Module 2 Flashcards
1
Q
The insertion of a molecule of water into another molecule, which forms an unstable intermediate compound that subsequently splits apart.
Barash Ch. 11
A
Hydrolysis
2
Q
The primary way amides, such as lidocaine and other amide local anesthetics, and esters, such as succinylcholine, are metabolized.
Barash Ch. 11
A
Hydrolytic reactions
3
Q
Reactions that remove electrons from a molecule.
Barash Ch. 11
A
Oxidation
4
Q
The single most important enzyme, accounting for 40% to 45% of all CYP-mediated drug metabolism.
Barash Ch. 11
A
CYP3A4
5
Q
Enzymatic reactions that metabolize drugs can be classified into (_____) and (_____) biotransformation reactions.
Barash Ch. 11
A
Phase I / Phase II
6
Q
True or False?
The passive elimination of drugs by passive glomerular filtration is a very efficient process.
Barash Ch. 11
A
False
The passive elimination of drugs by passive glomerular filtration is a very INefficient process
7
Q
What determines the concentration of a drug in the plasma or at the site of drug effect?
A
Pharmacokinetics
[Stoelting ch 2]
8
Q
A result from genetic modifications in metabolism; interactions with other drugs; or disease in the liver, kidney, or other organs of metabolism?
A
Pharmacokinetic Variability
[Stoelting ch2]
9
Q
What is the time frame of initial distribution after bolus injection?
A
Within 1 minute
Stoelting ch 2
10
Q
A compartment physically composed of those elements of the body that dilute the drug within the first minute after injection. Consists of Vessel Rich Group (VRG)
A
Central compartment
[Stoelting ch 2]
11
Q
Many anesthetic drugs are highly ___________ soluble and poorly soluble in _______.
A
Fat; water
[Stoelting ch 2]
12
Q
Protein binding affects the ________ of drugs as well as the _______.
A
Distribution; potency
[Stoelting ch 2]
13
Q
Most acidic drugs bind to___________. while most basic drugs bind to ________.
A
Albumin; alpha 1 acidic glycoprotein
[ Stoelting ch 2]
14
Q
The 4 basic pathways of metabolism are?
A
Phase 1 - oxidation - reduction - hydrolysis Phase 2 - conjugation
Stoelting ch 2
15
Q
The CYP450 enzyme is involved in what phase of metabolism?
A
Phase 1
Stoelting ch 2
16
Q
The rate of metabolism for most anesthetic drugs is proportional to drug ____________, rendering the clearance of the drug constant.
A
Concentration
Stoelting ch 2
17
Q
The rate at which drug flows out of the liver must be the rate at which the drug flows in to the liver, minus the rate at which the liver ______ the drug.
A
Metabolizes
Stoelting ch 2
18
Q
Renal excretion of drug involves what 3 things?
A
A) glomerular filtration
B) active tubular secretion
C) passive tubular reabsorption
Stoelting ch 2
19
Q
Nonionized molecules are usually _______ soluble and can diffuse across cell membranes.
A
Lipid
[Stoelting ch 2]
20
Q
The ______molecule is poorly lipid soluble and cannot penetrate lipid cell membranes easily.
A
Ionized
[Stoelting ch 2]
21
Q
The reason for the large differences in the pharmacological effect of oral and IV drug doses.
A
First-pass hepatic effect
22
Q
Route of drug administration that permits a rapid onset of drug effect due to bypassing the liver and preventing the first-pass hepatic effect.
A
Sublingual/ buccal route
Intravenous
(Stoelting ch 2)
23
Q
What organ excretes the most amount of drugs?
A
Renal system
24
Q
What is the formula for renal excretion?
A
Filtration - reabsorption + secretion at the level of the nephron
25
What is the definition of a nephron
It is the functional unit of the kidney
26
The liver is the most important organ for metabolism of drugs. Hepatic drug clearance depends on what three factors?
Barash Ch. 11
1. The intrinsic ability of the liver to metabolize a drug
2. Hepatic blood flow
3. The extent of binding of the drug to blood components
27
Where do drugs enter the nephron?
