Mod 1 - Clinical Pharm 8/14 Flashcards
Quiz 1
1
Q
Define pharmacokinetics.
A
what the body does to the drug
study of ADME
2
Q
Define pharmacodynamics.
A
what the drug does to the body
3
Q
Define clinical pharmacology.
A
study of drug effects on the body with an emphasis on the patient
4
Q
Define ADME.
A
A = absorption
D = distribution
M = metabolism
E = excretion
5
Q
why is it important to know the half-life of a drug?
A
to know when the patient will wake up and when you should redose
6
Q
why is it important to know the clearance time of a drug?
A
to know when the patient will be fully recovered and when they will fully clear the drug from their body
7
Q
the rate of absorption of a drug determines what?
A
how soon the drug effects will be seen after administration
8
Q
the amount of drug absorbed determines what?
A
the intensity of the drug response (i.e., bioavailability; F)
9
Q
drug distribution is determined by 1, 2, and 3.
A
- blood flow to tissues
- ability of drug to exit vascular system
- ability of drug to enter cells
10
Q
why is metabolism an important part of drug pharmacokinetics?
A
it enzymatically alters the drug’s structure to more readily clear it from the body - biotransformation
11
Q
what are 4 therapeutic consequences of drug metabolism?
A
- accelerated drug excretion
- drug inactivation
- activation of pro-drugs
- inc./dec. toxicity
12
Q
what does phase 1 metabolism accomplish? (3)
A
- uses oxidoreductases and hydrolases to make a drug more water soluble
- oxidation/reduction/hydrolysis
- can make a drug more OR less biologically active
13
Q
what does phase 2 metabolism accomplish? (3)
A
- uses transferases to attach endogenous polar compounds to the drug
- derivatives are highly polar & easily excreted
- makes compounds LESS biologically active
14
Q
which phase of drug metabolism plays a role in drug toxicity?
A
phase 1
15
Q
what are 5 ways drugs can be eliminated from the body?
A
- urine
- bile
- milk
- sweat
- expired air
16
Q
what organ is the most important organ in drug elimination?
A
kidney
17
Q
T/F - all of the drug is absorbed, distributed, metabolized, and excreted at the same time (there is no circulation of the drug).
A
False - continuous circulation of drug molecules until all has been metabolized and excreted
18
Q
what is the AUC (area under the plasma drug concentration-time curve)?
units?
dependent on?
A
reflects actual body exposure to a drug post-administration
mg*h/L
dependent on rate of elimination & dose
19
Q
define first-pass effect.
A
elimination of drug post-administration before reaching systemic circulation (e.g., during passage of gut wall, portal circulation, liver for drug given PO)
20
Q
define steady state.
A
condition in which the average total amount of drug in the body doesn’t change over multiple dosing cycles
21
Q
how many half-lives must you have to reach steady state when giving a drug?
A
3-5
22
Q
define therapeutic index.
A
comparison of amount of therapeutic agent that causes therapeutic effect to the amount that causes toxicity.
23
Q
define therapeutic range.
A
range of drug concentrations associated with reasonable probability of efficacy w/o undue toxicity in the majority of patients
24
Q
define volume of distribution.
A
theoretic concept relating the amount drug in the body (dose) to the concentration (C) of drug measured
- AKA a drug’s propensity to either remain in plasma or redistribute to other tissue compartments
25
half-life is (directly/inversely) proportional to clearance and (directly/inversely) proportional to volume of distribution.
inversely
directly
26
with a larger volume of distribution, there is more drug distributed (to the tissues/in the plasma) compared to the opposite.
to the tissues
27
if the drug conc. in plasma is too low, the drug _1_.
if the drug conc. in plasma is too high, the drug will cause _2_.
1. elicits no response
2. toxicity
28
define permissible therapeutic range.
between the min effective conc. and the max. effective conc., above which toxicity occurs.
