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The BIG Test > Pharmacology > Flashcards

Pharmacology Flashcards

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

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2
Q

Formula for VD

A

Amount of drug injected/plasma concentration

VD = Q/Cp t=0

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3
Q

What is pharmacokinetics?

A

What the BODY does to the DRUG

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4
Q

Do MR have a large VD in adults or neonates?

A

Neonates d/t their expanded ECF

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5
Q

Why do neonates need more Sux on a mg/kg basis?

A
  1. Larger VD
  2. 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
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6
Q

Smaller VD means…

A

Shorter half-life of elimination

Ex: Alfentanil

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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
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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

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9
Q

What organs are found in the central compartment?

A 
Liver*
Kidneys*
Lungs*
Heart
Brain 
VRG
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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

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11
Q

Drugs will be eliminated rapidly if…

A

Clearances are high
VD are small
T1/2 = Vd/Cl

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12
Q

How many half-lives are required to eliminate at least 98% of a drug?

A

6

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13
Q

Phase 1 Reactions

A 
Oxidation
Reduction
Methylation
Hydrolysis 
Cytochrome P450 system
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14
Q

Phase 2 Reactions

A

Glucuronidation
Glutathione conjugation
Sulfation
Acetylation

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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)

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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)
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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

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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

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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)

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20
Q

What is LD50/ED50?

A

Therapeutic index

*The larger the therapeutic index of a drug the greater margin of safety!

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21
Q

PCN shows a cross-sensitivity with…

A

Cephalosporins

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22
Q

Increased or decreased MAC in cocaine abuser?

A

Increased MAC

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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.
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24
Q

Weak Bases

A 
LA
Benzos
Ketamine
Opioids
Ephedrine
Phenylephrine 
NEGATIVE – Cl, SO4
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25
Q

What’s wrong with mixing a weak acid with a low pH solution?

A

Formation of a precipitate

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26
Q

Explain trapping of LA in fetal circulation.

A

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

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27
Q

The ______ the fetal pH, the greater the amount of local anesthetic in the ionized form remains trapped in the fetus.

A

Lower

*Maternal alkalosis and fetal acidosis will most facilitate trapping

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28
Q

What is the range of pKas for LA?

A

7.6-9.1

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29
Q

Why doesn’t local anesthetic work well in an acidotic foot?

A

LA is a weak base

If put in an acidotic environment, remains in ionized form

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30
Q

What LA will precipitate with bicarb?

A

Bupivacaine

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31
Q

Which ester LA is a weak acid?

A

Benzocaine

pKa 3.5 - almost completely ionized at physiologic pH - ideally suited for topical anesthesia

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32
Q

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.

A

Non-ionized
Faster

*Exception: Chloroprocaine (pka 9.1, 0% protein bound)

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33
Q

Lipid solubility indicates…
Protein-binding indicates…
pKa determines…

A

Potency - highly lipid soluble = very potent (and usually prolonged DOA)
DOA - highly protein bound = prolonged DOA
Speed of onset - lower pKa = faster onset

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34
Q

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?

A

Vascular absorption

  1. Presence of a vasoconstrictor
  2. Blood flow
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35
Q

High blood flow to an area does what to DOA and toxicity of a LA?

A

DOA is reduced

Toxicity is increased

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36
Q

Which results in higher blood concentrations after injection: epidural or subarachnoid?

A

Epidural

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37
Q

Rank tissues from HIGHEST to LOWEST blood flow.

A
  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!
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38
Q

How do LA work?

A

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

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39
Q

How many nodes of Ranvier must be blocked to stop nerve conduction for myelinated axons?

A

2-3 nodes

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40
Q

Conduction block is frequency dependent, which means what?

A

The greater the frequency of action potentials, the fast the nerve is blocked by LA

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41
Q

Where are voltage-gated Na channels found?

A

ONLY in the nerve’s axon

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42
Q

Differential Block after Spinal

A 
Sympathetic 
2-6 dermatomes
Sensory
2 dermatomes 
Motor
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43
Q

Metabolism fo Esters vs. Amides

A

Esters: plasma pseudocholinesterase
Amides: liver

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44
Q

What is the max dose for bupivacaine?

A

3 mg/kg (175 mg)

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45
Q

What is the max dose for lidocaine with and without Epi?

A

With Epi - 7 mg/kg (500 mg)

Without Epi - 4.5 mg/kg (300 mg)

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46
Q

What is the treatment of LA toxicity?