Afferent arteriole
28
After a drug goes through the afferent arteriole in the nephron where does go?
Bowman’s capsule
29
When a drug is not filtered in the kidney where does it go?
Efferent Arteriole
30
Can a drug be secreted more then once in the kidney?
Yes, if the drug is not secreted it will branch to the peritubular capillaries and allows the drug to be secreted again if it was not filtered.
31
True/False Does filtration care if a drug is metabolized?
False, the only thing that filtration cares about is if the drug is free and not bound to anything. Generally speaking, polar and ionized.
32
If a drug is unbound in the kidney where can it be filtered out at?
Glomerulus site
33
Is albumin in the urine a good or bad thing?
Bad! It is used as a marker for diabetics to determine the progression of kidney disease in the urine. High number of albumin is bad
34
Is it good or bad for reabsorption of a drug at the glomerulus?
Bad, it is important not to reabsorb the drug. The point of metabolism is to process a drug in a way that is more readily eliminated.
35
What is the entire point of metabolism?
To prevent reabsorption, make a drug more readily eliminated.
36
Does the body prefer lipid soluble drugs or water soluble
- Lipid soluble drugs bypass the GI tract and allows is to get reabsorbed into the body.
- Easily passes cell membrane with increased lipophilicity.
37
True or False?
All else being equal, an increase in the volume of distribution of a drug will increase its elimination half-life; while an increase in elimination clearance will decrease elimination half-life.
Barash Ch. 11
True
38
Most drugs must pass through cell membranes to reach their sites of action. Consequently, drugs tend to be relatively (_____), rather than (____).
Barash Ch. 11
lipophilic/hydrophilic
39
The theoretical volume of blood from which a drug is completely and irreversibly removed in a unit of time.
Barash Ch. 11
Elimination clearance/drug clearance/ rate of elimination. Expressed as mass/time.
40
Which highly perfused core circulatory components receive the highest relative distribution of cardiac output, and therefore, are the initial organs to reach equilibrium with plasma drug concentrations? (Vessel Rich Group)
(five organs)
Barash Ch. 11
The brain, lungs, heart, liver and kidneys.
41
What does the liver do to the molecule?
The liver metabolizes molecules and makes them more polar, more readily eliminated from the body.
42
Why is a polar molecule good?
More polar molecules prevent reabsorption.
43
What is ion trapping
Systematic administration of a weak base, such as opioid, can result in accumulation of ionic drug in the environment of the stomach
(The ph and the charge can be changed to prevent reabsorption)
44
Is reabsorption always bad?
No, reabsorption of electrolytes is good but reabsorption of the drug is not
45
What is secretion
The way the body releases the drug into the urine
46
What is the rate of elimination
| Formula
Elimination (Mass/time) = Clearance (volume/time) * (mass/volume) concentration. *Notice how units cancel to derive elimination as mass/time.
47
What is GFR
Flow rate of blood that is being filtered.
48
Where can creatine be found in the body ?
The muscles
49
What does creatinine measure
Kidney function
50
What is the best test to measure kidney function
24-hr urine collection
51
What is the gold standard for measuring kidney function
The measurement of inulin because it is freely filtered precise measurement of GFR. Rarely used.
52
What classifies chronic kidney disease
- Kidney problem > 3 months
- GFR< ml/min
- Increase in creatinine and decrease in GFR
53
What is the easiest way to determine kidney disease
- Decreased GFR
| - Increased Serum Creatinine
54
What does enzyme induction do
It increases drug metabolism
55
What does competitive inhibition do
Decrease drug metabolism
56
Where does metabolism occur
At the level of the enzyme
57
Why do drug reactions occur
Secondary to change in enzyme activity
58
What enzyme is responsible for more than 50% of unexpected drug reactions
CYP3A4
59
What increases drug metabolism?
Enzyme inducers
60
What happens when you make more enzyme
Rate of drug metabolism is increased. It increases VMAX (maximum rate of metabolism). A VMAX that can no longer increase indicated enzyme saturation.