29
what is "balanced anesthesia"?
name 3 things we want in a properly anesthetized patient.
administering multiple drugs together to provide safe & effective anesthesia
1. loss of consciousness
2. analgesia
3. muscle relaxation
30
Volume of distribution determines a drug's what?
dose
31
Clearance is determined by what?
organ function
32
AUC is the _?_ of a drug formulation.
bioavailability
33
Distribution of a drug influences what?
volume of distribution
34
Absorption of a drug determines the time to what?
efficacy
35
Elimination of a drug determines the _1_ and the time to _2_.
1. dosing interval
2. steady-state
36
define sedation.
change in mental state of a patient, resulting in unconsciousness
37
Name 4 things about sedated animals that you must keep in mind.
1. they are arousable
2. they can hurt you
3. they can hurt themselves
4. they can remember what happened while sedated
38
define immobilization.
change in mental state characterized by:
1. inability to voluntarily move
2. amnesia of events while immobilized may occur
39
define anesthesia.
change in mental state characterized by:
1. loss of consciousness
2. muscle relaxation
3. analgesia (prevention of pain info transmission to brain)
40
T/F - administering multiple anesthetic drugs has a higher margin of safety compared to administering a single anesthetic drug.
True
41
what drug types are used to cause loss of consciousness in a patient for multimodal anesthesia? (2)
1. IV anesthetics (like ketamine)
2. inhalant anesthetics
42
what drug types are used to cause muscle relaxation in a patient for multimodal anesthesia? (2)
1. benzodiazepines
2. alpha-2 agonists
43
what drug types are used for analgesia in a patient for multimodal anesthesia? (2)
1. opioids
2. local anesthetics
44
T/F - SQ/IM administration has the fastest time to maximal plasma concentrations.
False - IV
IV > SQ/IM > PO
45
what are the 3 therapeutic objectives when administering a drug?
1. therapeutic onset (how long does it take to work?)
2. length of desired effect (how long will it stay effective?)
3. local vs. systemic effect
46
briefly describe how anesthetic drugs affect the nervous system. (5)
1. anesthetic drug activates ion channel
2. hyperpolarization of neuron
3. dec. NTM release
4. inhibition of synaptic communication via inhibition of response of Ach receptors to NTM
5. preferentially inhibit post-synaptic receptors
47
name the 3 parts to the chemical structure of a local anesthetic drug.
1. lipophilic end
2. hydrophilic end
3. intermediate chain
48
local anesthetics tend to be (strong/weak) (acids/bases).
why?
weak bases
have both a lipid soluble end & a hydrophilic end
49
briefly describe the mechanism of action of local & regional anesthetics. (5)
1. anesthetic binds to Na+ channels, blocking action potential in peripheral nerves
2. anesthetic binds to AA residues at binding site
3. non-ionized form of anesthetic enters axonal membrane - converted to ionized form
4. ionized form binds to Na+ in open state - prolongs Na+ channel inactivation
5. Na+ entry blocked during inactivation
50
what do local anesthetics do to nerve transmission?
reversible block
51
Higher potency means it takes (more/less) drug to reach the desired effect
less
52
drug lipid solubility determines drug what?
potency
53
a higher pKa means the drug has a (slower/faster) onset of action
slower
54
the higher the tissue vascularity, the (slower/faster) the drug is absorbed
faster
55
how are amides eliminated from the body?
biotransformed in liver
56
how are esters eliminated from the body?
enzymatic plasma hydrolysis
57
what are 4 toxic effects of local anesthetic associated with the CNS?
1. depression
2. coma
3. excitement
4. seizures
58
what are 3 toxic effects of local anesthetic associated with the cardiovascular system?
with rapid IV administration:
1. hypotension
2. bradycardia
3. dysrhythmias
can be direct or mediated by CNS
59
T/F - if toxic effects are noted after administration of a local anesthetic, you can use a reversal.
