Pharm Unit 1 Flashcards
(185 cards)
1
Q
Pharmacokinetics definition
A
how the body handles the drug
2
Q
Pharmacodynamics definition
A
effect of the drug on the body
3
Q
ADME
A
absorption, distribution, metabolism, excretion
4
Q
What is area under the curve
A
the actual exposure of the body to the drug after administration
5
Q
what is Cmax
A
Maximum plasma drug concentration
6
Q
What is Tmax
A
time at which Cmax occurs
7
Q
How does solubility affect ADME
A
lipophillic vs. lipophobic (the more aqueous the drug, the faster it is absorbed)
8
Q
what is partition coefficient
A
The ratio of a drug’s concentrations in oil phase vs aqueous
9
Q
how does partition coefficient affect ADME
A
the higher the partition coefficient the more likely the drug will accumulate in fatty tissues
10
Q
how does ionization affect ADME
A
charged molecules (ionized) do not cross membranes by diffusion
11
Q
how does drug pKa affect ADME
A
the higher the pKa the slower it crosses
12
Q
what is pKa
A
pKa is the pH where unionized = ionize
non-ionized: easily diffuse
ionized: do not diffuse
13
Q
what is a prodrug
A
inactive precursors that are metabolized into active metabolites
14
Q
benefits of a prodrug
A
increases drug aqueous solubility
higher aqueous solubility = higher drug concentration within body
higher aqueous solubility = more likely to remain in the blood
improve ADME
15
Q
bioavailabilty definition
A
how much of drug is available to body after first/second pass metabolism
16
Q
first pass metabolism
A
first pass = liver metabolism
17
Q
low first pass drugs
A
IV drugs
18
Q
high first pass drugs
A
calcium channel blockers, beta blockers, diuretics, lidocaine
19
Q
how does a low first pas mean
A
bypasses liver- more bioavailability
20
Q
what does F=1.0 mean
A
F = bioavailability
F = 1.0 means 100% bioavailability
or 100% of the administered drug was able to be utilized by the body for the targeted effect
21
Q
where does Phase I and Phase II metabolism occur
A
- mostly liver
- gut
- kidneys
- lungs
- skin
22
Q
Phase I
A
reduction
oxidation
hydrolysis
23
Q
Phase II
A
glucuronidation
methylation
acetylation
24
Q
what happens when a drug inhibits a CYP enzyme
A
prevents metabolism of drugs that are metabolized by the specific enzyme
concentration of drug increases
25
hepatic enzyme inhibition
decrease effect of metabolic enzyme
prevents activation of drug metabolism in liver
concentration of drug increases
26
hepatic enzyme inhibition outcome
metabolizes slower = more effective = need less drug
decreased elim rate = increased half life
27
hepatic enzyme induction
increase effect of metabolic enzyme
increases activation of drug metabolism in liver
expected concentration of drug is lower
28
hepatic enzyme induction outcome
slow onset
long duration
metabolizes faster = less effective = need more drug
increased elim rate = decreased half life
29
plasma protein binding
more bound a drug is = less active drug is
30
capacity
availability to bind
31
affinity
rate of binding
32
albumin characteristics
high capacity for binding
low affinity for binding
33
alpha 1 acid glycoprotein characteristics
low capacity to bind
high affinity for binding
34
therapeutic range/index definition
ratio of effective dose compared to lethal dose
35
good therapeutic index
wide
36
bad therapeutic index
narrow
37
first order kinetics
amount of drug eliminated is proportional to amount in body
38
drug that follows first order kinetics
epinephrine
ibuprofen
zofran
39
drug that follows zero order kinetics
alcohol
phenytoin
40
zero order connectics