61
What is enzyme induction?
It increases the rate of metabolism, leads to increase in metabolites.
62
What happens if drug metabolism increases?
Drug concentration decreases.
63
Do chronic alcoholics make more or less enzymes ?
They make more so it increases the rate of metabolism.
64
What is competitive inhibition
Constrains drug metabolism, increases plasma drug concentration.
65
What happens in the presence of competitive inhibitors
Decreases the rate of drug metabolism, will decrease the dosage required.
66
What are two consequences of competitive inhibitor’s
1. Decreases metabolism so it makes less metabolites (this is good if metabolites are toxic)
2. If Metabolites are increased the drug concentration causes more side effects to occur
67
What is the most commonly prescribed drug in the US?
Statins
68
What is a statin
It is a cholesterol lowering agent
69
Where are statins metabolized at
CYP3A4-metabolite
70
What does more than one glass of grapefruit juice do to a person who is taking a Statin
Having more than one glass of grapefruit juice, especially at night, inhibits the CYP3A4 gene, which increases the amount of statin in the body
71
What is CYP3A4 inhibited by ?
Furanocumarins
72
What type of antacid should you not take with statins
H2 blockers
73
What do you H2 blockers do to your stomach when you’re taking a Staten
It takes the protons and pumps it out creating a hydrochloric acid
74
What are three molecules that bind to the Parietal cell
Histamine, acetylcholine, and gastrin
75
What is a specific name of an H2 blocker that inhibits the CYP3A4 gene and it increases Statin concentration in the body
Cimetidine
76
What do macrolides treat
Upper respiratory infections
77
What is MACE
Macrolides, azithromycjn, clarithromycin, erythromycin
78
Which mycin can you give a patient who is taking a statin and why
Azithromycin because it does not have CYP3A4 inhibition
79
What is Pharmogemonics
It is the study of how genetic factors affect drug metabolism. As with Asian glow
80
What is Asian glow
Eastern Asians have a predisposition when drinking alcohol that gives them an allergic reaction
81
In what regións in Asia do people commonly encounter Asian glow
Koreans, Taiwanese, and Japanese
Eastern Asian
82
What causes the Asian glow to occur
It is a release of histamine and prostaglandin that widen the arteries in veins causing a flushing appearance
(Vasodilation)
83
How can you treat Asian glow
1. Avoid drinking
2. Can use a anti-histamine (cimetidine)
3. Before you start drinking alcohol take a Zantac, or aspirin to decrease the production of prostaglandins
84
Which route of a drug is able to directly enter the systemic circulation, able to bypass the metabolically active intestinal mucosa, and the hepatic first-pass metabolism?
Barash Ch. 11
- Sublingual
| - Intravenous
85
Direct injection of local anesthetics and opioids into the intrathecal space bypasses the limitations of drug (___) and drug (___) of any other route of administration.
Barash Ch. 11
Absorption / distribution
86
The large surface area of the pulmonary alveoli available for exchange with the large volumetric flow of blood found in the pulmonary capillaries makes (___) administration an extremely attractive method by which to administer drugs.
Barash Ch. 11
Inhalational / Inhalation
87
True or False?
Once the concentration of drug in the brain tissue is higher than the plasma concentration of drug, there is a reversal of the drug concentration gradient so that the lipophilic drug readily diffuses back into the blood and is redistributed to the other tissues that are still taking up drug.
Barash Ch. 11
True
88
Pharmacokinetic term that describes all the processes that remove a drug from the body.
Barash Ch. 11
Elimination
89
Most drugs that are excreted unchanged from the body are (____) and therefore readily pass into urine or stool.
Barash Ch. 11
Hydrophilic
90
What enzymatic reaction that metabolizes a drug, which tends to transform a drug into one or more polar and potentially excretable compounds?
Barash Ch. 11
Phase I biotransformation reactions
91
What enzymatic reaction that metabolizes a drug to transform the original drug by conjugating a variety of endogenous compounds to a polar functional group of the drug, making the metabolite even more hydrophilic.