False - no reversal; supportive care and time
60
what happens if you add epinephrine to a local anesthetic block? (3)
1. prolongs block
2. inc. block intensity
3. dec. systemic absorption of block
61
what happens if you add bicarbonate to a local anesthetic block? (4)
1. inc. block onset
2. dec. pain of injection (via inc. pH)
3. dec. block duration
4. can cause drug precipitate in syringe
62
what do tranquilizers do to a patient?
calm patient/slow mentation without sedation
63
T/F - a patient can override tranquilizer effects.
True
64
what do sedatives do to a patient?
calm patient by slowing mentation and body functions
65
T/F - a patient can override sedative effects.
False
66
what drug class is considered a minor tranquilizer?
benzodiazepines
67
what are 3 drugs classed as benzodiasepines?
1. diazepam
2. midazolam
3. zolazepam
68
what 2 drug classes are considered major tranquilizers?
1. phenothiazines
2. butyrophenones
69
what are 2 drugs classed as phenothiazines?
1. acepromazine
2. chlorpromazine
70
what drug is classed as a butyrophenone?
azaperone
71
what is the mechanism of action of benzodiazepines?
enhances binding of GABA to alpha subunit of GABA(A) receptor
- inc. frequency of Cl- channel opening
- inc. Cl- movement into cell
- hyperpolarization of membrane
- reduced neuronal excitability
72
if resting potential of a membrane is lowered, the nerve requires (more/less) stimuli to depolarize.
more
73
what are 5 clinical uses of benzodiazepines?
1. mild sedative
2. centrally mediated muscle relaxation
3. anticonvulsant
4. works synergistically with other drugs
5. appetite stimulant (rabbits, cats)
74
T/F - diazepam is water soluble and can therefore be given IM or SQ.
False - cannot give IM/SQ
75
T/F - midazolam is water soluble and can therefore be given IM or SQ.
True
76
Benzodiazepines have a rapid onset of action (_1_) and duration of action could last anywhere from _2_ to _3_ depending on the route of administration.
1. 30-45sec
2. 45min
3. 2hr
77
what are 6 desired effects of benzodiazepines?
1. enhances sedation w/opioids
2. counteracts muscle rigidity
3. prevents seizure activity
4. reduces dose of injectable required
5. reduces dose of inhalant required
6. minimal cardiopulmonary effects
78
Diazepam vs. Midazolam
1. which should be used in geriatric patients?
2. which should be used for emergency treatment of seizures?
1. midazolam
2. diazepam
79
what is the name of the reversal for benzodiazepines?
Flumazenil
80
what are 4 commonly used alpha-2 agonists?
1. xylazine
2. medetomidine
3. dexmedetomidine
4. detomidine
81
what do alpha-2 agonists do? (3)
1. block norepinephrine release in CNS
2. activate alpha-2 receptors in dorsal horn of spinal cord for analgesic effects
3. activate alpha-2b receptors in vascular endothelium to cause vasoconstriction and hypertension
82
what route(s) can alpha-2 agonist be administered?
SQ, IM, IV
83
the duration of alpha-2 agonists is dose & species dependent. Heavy sedation can last _1_. Analgesia lasts for _2_.
1. 30-60min (sometimes 90min)
2. 15-60min
84
T/F - ideally, we want to use alpha-2 agonists for both sedation and analgesia.
False - sedation effects outlast analgesia effects
85
T/F - alpha-2 agonists have a reversal.
True
86
what are some profound cardiovascular effects that you may see with alpha-2 agonists? (3)
1. bradycardia
2. hypertension, commonly followed by hypotension
3. dec. CO
87
T/F - respiratory effects of alpha-2 agonists vary from respiratory depression to severe dyspnea.
True
88
Marked what is seen in ruminants with alpha-2 agonists? why?
hypoxemia - the lungs are the shock organ in ruminants
89
what are 4 effects that may occur with alpha-2 agonist administration?