amount of drug eliminated is fixed and independent of amount present in body
41
how to calculate loading dose
LD = (concentration x volume of distribution) / bioavailability (F)
42
when is half life predictable
if a drug follows first order kinetics
43
how to calculate half life
0.693/slope
44
what does half life mean for first order drugs
50% of drug is lost each half life
45
agonist definition
substance that mimics endogenous effect
46
antagonist definition
substance that blocks endogenous effect
47
partial agonist/antagonist
substance that has both agonist and antagonist properties
48
how does ED50 determine potency
lower ED50 = more potent
49
how to determine efficacy
higher the maximum point on curve
50
tolerance definition
occurs slowly over time and does not reverse rapidly after withdrawal of drug
51
Tachyphylaxis
occurs rapidly and reverses rapidly after withdrawal of drug
52
tolerance vs tachyphylaxis
tolerance = chronic
tachyphylaxis = acute
53
reversible/competitive action
drugs bind to receptor but can easily be kicked off by molecule with higher affinity
54
irreversible action
drug binds to receptor indefinitely
55
sedation definition
calming and drowsiness
56
hypnosis definition
produces drowsiness and facilitates deep sleep
57
anesthesia definition
global (reversible) CNS depression
58
what triggers MH
volatile anesthetics & succinylcholine
59
what happens in MH
mutation in RyR causes uncontrolled release of Ca2+ [IC] resulting in intense muscle contraction
60
MH key symptoms
extreme muscle metabolism
tachycardia
hypercarbia
hyperthermia
61
MH treatment
1. hyperventilate
2. give NaHCO3 (met. Acidosis)
3. give insulin/furosemide
4. give dantrolene (2.5mg/kg)
5. cool pt
6. treat other symptoms
62
barbiturates effects
*sedative
*hypnosis
*anticonvulsant
63
Barbiturates mechanism of action
increase duration of GABA Cl- chloride channel
64
barbiturate side effects
tissue damage
decrease BP / BF / ICP
increase HR
vasodilation
respiratory depression
hyperalgesia
histamine
65
Barbiturate drug interactions
precipitates w/ weak bases:
*Roc
* Lido
* Labetalol
* morphine
alcohol
benzos
opioids
66
Barbiturates Contraindications
elderly
anemic
shock
acute intermitent porphyria
67
barbiturate onset and duration
O= 10-20s (fast)
D = 8-20 min (short)
68
Barbiturate metabolism
CYP enzymes
69
barbiturate examples
phenobarbital
methohexital
70
benzos effect
sedation
anti-anxiety
hypnosis
muscle relaxation
anterograde amnesia
anticonvulsant
thrombophlebitis
71
benzos MOA
increases frequency of GABA Cl- channel opening
72
benzos side effects
pt may develop tolerance or dependance
73
benzos drug interactions
opioids: hypotension/resp depres
anesthetics: enhance potency
74
benzos onset
fast:
Midazolam < Diazepam < Lorazepam
75
benzos lipid solubility
high = high Vd
M>D>L
76
benzos metabolism
hepatic
77
benzos examples
Midazolam, Diazepam, Lorazepam
78
Midazolam contraindications
kidney failure
active metabolite alpha-hydroxy accumulates
79
benzos half life
D>L>M
(fastest onset has shortest half life)
80
flumazenil use
reverse benzos
81
flumazenil side effect
shorter duration than benzos
82
ketamine uses
anesthesia (unconsciousness)
analgesia
amnesia
depression
anticonvulsant (no change to seizure threshold)
83
ketamine MOA
NMDA receptor antagonist
- Glutamate receptor
84
ketamine side effects
dissociative anesthesia
hallucination
cardiac stimulant (incr HR/BP/CO)
incr CBF/ICP
bronchodilator
85
ketamine drug interaction
blocked by alpha and beta antagonists
decrease anesthesia requirements
- additive to VA, propofol, benzos
86
ketamin onset and duration