Barash Ch. 11
Phase II biotransformation reactions
92
Most common enzyme involved in phase 2 metabolism
UGTs- (UDP- Glucuronosyltransferase)- Glucuronidation reaction.
93
Enzymes involved in phase 2 metabolism.
UGTs (UDP- Glucuronosyltransferase)involved in Glucuronidation reaction., ( GSTs (Glutathione-s-transferase) involved in Glutathione conjugation, NATs(N-acetyltransferase) leads to Acetylation , SULTs (Sulfotransferase) leads to sulfation.
94
Acetaminophen is metabolized by which phase reaction.
95% of tylenol is metabolized by phase 2 enzymes.
95
Enzyme famous for polymorphism.
CYP2D6 (CODEINE)
96
First order kinetics.
| video-9
```
Rate of metabolism is proportional to drug concentration.
Half life(Time to metabolise 50% of drug) is constant.
```
97
What is zero order kinetics.
Rate of metabolism becomes independent of drug concentration. Rate of drug metabolism is constant. Rate of drug elimination is constant. Drug can build up in the body leads to toxicity
98
Name three drugs reach zero order kinetics quickly
| VIDEO-9
Aspirin, phenytoin & ETOH
99
What is elimination half life
Time it take to eliminate 50% of the drug in the body.
| 95% of drug is always eliminate after 4.5 half-lives
100
Formula to calculate elimination half life
0.693/ke (first order elimination constant)
OR
0.693xVd/cl
Vd is volume of distribution and cl is clearance
101
What is clearance
Volume of plasma that gets filtered of drug/Time
| unit is L/hr or ml/min
102
How to calculate Rate of elimination
Rate of elimination = clearancexplasma drug concentration
103
what is total clearance.
CL total= CL renal+ CL hepatic +CL lungs.
104
Clinical use of GFR (glomerular filtration rate)
GFR is used to to estimate changes in the renal clearance of drugs. Used as an indicator to select drug dose and choice .
105
DRUG CLEARANCE VS ELIMINATION.
Drug elimination refers to the irreversible removal of drug from the body by all routes of elimination. The declining plasma drug concentration observed after systemic drug absorption shows that the drug is being eliminated from the body but does not indicate which elimination processes are involved.
106
Total clearance
Renal clearance-urine
Hepatic clearance- Bile
Pulmonary clearance- Air
107
What are the main factors that affect tissue distribution of drugs? KT
Body composition, regional blood flow, and drug affinity for plasma proteins/tissue components.
108
The behavior of molecules with weak-moderate lipophilicity in obese patients is…. KT
Predictable as these drugs are mainly distributed in lean tissues and their doses based on ideal body weight. Ex: vecuronium and lithium.
109
Obesity can significantly alter..... KT
Tissue distribution and elimination of drugs, and may necessitate modified loading and/or maintenance doses of various drugs.
110
Obesity is defined as ..... KT
An excess of fat tissue compared with normal values for age and gender
111
An individual was said to be obese when ...... KT
The actual bodyweight exceeds the IBW by more than 20%
112
Body mass index (BMI) is…. kT
Bodyweight (in kg) divided by the square of the height in metres
113
The BMI of an overweight person is.... KT
≥25 to 29.9 kg/m2
114
The BMI of an obese person is.......... KT
≥30 kg/m2.
115
Obesity is divided into 3 classes: KT
Moderate (BMI 30.0 to 34.9), severe (BMI 35.0 to 39.9) and morbid (BMI ≥ 40.0).
116
How has the prevalence of obesity changed in the past 15 years? KT
Obesity has increased by
| between 10 and 40%. Most pronounced in young women.
117
Obesity affects which stages of pharmacokinetics? KT
Distribution and elimination/clearance
118
The main factors that affect the distribution of drugs in tissues are… KT
Body composition, regional blood flow and binding to plasma proteins
119
Obese individuals have a larger absolute ...... KT
Lean body mass (LBM), as well as fat mass, compared to normal healthy individuals of the same age, gender and height.
