2025 Intro to Clinical Anesthesia Exam 2 Flashcards
Pharmacokinetics
What the BODY does to the DRUG
Includes absorption, distribution, metabolism, and excretions of drugs.
Pharmacokinetics and drug dose determine ultimate drug concentration at site of action.
Pharmacodynamics
What the DRUG does to the BODY
Intrinsic sensitivity/responsiveness of the body’s receptors to a drug and mechanism by which these effects occur.
Differs greatly between patients.
Involves concepts of potency, efficacy, and therapeutic window
Structure-activity relationships link actions of drugs to their chemical structure.
Absorption
Process by which a drug moves from site of administration to the bloodstream
Many different routes of administration with differing rates of absorption.
Distribution
Once a drug is absorbed it is distributed by the bloodstream throughout the body.
Highly perfused organs = Vessel Rich Group (VRG)
Affected by several factors
These factors include the concentration of drug transporters in blood, pH, perfusion, body water composition, body fat composition, and most certainly disease conditions (e.g., volume depletion, burns, third spacing).
Biotransformation
The process of altering drug molecules
Usually takes place in the liver (also adipose, intestine, kidney, lung, skin)
Phase I- yields a polar, water-soluble metabolite, often still active
Oxidation with Cytochrome P450 (most common), reduction, hydrolysis
Phase II- yields large polar metabolite by adding hydrophilic groups to make inactive water soluble compounds for excretion.
Glucorinidation (most common), conjugation, acetylation, sulfation, methylation. Morphine has 2 active metabolites from glucuronidation.
Morphine 6 glucuronide is even more potent than morphine
Phase III- exists but beyond scope of this class
* Know these 3 PHASES*
Biotransformation Part 2
Cytochrome P450 (CYP) has many subfamilies that start with CYP
CYP3A4 accounts for 50% of cytochrome activity
Phase I, II, and III don’t necessarily happen in this order! Phase II to I
If CYP450 is inhibited then Drug level GOES UP
Acute EtOH use (occupies cytochrome)
Vitamin E, Grapefruit Juice, Thyroid hormone, Ciprofloxacin and Metronidazole, omeprazole
If CYP45 is induced then Drug level GOES DOWN
Chronic EtOH use, Tobacco, Modafanil, St John’s Wort, dexamethasone
Biotransformation Part 3
Why This Matters
Common substrates for P450 include anti-epileptics, warfarin (coumadin), oral contraceptive pills, and vitamin D
If exposed to inhibitors increased drug toxicity can occur
Old anticoagulated folks on coumadin drinking grapefruit juice/palomas
Patients with cirrhosis have damaged hepatocytes unable to carry out metabolic processes
Genetics play a part in how well a patient acetylates in Phase II
Monozygous or heterozygous for rapid acetylation
Elimination
Describes the way drugs and their metabolites are removed from the body.
Excretion of an unmetabolized drug in its intact form (hydrophilic)
Metabolic biotransformation followed by excretion (hydrophobic)
First-pass effect- hepatic metabolism plays a role in elimination of many drugs, exposed to liver from portal vein before systemic circulation.
Clinically- Chronic Kidney Disease and decreased function d/t age, CHF, Liver disease. All decrease First pass hepatic metabolism.
Pharmacodynamics: Terms to Know #1
Hyperreactive
Patients in whom low dose of drug produces expected pharmacologic effect you would see from the. normal dose. ie. a patient being a “lightweight”
Hypersensitive
This is an immune-mediated reaction to a drug… allergic response
Can be rash to anaphylaxis
Hyporeactive
Folks who need exceptionally large doses of drug for desired effect
Tolerance
Hypo reactivity acquired form chronic exposure to a drug or cross-tolerance.