O: 15-30 sec (fast)
D: 10-15 min (short)
87
ketamine analgesia onset
instant
88
ketamine analgesia duration
40 min
89
Ketamine contraindications
CAD
HTN
CHF
arterial aneurysms
90
Ketamine metabolism
CYP enzymes (hepatic)
active metabolite: Norketamine
high hepatic extraction
91
Ketamine excretion
renal (incl metabolites)
92
propofol MOA
increases affinity of GABA for GABA receptor
93
propofol uses
anesthesia induction/maintenance
sedataive
antiemetic
antipruritic
anxiolytic
anticonvulsant
94
propfol side effects
dystonic movements
decrease BP/resp
decr CBF/BV/ICP
hypertriglyceridemia
propofol infusion syndrome
pain w/injection
95
propofol infusion syndrome
acidosis
myocardial failyre
rhabdo
96
propofol drug interaction
reduce dose if used with versed or fentanyl
97
Propofol CI
elderly
hypovolemia
LV dysfunction
beta-blockers
98
propofol onset/duration
onset: 10-20 s (rapid)
duration: 2-8 min (short)
99
Fospropofol
water soluble pro-drug
prolonged onset/duration
100
etomidate use
sedation/induction
hypnotic
101
etomidate MOA
increases affinity of GABA for GABA receptor
102
etomidate side effects
seizures
muscle movements
suppressed adrenal function
PONV
decr CBF/ICP
decr SVR (CO mx'd)
103
etomidate onset/duration
O: 20-30 s (rapid)
D: 5 min
104
Etomidate metabolism
plasma esterases
CYP enzymes
105
precedex use
anxiolysis
sedation
analgesia
withdrawal treatment
epidural/regional
106
precedex MOA
alpha 2a agonist
decr NE release
decr sympathetics
107
precedex side effects
decr BP
decr HR
withdrawal (prolonged use)
nausea
108
precedex drug interactions
vasodilators
hypnotics
drugs that decr HR
109
precedex onset/duration
O: rapid
D: 20 min (2 hr half life)
110
Precedex CI
renal/hepatic insufficiency =. decr dose
111
doxapram use
repiratory/CNS stimulant (used for excessive resp depression)
COPD
112
doxapram side effects
seizure, dizzy, tachycardia, PONV
113
what does ED95 in NMB's mean
dose that gives 95% twitch suppression in 50% individuals
114
NMB dose compared to ED95
usually 1-2x ED95
115
what happens when 75% of N1 receptors are bound with NMB
some weakness
116
what happens when 95% of N1 receptors are bound with NMB
paralysis
117
Upregulation
An increase in the number of receptors on the surface of target cells
cells more sensitive to a hormone or another agent
118
What conditions cause the Ach receptor expression to be upregulated
neuron lesions
trauma
sepsis/infection
119
how is NMB dosing changed when Ach receptor expression is upregulated
more nondepolarizing (less depolarizing)
more receptors for the NMB to block
120
when is Ach receptor expression downregulated
myasthenia gravis, chronic AchE inhibitor use
121
how is NMB dosing changed when Ach receptor expression is downregulated
more depolarizing (less nondepolarizing)
less receptors for the NMB to block
122
succinylcholine MOA
binds Ach receptor
persistant depolarization
phase 1: depolarizing
phase 2: desensitizing
123
succinylcholine onset/duration
O: rapid
D:Short
124
Sux duration prolonged by
high dose/infusion
- decr metabolism
- hypothermia
- psuedocholinesterase def
125
sux metabolism
plasma psuedocholinesterase
metabolite: suxmonocholine
126
succinylcholine drug interaction
cholinesterase inhibitors (increase duration)
impacts NDMR
- phase 1: antagonistic
- phase 2: additive
127
succinylcholine contraindications
MH
decreased pseudocholinesterase activity (dibucaine 20)
hyperkalemia
128
sux side effects
decr HR
twitches
hyperkalemia
incr pressures
MMR
incr histamine
MH
129
Rocuronium/vecuronium clearance
hepatic
130
pancuronium/doxacuronium clearance
renal