120
Anthropometric calculation of Lean Body Mass....KT
LBM (kg) = a × TBW (kg) – b × [TBW/height (cm)]2
| where a and b are 1.10 and 120 for men and 1.07 and 148 for women.
121
Blood flow in fat is typically.. KT
Poor and accounts for only 5% of cardiac output compared to 22% in lean tissue and 73% in the viscera.
122
The livers of obese individuals frequently suffer from ... KT
Fatty infiltration Ex: nonalcoholic steatohepatitis
123
Obese individuals may be at an increased risk of... KT
CYP2E1-mediated toxicity of environmental agents.
124
maintenance dosage of propofol for obese patients may be established on the same basis as ...... KT
For lean patients, taking into account the TBW. There is no extra accumulation of Propofol in obese patients.
125
Fentanyl in obese patients… KT
Is distributed at least as extensively in the excess body mass as in the lean tissues, and the loading dose should account for total body mass.
126
The longer t1⁄2β of fentanyl elimination in obese patients suggests that .... KT
Maintenance doses should be prudently reduced in these individuals
127
Remefentanil doses for obese individuals should .... KT
Be calculated on the basis of IBW
128
Neuromuscular blockers are ..... KT
Polar and hydro- philic
129
IBW should be used to calculate ..... KT
doses of vecuronium in obese patients
130
Rocuronium should be administered to obese pa- tients on the basis of ....... KT
IBW and not TBW.
131
What is phase one when Asian flush occurs in the body
First the enzyme is ash (alcohol dehydrogenase)- take ethanol (ETOH)
And forms acetaldehyde, which make the molecule more polar
132
What is the normal gene in the body the metabolizes alcohol and is the abnormal gene for an Asian person
Normal = ALDH*1
Abnormal = ALDH*2
133
Why does Asian flushing occur ?
One parent has the abnormal gene ALDH*2 and passes it to the child
134
If only one parent passes the bad gene ALDH*2 to the child what kind of molecule is it
It is heterozygous and it is 100 times slower
135
What happens if both parents pass along the bad gene ALDH*2
The molecule is then homozygous and alcohol would make the child EXTREMELY sick
136
If someone has a heterozygous can they drink alcohol
They will still get sick but if they still drink they would be able to develop a tolerance and reaction would not be as bad
137
What is important to warn the patient who have a heterozygous gene and build up tolerance to alcohol?
They are at higher risk for developing esophageal cancer because they have the bad gene in their genetic makeup
138
What is disulfiram
It is a competitive inhibitor of the ALDH*2 gene and is used as an alcohol deterrent that will cause the person to get extremely ill if the drink alcohol.
It is used as a treatment for alcoholism
139
Which route of a drug is able to directly enter the systemic circulation, able to bypass the metabolically active intestinal mucosa, and the hepatic first-pass metabolism?
Barash Ch. 11
Sublingual
140
Direct injection of local anesthetics and opioids into the intrathecal space bypasses the limitations of drug (___) and drug (___) of any other route of administration.
Barash Ch. 11
Absorption / distribution
141
The large surface area of the pulmonary alveoli available for exchange with the large volumetric flow of blood found in the pulmonary capillaries makes (___) administration an extremely attractive method by which to administer drugs.
Barash Ch. 11
Inhalational / Inhalation
142
True or False?
Once the concentration of drug in the brain tissue is higher than the plasma concentration of drug, there is a reversal of the drug concentration gradient so that the lipophilic drug readily diffuses back into the blood and is redistributed to the other tissues that are still taking up drug.
Barash Ch. 11
True
143
Pharmacokinetic term that describes all the processes that remove a drug from the body.
Barash Ch. 11
Elimination
144
Most drugs that are excreted unchanged from the body are (____) and therefore readily pass into urine or stool.
Barash Ch. 11
Hydrophilic
145
What enzymatic reaction that metabolizes a drug, which tends to transform a drug into one or more polar and potentially excretable compounds?