Pharmacodynamics: Terms to know #2
Tachyphylaxis
Tolerance that develops with only a few doses of drug
Sodium thiopental, ephedrine, neosynephrine infusion, local anesthetics
Immunity
Hyporeactivity d/t formation of antibodies
Idiosyncracy
An unusual effect of a drug that occurs in small percentage of people that is not dose dependent
Propofol shakes, hiccups etc
Pharmacodynamics: Terms to know #3
Additive effect
When the action of two drugs acting together have combined effect of each agent given alone. Ex- Nitrous Oxide and Volatile Anesthetics
1 + 1 = 2
Synergistic Effect (hyperadditive)
Two dugs that interact to have an effect greater effect that each taken alone. Ex- Effect of Versed & Fentanyl on respiratory drive
1 + 2 = 6
Pro-drug
A medication that is metabolized after administration into a pharmacologically active compound ex Fospropofol to Propofol
Agonist vs Antagonist
Direct vs Indirect Agonism
Directly –acting receptor agonist is a drug that binds directly with its receptor to trigger its physiologic response.
Ex. Phenylephrine
Indirect-acting receptor agonist is a drug that produced its physiologic response by increasing the concentration of an ENDOGENOUS substrate (neurotransmitter or hormone) at receptor site
Ex. EPHEDRINE
Competitive vs non-competitive antagonism
Drug that binds to the receptor without activating it, and prevents an agonist from stimulating the receptor
Competitive antagonist
Can be overcome by increasing the concentration
Ex: β-Blockers, neostigmine
Non-competitive antagonist
Cannot be overcome
Ex: protamine & heparin
Routes of Administration: Alimentary Tract
Routes of Administration: Sublingual and Buccal
Routes of Administration: Rectal (PR)
Variable absorption based on proximal or distal administration
Avoids 2/3 of first pass metabolism
Produces less nausea than PO/Buccal
Emesis = loss of drug
Used in peds and in end of life care where dysphagia, ileus, or bowel obstruction can prevent progression of med through GI Tract
Ex Tylenol, Phenergan, opioids, and benzos
Routes of Administration: Transdermal
Routes of Administration: Intramuscular and Subcutaneous
Routes of Administration: Transtracheal
WILL ASK ABOUT THE DRUGS FOR THIS!!!
Routes of Administration: Intranasal
Easy test question about No 1st Pass
Routes of Administration: IV (Pros)
Intravenous- Pros
Most predictable onset, DOA, and Plasma concentration available
Bioavailability of 100%
Irritating and non-isotonic solutions can be administered intravenously since the intima (inner most layer) of the vein are insensitive
Drug dose titration in possible because of short duration of action and ability to monitor response
Drugs can be delivered at a uniform rate
Very large amount of infusion can be administered
Bypass first pass metabolism
Routes of Administration: IV (Cons)
Pain at injection site
Extravasation of some drugs can cause injury, necrosis
Once drug is injected, its action cannot be halted
High probability of bacterial contamination, so strict aseptic technique is required
Pharmacokinetics of Injected Drugs: Once its in, where does it go?
Compartment model
Volume of distribution
Ionization
Pharmacokinetics: Compartment Model
Central compartment
Rapid uptake of drug
Includes intravascular fluid and highly perfused tissues like lungs, heart, brain, kidney, and liver
75% of cardiac output, 10% of body mass
Peripheral compartment- slower uptake
Includes less vascular tissues like fat, bone, and inactive skeletal muscle
Drugs equilibrate between compartments and are eventually eliminated from the central compartment
Tissue group composition, relative body mass, and percentage of cardiac output.
Parameters of Injected Drugs
Bioavailability
Dose Response Curve
Potency
Plasma Concentration Curve
IV will reach elimination phase quicker
Effect-Site Equilibration: When do the drugs work?
