Week 1 Lecture Flashcards
1
Q
The term Pharmacology came from the Greek word ?
A
“pharmakon” (drug)
2
Q
Pharmacology can be defined as?
A
The science that studies the properties of chemicals
used as drugs for therapeutic purposes OR
Pharmacology is the science that broadly deals with the physical and chemical properties, action,
absorption, and fates of chemical substances termed drugs that modify biological function
3
Q
What does the body do to drugs?
A
Absorption Distribution Metabolism Excretion (ADME)
4
Q
Pharmcokinetics is the study of the ____ key physiological processes that govern the ____ _____ of drug fate in the body. This specifically looks at?
A
four, time, course, what the body does to drugs
5
Q
Pharmacodynamics (PD) is the study of ___/____ responses and selective _____ effect.
Specifically looks at ?
A
cell, tissue, receptor, what the drug(s) do to the body.
6
Q
Pharmacogenetics is the study of _____ _____ of response to drug therapy.
Why is this field of study important?
A
genetic, determinants
Important b/c able to identify genetic responses to every drug (because can not use same treatment for everyone).
7
Q
A drug is defined as a molecule that interacts with ________ molecular components of an organism
to produce _______ and _______ changes/effects.
Any _____ can be a drug and can affect ______ processes.
Drugs can ______, ______, _____ or ____ disease (pharmacotherapeutics)
It could be a prescription or over the counter (OTC)
A
specific, biochemical, physiologic, chemical, living, prevent, mitigate, diagnose, treat
8
Q
True or False: There is no unified system to classify drugs
A
True
9
Q
Drugs can be classified according to their ?
A
sources, chemical structures or biological effect
10
Q
What are some examples of organic drugs that are sourced from plants?
A
Digoxin, morphine, penicillin
11
Q
What are some examples of drugs sourced from animals?
A
Insulin, oxytocin
12
Q
What are some examples of inorganic drugs ?
A
Iron and calcium
13
Q
What are most of the drugs that we work with?
A
Synthetic drugs
14
Q
What are some examples of steroid drugs ?
A
Cholesterol, sex hormones, cortisol
15
Q
What are two examples of glycoside drugs?
A
Digoxin and digitoxin
16
Q
Barbituates are derived from?
A
Barbituric acid
17
Q
Cardiac ionotropes ______ cardiac contractility. An example of this type of drug is?
A
increase, benazepril
18
Q
Neuromuscular blockers block transmission between ?
A
a nerve muscle fiber.
19
Q
Examples of Antimicrobial drugs are
A
Bacteriostatic and bacteriocidal drugs
20
Q
Describe the three ways to name a drug.
A
Chemical name: describes the drug using chemical nomenclature.
Generic name (nonproprietary): shortened name originated during drug development.
Trade or brand name (proprietary): commercial name used for marketing. Simple catchy.
21
Q
The purpose of drug therapy is to ?,
A
induce a desired pharmacologic response
22
Q
For most drugs the degree of the pharmacologic response is related to the drug ________ at the _____ (_____).
A
concentration, tissue, receptor
23
Q
A drug crosses several ______ membrane barriers from its site of ________ to reach its
site of _____.
A
lipoidal, administration, action
24
Q
The processes that govern the movement of drugs across lipid-based biological membranes
are important and regulate its ?
A
absorption, distribution and excretion from the animal
25
Drugs move through the body by four mechanisms. Which of these are the most important?
1. Bulk flow
2. Passive diffusion
3. Carrier-mediated transport
4. Endocytosis or pinocytosis
Bulk flow and passive diffusion
26
Bulk flow is defined as movement across the _______ capillaries of the body from _____ to \_\_\_\_\_.
• Is dependent on the _______ of drug dissolved in the _____ or _____ fluid
• The ______ \_\_\_\_\_ of drug does not affect Bulk flow.
• Most drugs are characterized by a ______ \_\_\_\_\_ (\_\_) \< 350.
fenestrated, plasma, tissue, concentration, plasma, tissue, chemical nature, molecular weight, MW
27
True or False: If the drug is more concentrated, it has an easier time diffusing via bulk flow.
