Pharmacology Flashcards
(142 cards)
1
Q
Difference b/t elimination half-time and elimination half-life.
A
Half-time: PLASMA CONCENTRATION of drug
Half-life: TOTAL AMOUNT of drug
2
Q
Formula for VD
A
Amount of drug injected/plasma concentration
VD = Q/Cp t=0
3
Q
What is pharmacokinetics?
A
What the BODY does to the DRUG
4
Q
Do MR have a large VD in adults or neonates?
A
Neonates d/t their expanded ECF
5
Q
Why do neonates need more Sux on a mg/kg basis?
A
- Larger VD
- Immature NMJ - inadequate # of nicotinic receptors OR nicotinic receptors not as response to Ach
* Dosing is the same for NDMR - less drug required to block small # of channels
6
Q
Smaller VD means…
A
Shorter half-life of elimination
Ex: Alfentanil
7
Q
Zero Order Kinetics
A
Constant AMOUNT of drug is eliminated per unit time 2 mg per min *I have ZERO tolerance for APA! ALCOHOL PHENYTOIN ASA
8
Q
First Order Kinetics
A
Constant FRACTION of drug is eliminated per unit time
Natural log (ln)
One Compartment: looks just like zero
Two Compartment: fast curvilinear decline then linear
9
Q
What organs are found in the central compartment?
A
Liver* Kidneys* Lungs* Heart Brain VRG
10
Q
What is the alpha phase? Beta phase?
A
In reference to First Order Kinetics, two compartment model
alpha = distribution phase
beta = elimination phase
11
Q
Drugs will be eliminated rapidly if…
A
Clearances are high
VD are small
T1/2 = Vd/Cl
12
Q
How many half-lives are required to eliminate at least 98% of a drug?
A
6
13
Q
Phase 1 Reactions
A
Oxidation Reduction Methylation Hydrolysis Cytochrome P450 system
14
Q
Phase 2 Reactions
A
Glucuronidation
Glutathione conjugation
Sulfation
Acetylation
15
Q
Dose-Response Curves
Increased potency…shift to the left or right?
A
Shift to the LEFT
Left-shift = less drug required (increased receptor affinity)
16
Q
Dose-Response Curves
What does the slope of the line indicate?
A
# of receptors that must be occupied before a drug effect occurs Steep slope = majority of receptors must be bound (Ex: MR, inhaled anesthetics)
17
Q
Dose-Response Curves
What does the plateau indicate?
A
Efficacy or the ability of a drug to produce a given clinical effect
Higher plateau = greater efficacy
18
Q
Dose-Response Curves
What kind of shift would be observed in the presence of a competitive antagonist?
A
Shift to the RIGHT
NO change in efficacy (plateau)
NO change in slope
19
Q
Dose-Response Curves
What kind of shift would be observed in the presence of a non-competitive antagonist?
A
Shift to the RIGHT and DOWN
Decrease in slope!
Maximal effect cannot be achieved (noncompetitive block cannot be reversed by excess agonist)
20
Q
What is LD50/ED50?
A
Therapeutic index
*The larger the therapeutic index of a drug the greater margin of safety!
21
Q
PCN shows a cross-sensitivity with…
A
Cephalosporins
22
Q
Increased or decreased MAC in cocaine abuser?
A
Increased MAC
23
Q
Weak Acids
A
Barbiturates (Thiopental) Ibuprofen Propofol POSITIVE IONS – Na, Mg, Ca *The higher the pKa of a weak acid, the greater the amount of drug in non-ionized form at physiologic pH.
24
Q
Weak Bases
A
LA Benzos Ketamine Opioids Ephedrine Phenylephrine NEGATIVE – Cl, SO4
25
What's wrong with mixing a weak acid with a low pH solution?
Formation of a precipitate
26
Explain trapping of LA in fetal circulation.
pH of the fetus is lower than mom
Non-ionized form of LA crosses the placental barrier
Equilibrium reestablished
More LA is now in the ionized form (weak base into acidic baby)
Ionized LA is trapped in baby
27
The ______ the fetal pH, the greater the amount of local anesthetic in the ionized form remains trapped in the fetus.
Lower
| *Maternal alkalosis and fetal acidosis will most facilitate trapping
28
What is the range of pKas for LA?