The delay between dosing and onset reflects the time necessary for the circulation to deliver the drug to its site of action
Time between dosing and clinical effect
Example: Elderly tend to have a lower CO (β-Blockers or dec. EF) thus longer circ. time
A screaming child has a high heart rate, will circulate quicker
Distribution
Elimination of a drug causes net transfer of drug out of tissue back into circulation
Reservoir effect
Sevoflurane in Obese
Second dose effect
Greater effect then initial dose- rocuronium
Blood Brain Barrier
Ionization
Most drugs are weak acids or bases that exist as both ionized and non-ionized molecules
Non-ionized: lipid soluble, active
Ionized: water soluble, inactive
What determines the degree of ionization of a drug?
pK of Substrate
pK of surrounding fluid
Elimination Half-Time
Time necessary for the plasma [ ] of a drug to decrease to 50% during the elimination phase.
Clearance
Basic Unit Conversions to memorize
1 liter (L) = 1,000 milliliters (mL)
1 milliliter (mL) = 1 cubic centimeter (cc)
1 gram (g) = 1,000 milligrams (mg)
1 mg = 1,000 micrograms (mcg)
1 kilogram (kg) = 2.2 pounds (lbs.)
1 inch (in) = 2.54 centimeters (cm)
Shortcut: Converting lb to kg
To convert pounds to kilograms divide the number of pounds by 2, and then subtract 10%.
Example 150 lbs /2 = 75
Move decimal point one place to get 10% of 75 (7.5)
Subtract from your first number 75-7.5 = 67.5 kg
Not exact but great quick trick
Percentages in Solutions
Expressed in terms of weight per volume
% (W/V = g solute / 100 mL finished solution)
So 1% = 1 gram of drug [X] in 100 ml diluent
1 gram = 1000 mg
1000 mg/100ml = 10 mg/ml
1% Propofol = 10 mg/ml
So for any percentage in medicine
Drop the % and move the decimal place once to the right, and you have the concentration in mg/ml
0.5% Marcaine (Bupivacaine) is 5 mg/ml
2% lidocaine in 20 mg/ml
Temperature Conversions
What is 98.6 Degrees Fahrenheit in Celsius?
98.6-32 = 66.6
66.6/1.8 = 37 Degrees Celsius
This is the temp you want your patient
Patient arrives in pacu with a temperature of 35.6 Celsius. What’s this in Fahrenheit?
35.6 * 1.8 = 64.08
64.08 + 32 = 96.08
<36.0 Celsius in PACU gets noted
The Factor Label Method/ Dimensional Analysis
Using conversion factors of equal values as a bridge between units of measure.
Three steps used:
1. Determine the starting factor and the answer units
2. Formulate a conversion equation consisting of a sequence of labeled factors, in which successive units can be canceled until the desired answer unit is reached
3. Solve the conversion equation by use of cancellation and simple arithmetic
Drugs come in all sorts of concentrations
Phenylephrine – mcg/ml (after dilution)
Propofol mg/ml
Mannitol g/ml
Heparin Units/ml
Phenylephrine (neosynephrine) Example
10 mg/ml diluted into 250 ml Normal Saline
10 mg * (1000 mcg/mg) = 10,000 mcg of Phenyleprine
10,000 mcg / 250 ml = 40 mcg/cc
Ratios as Concentration
Written as mass of drug (grams) : Volume of solution (ml)
Epinephrine 1:1000 = 1 gram of epi in 1,000 ml of solution
Same as 1 mg epi/ 1 ml
Or 0.1%
Epinephrine 1:300,000 = 1 gram of epi in 300,000 ml of solution
Same as 1 mg epi/300 ml solution
Or 0.1 mg epi in 30 ml of solution.
Ratios example question
You are going to bolus an epidural for a C-section and select 2% Lidocaine with Epi 1:200,000 in a 20 cc vial
How Much mcg of Epi is in there?
