1D1 Flashcards
1
Q
IV abbreviation
A
intravenous
2
Q
IM abbreviation
A
intramuscular
3
Q
SC abbreviation
A
subcutaneous
4
Q
what are the barriers that the drug can pass
A
GI tract - enteral
IV - parental “around GI”
5
Q
BSA equation
A
square root (ht*wt/3600)
6
Q
inches to cm
A
2.54 cm/in
7
Q
lbs to kg
A
1kg/2.2lbs
8
Q
what is the full flow in adults
A
50 cc/kg
9
Q
what is the full flow in neonates
A
150 cc/kg
10
Q
what is the CI full flow for adults
A
2.4
11
Q
what is the CI full flow for neonates
A
2.6-3.0
12
Q
what is pharmacokinetics
A
what the body does to a drug
refers to the movement of drug into, through, and out of the body
13
Q
pharmacokinetics is the time course of its
A
absorption, bioavailability, distribution, metabolism, and excretion
14
Q
what is pharmacodynamics
A
what a drug does to the body
the relationship b/w drug concentration at the site of action and the resulting effect
15
Q
what does pharmacodynamics involve
A
receptors, binding, post receptor effects, and chemical interactions
16
Q
the effect of a drug present at the site of action is determined by
A
that drug’s binding with a. receptor
17
Q
what is drug absorption
A
is the transfer of a drug from the site of administration to systemic circulation.
18
Q
the main factor that relates to absorption is
A
the route the drug enters the body
it come in contact w/ several membranes. Drugs pass some membranes but not others
19
Q
Two major routes of administration
A
– Enteral: Administration by mouth, enters through mucosal membrane
– Parenteral: Administration of a drug directly into systemic circulation or vascular tissue
20
Q
Physiological considerations in absorption are :
A
– blood flow
– total surface area
– time of arrival of the drug and time of drug at absorption site.
21
Q
Other considerations for absorption are
A
solubility, chemical stability and how soluble the drug is in lipids
22
Q
Enteral Administration (PO)
A
Oral Administration, Sublingual, Buccal, and Rectal
23
Q
advantages of enteral admin
A
Can be self administered and over-dose can be over come by antidote (activated charcoal).
24
Q
disadvantages of enteral admin
A
Drugs absorbed in the GI tract enter portal (hepatic) circulation before being distributed into systemic circulation. These drugs will undergo first pass metabolism in the liver which limits the efficacy of the drug. First pass metabolism decreases the amount of drug that enters systemic circulation.
25
Parenteral
direct delivery of drugs into systemic circulation
26
what are some examples of parenteral delivery
```
– Intramuscular (IM) Lipid based drugs are absorbed slowly and aqueous based drugs are absorbed rapidly.
– Intravascular (IV)
– Subcutaneous (SC)
– Intrathecal (IT)
– Intraperitoneal (IP)
– Intradermal (ID)
– Inhalation
```
27
advantages of parenteral delivery
Provides rapid onset of pharmacologic effect and maximum control over circulating levels of drug. A
28
disadvantages of parenteral delivery
Unlike drugs administered via the GI tract, drugs given IV cannot be recalled by strategies like emesis or binding to activated charcoal. Requires specialized training to gain IV access. Potential risk of systemic infection from IV site.
29
Bioavailability
is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation
30
if 100 mg of a drug is given and 70 mg are absorbed unchanged into systemic circulation, what is the bioavailability
0.7 or 70 %.
31
Factors that influence bioavailability include:
irst pass hepatic metabolism
| – Solubility of the drug!
32
fat is very hydrophilic drugs are poorly absorbed because
they cannot pass through lipid dense cell membranes.
33
Extremely hydrophobic drugs are also poorly absorbed because
the are insoluble in aqueous body fluids.
34
what drugs are absorbed most readily
small non-ionized lipid soluble drugs
35
drug associated factors
- passive diffusion
- facililtated diffusion
- aqueous channels
- active transport
36
Passive diffusion:
fast for lipophilic, nonionic and small molecules. Slow for hydrophilic Ionics, or large molecules
37
Facilitated diffusion
is the process of spontaneous passive transport of molecules or ions across a biological membrane via specific transmembrane integral proteins
Chemically similar drugs compete for a carrier
38
Aqueous Channels
Small hydrophilic drugs diffuse by concentration gradients (high >>>low) thru aqueous pores.
