Controlled Subs, Adverse Drug Events, & Pharmacogenomics Flashcards
1
Q
Under the Title 21 United States Code (USC) Controlled Substances Act (CSA) , congress gave the United States Drug Enforcement Administration (DEA) authority to
A
Set the schedule of controlled substances
Control and enforcement of laws related to these substances
2
Q
The Controlled Substances Act (CSA) places all drugs, substances, and certain chemicals used to make drugs into _____ distinct categories or schedules
A
five (5)
3
Q
what are the drug categories dependent on
A
drug’s acceptable medical use
drugs potential for abuse
drug’s safety or dependence liability
4
Q
what is a determinate factor in the scheduling of the drug
A
abuse rate
5
Q
considered the most dangerous class of drugs with a highest potential for abuse
A
schedule I
6
Q
represents the least potential for abuse
A
schedule 5
7
Q
what are schedule I drugs
A
substances or chemicals defined as drugs with no currently accepted medical use and a high potential for abuse
most dangerous of all the schedules
8
Q
what are ex of schedule I drugs
A
Heroin
Lysergic acid diethylamide (LSD)
3,4-methylenedioxymethamphetamine (ecstasy)
Peyote (some controversy regarding religious use by Native American People who have used it for centuries)
Small spineless cactus native to the desert of south TX and north
9
Q
Small spineless cactus native to the desert of south TX and north Mexico (contains psychoactive alkaloids, particularly mescaline) used by Native Americans
A
peyote
10
Q
what are schedule II drugs
A
substances or chemicals defined as drugs but with a high potential for abuse; less than Schedule I drugs
can potentially lead to severe psychological or physical dependence
dangerous
11
Q
schedule II ex
A
Morphine & Fentanyl (100x more powerful than morphine)
Hydrocodone & combination acetaminophen with < 15 mgs of hydrocodone per dosage unit (e.g., Vicodin)
Oxycodone (OxyContin)
Cocaine (powerful local anesthetic and vasoconstrictor-not used much for medicinal purposes in the U. S.)
Methamphetamine
Methadone (used in drug addiction/detoxification programs)
Meperidine (Demerol)
Adderall and Ritalin (used for ADHD)
12
Q
what are schedule III drugs
A
substances or chemicals defined as drugs with a moderate to low potential for physical and psychological dependence
abuse potential is less than that of Schedule I & II drugs but greater than Schedule IV drugs
13
Q
ex of schedule III
A
Products containing < 90 milligrams of codeine per dosage unit (Tylenol with codeine)
Ketamine (used as a general anesthetic but abused as a recreational drug-hallucinogenic effects)
Anabolic steroids –Testosterone
Marijuana (cannabis) – Moved from Schedule 1 in May 2024
Many states now have legalized medicinal and recreational use
14
Q
what are schedule IV drugs
A
substances or chemicals defined as drugs with a low potential for abuse and low risk of dependence
15
Q
ex of schedule Iv
A
Xanax (alprazolam, a benzodiazepine used to treat anxiety and panic disorders)
Valium
Ativan (Benzodiazepine; treats anxiety, anxiety with depression, and insomnia
Ambien
Tramadol (non-narcotic pain medication)
16
Q
what are schedule V drugs
A
substances or chemicals defined as drugs with lower potential for abuse than Schedule IV
usually used for antidarrheal, antitussive & analgesic purposes
consist of preparations containing limited quantities of certain narcotics
17
Q
consist of preparations containing limited quantities of certain narcotics
A
schedule V
18
Q
schedule V ex
A
Cough preparations with < 200 mgs of codeine or per 100 milliliters (e.g., Robitussin AC)
Lomotil (for diarrhea)
Lyrica (for nerve pain/neuropathy)
19
Q
Drug effects on the body can be
A
therapeutic effects
adverse effects (ADRs)
20
Q
what are ADRs
A
Any undesirable action - side effects
toxicity reactions
21
Q
maybe b/w 4th & 6th leading cause of death in US
A
ADRs
22
Q
what is included in ADRs
A
undesired effects, many which can be tolerated
these are generally reversible upon drug discontinuation
they are dose-related
23
Q
toxicity reactions seen in ADRs
A
esults in cell & tissue damage
permanent and generally intolerable reactions
24
Q
what is dose related
A
will get better or worse based on the dose you have taken
25
the more you take the more you get the side effect or the more you take the more the side effect diminishes
dose related
26
Opiate analgesics and drugs for general anesthesia (GA) accounted for more than _____ of all drugs implicated in ADRs
50%
27
In the Thiesen, et al (2013) study, other factors that increased the risk of ADR were
increasing age of child (1.06 each yr)
incrasing # of drugs (1.25 for each additional drug)
oncological treatment (1.90 compared to other Rx)
28
ADRs were common in hospitalized children
yes
29
Children who had undergone GA were at 2x greater risk of developing an ADR
false
6x
30
______ & _____ were a significant cause of ADRs in hospitalized children
GA agents and opiate analgesics
31
why older children are at risk? why is age a risk factor?