1g :200,000 ml / X grams : 20 ml
200,000 ml * X grams = 1 g * 20 ml
X grams = (1g * 20 ml)/(200,000 ml) = 0.0001 g * (1000 mg/1g) *(1000 mcg/1 mg) =
100 mcg of epi in the vial
When working with ratios
When working with ratios, see how many times the second number goes into 1,000,000 and that’s the number of mcgs/cc
1:200,000 = 5 mcg/cc
1:10,000 = 100 mcg/cc
1:1000 = 1000 mcg/cc or 1 mg/ml
Common question:
How much Epi and Lido in a given set of numbers
Lidocaine and Epi together
Random Sidebar- Epi in Lido
We put Epinephrine in local anesthetic for a few reasons
Local vasoconstriction slows elimination of local anesthetic from injection site.
Vasoconstriction also offers hemostasis
Decreased toxicity
Max lidocaine dose is 5 mg/kg without epi and 7 mg/kg with it
Drug Calculations Ratios
Epinephrine is supplied as 1g of epi in ml’s of diluent
Ex Emergency syringe epi is 1:10,000
1:10,000 = 1 g epi in 10,000 ml
1g/10,000 ml = 1,000 mg/10,000 ml
1,000 mg/10,000 ml = 0.1 mg/cc
0.1 mg/ml = 100 mcg /cc
ORRRRRRRRR divide 10,000 into 1,000,000
100 mcg/cc
Drug Infusions
Infusions are either expressed as a [unit of measure]/unit time
Phenylephrine 25 mcg/minute
Or as a [unit of measure]/kg/unit of time
Epinephrine 0.1 mcg/kg/min
Question: How many cc/hr is a levophed (norepinephrine 16 mcg/cc) running at to deliver 0.05 mcg/kg/min for a 70 kg patient?
Units Cancellation
Drug Calculations
What is the concentration in an infusion bag of phenylephrine where two vials (10 mg/ml) are mixed in a 250 ml bag of normal saline?
[Unit of measure] 10 mg (x2) = 20 mg
Divide by [amount of diluent] 250 ml
20 mg/250 ml = 0.08 mg/ml = 80 mcg/ml
How many ml’s of 1:1000 epinephrine need to be added to a 20 ml bottle of 0.25% bupivacaine to achieve a 1:200,000 concentration?
1:200,000 epi = 1,000 mg/ 200,000 ml (This is your target concentration)
1,000 mg/200,000 ml = 0.005 mg/ml
0.005 mg/ml x 20 ml in bottle = 0.1 mg or 100 mcg of drug needed
1:1000 epi = 1g/1000ml = 1000 mg/1000ml = 1 mg/ml
0.1 mg/ (1mg/ml) = 0.1 ml
How many mL/hr should we set an infusion pump at in order to deliver 5 mcg/kg/min to an 80 kg patient of dobutamine (2000 mcg/mL)?
Problem #1
A 60 kg patient is here to have an elective tubal ligation for sterilization. Propofol (10 mg/ml) has been chosen as the agent for induction and maintenance of anesthesia. Assuming an induction dose of 2 mg/kg, how many cc of propofol will you give on induction?
How many ml/hr will we run the infusion to deliver 120 mcg/kg/min?
Problem #2
You are to give Ancef (Cefazolin) as your prophylactic antibiotic to a 20 kg child before their inguinal hernia repair. It comes as 1 gram of lyophilized (freeze dried) drug in a vial that holds around 10 ml of diluent. Dose is 25 mg/kg.
If you reconstitute the med in 10 ml of normal saline, what is your dose of cefazolin in mg and the volume administered to lil’ Timmy?
Problem #3
You are called by the charge nurse on the OB deck and told the patient in rm 10 will need to go for C-section for failure to progress. You remember placing an epidural in this lady a few hours ago. After checking that the epidural has been working bilaterally you begin to incrementally give a total of 15 ml of 2% lidocaine with 1:200,000 epinephrine in her epidural. How much of each agent are you administering in total?
Problem #4
As part of a TIVA for a 5 level thoracic spinal instrumentation case, you’ve elected to use a sufentanil (sufenta) infusion. The patient is 95 kg and your starting infusion rate will be 0.3 mcg/kg/hr. It is supplied as seen on the right and needs to be diluted to 5 mcg/cc for infusion admin. How much diluent will you use, and at what rate should the infusion pump be set in ml/hr?