Barash Ch. 11
Phase I biotransformation reactions
146
What enzymatic reaction that metabolizes a drug to transform the original drug by conjugating a variety of endogenous compounds to a polar functional group of the drug, making the metabolite even more hydrophilic.
Barash Ch. 11
Phase II biotransformation reactions
147
What is pharmacokinetics?
[V1-6]
How does the drug concentration change as it moves through the different compartments of your body
"what your body does to the drug"
148
What is absorption?
[V1-6]
The process of a substance entering the systemic circulation
149
Where does absorption take place in the body?
[V1-6]
Where absorption occurs depends on route of administration.
• If you take a drug orally – GI tract
• If you take an inhaler - lungs
150
What is distribution?
[V1-6]
The dispersion of a substance throughout fluids and tissues of the body; Process of going from vascular space to extravascular space
151
Where does distribution take place?
[V1-6]
Starts taking place in vascular space (plasma) and goes to extravascular space (fat, muscle, interstitial space)
152
What is metabolism?
[V1-6]
The irreversible transformation of parent compounds into daughter compounds.
Enzymes do this biotransformation process to transform it into a more polar molecule and get it ready for elimination
153
Where does metabolism take place?
[V1-6]
Liver
| sometimes in the intestines as well
154
What is elimination?
[V1-6]
The removal of substances from the body
155
Where does elimination take place?
[V1-6]
Kidneys (most of the time)
156
What is bioavailability?
[V1-6]
The fraction of the administered dose that’s reaches the systemic circulation
157
What are the two main determinants of bioavailability?
[V1-6]
Properties of the drug and route of administration
158
What is the bioavailability of a drug given IV?
[V1-6]
1 because the drug is given directly into circulation
159
Volume of distribution
[V1-6]
Vd = total mass absorbed / [Concentration of plasma]
160
What is volume of distribution (Vd) used for in clinical practice?
[V1-6]
helps providers figure out how much total drug they need to give to reach a desired plasma concentration
161
Two clinical conditions that affect Vd
[V1-6]
Protein deficiency (low albumin levels) and increased capillary permeability (septic shock)
162
Do we measure extravascular concentration or intravascular concentration to determine Vd?
[V1-6]
Intravascular
163
Where in the liver cells does metabolism take place?
[V1-6]
smooth endoplasmic reticulum
164
Routes of administration that do NOT undergo first pass metabolism
[V1-6]
Sublingual, IM, IV
165
Two routes of administration that are subject to first pass metabolism
[V1-6]
oral and rectal
166
Three possible outcomes of metabolism
[V1-6]
1) active molecule becomes inactive and vice versa
2) toxic to nontoxic metabolite and vice versa
3) molecule becomes more water soluble
167
Drug properties that impact Vd
[V1-6]
Size of drug--Large drugs will stay in plasma, thus have a low Vd;
Binding--Plasma protein binding = low Vd, Extravascular protein binding = high Vd; Hydrophilic or lipophilic---Lipophilic (extravascular) = high Vd, Hydrophilic (stays in plasma) = low Vd
168
What the body "does" to the drug
PPT
Pharmacokinetics
169
Pharmacokinetics describes the __________,__________,___________, & _____________ of drugs.
PPT
Absorption, distribution, metabolism and elimination (ADME)
170
The plasma or serum concentration range within which a drug is likely to produce its effects.
PPt
Therapeutic Range (TR)
171
Describes the relationship between drug concentration and the response.
PPT
Pharmacodynamics
172
process by which a drug proceeds from the site of administration to the site of measurement (usually blood, plasma, or serum)
PPT
Absorption
173
process of reversible transfer of drug to and from the site of measurement (between blood and tissue)
PPT
Distribution
174
process by which a drug is structurally changed for purposes of detoxification and elimination
PPT
Metabolism
175
the irreversible loss of drug from site of measurement
PPT
Elimination (Excretion)
176
The fraction of administered drug that reaches general circulation.
PPT
- Bioavailability
177
Bioavailability is influenced by
PPT
gut function, gut perfusion (CHF), route of administration, first-pass metabolism
178
Combined action of intestinal and liver enzymes on drugs, or loss of a drug given orally, before it reaches systemic circulation.