A

Lipid emulsion
20% Intralipid
2 mL/kg
0.5 mL/kg/min

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47
Q

Order of Toxic Manifestations of LA

A 
Circumoral and tongue numbness
Lightheadedness and tinnitus 
Visual disturbances
Muscular twitching
Unconsciousness
Convulsions
Coma
Respiratory arrest
Cardiovascular collapse
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48
Q

What is the therapeutic plasma concentration of lidocaine?

A

2-4 mcg/mL

At 3 mcg/mL - circumoral and tongue numbness

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49
Q

Concerns with Ester LAs

A

Prolonged action in a patient with atypical pseudocholinesterase
Prolonged action if patient is on acetylcholinease inhibitors (edrophonium, physostigmine, echothiophate)

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50
Q

PABA is a metabolic end-production of ester or amide metabolism?

A

Ester

*This metabolite may mediate the hypersensitivity rxns

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51
Q

Which LA is a vasoconstrictor and is naturally-occurring?

A

Cocaine

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52
Q

Administration of what 4 LA may induce the development of methemoglobinemia?

A
  1. Prilocaine - metabolite = O-toluidine (oxidizing agent)
  2. EMLA cream
  3. Benzocaine
  4. Cetacaine

(Met-Hgb has iron in the ferric state Fe3+)

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53
Q

What is the treatment for Methemoglobinemia?

A

Methylene Blue 1-2 mg/kg

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54
Q

Ester LA are derivates of what?

A

Benzoic acid

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55
Q

Which contributes more to the hypotension after spinal and epidural anesthesia: decrease in preload 2ndary to venodilation OR decrease in SVR?

A

Decrease in preload 2ndary to venodilation

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56
Q

Max doses of ester LAs. All are 200 mg EXCEPT…

A

Procaine - 1000 mg

Chloroprocaine - 800 mg

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57
Q

What ester LA is the most toxic?

A

Tetracaine - hydrolyzed by plasma cholinesterase much more slowly

58
Q

What ester LA is the least potent?

A

Procaine

59
Q

What ester LA is the least toxic?

A

2-Chloroprocaine

60
Q

Which amide LA is least toxic?

A

Prilocaine

61
Q

What are the 3 least potent amides?

A
  1. Lidocaine
  2. Mepivacaine
  3. Prilocaine
62
Q

Which amide LA is most cardiotoxic?

A

Bupivacaine

*Binds to gated Na channels with great intensity

63
Q

What are the advantages of Ropivacaine over Bupivacaine?

A

Less cardiotoxic

Less motor blockade

64
Q

Hypersensitivity reactions are more common with esters or amides.

A

Esters

B/c of PABA

65
Q

What are the 3 most cardiotoxic LA?

A
  1. Bupivacaine
  2. Etidocaine
  3. Ropivacaine
    * BB, digitalis, and CCB may decrease the threshold for cardiotoxicity
66
Q

In general, lipid solubility/potency is increased by increasing the total # of _____ atoms in the molecule.

A

Carbon

67
Q

Epinephrine does not prolong the DOA for what 3 LA?

A
  1. Bupivacaine
  2. Ropivacaine
  3. Etidocaine
68
Q

Oil:Gas Partition Coefficients

A 
Halothane 224
Isoflurane 91
Sevoflurane 47
Desflurane 19
N2O 1.4
69
Q

All volatile agents decrease BP, but which agent the least?

A

Sevoflurane

70
Q

All volatile agents decrease SVR, but which agents the least?

A

Halothane

Sevoflurane

71
Q

Which volatile agent decreases CO the most?

A

Halothane

72
Q

Which volatile agent decreases CO the least?

A

Isoflurane

73
Q

Which volatile agent increase HR?

A

Isoflurane

74
Q

Which volatile agent causes sensitization to catecholamines?

A

Halothane

75
Q

The solubility of a gas in a liquid _______ as temp increases.

A

Decreases
More inhalational agent will dissolve in blood if the patient is hypothermic
*Le Chatelier’s law explains this

76
Q

What does the blood:gas partition coefficient tell us?

A

Speed of onset and offset

*Ostwald solubility coefficient

77
Q

Brain uptake is directly or inversely related to CO?

A

Inversely

78
Q

Blood:Gas Partition Coefficients

A 
Halothane 2.5
Isoflurane 1.46
Sevoflurane 0.65
Desflurane 0.42
N2O 0.46
79
Q

The more soluble the agent, the greater the blood:gas partition coefficient, the _____ the uptake.

A

Slower
*Slow uptakes - small Fa/Fi ratios - low uptake curve
Halothane - B:G 2.5, very soluble, slowest uptake

80
Q

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.