Infusion Rate
0.3 mcg/kg/hr needed given 5 mcg/ml Sufenta in 50 ml, 95 kg patient
[0.3 𝑚𝑐𝑔/(𝑘𝑔 ∗ℎ𝑟) * 95 kg] / (5mcg/ml) = 5.7 ml/hr
Problem #5
During the spine case, your patient’s temperature drops to 35.4 deg Celsius. What is this temperature in Fahrenheit?
[35.4 * (9/5)] = 63.72 + 32 = 95.72
Can also multiple by 1.8 instead of 9/5 if easier to remember
Pharmacokinetics of Inhalational Agents
Not much is known about the exact mechanism of action, of inhalational agents.
We do know that their end effect is dependent on the tissue concentration of the agent in the pts. Central nervous system.
There are multiple factors influencing the uptake and elimination of inhalational anesthetics.
Factors affecting Inspiratory and alveolar concentration
Inspiratory concentration depends on multiple things:
Amount of fresh gas flow
The volume of the the breathing system
Amount of absorption by the circuit and anesthesia machine.
(If change a CO2 absorber mid surgery, will have to turn up vaporizer)
***The goal is to have your inspired gas (agent) concentration as close to fresh gas concentration as possible.
What is Alveolar partial pressure????
This alveolarpartial pressure of a gas is the driving force for the diffusion of that gas across the alveolar membranes, through pulmonary capillary walls, and into the arteriolar blood flow and erythrocytes for transport throughout the body into peripheral tissues
Partial pressure gradients drive the movement from one compartment to the other
Factors affecting Inspiratory and alveolar concentration
What affects Alveolar concentration???
Solubility of the agent in the blood
Alveolar blood flow
The difference in partial pressure between alveolar gas and venous blood. (Blood/Gas partition coefficient)
Volatile agent solubility
The solubility of an agent determines the amount of agent that is taken up in blood or a given tissue.
The higher a VA solubility the higher the amount that is taken up in the blood (pulmonary circulation) and the greater the amount is needed to reach the clinical depth of agent needed for anesthesia.
The solubilities of VA’s are expressed as partition coefficients
Desflurane - very quick acting because not soluble in blood, so gets to brain quicker
Sevoflurane - not as quick, because is more soluble in blood, so less gets to brain as quick
Alveolar Blood Flow
Alveolar blood flow in the absence of any right to left shunting is equal to Cardiac output.
CO / alveolar BLOOD flow- ↑ CO acts the same as ↑ solubility because as the CO increases it promotes increased anesthetic uptake and that slows the rise in Alveolar partial pressure. Delaying induction
No CO = no uptake = no anesthesia
This relationship with CO and increased uptake of agent is not as pronounced if the VA has a low blood/gas solubility.
Effects Isoflurane more than Sevoflurane
Alveolar to venous partial pressure gradient
This gradient depends on the uptake of the VA into different tissues
Three factors determine the transfer of VA from blood to tissues
The solubility of the VA into a specific tissue
The bloodflow to that tissue
The difference in partial pressure between that tissue and arterial blood.
Ventilation
One way to counter act the decline of alveolar partial pressure (driving force for your VA). By the uptake of agent into the blood stream is to increase the alveolar ventilation.
Increasing your alveolar ventilation will help you quickly replace the VA that is being taken up by the pulmonary circulation.
This is more affective for more soluble agents.
What determines Alveolar partial pressure again?
Inflow of anesthetic gas to alveoli (FA)
Ventilation- increased ventilation = faster induction
Concentration- increased concentration = faster induction
Concentration effect
Second gas effect
Second gas effect
What is second gas effect in Anesthesia?
The second gas effectoccurs when a soluble first gas such as nitrous oxide is delivered in high inspired concentrations. Alveolar-capillary uptake of the first gas increases the alveolar concentrations of other gases present, accelerating their uptake.