131
atracurium/cisatracurium clearance
hoffman
132
rocuronium side effects
incr HR
decreased dose in liver failure/pregnancy
133
pancuronium side effects
decreased dose in kidney failure
incr BP
incr HR
134
pancuronium duration
long acting (60-120min)
135
atracurium side effects
histamine release & toxic metabolite (laudanosine)
decr BP/HR/SVR
bronchospasm (asthmatics)
136
roc onset/duration
onset: 1.5min
duration: 35-75 min (intd)
137
vecuronium o/d
onset: 2-3min
duration: 45-90 min (intd)
138
atracurium o/d
onset: 2.5-3 min
duration: 30-45 (intd)
139
neostigmine MOA
AChE inhibitor
140
neostigmine onset/duration
O: 5-10 min
D: 1 hr
141
atropine/glycopyrrolate MOA
muscarinic receptor antagonist
142
glycopyrrolate dosing
0.2 mg glyco/ 1 mg neostigmine
143
Atropine onset and duration
fast onset
short duration
144
glycopyrrolate onset and duration
slow onset
long duration
145
which antimuscarinic should be used with neostigmine or pyridostigmine
glycopyrrolate
146
which antimuscarinic should be used with edrophonium
atropine
147
Edrophonium onset and duration
onset: 1-2 min
duration: 1 hr
148
Pyridostigmine onset and duration
onset: 10-12 min
duration: over 2 hr
149
neostigmine onset and duration
onset: 5-10 min
duration: 1 hr
150
how many Ach receptors have to be blocked for a decrease in twitch height
75%
151
how many Ach receptors have to be blocked for a disappearance of a twitch
90-95%
152
antimuscarinic side effects
overractive sympathetics
mental status impacts (elderly)
153
cholinesterase inhibitor side effect
parasympathetic activation
154
which opiod does not accumulate over a constant infusion
remifentanil
155
what are the different opiod receptors
mu, kappa, delta, sigma
156
opioid mechanism
bind receptors in CNS
decr VGCa++
incr VG K+
hyperpolarization
decr release Ach/Ne/5Ht/sub p
157
where are opiod receptors located
CNS and peripheral nociceptors
158
opioid side effects
hyperalgesia
tolerance/dependence
respiratory depression
decr CBF/ICP/CMO2C
chest wall regidity
miosis
pruritis
PONV
histamine
159
opioid effects
analgesia
euphoria
sedation
160
what is responsible for opioid metabolite excretion
kidneys
161
what is the risk of using meperidine with renal dysfunction
buildup of active metabolite = seizure risk
(noremeperidine)
162
where are opioids metabolized
liver
163
Naloxone MOA
opioid receptor antagonist
164
naltrexone MOA
long acting opioid antagonist
165
what are the mixed agonist/antagonist opioids
butorphanol
nalbuphine
buprinorphine
166
how can buprenorphine act as a mu antagonist
high affinity for receptor but low activity
167
mixed opiod agonist/antagonist DOA
longer (up to 10 hr)
168
naloxone onset
1-3 min
169
naloxone dosing
0.4-2 mg every 2-3 min as needed
170
COX inhibitors
aspirin, colchesine
171
COXi MOA
irreversibly inhibit COX enzymes (inhibit prostaglandin synthesis)
172
COXi side effects
bleeding
173
NSAID benefits
reduced opiod dosing
174
NSAID MOA
reversibly inhibit cox enzymes
175
NSAID side effects
renal insufficiency & bleeding
176
acetaminophen class
analgesic
antipyretic
177
acetaminophen MOA
inhibits COX 1 & COX 2
178
acetaminophen side effects
liver damage in large doses
179
acetaminophen IV onset and duration
onset: 5-10 min, duration: 4-6 hr
180
acetaminophen max dose
4g/24 hrs
181
Does acetaminophen have anti-inflammatory effects?
nope
182
Acetaminophen Contraindications
liver disease
183
NSAID contraindications
renal disease
184
how long is ketorolac indicated for?
short term- no longer than 1 week
185
how does drug pKa affect ADME
the higher the pKa the slower it crosses