because they are more active and more exposed to exposure to other infections and things that younger ones might not have exposure to
32
what is a monograph
package inserts that must accompany prescription drugs in the pharmacy inventory
contain information about the drug, including a listing of adverse effects
33
FDA requires that all ADRS observed for the drug to be included in the
monograph
34
ADRs are reported by
Systems/organs affected
Percentage of population affected
35
ADRs can be categorized according to
body or organ system affected (skin, cardiovascular, respiratory, etc.)
general side effects that affect whole body (malaise, fatigue, boy pain, back pain)
36
Signs of an ADR in the Nervous System can include
Dizziness
Drowsiness
Confusion
Depression
Delusions (belief or altered realty despite evidence to the contrary)
Hallucinations (sensory experiences that appear real but are not)
Anxiety or hyper-excitability/hyperactivity
Decreased mental acuity
Altered judgment
Delayed reaction time
Headaches
37
Signs of an ADR in the Eyes, with eyelids and conjunctiva being the frequent targets for drug toxicity
Blurred/double vision
Increased ocular pressure
Damage to the retina and optic nerve
Erythema multiforme
38
Stevens-Johnson Syndrome
Painful skin rash that spreads and blisters
Increased risk if the patient has a gene called HLA-B 1502
skin & mucuous membranes on the inside are affected
39
what is Erythema multiforme and signs
skin disorder that's considered an allergic reaction to an infection or medicine
Allergic reaction to some antibiotics, NSAIDs, and infections
Allergic reaction involves mucous membranes, skin and eyelids
Produces variety of skin lesions from bumps, plaques, to blisters
In its most severe form, it is called Stevens-Johnson Syndrome
40
Signs of an ADR in the Auditory-vestibular systems can include
Dizziness
Vertigo
Other balance disorders
Hearing loss
Tinnitus
41
the most common side effects of medications
tinnitus & dizziness
42
Signs of an ADR related to the Skin can include
Drug-induced itching and redness
Acne
Alopecia
Herpes simplex
A viral infection, caused by a group of herpes viruses that can produce cold sores, genital inflammation, or conjunctivitis
Sweating
Urticaria (hives)
Skin ulcers
Steven Johnson syndrome (affects skin & mucous membranes)
43
viral infection, caused by a group of herpes viruses that can produce cold sores, genital inflammation, or conjunctivitis
herpes simplex
44
Drug hypersensitivity and allergies are an adverse drug reaction
true
45
why do Drug hypersensitivity and allergies occur
due to the immune system
46
how does the immune system attack a drug
The immune system is a constellation of responses mounted by the body to attacks from outside the body
47
anything that is coming in from the body elicitating an allergic reaction or immune response
antigen
48
any substance, from a virus to a wood sliver, that elicits an immune response
antigen
49
antigen specific
iparts of the immune system recognize and act against particular antigens
50
parts of I.S. is systemic
not confined to the initial infection site but work throughout the body
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parts of I.S. have memory
recognize and mount an even stronger attack to the same antigen the next time
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how to vaccines work
you take covid vaccine and now when you get covid next time the body has a quick response and doesn’t make virus multiply and make you sick
53
The most important component of the immune system is
Self/Non-self Recognition
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what is Self/Non-self Recognition
achieved by every cell displaying a marker based on the major histocompatibility complex (MHC)
55
what are mhc
group of genes that code for cell surface proteins essential for the immune system
56
Any cell not displaying marker MHC is treated as non-self and attacked
true
57
examples of autoimmune diseases
multiple sclerosis (MS), sudden sensorineural hearing loss, rheumatoid arthritis, and Type 1 diabetes