7.6-9.1
29
Why doesn't local anesthetic work well in an acidotic foot?
LA is a weak base
| If put in an acidotic environment, remains in ionized form
30
What LA will precipitate with bicarb?
Bupivacaine
31
Which ester LA is a weak acid?
Benzocaine
| pKa 3.5 - almost completely ionized at physiologic pH - ideally suited for topical anesthesia
32
The lower the pKa of the LA, the greater the proportion of LA in the ______ form at pH = 7.4 and the ______ the onset of the conduction block.
Non-ionized
Faster
*Exception: Chloroprocaine (pka 9.1, 0% protein bound)
33
Lipid solubility indicates...
Protein-binding indicates...
pKa determines...
Potency - highly lipid soluble = very potent (and usually prolonged DOA)
DOA - highly protein bound = prolonged DOA
Speed of onset - lower pKa = faster onset
34
The loss of LA from the injection site is primarily by _______. The rate of absorption of LA from an injection site is influenced by what 2 things?
Vascular absorption
1. Presence of a vasoconstrictor
2. Blood flow
35
High blood flow to an area does what to DOA and toxicity of a LA?
DOA is reduced
| Toxicity is increased
36
Which results in higher blood concentrations after injection: epidural or subarachnoid?
Epidural
37
Rank tissues from HIGHEST to LOWEST blood flow.
1. IV - HIGH blood flow
2. Tracheal
3. Intercostal
4. Caudal
5. Paracervical
6. Epidural
7. Brachial Plexus
8. Subarachnoid, Sciatic, Femoral
9. Subcutaneous - LOW blood flow
* In Time, I Can Please Everyone But Susie and Sally!
38
How do LA work?
Block Na channels
Non-ionized form diffuses into the nerve axon
Ionized form binds to receptors on the Na channel when the channel is in the inactivated state
39
How many nodes of Ranvier must be blocked to stop nerve conduction for myelinated axons?
2-3 nodes
40
Conduction block is frequency dependent, which means what?
The greater the frequency of action potentials, the fast the nerve is blocked by LA
41
Where are voltage-gated Na channels found?
ONLY in the nerve's axon
42
Differential Block after Spinal
```
Sympathetic
2-6 dermatomes
Sensory
2 dermatomes
Motor
```
43
Metabolism fo Esters vs. Amides
Esters: plasma pseudocholinesterase
Amides: liver
44
What is the max dose for bupivacaine?
3 mg/kg (175 mg)
45
What is the max dose for lidocaine with and without Epi?
With Epi - 7 mg/kg (500 mg)
| Without Epi - 4.5 mg/kg (300 mg)
46
What is the treatment of LA toxicity?
Lipid emulsion
20% Intralipid
2 mL/kg
0.5 mL/kg/min
47
Order of Toxic Manifestations of LA
```
Circumoral and tongue numbness
Lightheadedness and tinnitus
Visual disturbances
Muscular twitching
Unconsciousness
Convulsions
Coma
Respiratory arrest
Cardiovascular collapse
```
48
What is the therapeutic plasma concentration of lidocaine?
2-4 mcg/mL
| At 3 mcg/mL - circumoral and tongue numbness
49
Concerns with Ester LAs
Prolonged action in a patient with atypical pseudocholinesterase
Prolonged action if patient is on acetylcholinease inhibitors (edrophonium, physostigmine, echothiophate)
50
PABA is a metabolic end-production of ester or amide metabolism?
Ester
| *This metabolite may mediate the hypersensitivity rxns
51
Which LA is a vasoconstrictor and is naturally-occurring?
Cocaine
52
Administration of what 4 LA may induce the development of methemoglobinemia?
1. Prilocaine - metabolite = O-toluidine (oxidizing agent)
2. EMLA cream
3. Benzocaine
4. Cetacaine
(Met-Hgb has iron in the ferric state Fe3+)
53
What is the treatment for Methemoglobinemia?
Methylene Blue 1-2 mg/kg
54
Ester LA are derivates of what?
Benzoic acid
55
Which contributes more to the hypotension after spinal and epidural anesthesia: decrease in preload 2ndary to venodilation OR decrease in SVR?
Decrease in preload 2ndary to venodilation
56
Max doses of ester LAs. All are 200 mg EXCEPT...