A 
N2O - 99%
Desflurane - 91%
Sevoflurane - 85%
Isoflurane - 73%
Enflurane - 65%
Halothane - 58%
81
Q

Nitrous oxide equilibrates with all tissues within about…

A

2.5 hrs

82
Q

Which is less soluble in blood…N2 or N2O?

A

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
Q

Explain the concentration effect.

A 
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
Q

Explain the second gas effect.

A

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
Q

Explain the dilutional effect when N2O is turned off.

A

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
Q

Name something about the chemical formula for each volatile agent.

A

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
Q

What is the name of the C-O-C functional group?

A

Ether bond

*ALL of the volatile agents are ethers EXCEPT Halothane (alkane derivative)

88
Q

Which 3 volatile agents are methyl ethyl ethers?

A
  1. Enflurane
  2. Isoflurane
  3. Desflurane - completely halogenated
    (*Sevo is a methyl isopropyl ether)
89
Q

Volatile agents halogenated exclusively with fluorine are less soluble in blood. Which 2 volatile agents have only fluorine as the halogen substitutions?

A
  1. Desflurane

2. Sevoflurane

90
Q

List 4 contraindications to the use of N2O.

A
  1. Closed pneumo
  2. Tympanoplasty (middle ear surgery)
  3. Pneumocephalus
  4. VAE
91
Q

Other Concerns with N2O.

A

Increases PVR and PAP
Increases CBF and ICP
Risk of PONV

92
Q

There is approx. ___ reduction in MAC for every 1% of nitrous oxide delivery.

A

1%

93
Q

By what mechanism does Isoflurane cause hypothermia?

A

Depresses the temp regulating centers of the hypothalamus

94
Q

How do volatile anesthetics alter the ventilatory responses to CO2? To hypoxemia?

A

Dose-dependent decreases in response to CO2

0.1 MAC completely blocks the ventilatory response to hypoxemia

95
Q

Which 2 volatile agents least depress the baroreceptor reflex?

A
  1. Isoflurane
  2. Desflurane
    HR tends to increase reflexly with the decrease in BP
96
Q

Water is added as a preservative to which volatile anesthetic agent?

A

Sevoflurane

97
Q

An inhalational agent has a large blood:gas partition coefficient, what does this mean?

A

Highly blood soluble
Uptake by the blood will be fast
Speed of onset and the rise in Fa/Fi is slow

98
Q

Meyer-Overton Theory

A

Anesthesia occurs when a sufficient # of anesthetic molecules dissolves in the lipid bilayer of neuronal membranes
The membranes expand - keep channels closed

99
Q

Inhaled anesthetics work on what receptors?

A

GABA

100
Q

For most volatile agents, the highest MAC values are for what age group?

A

Infants 1-6 mo

Sevoflurane is the exception - highest in the neonate 0-30 days

101
Q

Which electrolyte abnormality will cause MAC to increase? To decrease?

A

Increased MAC - hypernatremia

Decreased MAC - hypercalcemia, hyponatremia

102
Q

Vapor Pressures

A 
Halothane - 244
Isoflurane - 240
Enflurane - 172
Sevoflurane - 157
Desflurane - 669
103
Q

How are volatile anesthetics metabolized?

A

Liver
Cytochrome P-450
Oxidative processes

104
Q

What % of each of the volatile agents are metabolized?

A 
Halothane - 20%
Sevoflurane 3-5%
Enflurane - 2%
Isoflurane - 0.2%
Desflurane - 0.02%
105
Q

What 2 things does halogenation do?

A
  1. Decreases flammability

2. Decreases toxicity

106
Q

What are the acceptable levels of inhaled agents in the OR?

A

N2O + volatile agent - 25 ppm + 0.5 ppm

Volatile agent - 2 ppm

107
Q

Where and how is N2O metabolized?

A

Metabolized into N2 in the intestine by anaerobic bacteria

Reductive processes

108
Q

What are 2 adverse effects of Etomidate?

A
  1. Directly depresses cortisol output from the adrenal cortex
  2. Depresses the immune system
109
Q

How are the IV anesthetics primarily terminated after bolus injection?

A

Redistribution

110
Q

Do benzos have muscle relaxant actions? Are they protein bound?

A

Yes

They are extensively protein bound

111
Q

What is the antagonist of benzos?

A

Flumazenil 0.2 mg IV
Series of small doses up to a total of 5 mg
Nonspecific antagonists: physostigmine, aminophylline

112
Q

Name 2 induction agents that are associated with excitatory phenomena.