The second gas effect, despite its persistence in examination questions, is probably insignificant in the clinical practice of anesthesiology.
Concentration effect
The slowing of induction can be counteracted by simply increasing the concentration of the delivered VA.
Doing this also increases the rate of rise of you alveolar concentration
If you have 50 percent of your VA taken up and your concentration is 30% (30 parts agent in 100 parts gas). After uptake you will have 15 parts agent in 85 parts gas total and a concentration of 17.6%
If you up your concentration to 80% (80 parts agent in 100 parts gas) after your 50% uptake you have 40 parts agent in 60 parts total gas. Your concentration of agent will be 67%
Metabolism and Elimination of Volatile agents
To wake up (recover/emerge) a pt. from volatile anesthetics we need to lower the concentration of volatile agent in the brain tissue.
Three ways to lower this tissue concentration
Biotransformation/metabolism
Transcutaneous loss
Exhalation - MAIN WAY
Biotransformation/Metabolism play a very small role in emergence unless you are using very soluble agents.
Transcutaneous loss is super minimal so FORGET ABOUT IT
Exhalation
The most important way of lowering that brain tissue concentration.
This route of elimination utilizes the alveolar membrane and relies on many of the same factors we rely on for a speedy and efficient Induction of anesthesia
Elimination of rebreathing (lowering or turning off you VA)
High FRESH gas flow
Low anesthetic-circuit volume
Decreased agent solubility
High cerebral blood flow (etco2 low, have been over breathing them)
Increased Ventilation
Length of administration (Sevoflurane gets more of an art to wake someone up the longer you had it running)
Diffusion Hypoxia
Diffusion Hypoxia occurs only when using Nitrous Oxide
The elimination of Nitrous is soooo quick that oxygen and carbon dioxide concentrations in alveolar gas are diluted causing a brief hypoxia
A way to combat this is to administer 100% oxygen for at least 5 to 10 mins after turning off your Nitrous
Pharmacodynamics of Volatiles
Yellow - Sevoflurane
Purple - Isoflurane
Red - Halothane
Blue - Desoflurane
MINIMUM ALVEOLAR CONCENTRATION
Amount of an agent that prevents movement in response to a supramaximal painful stimulus (i.e. skin incision) in 50% of patients.
Additive when used with N2O (1/2 MAC VA + ½ mac N20) = 1 MAC
Considered the ED50 of inhaled anesthetic
1.3 MAC prevents movement in 95% of patients
6% decrease in MAC per decade of age (if younger need more)
MAC is not affected by sex or duration of agent administration
.3% is considered awake
Factors Effecting MAC
Likes this table for test questions
Nitrous Oxide
Colorless and basically odorless (great for inhalational use)
Although non explosive and non flammable N2O is still capable of supporting combustion.
Cardiovascular effects
N2O stimulates the sympathetic nervous system, because of that you see slightly elevated/no change in ABP, CO, and HR even though N2O is a myocardial depressant.
Respiratory effects
Increases Respiratory rate (tachypnea) and decreases tidal volume
Significant depression of Hypoxic drive (your ventilatory response to arterial hypoxia)
Cerebral effects
N2O will increase cerebral blood flow and cerebral blood volume, therefore causing an increase in Intercranial Pressure.
Increases Cerebral Oxygen consumption (CMRO2)
Concentrations below MAC can/may provide Analgesia for minor procedures (dental, labor pain, and minor surgical procedures)
Neuromuscular
Provides zero muscular relaxation regardless of concentration
DOES NOT trigger MH
Renal
N2O decreases renal blood flow by increasing renal vascular resistance
Decreases GFR (glomerular filtration rate) and UO (urinary output)
Hepatic
Zero to no change
Gastrointestinal
Increases the risk of post op nausea and vomiting
Biotransformation and Toxicity
Eliminated almost entirely by exhalation
Prolonged exposure to anesthetic concentrations of N2O can result in bone marrow depression, and even neurologic deficiencies
Due to its teratogenic effects, nitrous is avoided in pregnant pts that are not in their third trimester
Nitrous Oxide Contraindications and Altitude
Nitrous Oxide and Altitude
The difference between the analgesic effects of nitrous oxide at increasing altitudes was statistically significant.