1. hyperglycemia due to inhibited insulin release - concern with diabetics
2. emesis & alteration in GI motility - cats > dogs
3. xylazine in cattle - implicated in abortions
4. inc. urine production due to blocked effects of ADH
90
name 3 alpha-2 agonist reversals (alpha-2 antagonists).
1. yohimbine
2. tolazine
3. atipamazole
91
T/F - acepromazine is an antipsychotic drug that is always dependable for clinical use.
False - not dependable!
92
what is acepromazine's mechanism of action? (2)
1. blocks dopamine receptors in basal ganglia & limbic system - antiemetic effect
2. blocks alpha-2 adrenergic receptors - peripheral vasodilation
93
Acepromazine can be used to reduce the incidence of adverse effects of other drugs. What effects does it provide? (3)
1. antiemetic
2. antihistamine
3. mild antiarrhythmic
94
Acepromazine has a (slow/fast) onset with a relatively (short/long) duration time.
slow
long
95
Acepromazine is metabolized by the _1_ and metabolites are excreted via the _2_.
1. liver
2. kidney
96
what are 4 cardiovascular effects of acepromazine?
1. hypotension - alpha-1 adrenergic receptor blockade
2. dec. CO
3. mild antiarrhythmic
4. splenic contraction of RBCs (reduces PCV)
97
what are 3 GI effects of acepromazine?
1. antiemetic
2. delays gastic emptying
3. dec. lower esophageal sphincter tone
98
T/F - you should not use acepromazine if patient plans to undergo a skin test.
True - it has antihistamine effects
99
T/F - acepromazine provides analgesic effects.
False
100
what is an essential function of opioid drugs?
opioids alter ion currents = hyperpolarization of neuronal membranes
101
T/F - there are quantified sedative effects of opioids for each species, including potency and efficacy.
False - opioid sedative effects vary by species, with varying potency and efficacy
102
ultrapotent opioids can cause _1_ and even _2_.
1. severe respiratory depression
2. death
103
explain the difference between efficacy and potency.
efficacy = how effective a drug is at binding to a receptor and eliciting a response
- higher efficacy = stronger binding
potency = how much of a drug is needed to elicit a response
- higher potency = less drug needed
104
define agonist.
what is the difference between a full and partial agonist?
activates a specific receptor
full agonist = binds strongly to and fully activates receptor to get full effect
partial agonist = activates receptor, but to lesser degree than full agonist
105
define antagonist/agonist.
has antagonistic effect for one receptor while agonistic effect for another
- can block action of another drug if given simultaneously
106
define antagonist.
drug that blocks other drugs by binding to a receptor without activating it
107
Name 5 full agonist opioids of the mu receptor.
1. morphine
2. methadone
3. pethidine
4. fentanyl
5. remifentanil
108
name 1 partial agonist opioid for the mu receptor.
buprenorphine
109
what are the 3 opioid antagonists of the mu, kappa, delta, and sigma receptors?
1. naloxone
2. naltrexone
3. nalmefene
110
what are 4 clinical uses of opioids?
1. analgesics
2. sedation
3. chemical restraint
4. dec. doses of other drugs used
111
T/F - opioids must be highly controlled federally because they have a high abuse potential.
True
112
Opioids can cause _1_, which is a cardiovascular effect, and _2_, which occurs most commonly with morphine and meperidine. The latter can result in marked _3_ and _4_.
1. bradyarrhythmias
2. histamine release
3. vasodilation
4. hypotension
113
Opioids can cause _1_, which has a limited clinical significance in (SA/LA) unless overdosing and in combo with other similar acting drugs but can be fatal in (SA/LA).
1. respiratory depression
SA
LA
114
What are 7 other opioid effects that do not include cardiovascular or respiratory effects?
1. vomiting
2. severe nausea
3. defecation
4. severe constipation
5. excitatory effects
6. mydriasis (cats)
7. thermoregulation effects (panting in dogs)
115
T/F - there is no effect on chronic opioid use.
False - can build up tolerance
116
T/F - opioids undergo extensive first-past metabolism if given orally.