Procaine - 1000 mg
| Chloroprocaine - 800 mg
57
What ester LA is the most toxic?
Tetracaine - hydrolyzed by plasma cholinesterase much more slowly
58
What ester LA is the least potent?
Procaine
59
What ester LA is the least toxic?
2-Chloroprocaine
60
Which amide LA is least toxic?
Prilocaine
61
What are the 3 least potent amides?
1. Lidocaine
2. Mepivacaine
3. Prilocaine
62
Which amide LA is most cardiotoxic?
Bupivacaine
| *Binds to gated Na channels with great intensity
63
What are the advantages of Ropivacaine over Bupivacaine?
Less cardiotoxic
| Less motor blockade
64
Hypersensitivity reactions are more common with esters or amides.
Esters
| B/c of PABA
65
What are the 3 most cardiotoxic LA?
1. Bupivacaine
2. Etidocaine
3. Ropivacaine
* BB, digitalis, and CCB may decrease the threshold for cardiotoxicity
66
In general, lipid solubility/potency is increased by increasing the total # of _____ atoms in the molecule.
Carbon
67
Epinephrine does not prolong the DOA for what 3 LA?
1. Bupivacaine
2. Ropivacaine
3. Etidocaine
68
Oil:Gas Partition Coefficients
```
Halothane 224
Isoflurane 91
Sevoflurane 47
Desflurane 19
N2O 1.4
```
69
All volatile agents decrease BP, but which agent the least?
Sevoflurane
70
All volatile agents decrease SVR, but which agents the least?
Halothane
| Sevoflurane
71
Which volatile agent decreases CO the most?
Halothane
72
Which volatile agent decreases CO the least?
Isoflurane
73
Which volatile agent increase HR?
Isoflurane
74
Which volatile agent causes sensitization to catecholamines?
Halothane
75
The solubility of a gas in a liquid _______ as temp increases.
Decreases
More inhalational agent will dissolve in blood if the patient is hypothermic
*Le Chatelier's law explains this
76
What does the blood:gas partition coefficient tell us?
Speed of onset and offset
| *Ostwald solubility coefficient
77
Brain uptake is directly or inversely related to CO?
Inversely
78
Blood:Gas Partition Coefficients
```
Halothane 2.5
Isoflurane 1.46
Sevoflurane 0.65
Desflurane 0.42
N2O 0.46
```
79
The more soluble the agent, the greater the blood:gas partition coefficient, the _____ the uptake.
Slower
*Slow uptakes - small Fa/Fi ratios - low uptake curve
Halothane - B:G 2.5, very soluble, slowest uptake
80
List the order of volatile agents as they are seen on the uptake curve graph. Start with the agent that represents the top curve.
Write in the % equilibrated at 30 min.
```
N2O - 99%
Desflurane - 91%
Sevoflurane - 85%
Isoflurane - 73%
Enflurane - 65%
Halothane - 58%
```
81
Nitrous oxide equilibrates with all tissues within about...
2.5 hrs
82
Which is less soluble in blood...N2 or N2O?
N2 is 34x less soluble in blood than N2O
*When N2O is turned on, distensible gas spaces expand and nondistensible gas spaces increase in pressure - this is due to Fick's law of diffusion
83
Explain the concentration effect.
```
N20 is turned on
N2O is super soluble
More N2O leaves the alveoli
Alveoli shrink in size
Alveolar concentration of N2O remains high
More rapid uptake
aka overpressuring
*Fick's law of diffusion
```
84
Explain the second gas effect.
Same as concentration effect
Now the concentrations of both N2O and another gas remain elevated
Increases the rate of diffusion
*Fick's law of diffusion
85
Explain the dilutional effect when N2O is turned off.
The reverse of the concentration effect occurs
Alveoli expand and gases such as CO2 and O2 are diluted - diffusional hypoxia
*Fick's law of diffusion
86
Name something about the chemical formula for each volatile agent.
Halothane - only one with Br, (alkane)
Isoflurane - 5 F, Cl (methyl ethyl ether)
Desflurane - 6 F, completely halognated w/ F
Sevoflurane - 7 F, (isoprop)
87
What is the name of the C-O-C functional group?
Ether bond
| *ALL of the volatile agents are ethers EXCEPT Halothane (alkane derivative)
88
Which 3 volatile agents are methyl ethyl ethers?
