of microsomal enzymes can lead to tolerance. drugs are metabolized quicker, but prodrugs might stay around longer This can enhance toxin reactions. Examples Pheno, phenylbutazone, griseofulvin, and rifampin; enhances bioactivation
65
Enzyme inhibition
will result in a longer half life of the drug, slows down bioactivation
66
excretion
removal of the drug from the body; KIDNEY
67
Renal excretion
1. glomerular filtration 2. active tubular secretion 3. tubular reabsorption
68
Acidification of urine will cause
Acidification of urine with ammonium chloride or methionine will cause weak basic drugs to be ionized and enhance their excretion.
69
Alkaliniziation of urine
Alkalinization of urine with sodium bicarb or potassium citrate will cause weak acids to be ionized and enhance their excretion.
70
Hepatic Excrection
typically an active transport of drugs and conjugates from the hepatic sinusoids to the bile canaliculi
71
Summation
Two drugs with additive effects
72
synergism
two drugs have greater efficacy when combined
73
Anatagonism
decreased effects occur when one or both drug reduces the action of the other
74
chemical anatgonism
drugs chemically react to each other causing inactivation of one or the other
75
physiologic antagonism
the drugs work differently and have OPPOSING physiological effects that cancel each other out
76
Pharmacokinetic antagonism
one drug reduces the concentration of the other drug at its site of action by interfering with its ADME processes

Pharm (19 decks)

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