True
117
how are opioids eliminated? (2)
1. urine
2. bile
118
Naloxone vs. Naltrexone
(opioid reversals)
1. which does NOT cross the blood-brain-barrier?
2. which can you only get in the human form (i.e., you can't get it in the vet form)?
3. which one reverses all opioid activity but has the potential for renarcotization?
4. which one is given in tablets to help treat addiction?
1. naltrexone
2. naloxone
3. naloxone
4. naltrexone
119
name 2 injectable general anesthetics that are classified as barbituates.
1. pentobarbital
2. thiopental
120
name 2 injectable general anesthetics that are classified as non-barbituate sedatives.
1. propofol
2. alfaxalone
121
name 2 injectable general anesthetics that are classified as dissociative anesthetics.
1. ketamine
2. tiletamine
122
what does pentobarbital depress?
CNS
- anesthesia >> apnea >> cardiac arrest
123
T/F - pentobarbital is not a controlled drug.
False - schedule 2 & 3
124
T/F - pentobarbital persists in the environment for a LONG time.
True
125
T/F - propofol is very lipophilic.
True
126
Propofol 28 contains _1_, which may be toxic to _2_, esp. with repeated boluses.
1. benzyl alcohol
2. cats
127
propofol potentiates _?_ activity, which decreases cerebral metabolic rate.
GABA
128
Propofol pharmacokinetics can vary depending on the signalment of the patient. Give 3 examples of this.
1. Greyhounds have higher volume of distribution - higher plasma conc. than others given same dose
2. geriatric dogs have slower clearance than younger dogs
3. CRI = longer recovery time in cats
129
define inotrope.
drugs that inc. or dec. heart contractility
- positive inotrope = inc. contractility
- negative inotrope = dec. contractility
130
Propofol is a (positive/negative) inotrope and causes dose-dependent (hypo/hyper)tension due to systemic vaso(dilation/constriction). It also causes dose-dependent _?_, and apnea is common.
negative
hypotension
vasodilation
respiratory depression
131
Propofol has been used to treat seizures in animals due to a dec. in _1_, _2_, and _3_.
1. ICP
2. cerebral metabolic rate
3. intraocular pressure
132
T/F - propofol has an analgesic effect.
False!
133
T/F - propofol is a federally controlled drug.
False - state by state
134
T/F - alfaxalone is a non-hormonal steroid and acts on the GABA-A receptor.
True
135
T/F - alfaxalone is highly lipophilic.
True
136
Alfaxalone is metabolized primarily by the _1_ and excreted mostly by the _2_, with some excreted in the _3_.
1. liver
2. kidneys
3. bile
137
dissociative anesthetics work primarily on the NMDA receptor.
1. what does NMDA stand for?
2. what does blocking the NMDA receptor do?
1. N-methyl-D-Aspartate
2. prevents movement of Ca++, Na+, and K+ and thus, no nerve conduction = analgesia
138
Dissociative anesthetics, besides antagonizing NMDA receptors, also work on opioid receptors. Which ones?
Mu > kappa
139
T/F - dissociative anesthetics have a high volume of distribution but a low bioavailability.
False - high Vd & F
140
T/F - recovery can be rough with dissociative anesthetics.
True
141
what 3 cardiovascular effects do dissociative anesthetics have?
1. inc. HR
2. inc. CO
3. inc. BP
142
what 2 respiratory effects do dissociative anesthetics have?
1. mild resp. depression
2. may retain airway reflexes (cough, swallow)
143
with dissociative anesthetics, seizure-like activity has been seen in what species with what drug?
Tigers & telazol
144
T/F - if you are seeing movements (blinking, swallowing, salivation, poor muscle relaxation) with a patient under dissociative anesthetics, you should turn up the vaporizer.
False - use dissociatives in conjunction with other drugs
145
dissociative anesthetics are metabolized by the _?_ in most species.
liver
146
cats excrete dissociative anesthetics via the _?_.
kidney