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Sometimes the process breaks down and the immune system attacks the body’s own cells
autoimmune disease
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instances when the immune response to innocuous substances is inappropriately overwhelming
allergies
60
two main fluid systems in the body that are partof the immune system and also transport agents of this system
Hematopoietic (blood) and Lymphatic systems
61
cells of hematopoietic system
Erythrocytes or red blood cells (RBCs) - Carry oxygen
Leukocytes or white blood cells (WBCs) - Fight infections
Thrombocytes or platelets - Help control bleeding
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Carry oxygen
Erythrocytes or red blood cells (RBCs)
63
fight infections
Leukocytes or white blood cells (WBCs)
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help control bleeding
Thrombocytes or platelets
65
simpe substances that elicit this response of allergies is called
allergens
66
clear, transparent, and colorless
lymph
67
what is lymph
clear, transparent, and colorless
flows in the lymphatic vessels alongside the blood vessels, bathing tissues and organs in its protective covering
68
examples of allergens
dust & pollen
69
what are lymph nodes
Along the lymph vessels
filters lymphatic fluid
70
area where antigens are usually presented to the immune system
lymph nodes
71
RBCs, WBCs, & thrombocytes and platelets all develop from a common cell in the bone marrow
true
develop at the pluripotent hematopoietic stem cell
72
how do the different cell types differentiate
They differentiate into these different cell types by interactions with dozens of glycoproteins called hematopoietic growth factors
73
glycoproteins
hematopoietic growth factors
74
what are pluripotent hematopoietic stem cell
whatever organ or system they go in, they will becomes cells or organs of that area
type of stem cell that can differentiate into cells from any of the three germ layers in the body, and are thought to be the source of most cell types.
75
what are glycoproteins
they have a carbohydrate (sugar) attached to proteins
76
hematopoietic growth factors
naturally occurring substances which regulate the production of circulating blood cells
77
what are the two divisions of leukocytes
Granulocytes (containing large granules in the cytoplasm)
Agranulocytes (without granules)
78
what are leukocytes
WBCs
79
difference between granulocytes and agranulocytes
Granulocytes (containing large granules in the cytoplasm)
Agranulocytes (without granules)
80
what are agranulocytes
lymphocytes (single large nucleus, no granules)
81
what are lymphocytes
single large nucleus, no granules)
82
what do lymphocytes contain
Consisting of B cells, T cells, and monocytes
Lymphocytes circulate in the blood and lymph systems and make their home in the lymphoid organs
83
primary organs of the immune system include
Bone marrow (B lymphocyte production)
Thymus gland (T lymphocyte production)
T and B cells are the main cells of the lymphatic system
84
where does everything come from
Bone marrow
85
B lymphocyte production
bone marrow
86
T lymphocyte production
thymus gland
87
They are produced in the bone marrow and mature in the thymus
t cells?
88
main cells of the lymphatic system
t and b
89
differentiate between t and b cells
T cells are involved in cell-mediated immunity
Cell-mediated immunity does not depend on antibodies for its adaptive immune functions and is primarily driven by mature T cells
B cells are involved in humoral immunity (related to antibodies)
Humoral immunity produces antigen-specific antibodies and is primarily driven by B cells
90
what is the function of t and b cells
to recognize specific “non-self” antigens, during a process known as antigen presentation
91
involved in humoral immunity (related to antibodies)
b cells
92
are involved in cell-mediated immunity
t cells
93
cell mediated immunity
Cell-mediated immunity does not depend on antibodies for its adaptive immune functions and is primarily driven by mature T cells
94
humoral immunity
Humoral immunity produces antigen-specific antibodies and is primarily driven by B cells
95
how does immune system recognize cells?