39
Active transport:
Same as facilitated diffusion except that ATP powered drug transport against concentration gradient (low>>high)
40
Patient-associated factors that affect drug absorption
– food in GI tract
– renal disease
– liver disease
41
Drug Distribution
drug leaves the bloodstream and enters the extra-cellular fluid and or cells of tissue.
42
Drugs are distributed into
major body fluids
43
Delivery of a drug to the extra-cellular fluid depends on: (4)
1. blood flow
2. capillary permeability: membrane permeability
3. degree of protein binding to plasma proteins
4. relative solubility of the drug
44
Some drugs can not cross the blood-brain barrier therefore
they will not work in the brain
45
what are some barriers the drug must break thru
blood brain barrier
blood-placenta barrier
blood-testes barrier
46
the binding of drugs to proteins such as albumin results
in less drugs free (not bound) in the blood available to enter the target organ.
47
Depot Storage
a body area in which a substance, e.g., a drug, can be accumulated, deposited, or stored and from which it can be distributed
48
Lipophilic drugs get stored and accumulate in
fat
these drugs are released slowly from fat stores
49
calcium binding drugs accumulate in
teeth and bone
50
heparin is heavily bound to
proteins
51
Volume of distribution (Vd ):
calculated value of volume that would be required to contain the d
administered dose that was evenly distributed at the concentration measured in plasma.
52
if the Vd = 3 liters, where does it get distributed to?
distributed in plasma only (plasma volume = 3 liters).
53
Vd = 16 liters is likely distributed in
extracellular water (3L+13L)
54
Vd >46 liters is likely sequestered in
a depot because the body only contains 40-46 liters of fluid.
55
In general, drugs with a short T1/2 have
a small VD and rapid clearance
56
Drugs with a long T1/2 (lipid soluble) have
a larger VD and slower elimination rate.
57
Drug Metabolism
the biotransformation process of making a drug more polar and water soluble
58
Biotransformation occurs mainly in
the liver and is therefore often called hepatic metabolism.
59
Metabolic reactions can transform
– An active drug into less-active or inactive forms
| – a PRODRUG (inactive or less-active drug) into a more active drug (Plavix)
60
drug metabolism is split into what two phase
- phase 1 (non-synthetic)
| - phase 2 (synthetic)
61
phase 1 of drug metabolism is when
drugs oxidized or reduced to a more polar form
62
what is an example of phase 1 drug metabolism
Cytochrome P450 (liver microsomal) drug oxidation, reduction and hydrolysis
63
phase 2 of drug metabolism is when
a polar group is conjugated to the drug
| this increase the clarity of the drug
64
Drugs undergoing phase II reactions may have already undergone
Phase 1
65
what is an example of phase 2 drug metabolism
glutathione
66
Drug Excretion
the elimination of the un-metabolized drug and its metabolites from the body
67
most drugs are excreted in
urine via active glomerular filtration
-others in feces or expired air
68
what is enters-hepatic ciruclation
when drugs are excreted in the feces, the bile may become concentrated before entering into the intestines
this can extend the duration of the drug in the body
69
Drug excretion in the urine is affected by
Glomerular filtration
Tubular Secretion
Tubular Reabsorption
70
Because drugs, metabolites, and toxins are concentrated in the kidney, the kidney is at risk for what
chemical induced toxicity
-renal failure patients may be due to drug accumulation
71
drug clearance
Volume of fluid that would be completley cleared of drug per unit time
- can be directly measured in the body
- calculated value in liters/hr
72
clearance equation
Elimination rate (mg/hr)/ Drug Concentration (mg/L)
73
Elimination half-time (t 1/2)
time necessary for plasma concentration to decrease by 50%.
- shortened with small Vd and rapid clearance
- Prolonged with high lipid solubility and large Vd.