True
28
Passive diffusion is defined as the movement of a across ____ \_\_\_\_\_\_\_ (\_\_\_\_\_\_\_
diffusion) and depends on what host and drug factors?
cell membranes, transmembrane
1. Lipid solubility of the drug
2. Environmental pH
3. Surface area
4. Thickness of the membrane to be tranversed (edematous V/S normal tissues)
5. Concentration of diffusible drug
29
What is the most common method by which compounds move through the body?
Passive diffusion
30
Lipid solubility of the drug is influenced by what drug characteristics?
31
A ratio greater than __ suggests greater distribution and high ______ \_\_\_\_\_\_\_.
1, lipid solubility
32
Most of drugs are either ?
weak acids or weak bases
33
Drug pka is defined as?
pKa = pH at which 50% of the drug exists in the ionized state and 50% in the nonionized, lipid-soluble state
34
A drug will be more _______ and more likely to ______ into tissues when present in a "\_\_\_\_" environment.
Drugs will be trapped by ______ when present in an "unlike" environment.
nonionized, diffuse, like, ionization
35
If a drug was located in the stomach
Weak acids are better absorbed in _____ conditions
Weak bases are ______ absorbed in acidic conditions
acidic, poorly
36
If we were located in the gut...
Weak acids are poorly absorbed in ______ conditions
Weak bases are ______ absorbed in alkaline conditions
alkaline, better
37
The Henderson-Hasselbalch equation enables you to calculate the _______ \_\_\_\_\_\_ of a drug or to determine the _______ of a drug across a _______ \_\_\_\_\_\_\_.
percent (%) ionized, concentration, biological membrane
38
If the drug is a weak acid:
39
If the drug is a weak base
40
Carrier-mediated transport
The laws of ______ and ___ partitioning do not govern transmembrane flux of drugs.
The body can exert control and selectivity over the chemicals that are allowed to enter.
diffusion, pH
41
Facilitated diffusion is an example of ______ \_\_\_\_\_\_ transport. Active transport is an example of _______ \_\_\_\_\_\_\_\_ transport.
What is an example of facilitated diffusion?
carrier-mediated, carrier-mediated, Passive transport (nonactive)
42
Drugs are normally not \_\_\_\_\_\_\_\_\_, so transporters help.
lipphyllic
43
Transport systems are normally characterized by ______ and \_\_\_\_\_\_\_.
Drugs transported normally cannot cross the
membrane by ______ \_\_\_\_\_\_\_ because they
are not \_\_\_\_\_\_\_\_.
specificity, saturability, passive diffusion, lipophilic
44
Carrier mediated transport is important for
the ___ absortion of essential ______ and ____ (e.g., β-lactams), ______ \_\_\_\_\_ (e.g., glucose), the _______ of drugs from the CSF, and ______ and _____ excretion of drugs
GI, nutrients, drugs, Cellular uptake, removal, biliary, renal
45
Facilitated diffusion - Passive transport (nonactive)
• ______ protein binds to drugs and carries them across the membrane.
• It does not require ________ \_\_\_\_\_
• It does not operate _____ a concentration gradient
Carrier, cellular, energy, against
46
Facilitated diffusion - Passive transport (nonactive)
Examples?
* Reabsorption of glucose by the kidney
* Absorption of vitamin B12 from the intestine
* Ion channels: Na+, Ca2+, Cl-, H+, K+
47
Active transport
• Drug transport is conducted by ______ \_\_\_\_\_ _____ through the membrane
• It requires ______ \_\_\_\_\_ to move a drug against its concentration gradient. Energy is
driven by the ______ of adenosine triphosphate.
specific carrier proteins, cellular energy, hydrolysis
48
Active transport may also occur in the opposite direction to ______ a drug after it has been \_\_\_\_\_\_.
remove, absorbed
49
The MDR1 protein is also referred to as the ?
What role does MDR1 and ABC transporter play?
The MDR1 protein is encoded by?
How large is this protein?
MDR1 is highly expressed at the \_\_\_\_\_-\_\_\_\_\_ barrier, at the \_\_\_\_\_\_-\_\_\_\_\_ barrier and also in \_\_\_\_\_\_, \_\_\_\_\_\_, \_\_\_\_\_\_\_, and \_\_\_\_\_\_\_.