protein that sits on the membrane of all cells
- every cell displaying a marker based on the major histocompatibility complex (MHC)
96
secondary organs for the immune system include (at/near portals of entry for pathogens)
Adenoids, tonsils, spleen, lymph nodes, Peyer's patches (within the intestines), and appendix
97
WBCs originate in the _______ and then migrate to the________organs
bone marrow
other primary and secondary lymph
98
what is another term for antibodies
immunoglobulins (Igs)
99
what are antibodies/Igs
play a very important role in the immune system
These are large, Y-shaped proteins secreted by the plasma and are offspring (clones) of primed B cells
100
what are antibodies used for
used by the immune system to identify and neutralize foreign objects such as bacteria and viruses
antibody recognizes a unique molecule of the pathogen called an antigen
101
antibody recognizes a unique molecule of the pathogen called
an antigen
102
Antibodies constitute the _____ part of the blood proteins
gamma globulin
103
The antibodies inactivate antigens through various mechanisms
true
104
Development of Antibodies or Immunoglobulins (Igs)
immuno competent but immature b lymphocyte is stimulated to maturity
When an antigen binds to its surface receptors, the B cell is sensitized or primed and undergoes clonal selection reproducing by mitosis
Most of the family of these clones become plasma cells
These cells, after an initial lag (up to 14 days), produce highly specific antibodies at a rate of ~ 2000 molecules/second for 4 to 5 days
The other B cells become long-lived memory cells
105
plasma cells, after an initial lag (up to 14 days), produce highly specific antibodies at a rate of ~ 2000 molecules/second for______ days
4 to 5 days
This action is needed to neutralize the antigen quickly
106
what is the primary immune response
plasma cells, after an initial lag (up to 14 days), produce highly specific antibodies at a rate of ~ 2000 molecules/second for______ days
107
what do the other b cells do in memory cells
They will participate in the secondary immune response which is quicker and more effective
108
most abundant Igs
IgG - 76%
109
IgG dominates in the secondary immune responses
true
110
IgG is the only antibody that crosses the
placental barrier to the fetus
111
dominates in primary immune responses
IgM
112
responsible for the 3 to 6 month immune protection of newborns that is conferred by the mother
IgG
113
why is IgG important for babies and fetuses
IgG is the only antibody that crosses the placental barrier to the fetus
responsible for the 3 to 6 month immune protection of newborns that is conferred by the mother
newborn immune system is immature and cannot protect the fetus or the newborn
takes around 3 mos to have any immune response
114
waht is the IgG
most dominant immunoglobulin and only one to cross placental barrier to provide immunity to fetus
115
Immunity can be either
Natural or artificial
Innate or acquired/adaptive
Active or passive
116
Active natural
contact with infection
Develops slowly, is long term, and antigen specific
117
Active artificial
immunization-vaccines)
Develops slowly, lasts for several years, and is specific to the antigen for which the immunization was given
118
Passive natural
trans-placental mother-to-child)
Develops immediately, is temporary, and affects all antigens to which the mother has immunity
119
Passive artificial
injection of gamma globulin
Develops immediately, is temporary, and affects all antigens to which the donor has immunity
120
what do vaccines offer
Active Artificial Immunization
121
how do vaccines teach the body's immune system to recognize and block viruses
Vaccines activate T cells to detect viruses, with their activity peaking 10 to 18 days after vaccination. They also instruct B cells to produce antibodies that block the virus from replicating and direct T-killer cells to destroy infected cells
122
what do all types of vaccines do
All vaccines leave the body with "memory" T-lymphocytes and B-lymphocytes that remember how to quickly fight the specific virus if it reappears in the future.
123
explain how covid 19 vaccines work
COVID-19 mRNA vaccines introduce a "spike protein" from the virus into our muscle cells, which use it to produce the protein. Once spike protein is made, the cells break down and eliminate the original injected spike proteins. The immune system recognizes the spike protein as foreign, builds an immune response, and creates antibodies, similar to a natural infection. This process trains the body's memory cells to recognize and quickly defend against future COVID-19 infections, providing protection without the risk of illness.