It is concluded thatmoderate altitudes significantly reduce the effectiveness of nitrous oxidein a manner directly related to the partial pressure of nitrous oxide at each altitude.
Soooo if you’re working in DENVER it not soo good
Isoflurane
Cardiovascular
Minimal left ventricular depression
Increase in HR helps maintain CO
Decreases SVR and ABP
Rapid increases in ISO concentration can lead to increased HR and ABP (very hard to rapidly increase… Desflurane is the opposite)
CORONARY STEAL, Isoflurane will dilate coronary arteries but not as strongly as other drugs, so its possible that ISO can cause blood flow to divert away from arteries with FIXED STENOTIC LESIONS. Reverse robin hood. Stealing from the poor giving to the rich.
Respiratory
Increases RR less than other VA’s and Decreases TV
Low concentrations will blunt the response to Hypoxia and Hypercapnia
Tends to irritate upper airway reflexes but is actually a pretty good bronchodilator
Cerebral
@ greater than 1 MAC ISO will increase CBF and intercranial pressure. (@ less than 1 MAC it doesn’t) This can be overcome by increasing the ventilation rate.
Reduces pts cerebral metabolic oxygen requirements and @ 2 MAC it will produce an electrically silent EEG
Neuromuscular
Will provide Muscular relaxation
Renal
Decreases RBF, GFR and UO
Hepatic
Total hepatic blood flow is decreased
Biotransformation and Toxicity
Metabolized in to fluoride ions but highly unlikely to cause Nephrotoxicity
Contraindications and drug interactions
CAN trigger MH
Nondepolarizing neuromuscular relaxants are potentiated by ISO
Desflurane
Cardiovascular
Decline in SVR, ABP and minimal to NO change in CO
With rapid increases in Concentration levels you can have an increase in HR, BP and catecholamine levels (much more pronounced than with ISO). Easily attenuated with Fentanyl or Beta blockers (esmolol/ metoprolol)
Respiratory
Increases in RR and decrease in TV
Overall decrease in alveolar ventilation leading to an increase in PaCO2
Depressed response to Hypercapnia
Not good for inhalational inductions due to its pungent smell
Cerebral
Directly dilates cerebral vasculature increasing CBF, CBV and intercranial pressure
Decreases CMRO2 significantly and that leads to slight cerebral vasoconstriction which helps moderate and change in CBF
With DES the cerebral vasculature remains responsive to changes in PaCO2, so hyperventilation can be used to negate increased ICP
Neuromuscular
Desflurane causes a dose dependent decrease in the response to Neuromuscular twitch monitors
Renal
As cardiac output declines so will urinary output and GFR
Hepatic
Very little to no metabolism of DES,
As long as Hepatic perfusion is maintained intra-op, there is very little Hepatic impact
Biotransformation and Toxicity
VERY LITTLE metabolism with DES
DES more than any other VA is degraded by desiccated CO2 absorbent (more with barium hydroxide lime than with sodium and potassium hydroxide)
When degraded DES can lead to clinically dangerous levels of CO (don’t leave the oxygen flowing)
Contraindications
Triggers MH
Sevoflurane
Slightly more soluble than DES and slightly less soluble than ISO
Non-pungent smell and SEVO’s rapid increases in alveolar anesthetic concentration make SEVO a great choice for Inhalational inductions
Cardiovascular
Mildly depresses myocardial contractility
Decreases SVR and ABP but less than ISO
Little to no change in HR so therefore little to no change in CO
Respiratory
Increase in RR and decrease in TV
Potent bronchodilator similar to ISO
Cerebral
Slight increase in CBF and ICP
At higher concentrations SEVO seems to impair a pts ability to autoregulate their own CBF.