1. P-Glycoprotein OR the multidrug resistance protein
2. IDK
3. multidrug-resistance gene MDR1/ABCB1
4. 170 kDa
blood-brain, blood-testis, kidney, liver, intestine, placenta
50
The function of MDR1 is to keep ______ compounds out of _______ tissues
exogenous, critical
51
Endocytosis or pinocytosis is not a ?
Cells may absorb drugs by?
• A compound binds to the ______ of the membrane, the membrane \_\_\_\_\_\_\_
and ______ the compound.
primary mechanism
Endocytosis.
surface, invaginates, interiorizes
52
There are different methods available for administering drugs to animals
Enteral administration
Parenteral administration
Others
53
What is the most common route of drug administration?
Enteral administration
54
Examples of enteral administration are?
oral
intrarumenal
rectal
55
Types of Parenteral administration
IV, IM, SC
56
Which routes of administration are **occasionally** used?
Intraarterial
Intramedullary
Intracardiac
Intrathecal
Intrathoracic
Subarachnoid
57
Which routes of administration are common but **less frequently** used ?
Epidural
Intradermal
Intratracheal
IP
58
Other routes of administration are?
inhalation (pulmonary route)
topical (local application)
Oral transmucosal (OTM)
59
Choice of the route of administration is generally based on
• ________ properties of the drug
• _________ to be used
• __________ indications
• _________ of the disease
• Target \_\_\_\_\_\_\_
Physicochemical, Formulation, Therapeutic, Pathophysiology, species
60
The _______ of administration might influence
the _____ and _____ of absorption but should
not influence the _______ or \_\_\_\_\_.
route, rate, extent, distribution, clearance
61
The manufacturer‘s recommendations should ?
always be followed carefully.
62
The purpose of drug therapy is to ?
induce a desired pharmacologic response
63
For the most drugs the degree of the pharmacologic response is related to the drug _______ at the tissue (\_\_\_\_\_\_) aka _____ \_\_\_\_\_.
A drug crosses several _______ \_\_\_\_\_\_\_ ______ from its site of administration to reach its site of action.
concentration, receptor, target site, lipoidal membrane barriers
64
The processes that govern the movement of drug across lipid-based biological membranes are
important and regulate its ?
absorption, distribution and excretion from the animal.
65
For the most drugs the magnitude of pharmacologic response is ________ related to the drug _________ at the tissue (\_\_\_\_\_\_\_). Since tissue samples cannot be collected easily, drug concentrations at the tissue site are
approximated by measuring "\_\_\_\_\_ _____ \_\_\_\_\_\_\_" (\_\_\_\_)
proportionaly, concentration, receptor, plasma drug concentrations, PDCs
66
Determinants of PDC
These movements largely, but not exclusively depend on _______ diffusion of the drug and include:
- Absorption from the site of _______ to _____ circulation
- Distribution of the drug from _____ circulation to ______ and back again
- Metabolism of the drug and its _____ from the body
- Excretion
passive, administration, systemic, systemic, tissues, elimination
67
These movements are \_\_\_\_\_, occurring ______ and their effects determine ___ at any time during the dosing interval after _______ of a fixed dose
dynamic, simultaneously, PDC, administration
68
Determinants of Plasma Drug Concentration (PDC)
After parenteral or oral administration, drug should be \_\_\_\_\_\_. Once in circulation, if they are not bound to _____ \_\_\_\_\_\_ they can be distributed. Elimination occurs by ______ metabolism and _____ or _____ excretion.
absorbed, plasma protein, hepatic, renal, biliary
The drug must be first absorbed after a drug administration.
Once in circulation, drug not bound to plasma protein (free
drug) is distributed into tissues, where it can be bound to
tissues or distributed back to circulation.
Elimination of the drug from the body occurs by hepatic
metabolism and renal or biliary excretion of the drug or its
metabolites.
69
Absorption is defined as ?
the movement of the drug from the site of administration into the blood.
70
All routes of administration except ____ involve an absorption process. Administrated drugs must cross _____ or _____ membranes before getting into the bloodstream
IV, one, more
71
Oral (gastrointestinal absorption)
Main role of GI-tract is _____ and ______ \_\_\_\_\_\_. GI-Tract present a important degree of _______ relative to morphology and physiology. This causes a regional variations in drug \_\_\_\_\_\_.
digestion, nutrient, absorption, heterogeneity, absorption
72
What is the major obstacle of gastrointestinal absorption?