124
The target cells in the immune system of immediate-type reaction are
mast cells and basophils (type of WBC)
125
where are mast cells found
in connective tissue and basophils
126
similarities between mast cells and basophils
They both contain histamine, an important chemical for fighting infections
127
what is a negative of histamines
when released into the body inappropriately or in too high a quantity, histamine is a potentially devastating substance resulting in allergic reactions
128
It takes between _____ days of sensitizing exposure for the mast cells and basophils to become primed with IgE antibodies
7 to 10
129
what is the allergic cascade
explains how the body overreacts to harmless substances, leading to the symptoms we associate with allergic reactions
second exposure to the same allergen that causes a destructive dominoeffect in the system
130
may act as specific antigens to mast cells and basophils
drugs or drug metabolites
131
part of the immune system and contains granules rich in histamine and heparin(anticoagulant to prevent blood clots)
mast cell
132
Antigens combines with adjacent molecules of the IgE antibodies that have become attached to the mast or basophil cell surface
The antigen-antibody combination causes release of histamine resulting in allergic manifestations
true
133
type 1 reactioin
mediated by IgE
134
what are the most severe reactions
anaphylaxis
asthma symptom
dermatitis
135
type II reactions are mediated by
IgG & IgM
136
what happens in type II reactions
hemolysis (break down) of red blood cells (blood disorder)
e.g., some forms of anemia, blood transfusion reactions and some types of tissue transplant rejection
137
Type III reaction mediated by
IgG
138
type III reactions caused by IgG
arthralgia (muscle/joint pain) and fever
lymphadenopathy (swollen lymph nodes)
139
which immunoglobulin is most active in each type of reactions and an example of each
Type I reaction medicated by IgE
anaphylaxis
typeII reaction mediated by IgG, IgM
some forms of anemia
type iii reaction mediated by IgG
arthralgia (muscle/joint pain) and fever
lymphadenopathy (swollen lymph nodes)
140
what is anaphylaxis
anaphylactic shock is a severe, progressive, whole-body allergic reaction to a chemical that has become an allergen
141
what happens in anaphylaxis
After being exposed to a substance such as bee sting venom and suffering a mid allergic reaction, the person's immune system becomes sensitized to it
When the person is exposed to that allergen again, anaphylaxis happens quickly after; it is severe, and potentially life threatening
142
Some drugs may cause an anaphylactic-like (anaphylactoid) reaction when people are first exposed to them
yes
e.g., morphine, radiographic contrast material like iodine, aspirin, etc.
143
anaphylactoid
These are systemic not immune system reactions that do NOT require prior sensitization to an antigen as required in true anaphylaxis
The symptoms, risk of complications, and treatment, however, are the same for both types of reactions
ex:Some drugs may cause an anaphylactic-like (anaphylactoid) reaction when people are first exposed to them like aspirin
144
Anaphylaxis is life-threatening and can occur at any time within minutes to a couple of hours
true
145
common causes of anaphylaxis
Drugs - penicillin & anesthesia meds
Food allergies - peanuts & shellfish
Insect bites - bee stings and fire ants
146
risks of anaphylaxis
history of any type of allergic reaction
For some people it may appear to occur with no known cause
But that is usually because first exposure caused mild/no symptoms
147
immune response =
anaphylaxis
148
no immune response and why it can happen with the first exposure =
anaphylactoid
149
During anaphylaxis, tissues in different parts of the body release histamine and other substances, which causes the airways to tighten and leads to other symptoms like
Abdominal pain
Anxiety
Chest discomfort or tightness, wheezing, pulmonary edema
Cough and difficulty breathing
Difficulty swallowing due to swelling of the throat
Dizziness, light-headedness, unconsciousness
Skin redness, hives, itchiness, pale and blue skin (from lack of O2)
Nausea/vomiting and diarrhea
Weak and rapid pulse and low blood pressure
Abnormal heart rhythm
Slurred speech
Swelling of the face, eyes, and/or tongue
Mental confusion
150
signs and symptoms of anaphylaxis
lip swelling, rashes, difficulty breathing, skin redness, abdominal pain
151
treatment for anaphylaxis
Epinephrine (adrenaline) to reduce body's allergic response
Oxygen to help compensate for restricted breathing
Intravenous (IV) antihistamines and cortisone to reduce inflammation and swelling in order to open airways
A beta-agonist (such as albuterol) to relieve breathing symptoms
152
reduce body's allergic response
Epinephrine (adrenaline)
153
help compensate for restricted breathing
O2
154
reduce inflammation and swelling in order to open airways
Intravenous (IV) antihistamines and cortisone
155
relieve breathing symptoms
beta-agonist (such as albuterol)
156
An anaphylactoid or an anaphylaxis/anaphylactic shock is an EMERGENCY medical condition
true