PPT
First-Pass effect
179
Benefits of Oral route administration
PPT
Non-invasive, most common, increases patient compliance
180
Disadvantages of oral route administration
PPT
Not appropriate for all drugs, GI side effects, dosing frequency of some drugs
181
Benefits and disadvantages of topical route of administration.
PPT
Treats local areas, decreases systemic effects, slow onset, not useful for most drugs
182
Benefits and disadvantages of rectal route of administration
PPT
useful in unconscious patients, absorption is unpredictable, avoids first pass metabolism by the liver
183
Benefits and disadvantages of Sub cutaneous & IM injections
PPT
Provides steady absorption of drugs, limited to non-irritating compounds, can cause tissue necrosis
184
Affects how drugs are administered and supplied
PPT
Solubility
185
Solubility is measured as a ratio of
PPT
oil to water partition coefficient
186
Oil used in most medications is called
PPT
Octanol
187
Medications must be ________ to cross the lipid bilayer.
PPT
Lipophilic
188
The larger the solubility ratio the
PPT
More lipid soluble the substance is
189
Solubility of anesthetic gases is measure using what
PPT
Blood to gas partition coefficient
190
Most drugs are absorbed by
PPT
Passive diffusion
191
Most drugs are salts of
PPT
Weak acids or weak bases
192
Drugs are preferentially absorbed in which form
PPT
Unionized form
193
The fraction of the drug available in unionized form depends on
PPT
The Dissociation Constant (pKa) & the pH of the environment
194
The more ________, the higher the absorption
PPT
Lipophilic
195
The pH at which ionized and unionized forms are in a 1:1 ratio
PPT
pKa
196
pH is defines as
PPT
- log [H+]
197
pH for weak acids to be absorbed
PPT
LOW
198
pH for weak bases to be absorbed
PPT
High
199
With weak acids as pH increases, % ionized form ________
PPT
increases
200
With weak bases as pH increases, % ionized form __________
PPT
Decreases
201
The active form of the drugs
PPT
Unionized form
202
In weak bases if pH>pKa than what form predominates
PPT
Unionized
203
In weak bases if pH
Ionized
204
In weak acids if pH
Unionized
205
In weak acids if pH>pKa than what form predominates
PPT
Ionized
206
Most drugs move across membranes by
PPT
simple diffusion
207
The rate at which drugs diffuse through membranes is given by what equation
PPT
Fick's equation
208
Diffusion rate is dependent on __________ and __________
1. [drug]
2. gradient across a membrane
(Fick's equation)
209
drug properties that effect their transfer across membranes
PPT
1. Molecular size
2. degree of ionization
3. lipid solubility
4. protein binding
210
Other factors that effect the transfer of drugs across membranes
PPT
1. Blood flow to target tissue
| 2. [gradient] of drug across membranes
211
Transports drug molecule to site of activity
PPT
Vasculature
212
Carrier mediated process, moves down the concentration gradient
PPT
Facilitated Diffusion
213
Carrier mediated, requires energy, can move against concentration gradient
PPT
Active Transport
214
Passive diffusion ________ be saturated
PPT
CANNOT
215
Two main plasma proteins that drugs bind to
PPT
Albumin & Alpha1-acid glycoprotein
216
Protein Bound drugs stay in
PPT
the intravascular space
217
Patients with hypoproteinemia are more sensitive to IV drugs as a result of
PPT
Decreased protein binding
218
_______% of circulation thiopental is protein-bound
PPT
65-85%
219
Administration route that bypasses absorption
PPT
IV
220
Organs that have enzymes that metabolize drugs
PPT
Liver, GI tract, Lung
221
Metabolites may be
PPT
active or inactive
222
Active metabolite of codeine
PPT
morphine
223
metabolism that makes the drug more polar and water soluble
PPT
Phase I Reactions
224
Phase 1 reactions include
PPT
oxidation, reduction, and hydrolysis
225
Phase II reactions are
PPT
conjugation reactions
226
Examples of Phase II conjugation reactions
PPT
Glucuronidation, acetylation,
| sulfation
227
The const common phase II conjugation reaction
PPT
Glucuronidation
228
______ acetylators are more prone to toxicity with amides
PPT
SLOW (50% caucasians)
229
Population that has a high percent of fast acetylators
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Asian
230
Phase I metabolism is enzymatic therefore it can be
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Saturated
231
Metabolism of drugs in hepatocytes of the liver occurs in
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Smooth endoplasmic reticulum (SER)
232
loss of electrons
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Oxidation