The enormous interspecies diversity in comparative gastrointestinal anatomy and physiology. Also, drugs won't be absorbed in the same way in different regions in the body.
73
Most drugs reach systemic circulation after absorption from the ______ \_\_\_\_\_\_ because of the ____ surface area)
small intestine, large
74
The rate and extent of drug absorption in the GI tract depend on:
o GI- \_\_\_
o Surface \_\_\_\_\_
o \_\_\_\_\_\_
o _______ of drug
o ________ and ________ of the mucosal epithelium
o Intestinal _____ \_\_\_\_\_
pH, area, Motility, Concentration, permeability, thickness, blood flow
75
After GI absorption, drugs enter the _____ \_\_\_\_\_ and then the \_\_\_\_\_\_.
portal vein, liver
76
Drugs that undergo first-pass metabolism may not reach _____ \_\_\_\_\_ in concentrations
sufficiently high to cause a \_\_\_\_\_.
systemic circulation, response
77
In the oral cavity, the is the sublingual area is the route for _______ drugs. Example = \_\_\_\_\_\_. You can place ______ \_\_\_\_\_\_\_ or use ______ \_\_\_\_\_\_\_ (?) in the buccal mucosa.
systemic, nitroglycerin, polymer patches, feline oral sprays
78
In the _________ and ______ portion of the stomach this part of the GI tract, it will be _____ \_\_\_\_\_\_ for drugs to be absorbed due to the _______ epithelium.
esophagus, cranial, more difficult, cornified
79
The stomach contains ______ mucosa, which allows for \_\_\_\_\_\_\_\_. However surface _______ may be a barrier to some drugs. Furthermore, its ______ and ______ creates a ______ environment for drugs and therefore promotes promotes drug absorption _____ the GI tract.
simple, absorption, mucus, acidity, motility, hostile, down
80
The SI is the primary site for most drug absorption due to ____ and ______ \_\_\_\_\_. ____ \_\_\_\_\_ is much greater here than it is in the stomach and the presence of _______ which increase SA. If there is no \_\_\_\_\_\_, then the drug would ____ be easily absorbed.
pH, epithelial lining, Blood, flow, microvilli, microvilli, not
81
\_\_\_\_\_\_\_ have a higher permeability to
many drugs than humans.
Dogs
82
Epithelial and bacterial biotransformation occurs in the?
This process is also called?
Small intestine, presystemic metabolism
83
First pass effect is when drugs travel to the \_\_\_\_\_\_.
Second first-pass effect occurs in the \_\_\_\_. Not as important as ?.
liver, SI, hepatic metabolism
The epithelial cells of the intestine are endowed with the necessary enzymes for drug metabolism.
84
Third first-pass effect is defined as?
Resident microbial population are capable of metabolizing specific drugs. This kind of metabolism are not as important as hepatic metabolism.
85
In order for a drug to be absorbed across the intestinal mucosa, the drug must be first
dissolved in the ?
aqueous intestinal fluid
86
List and define the important steps of (oral) gastrointestinal absorption.
1. Disintegration= A solid dosage form (e.g. tablet) physically disperses so that its particles can
be exposed to the Gastrointestinal fluid (GIF)
Gastrointestinal fluid = GIF
2. Dissolution = The drug molecules enter into solution, "pharmaceutical phase"
87
Parenteral route
o Parenteral dosage forms are manufactured under strict guidelines that eliminate ________ and _______ contamination
o Sterile preparations must be administered using ______ techniques
o Dose must be \_\_\_\_\_\_
o ________ reactions are a possibility
microbial, particulate, aseptic, accurate, Painful
88
Parenteral route
o The primary therapeutic parenteral routes are?
o The barrier to absorption is less than found in oral or topical delivery because ???
o The total drug dose is known and injected into ____ \_\_\_\_\_\_ \_\_\_\_. Systemic capillaries drain into the _______ circulation.
subcutaneous (SC) and intramuscular (IM), well perfused tissue, venous
89
Parenteral routes bypass all of the body‘s ______ \_\_\_\_\_\_. If you are giving drugs orally, must go through ?
defensive mechanisms, stomach, SI, etc.