A
  1. Methohexital

2. Etomidate

113
Q

Ketamine is related chemically to which drug of abuse?

A

Phencyclidine

114
Q

What receptors does Ketamine work on?

A 
Antagonistic at NMDA
Non-NMDA glutamate receptors 
Nicotinic receptors 
Muscarinic receptors 
Opioid receptors - kappa 
Sigma receptors (dysphoria)
115
Q

Which non-opioid anesthetic produces bronchodilation?

A

Ketamine

116
Q

What is the chemical name for Etomidate?

A

Imidazole derivative

117
Q

What is in Etomidate that causes pain on injection?

A

Additive - propylene glycol

118
Q

What 3 drugs are most likely to cause venous thrombosis and phlebitis after IV administration?

A
  1. Diazepam
  2. Lorazepam
  3. Etomidate
    * All dissolved in propylene glycol
119
Q

Which produces are greater decrease in BP? Thiopental or propofol?

A

Propofol

120
Q

What is another name for propofol?

A

2,6-diisopropylphenol

121
Q

In addition to metabolism in the liver, propofol undergoes an extrahepatic route of elimination. Identify this route.

A

Lungs

122
Q

In what 2 ways does Clonidine produce its effects?

A
  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
Q

Why is it not safe to abruptly withdraw Clonidine?

A

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
Q

What is your anesthetic concern for the patient on chronic clonidine therapy?

A

Perioperative hypothermia

Alters central thermoregulatory control

125
Q

How much does pretreatment of patients with clonidine decrease MAC?

A

50%

126
Q

Name 3 direct acting vasodilators.

A
  1. Hydralazine - arterial > venous
  2. Nitroprusside - arterial + venous
  3. Nitroglycerine - venodialtor
127
Q

List the 4 contraindications for using nitroprusside.

A
  1. Liver disease
  2. Kidney disease
  3. Hypothyroidism
  4. Vit B-12 def
128
Q

Cyanide Toxicity and Nitroprusside
How?
S/S?
Tx?

A

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
Q

When the nitroprusside infusion is started, you observe that PaO2 decreases. Why did this happen?

A

Presumed to inhibit HPV
Shunt increases
Increased V/Q mismatch
Decreased PaO2

130
Q

The therapeutic benefit of nitroglycerine in the treatment of MI is attributable to what action?

A

Venodilator
Decreases preload, SV, CO, BP
Reduction in myocardial work
Reduced myocardial O2 consumption

131
Q

What syndrome occurs in 10-20% of patients treated chronically (> 6 mo) with hydralazine?

A

Systemic lupus erythematosus-like syndrome

Slow acetylators

132
Q

Hydralazine, nitroglycerine, and sodium nitroprusside all may cause angina. How?

A

Hydralazine - reflex increase in HR and CO
Nitroglycerine - if DBP falls excessively
Sodium nitroprusside - coronary steal

133
Q

Antidysrhythmic Classes

A

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
Q

Identify 4 drugs for cardiac dysrhythmias d/t digoxin toxicity.

A
  1. Lidocaine
  2. Procainamide
  3. Phenytoin
  4. Propranolol

*Enhance dig toxicity: HYPOkalemia, HYPERcalcemia, HYPOmag

135
Q

What 4 drugs should you avoid with digitalis?

A
  1. Quinidine
  2. Sux
  3. Beta agonists
  4. Calcium
136
Q

What is your concern with giving phenytoin to the hyperglycemic patient?

A

Phenytoin partially inhibits insulin release

137
Q

Explain how digitalis works.

A 
Inhibits the Na-K pump
Sodium accumulates in the cell 
Na-Ca exchange system is inhibited 
Ca accumulates in the cell 
Contractility increases
138
Q

Which CCB causes a reflex increase in HR?

A

Nifedipine

139
Q

Which CCB is used for coronary artery vasospasm? Cerebral artery vasospasm?

A

Coronary - nifedipine, diltiazem

Cerebral - nimodipine

140
Q

Chemotherapeutic Agents

A

Doxorubicin - Heart (2-32%) - ECHO
Bleomycin - Lungs (10-25%) - PFTs - restrictive
Cisplatin - Kidney
Cyclophosphamide, streptozocin, methotrexate - Liver

141
Q

Melatonin enhances the activity of what drug class?

A

Benzos

142
Q

All immunosuppressive regimens carry what 3 major risks?

A
  1. Infection
  2. Malignancy
  3. Vascular disease

The BIG Test (21 decks)

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