74
Zero order kinetics
rate of elimination is constant, independent of drug concentration (i.e. alcohol, phenytoin, salicylates)
75
First order kinetics
rate of elimination occurs dependent of drug concentration
| - the higher the t1/2, the less percentage of drug remains
76
if the t 1/2 = 1, how much remains
1/2
77
if t 1/2 = 5, how much remains?
3.125%
78
anesthetic properties of hypothermia
Increased solubility of volatile anesthetics
79
during hypothermia, fluid shifts from ____ space to ____ space altering ___
intravascular space to interstitial space altering Vd
80
hypothermia causes a ____ absorption of drugs administered routes other than IV
decreased
81
drugs with pulmonary uptake are sequestered during
CPB and released when CPB is terminated
82
hepatic clearance of drugs altered by
altered hepatic blood flow and drugs administered during CPB like vasopressors
83
hypothermia causes activation of what
autonomic and endocrine reflexes which alters peripheral vasoconstriction
84
peripheral vasoconstriction results in decreased re-uptake of
drugs from peripheral tissues
85
hypothermia inhibits
enzyme function therefore decreasing metabolic function
86
hypothermia decreases in clearance causes
increased t1/2
drug excretion secondary to decreased GFR, renal perfusion, and tubular secretion
87
hypothermia causes a decrease release of
excitatory neurotransmitters such as glutamate and glycine
88
hemodilution causes a sudden increase in
Vd due to prime volume
89
hemodilution cases a decrease in _____, which will result in alteration of bound vs free fraction of drugs
protein binding
90
hemodilution causes a immediate decrease in what? which will ultimately affects drugs sequestered to RBCs
Hematocrit
91
hemodilution dilutes
plasma level of drugs
92
hemodilution alters what, which will affect distribution and clearance
blood organ flow affecting distribution and clearance
93
once hemodilution occurs, ,the drug travels where?
down it's concentration gradient to facilitate equilibrium, restoring the state of increased free fraction during and after CPB
94
hemodilution causes ____ ____ between central and peripheral compartments
volume distribution
95
during Hemodilation, what acid and base and electrolyte changes occur? (3)
a) Acidosis from CPB affects response to catecholamine
b) pH vs alpha stat blood gas strategy affect degree of ionization and protein binding
c) acid-base changes can alter electrolyte balance
96
what size membrane is the hemoconcentration?
70 kDa membrane to remove plasma water
97
what can and can't pass through hemoconcentrator
can't b/c too large: cellular components in blood, RBC, WBC, Plasma, platelets
can: small water soluble drugs, ions, metabolites
98
Sieving Coefficient
is the ratio of ultrafiltrate [Cf ] of a solute to the plasma [ Cp]
of that solute. In other words, how readily a solute is pulled off
99
cell save causes a loss of what
blood plasma
| drugs that are bound to plasma proteins and drugs that are circulating free in plasma
100
in cell saver, there is an increase in _____ and decrease in _____
increase in edema
| decrease in oncotic pressure
101
pharmacodynamics is
what a drug does to the body
102
pharmacodynamics involves
- receptor binding
- post receptor effects
- chemical interactions
103
pharmacodynamics is the relationship b/w
drug concentration at the site of action and the resulting effect
including: time course, intensity, adverse effects
104
the effect of a drug present at the site of action is determined by
that drug's binding with a receptor
105
the plasma membrane of a human cell has what kind of permeable and what does it help control?
selectively permeable
helps control what moves in and out of the cell
106
the surfaces of plasma membranes generally have what on them
studded with proteins that perform different functions
107
protein molecules are referred to as
receptors
108
molecules which bind to receptors are called
ligands
109
what is an example of ligands
neurotransmitters
| hormones or drugs
110
Drug receptors
Any cellular macromolecule that a drug binds to initiate its effects.
111
receptors are
proteins or glycoprotein present on the cell surface, on an organelle within the cell, or in the cytoplasm
112
when a drug bind to a receptor, one of these actions occur:
1. ion channel is opened or closed
2. biochemical messenger "2nd messender" is activated
3. a normal cellular function is physically inhibited
4. a cellular function is "turned on"
113
definition of drug
chemical substance that interacts with a biological system to produce a physiologic effect.