90
SC and IM administration:
o Moderately irritating preparations can be injected _________ , but _____ reaction and
\_\_\_\_\_\_ may become evident with time so must be careful when deciding.
o Duration of drug action for IM is ______ than IV but most often slightly ______ than SC administration
o Usually the rate of absorption from SC administration is _______ \_\_\_\_\_\_ than from IM sites
intramuscularly, tissue, necrosis, longer, shorter, slightly slower
91
Parenteral route
Intraperitoneal (IP) administration
o The peritoneal absorption is very \_\_\_\_\_\_\_
o ____ injection is often used in toxicology in rodents
o _____ volumes can be administered
o There is a good "mixing" of the injection with the ______ \_\_\_\_\_
o The majority of drug absorbed after IP administration enters the ______ \_\_\_\_ and undergoes \_\_\_\_\_-pass hepatic metabolism
efficient, IP, Large, peritoneal fluid, portal vein, first
92
Parenteral route
Intravenous administration (IV)
o It does not involve an ______ \_\_\_\_\_\_
o Immediately _____ blood levels and _____ \_\_\_\_\_ of action
o Drugs are administered directly into a ____ usually through IV catheter
o _______ fluid volume can be injected
o ______ solutions are preferable
o ________ and ______ solutions can be injected if done slowly and carefully
absorption process, high, rapid onset, vein, Large, Aqueous, Irritating, nonisotonic
93
Inhalation (pulmonary route)
\_\_\_\_\_\_\_, _____ agents and _____ particles usually are rapidly absorbed from the ______ and _____ into the _________ circulation
Gases, volatiles, fine, airways, alveoli, pulmonary
94
Particles less than 2 μm (produced by nebulization) are inspired into the ______ \_\_\_\_ and \_\_\_\_
terminal ducts, alveoli
95
Particles less than ___ μm may reach the respiratory bronchioles.
5
96
Particles 5 to 10 μm in size may reach the ______ respiratory tract and _____ airways
5, 10, upper, larger
97
Inhalation (pulmonary route)
• Response is _____ because of the large _____ \_\_\_\_\_ of the lungs and large ____ \_\_\_\_ to the lungs.
• Cells lining the alveoli are very _____ and profusely bathed by \_\_\_\_\_\_\_.
• Compounds absorbed in the lung will enter the oxygenated _______ \_\_\_\_\_ that drain to the systemic arterial circulation
• Used for ______ \_\_\_\_\_\_ e. g. Isoflurane
rapid, surface area, blood flow, thin, capillaries, pulmonary veins, gas anesthesics
98
Topical administration
o Drugs can be applied topically to the ______ and its \_\_\_\_\_\_
o Drugs can be applied to a variety of ________ \_\_\_\_\_\_\_
skin, adnexa, mucous membranes
99
Topical administration routes:
Used routes?
* Sublingual
* Intravaginal
* Intranasal
* Intrauterine
* Rectal
* Preputial
* Ocular
* Aural (otic)
The achievement of effective systemic concentrations
are offen not required for what is an essentially local
therapeutic effect
100
Oral trans-mucosal (OTM) or buccal drug administration
o Drugs are given by mouth with the intent of absorption occurring through the _______ of the mouth
o The major advantage is to avoid the \_\_\_\_\_-pass metabolism and bypass the ______ \_\_\_\_ environment
mucosa, first, harsh GI
101
Bioavailability (F) is defined as the ________ of an administered dose of drug that reaches _____ \_\_\_\_\_\_
percentage, systemic circulation
102
The bioavalability is determined only by comparing _____ levels of a drug after a particular route of administration with the levels achieved by ____ administration. Why?
plasma, IV, B/c when you use IV admin, 100% of drug reaches systemic circulation. This is the only route.
103
F of an IV dose = ?
100% or 1
104
All other routes of administration
will have an F =?
less than 1
105
If 100 mg of a drug is administered orally and 70 mg is absorbed unchanged, the bioavailability is = ?
0.7 or 70%
106
What is the bioavailability formula?
The amount of drug collected after administration by the route under study is divided by that
collected after IV administration
o When drug concentrations in blood are assayed, total absorption is determined by measuring
the area under the (concentration-time) curve (AUC)
Every time you want bioavailbility, you need to use this formula.