1. Enflurane
2. Isoflurane
3. Desflurane - completely halogenated
(*Sevo is a methyl isopropyl ether)
89
Volatile agents halogenated exclusively with fluorine are less soluble in blood. Which 2 volatile agents have only fluorine as the halogen substitutions?
1. Desflurane
| 2. Sevoflurane
90
List 4 contraindications to the use of N2O.
1. Closed pneumo
2. Tympanoplasty (middle ear surgery)
3. Pneumocephalus
4. VAE
91
Other Concerns with N2O.
Increases PVR and PAP
Increases CBF and ICP
Risk of PONV
92
There is approx. ___ reduction in MAC for every 1% of nitrous oxide delivery.
1%
93
By what mechanism does Isoflurane cause hypothermia?
Depresses the temp regulating centers of the hypothalamus
94
How do volatile anesthetics alter the ventilatory responses to CO2? To hypoxemia?
Dose-dependent decreases in response to CO2
| 0.1 MAC completely blocks the ventilatory response to hypoxemia
95
Which 2 volatile agents least depress the baroreceptor reflex?
1. Isoflurane
2. Desflurane
HR tends to increase reflexly with the decrease in BP
96
Water is added as a preservative to which volatile anesthetic agent?
Sevoflurane
97
An inhalational agent has a large blood:gas partition coefficient, what does this mean?
Highly blood soluble
Uptake by the blood will be fast
Speed of onset and the rise in Fa/Fi is slow
98
Meyer-Overton Theory
Anesthesia occurs when a sufficient # of anesthetic molecules dissolves in the lipid bilayer of neuronal membranes
The membranes expand - keep channels closed
99
Inhaled anesthetics work on what receptors?
GABA
100
For most volatile agents, the highest MAC values are for what age group?
Infants 1-6 mo
| Sevoflurane is the exception - highest in the neonate 0-30 days
101
Which electrolyte abnormality will cause MAC to increase? To decrease?
Increased MAC - hypernatremia
| Decreased MAC - hypercalcemia, hyponatremia
102
Vapor Pressures
```
Halothane - 244
Isoflurane - 240
Enflurane - 172
Sevoflurane - 157
Desflurane - 669
```
103
How are volatile anesthetics metabolized?
Liver
Cytochrome P-450
Oxidative processes
104
What % of each of the volatile agents are metabolized?
```
Halothane - 20%
Sevoflurane 3-5%
Enflurane - 2%
Isoflurane - 0.2%
Desflurane - 0.02%
```
105
What 2 things does halogenation do?
1. Decreases flammability
| 2. Decreases toxicity
106
What are the acceptable levels of inhaled agents in the OR?
N2O + volatile agent - 25 ppm + 0.5 ppm
| Volatile agent - 2 ppm
107
Where and how is N2O metabolized?
Metabolized into N2 in the intestine by anaerobic bacteria
| Reductive processes
108
What are 2 adverse effects of Etomidate?
1. Directly depresses cortisol output from the adrenal cortex
2. Depresses the immune system
109
How are the IV anesthetics primarily terminated after bolus injection?
Redistribution
110
Do benzos have muscle relaxant actions? Are they protein bound?
Yes
| They are extensively protein bound
111
What is the antagonist of benzos?
Flumazenil 0.2 mg IV
Series of small doses up to a total of 5 mg
Nonspecific antagonists: physostigmine, aminophylline
112
Name 2 induction agents that are associated with excitatory phenomena.
1. Methohexital
| 2. Etomidate
113
Ketamine is related chemically to which drug of abuse?
Phencyclidine
114
What receptors does Ketamine work on?
```
Antagonistic at NMDA
Non-NMDA glutamate receptors
Nicotinic receptors
Muscarinic receptors
Opioid receptors - kappa
Sigma receptors (dysphoria)
```
115
Which non-opioid anesthetic produces bronchodilation?
Ketamine
116
What is the chemical name for Etomidate?
Imidazole derivative
117
What is in Etomidate that causes pain on injection?
Additive - propylene glycol
118
What 3 drugs are most likely to cause venous thrombosis and phlebitis after IV administration?
1. Diazepam
2. Lorazepam
3. Etomidate
* All dissolved in propylene glycol
119
Which produces are greater decrease in BP? Thiopental or propofol?