233
Gain of electrons
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Reduction
234
Addition of -OH group to a molecule
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Hydroxylation
235
Break down of molecules by the addition of water
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Hydrolysis
236
When a drug increases the amount of available enzymes
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Induction
237
Induction results in
PPT
shorter half-life
238
Phase II reactions are also known as
PPT
synthetic reactions
239
Common phase II reactions involve the attachment of __________ to the molecule, rendering the compound water soluble
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a sugar group
240
Orally given drugs are carried via portal vein circulation to the liver where they are metabolized
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First Pass metabolism
241
What is the most important patient specific factor factor that influences elimination
PPT
Renal Function
242
Elimination occurs through 2 processes
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Metabolism & excretion
243
Irreversible loss of a drug in the chemically unchanged form
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Excretion
244
The primary site of excretion
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Kidney
245
Rate of drug removal at a given time
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Clearance (CL)
246
Theoretical volume of plasma that is completely cleared of drug at a given time
PPT
Clearance (CL)
247
Units of clearance
PPT
mL/min
248
formula used to calculate creatinine clearance
PPT
Cockroft-Gault equation
249
Creatinine clearance (CLcr) is needed in order to determine
PPT
Dosing regimen
250
Relates to the amount of the drug in the body to the concentration of the drug in the plasma
PPT
Volume of Distribution (Vd)
251
Hypothetical value that tells us about distribution characteristics of a drug
PPT
Apparent volume
252
Formula for Vd
PPT
Dose/Cp0
253
Units for Vd
L/kg
254
Used to determine if a drug is removed by dialysis
PPT
Vd
| high Vd are not removed effectively
255
Time it takes for the drug concentration in the plasma to fall by one half
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Elimination Half-Life (t1/2 beta)
256
How many half-lives does it take for a drug to reach a steady state
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4 to 5 half lives (Video says 4.5)
257
Have a proportionally larger extracellular fluid (ECF) volume than adults
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Neonates (up to 18 months)
258
ECF in adults
~ 20%
259
ECF in neonates
~ 40%
260
A higher Vd results in
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Longer time for elimination
261
In the Two-compartment model the central compartment (VRG) can be sampled through
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the blood
262
In the two compartment model, this compartment cannot usually be sampled
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Peripheral compartment
263
In _________, a constant amount of drug is eliminated per unit time.
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Zero Order Kinetics
264
In zero order kinetics, __________ can occur as a result of constant drug elimination regardless of drug concentration.
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Accumulation
265
In First order Kinetics a ____________ is eliminated per unit time.
PPT
Constant fraction
266
Most drugs undergo which kinetics
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First order Kinetics
267
In the first order kinetics two compartment model the fast decline in [drug plasma] represents (curvilinear part of graph)
PPT
distribution from central to peripheral compartment
268
In the first order kinetics two compartment model the slow decline in [drug plasma] represents (linear part of graph)
PPT
Elimination
269
Formula for T1/2beta
PPT
0.693Vd/Cl
270
What is the value for the proportionality constant
PPT
0.693
271
Elimination constant
PPT
Ke
272
Formula to T1/2
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T1/2 = 0.693/Ke
273
Css represents where the rate of infusion = the rate of ___________
PPT
Elimination
274
The time necessary for plasma drug concentration to fall by 50% or other percentage after a continuous infusion of specific duration.
PPT
Context Sensitive Half-Time
275
How far plasma concentration must decrease to reach levels compatible with awakening.
PPT
Time to recovery