107
108
The greater the bioavailability or extent of absorption of a drug, the greater the ?
anticipated pharmacologic response
109
Bioavailability is used to predict drug _______ after different routes of administration. If you have a good bioavailability, most of drug will reach ______ \_\_\_\_\_\_\_.
efficacy, systemic circulation
110
Once a drug reaches the systemic circulation following any route of administration, it must be distributed from the _______ compartment to ________ tissues. This compartment is the \_\_\_\_\_\_.
central, peripheral, blood
111
There are numerous tissues to which a drug may be distributed
• In some cases, drugs may be stored in ______ and ______ released back into the _____ circulation (low blood flow/mass ratio)
• If the animal is a food-producing species, such tissue storage may result in ______ in the edible meat products.
tissues, slowly, systemic, residues
112
What are the major factors that determine drug distribution to and from tissues?
1. Drug lipid solubility and its ability to penetrate cell membranes
2. Regional blood flow (flow/mass ratio)
3. Concentration gradient established between the blood and tissue
4. The degree to which the drug is bound to plasma or tissue proteins
5. The presence of transport proteins
113
Which tissues have a high blood flow/mass ratio?
Brain, heart, liver, kidney, endocrine glands
114
Which tissues have an intermediate blood flow/mass ratio?
Muscle, skin
115
Which tissues have a low blood flow/mass ratio?
Adipose tissue, bone
116
In the kidney, the renal cortex receives \_\_\_\_% of cardiac output. The renal medulla receives a _____ \_\_\_\_\_\_ of this blood flow.
25, small fraction.
117
Following entry into the circulatory system a drug is distributed in association with _____ \_\_\_\_\_
• ____ \_\_\_\_\_ cells may also be responsible for transport of drugs but occurs seldom
• The transport of compounds by ____ is less important.
plasma proteins, Red blood, lymph
118
The binding of lipid-soluble drugs to _____ \_\_\_\_\_ facilitates their circulation.
Weakly acidic drugs tend to bind to \_\_\_\_\_\_\_.
Weakly basic drugs tend to bind to \_\_\_\_\_\_\_\_\_\_\_.
plasma proteins, albumin, alpha1-glycoprotein.
119
There is a _______ (\_\_\_\_\_\_) binding with most of therapeutic drugs. Why?
• A molecule bound to a plasma protein moves throughout the circulation until it \_\_\_\_\_\_
• ________ occurs when the _____ for another tissue component is ________ than that for the plasma protein.
reversible, noncovalent, B/c you want the drug to be dropped off at its target tissue.
dissociates, Dissociation, affinity, greater
120
1. The plasma protein binding can affect the _____ \_\_\_\_\_\_ since only the ______ drug is able to
cross cell membranes. Why?
2. What is the effect of plasma protein binding on a drug?
3. The protein binding limits ______ \_\_\_\_\_. It slows the rates of \_\_\_\_\_\_\_
and/or \_\_\_\_\_\_. Why?
1. drug distribution, free, B/c binding to plasma protein allows them to travel through systemic circulation and reach target tissues. Once reach target tissues they must dissociate.
2. Binding does not prevent a drug from reaching its site of action but slows it down.
Effect on the response to a drug
3. glomerular filtration, metabolism, secretion, Drugs can be filtered out if not bound to plasma protein.
121
Protein binding are expressed in terms of ?
Percent of drug bound.
122
What happens when a compound has a high affinity for a protein?
The percent of drug bound falls when the drug concentration exceeds the value that saturates the binding site.
123
Binding capacity negatively affects?
Distribution of drug
124
Competition for the same site on plasma proteins may have important consequences
specially when?
One of the potential ligands has a very high affinity
125
If drug A were bound 98% and 10% of it is displaced by drug B, what is the amount of free drug A?
The amount of free drug A increases from 2% to 12%
126
If Drug A were bound 30 % and 10% displaced by drug B, the result is ?
the amount of free drug A increases from 70% to 73%
127
Define distribution equilibrium (DE)
DE, or steady-state, is defined as the amount of drug leaving plasma for tissues is equivalent to the
amount of drug leaving tissues for plasma.
128
DE may not ever be achieved because ?
a drug is continually being eliminated. This is called pseudoequillibrium.