114
the more of an agonist drug occupying a receptor...
the greater the response
115
antagonsists are drugs that
- bind to their targets and form a drug- receptor complex without causing activation or response
- can block the receptor to its endogenous activator, therefore blocking normal function
116
agonists activate the receptors of a produce a response known as
full agonists
-have positive efficacy
117
receptor occupancy by antagonists is important if the drug is a
competitive antagonist
competes for occupancy with another drug or with the receptor's normal mediator
118
the amount of drug occupying will determine
any response
119
Competitive Antagonist
A drug that “competes” with the endogenous ligand for binding to the active site on a receptor.
120
how can competitive antagonist be overcome
by increasing the concentration of the agonist.
121
Chemical Antagonist
: a drug that binds with another drug that rendering it inactive
122
Irreversible Antagonist:
A drug antagonist that cannot be overcome by increasing the agonist concentration (covalent modification).
123
Affinity
is a measure of the tightness(strength) that a drug binds to the receptor
124
Intrinsic activity
is a measure of the ability of a drug once bound to the receptor to generate an effect activating stimulus and producing a change in cellular activity.
125
drugs that interact with receptors can be classified as being
agonists or antagonists
126
Agonists once bound to the receptor can....
activate or enhance cellular activity
can be full, partial, or inverse
127
Antagonists can prevent
the binding and the action of agonists
128
Antagonists can be
competitive or non-competitive
129
Dissociation Constant (KD)
the concentration of drug required in solution to achieve 50% occupancy of its receptors
130
Efficacy
the degree a drug is able to induce maximal effect.
131
If drug A decrease MAP by 20 mmHg and drug B decreases MAP by 10 mmHg, which has greater efficacy?
A has greater efficacy than drug B
132
Potency
amount of drug required to produce 50% of the maximal response
that the drug is capable of inducing
133
Effective Concentration 50% (EC50)
Concentration of drug which induces a specific clinical effect in 50% of the subjects to which the drug is given
134
Lethal Dose 50% (LD50)
Concentration of drug which induces death in 50% of the subjects which the drug is given
135
Therapeutic Index
measure of the safety of a drug.
| Calculated by dividing LD50/ EC5
136
Margin of Safety
margin between therapeutic and lethal dose of drug
137
Altered Absorption
drug may inhibit absorption of another drug across biological membrane: ie: anti-ulcer drugs coat the stomach and decrease GI absorption of other drugs
138
Altered Metabolism
drugs can alter P450 isoenzymes wich affect other drug actions.
139
Plasma Protein competition
drugs that bind plasma proteins may compete w/other drugs for that binding site
140
Altered Excretion
drugs may act on the kidney to reduce excretion of specific agents
141
addition
response elicited by combined drugs is Equal to the combined responses to the individual drugs. 1+ 1 = 2
142
Synergism
response elicited by combined drugs is Greater than the combined responses of individual drugs. 1 +1 = 3
143
Potentiation
a drug which has no effect enhances the effect of the second drug. 0 + 1 = 2
144
Antagonism:
rug inhibits the effect of another drug. Usually, antagonist has no inherent activity. 1 + 1 = 0
145
Tolerance
a decreased response to a drug. Clinically, the dose of a drug must be increased to achieve same effect: ie long term pain management is a metabolic tolerance
146
Downregualtion
is decrease number of receptors binding sites ( tolerance) caused by continuous stimulation
147
Upregulation
occurs by lack of stimulation causing an increase in the number of receptor binding sites (sensitivity)
148
Dependence
a patient needs a drug to “function normally”. Detected when drug is stopped a withdrawal symptoms occur.
149
Withdrawal
drug is no longer administered to dependent patient. Symptoms often are the opposite of the effects achieved by the drug.
150
Cross tolerance / cross dependence:
tolerance or dependence develops to different drugs which are chemically or mechanistically related. : Methadone replaces heroin
151
how is drug metabolism related to age?
drug metabolism is underdeveloped in infants and depressed in the elderly.