157
examples of teratogen drugs to fetal development
isotretioin (Accutane) for severe cystic acne (99% teratogenic)
Thalidomide, first marketed in the late 1950s as a sedative and was used in the treatment of nausea in pregnant women
Banned by 1961 in most countries due to limb reduction defects (phocomelia) in offspring of mothers who took the drug
Other effects later attributed to thalidomide included
Congenital heart disease, malformations of inner and outer ear, and ocular abnormalities
158
thalidomide effects
limb reduction defects (phocomelia) in offspring
Congenital heart disease, malformations of inner and outer ear, and ocular abnormalities
159
infectious teratogens
rubella (German measles)
160
causes from rubella
Can cause significant hearing loss, heart, neurological, and eye defects
161
environmental factors that are teratogen
radiation
Can cause miscarriage, birth defects, intellectual disability, intrauterine growth retardation, and childhood cancers like leukemia
162
causes from radiation
Can cause miscarriage, birth defects, intellectual disability, intrauterine growth retardation, and childhood cancers like leukemia
163
Drugs that are teratogenic may still be approved by the FDA, if
The therapeutic benefits outweigh the risk
Physician labeling clearly contraindicates use during pregnancy
164
benefits of taking thalidomide
useful for treating leprosy, multiple myloma, and some AIDS symptoms
165
why does fda still approve teratogenid drugs but not drugs that cuase cancers
only affects small segment of populatioin and labeling can control it
166
improve risk vs. benefit assessment of drugs used for pregnant and nursing mothers
The FDA implemented new Pregnancy and Lactation Labeling Rule (PLLR-The Final Rule) (in effect June 2015
167
PLLR recommendations categories
fetal risk summary
clincial considerations
data
168
describe fetal risk summaries
Characterizes the likelihood, from both human and animal data, that a drug increases the risk of four types of developmental abnormalities
Structural anomalies, fetal and infant mortality, impaired physiologic function, and alterations to growth
169
4 categories of fetal risk summary
Structural anomalies, fetal and infant mortality, impaired physiologic function, and alterations to growth
170
clincal considerations
Discussing fetal risk from inadvertent exposure and prescribing decisions based on drug effects on labor, delivery, and fetus
171
data
Detailed discussion of available data; human data appears before animal data
172
The human genome contains ~ 3 billion nucleotides making up ~ 25,000 genes that may encode > 100,000 proteins
true
173
what is pharmacogenomics
aka pharmacogenetics
study of the role of the genome in drug response – a combination of pharmacology & genetics
fast emerging field that studies how the genetic makeup of a patient affects their response to drugs
174
combo of pharmacology and genetics
pharmacogenomics
175
fast emerging field that studies how the genetic makeup of a patient affects their response to drugs
pharmacogenomics
176
Drug target receptors are sufficiently common in the population such that most medications act as intended on most people
true
177
examples of inter individual differences
in genes that encode these drug targets OR
in genes that encode proteins for drug metabolism
178
Genomes of humans are ______ identical regardless of race, ethnicity, or geographic region
~ 99%
179
this 1% leads to
possibility of ~3 million differences in individual base pairs throughout the genome
180
If one nucleotide in a specific position is exchanged with another nucleotide, the alteration is referred to as a
Single nucleotide polymorphism or SNP (pronounced “SNIP”)
181
Majority of nucleotide variations are
SNPs
182
other mutation or variation examples
Insertions, deletions, duplications, and translocations of one or more nucleotides or even entire chromosomes
183
SNPs or other genetic variations can affect protein amount or function by
altering coding sequence of transcription or mRNA translation, which could be pharmacologically important
184
Genetic polymorphisms in pharmacokinetics are common in major enzymes that metabolize both
phase I and II
185
example of polymorphisms
succinylcholine by the enzyme serum cholinesterase
186
inherited variation of enzymatic hydrolysis of the short-acting muscle relaxant
succinylcholine by the enzyme serum cholinesterase
187
1 in ~ every 2000 Caucasians has a genetic alteration of the plasma enzyme serum cholinesterase
true
188
enzyme serum cholinesterase function
to metabolize the muscle relaxant succinylcholine (given IV with general anesthesia)
189
why is it important to know the ethnicity with polymorphism
190
The altered enzyme has a 1000 fold decreased affinity for succinylcholine, causing
Decreased metabolism, slow elimination, & prolonged circulation
191
A sufficiently high plasma level of succinylcholine would lead to respiratory paralysis and death if not supported with artificial respiration till the drug clears from the body
true
192
cytochrome P450 (CYP) liver enzymes metabolize >____ classes of drugs
30