129
DE is less likely to be achieved for drugs with a _____ \_\_\_\_-\_\_\_\_, particularly when administered at a _____ dosing interval.
short half-life, long
130
Drugs that accumulate (given at a dosing interval that is shorter than the half-life) are ______ likely to reach the a state of equilibrium between doses.
more
131
Some organs have unique anatomic barriers to drug penetration. What is the most classic example? Explain.
Blood-brain barrier (BBB) This barrier has a glial cell layer interposed between the capillary endothelium and the nervous tissue. Only nonionized lipid-soluble compounds can penetrate this barrier. Similar considerations apply to ocular, prostatic, testicular, synovial, mammary gland and placental drug distribution.
132
A few tissues possess selective transport mechanisms that accumulate specific chemicals ______ concentration gradients.
For example the blood-brain barrier has \_\_\_\_\_, **-**\_\_\_ \_\_\_\_\_, and _______ \_\_\_\_\_\_. The blood-brain barrier also possesses drug efflux transport mechanisms that ________ drug from the ______ sites
against, glucose, L-amino acid, transferrin transporters, remove, protected
133
Describe the MDR1 mutation in collies.
What is this disease characterized by?
The mutation causes a non-functional MDR1 protein at the blood brain barrier, which causes the passage of drugs into the CNS.
Neurotoxicity to ivermectin in MDR1 defect is characterized by: Depression, Ataxia, Somnolence, Salivation, Tremor, Coma, Death
134
Depending on the ____ and the mechanism of \_\_\_\_\_, drugs that are MDR1 substrates can cause severe _______ leading to \_\_\_\_
dosis, action, depression, death
135
In Ivermectin Sensitive Collies, there is a _______ of 4 nucleotides --\> ?
Big difference is the size between the intact MDR1 and defective MDR1. The defective MDR1 is _____ in size.
deletion, premature stop-codon, 91 AS
136
Define the volume of drug distribution
Vd is the volume to which a drug would have to be distributed if it were throughout the body in the same concentration as that measured in the plasma after IV administration of a known dose.
137
Using the Vd formula, solve the following
Adding 5 g (5000 mg) of dextrose (considered the dose) to each of two beakers (A and B) containing a different and unknown volume of water. The dextrose is allowed to distribute equally throughout the beaker.
• If the concentration of beaker A is 5% ( 50 mg/mL), then the volume of water in the beaker
must be ?
• If the concentration of beaker B is 2.5% (25 mg/mL), then the volume of water in the beaker
is ?
100 mL ( Vd = 100 mL) , 200 mL
138
Vd differences among species and ages can dramatically affect ?
PDC
139
Diseases associated with ____ \_\_\_\_\_ or ____ are likely to increase the Vd of many drugs (and thus _______ PDC).
fluid retention, obesity, decrease
140
\_\_\_\_\_\_ or _____ \_\_\_\_\_ is likely to decrease Vd and thus increase PDC
Dehydration, weight loss
141
The size of the apparent Vd may indicate the ____ \_\_\_\_\_ to which the drug is distributed
body compartment
142
Any factor that increases Vd will tend to _____ PDC but prolong the ______ half-life and thus the ______ of drug in the body.
decrease, elimination, presence
143
Drug redistribution is relevant only for drugs for ?
which an immediate effect can be realized (i.e., general anesthetics)
144
Drugs showing the redistribution phenomenon are ?
highly lipid soluble
145
The phenomenon of redistribution involves the rapid distribution of drugs to a \_\_\_\_-blood-flow organs such as the ____ followed by rapid ________ to _____ tissues and then to _____ tissues
high, brain, redistribution, lean, fatty
146
\_\_\_\_\_\_\_\_\_\_\_ and _________ undergo a phenomenon of redistribution.
Thiobarbituates, propofol
147
After a rapid IV bolus of thiobarbituates and propofol, these drugs distribute first into a ______ \_\_\_\_\_\_\_ _____ and ______ blood-flow organs. The drug effect rapidly terminates, primarily because?
Which animals tend to have prolonged recovery?
central blood pool, high,
of redistribution from the brain to lean tissues, such as muscle and continued redistribution to fatty tissues.
Hounds/animals that lack body fat.