152
drugs and pregnancy relationship
Some drugs can cross the placenta and affect the fetus. Some drugs enter the milk production
153
drug metabolism and Smoking and drinking habits relationship
Both smoking and drinking induce P450 liver enzymes. This accelerates the metabolism of some drugs. Some prodrugs may be metabolized to more active forms and cause toxicity.
154
drug metabolism and Liver and Kidney disease relationship
Dose reductions maybe necessary in patients with liver or kidney dysfunction. Failing kidneys excrete fewer drug metabolites. Failing livers metabolize drugs poorly.
155
Pharmacogenetics:
some genetic conditions affect drug metabolism
156
Drug interactions
what other medications are patients taking
157
Psychosocial factors
poor patient compliance is cause of many drug failures.
158
what does heparin cause
anticoagulation via binding with antithrombin III and increase its anticoagulant effect at least 1000-fold
159
once AT III is activated by heparin, what happens
the major physiologic inhibitor of the conversion of prothrombin II to thrombin IIa and factors IXa and Xa
160
pump prime dose of heparin
5,000 to 10,000 units
161
full dose heparin
300-400 units/kg given by anesthesia prior to cannulation
162
1/2 life of hepatin
1-2 hrs
163
reversal of heparin
protamine sulfate (antagonist to heparin)
164
what are antifibrinolytics
aminocaproic acid (Amicar) / tranexamic acid (TXA)
165
both antifibrinolytics inhibit
fibrinolysis by binding with plasminogen
166
once antifibinolytics bind with plasminogen, what does that cause
plasminogen cannot bind to fibrin and cannot activate plasmin
no plasmin activation = no clot breakdown
167
pump prime dose of amicar and TXA
amicar: 10 grams
TXA: 1 gram
168
what is albumin
blood volume expander
169
5% albumin =
oncotically equal to human plasma
170
25% albumin =
5x oncotically equal to human plasma
171
albumin may be added to
increase the oncotic load of pump prime to help prevent third spacing of crystalloid prime
172
what is mannitol
osmotic diuretic that prevents reabsorption of sodium and water in the renal tubule
173
mannitol increase
unrinary output
174
mannitol is a ___ ___ ____ scavenger
mannitol is an oxygen free radical scavenger
175
what must you make sure before adding mannitol to prime
make sure your pt has working kidneys before adding to prime
176
vasopressors treat
hypotention
177
vasopressors are used to
increase systemic vascular resistance (SVR)
178
what are two common vasopressors
phenylephrine and norepinephrine
179
what does phenylephrine bind to and cause
binds to alpha1 receptors causing vasoconstriction
| -mimics the effect of endogenous NE
180
phenylephrine adult dose
100 mcg/ml
181
what does norepinephrine acts at
alpha1 and alpha2 receptors to elicit vasoconstriction
182
norepinephrine adult dose
16 mcg/ml
183
which vasopressor is more potent vasoactive drug?
phenylephrine
184
what are the anti-arrhythmia drug? (3)
1. magnesium
2. lidocaine
3. amiodarone
185
magnesium is given when
cross clamp is removed to prevent atrial dysthymia's (SVT)
adult dose: usually 2 grams
186
what is lidocaine
Sodium channel blocker that is given when cross- clamp is removed to prevent ventricular dysrhythmia’s
dose: 1-2 mg/kg
187
what does amiodarone affect
Affects multiple channels: Potassium (K) channel
blockers
-extend the plateau phase of the action potential by blocking K+ channels
-They effectively prolong repolarization
dose: 150 mg
188
vasodilators treat
hypertension
189
what are some vasodilators
nitroglycerin and nitroprusside
190
nitroglycerin works by
relaxing the vascular smooth muscle inside blood vessels and increasing the supply of blood and oxygen to the heart while reducing its workload
191
what is nitroglycerin MOA
via release of nitric oxide (NO)
dilates venous system bigger then arterial system
used to treat high BP and angina
192
nitroprusside primarily dilates
arterial system with little effect on venous system
193
MOA of nitroprusside
via Nitric Oxide but liberated through different mechanism
| -toxic at high doses over prolonged time