Propofol
120
What is another name for propofol?
2,6-diisopropylphenol
121
In addition to metabolism in the liver, propofol undergoes an extrahepatic route of elimination. Identify this route.
Lungs
122
In what 2 ways does Clonidine produce its effects?
1. Stimulates alpha-2 receptors of inhibitory neurons in the vasomotor center of the medulla oblongata (decreasing sympathetic outflow)
2. Stimulates alpha-2 receptors in the surface membrane of the presynaptic nerve terminal (decreasing release of NE)
123
Why is it not safe to abruptly withdraw Clonidine?
Rebound HTN 8-36 hours after last dose
Tx: Clonidine, hydralazine
*BB only in the presence of alpha-adrenergic blockade to avoid unopposed alpha-vasoconstricting actions
*TCA potentiate the pressor effects of NE
124
What is your anesthetic concern for the patient on chronic clonidine therapy?
Perioperative hypothermia
| Alters central thermoregulatory control
125
How much does pretreatment of patients with clonidine decrease MAC?
50%
126
Name 3 direct acting vasodilators.
1. Hydralazine - arterial > venous
2. Nitroprusside - arterial + venous
3. Nitroglycerine - venodialtor
127
List the 4 contraindications for using nitroprusside.
1. Liver disease
2. Kidney disease
3. Hypothyroidism
4. Vit B-12 def
128
Cyanide Toxicity and Nitroprusside
How?
S/S?
Tx?
Ferrous iron of nitroprusside reacts with sulfhydryl groups in RBCs and releases cyanide
S/S: metabolic acidosis (*base deficit), cardiac arrhythmias, increased venous oxygen content (unable to utilize oxygen), tachyphylaxis
Tx: sodium thiosulfate 150 mg/kg IV over 15 min, if no improvement - sodium nitrate 5 mg/kg IV or Vit B12
129
When the nitroprusside infusion is started, you observe that PaO2 decreases. Why did this happen?
Presumed to inhibit HPV
Shunt increases
Increased V/Q mismatch
Decreased PaO2
130
The therapeutic benefit of nitroglycerine in the treatment of MI is attributable to what action?
Venodilator
Decreases preload, SV, CO, BP
Reduction in myocardial work
Reduced myocardial O2 consumption
131
What syndrome occurs in 10-20% of patients treated chronically (> 6 mo) with hydralazine?
Systemic lupus erythematosus-like syndrome
| Slow acetylators
132
Hydralazine, nitroglycerine, and sodium nitroprusside all may cause angina. How?
Hydralazine - reflex increase in HR and CO
Nitroglycerine - if DBP falls excessively
Sodium nitroprusside - coronary steal
133
Antidysrhythmic Classes
Class I - Block Na channels - membrane stabilizers
Class II - Beta blockers - decrease phase 4 depolarization
Class III - Block K channels - prolong repolarization (amiodarone)
Class IV - CCB
134
Identify 4 drugs for cardiac dysrhythmias d/t digoxin toxicity.
1. Lidocaine
2. Procainamide
3. Phenytoin
4. Propranolol
*Enhance dig toxicity: HYPOkalemia, HYPERcalcemia, HYPOmag
135
What 4 drugs should you avoid with digitalis?
1. Quinidine
2. Sux
3. Beta agonists
4. Calcium
136
What is your concern with giving phenytoin to the hyperglycemic patient?
Phenytoin partially inhibits insulin release
137
Explain how digitalis works.
```
Inhibits the Na-K pump
Sodium accumulates in the cell
Na-Ca exchange system is inhibited
Ca accumulates in the cell
Contractility increases
```
138
Which CCB causes a reflex increase in HR?
Nifedipine
139
Which CCB is used for coronary artery vasospasm? Cerebral artery vasospasm?
Coronary - nifedipine, diltiazem
| Cerebral - nimodipine
140
Chemotherapeutic Agents
Doxorubicin - Heart (2-32%) - ECHO
Bleomycin - Lungs (10-25%) - PFTs - restrictive
Cisplatin - Kidney
Cyclophosphamide, streptozocin, methotrexate - Liver
141
Melatonin enhances the activity of what drug class?
Benzos
142
All immunosuppressive regimens carry what 3 major risks?
1. Infection
2. Malignancy
3. Vascular disease