Neuromuscular
Sevoflurane produces enough muscle relaxation after an inhalational induction that you could intubate with just SEVO alone.
Renal
Decreased renal blood flow
Possible renal tubule impairment due to the metabolism of SEVO in to Flouride ions
Metabolism
P450 metabolizes SEVO about 10 to 25 times more than it does ISO or DES.
COMPOUND A…………….. Who cares unless you’re a lab rat
Drug interactions and contraindications
Triggers MH
Severe hypovolemia (blood loss/trauma)
Potentiates NDMRs
Halothane
May only encounter if doing mission trips
Sweet smell, non-irritating makes it good for inhalational induction
Thymol preservative
Metabolized up to 20% leads to Halothane Hepatitis
High potency
Direct myocardial depression of LV contractility
Cardiac Sensitization to catecholamines lead to arrythmias
Cassidy’s White Board
Kris’s White Board
Summary of Organ System Effects: Inhalational Agents
BARBITURATES
Examples include thiopental and methohexital
MECHANISMS OF ACTION
Depress the reticular activating system in the brainstem, which controls consciousness
Primary MOA is binding to the GABA receptors and potentiate the action of GABA
GABA is primary inhibitory neurotransmitter in CNS
High lipid solubility and fast redistribution account for the fast uptake and quick recovery/wake up from Barbiturates.
Thiopental was great for neuro inductions
3-5 mg/kg induction dose
Neuroprotective
Decreased ICP, by decreasing CBF and CBV
No longer available stateside because of use in lethal injection
Still on boards, yay
METHOHEXITAL (BREVITAL)
Barbiturate
METHOHEXITAL (BREVITAL)
Still used for ECTs (electro convulsant therapy)
Induction dose around 50-120 mg
Comes as 1% solution
Ultrashort because of quick redistribution
Rapidly cleared and less accumulation
Does not increase seizure threshold, making it perfect for ECT
How IV Dose goes through body
FIGURE 9–2 Distribution of thiopental from plasma to the vessel-rich group (VRG; brain, heart, liver, kidney, endocrine glands), to the muscle group (MG), and finally to the fat group (FG). Propofol follows the same pattern but on a different time scale. (Modified with permission from Price HL, Kovnat PJ, Safer JN, et al. The uptake of thiopental by body tissues and its relation to the duration of narcosis. Clin Pharmacol Ther. 1960 Jan;1(1):16-22.)
Etomidate (Amidate)
Depresses RAS and mimics GABA
Highly lipid solubility at physiologic pH
Metabolism is hepatic (almost 100%) and hydrolyze by plasma esterases
Elimination in urine
Cardio stable but cerebral protectant (no effects on sympathetic tone or myocardial function)
Decreases CBF,CBV while cerebral perfusion is maintained due to minimal myocardial depression.
Commercial preparation has 33% propylene glycol- burns like hades
Come as 0.2% (2 mg/cc)
Propofol (Diprivan)
Mechanism of Action
Achieves induction of general anesthesia by binding to the GABA receptor and increasing the binding affinity of GABA for the GABAa receptor.
DISTRIBUTION
Very Rapid onset of action and a very short intial distribution half life 2-8 mins giving it a very rapid recovery and it has less of a hangover than etomidate, thiopental, and methohexital.
BIOTRANSFORMATION
Very HIGH clearance rate of Propofol, after it is metabolized in the Liver to inactive metabolites
Long term infusions in critically ill kids and young neuro-surgical pts. can result in sporadic cases of Lipemia, metabolic acidosis, and death. (PROPOFOL INFUSION SYNDROME)
EXCRETION
Primarily excreted in urine and End stage renal Disease does not affect clearance.
PROPOFOL (DIPRIVAN): Effects on Organ Systems
Ketamine (Ketalar)
Phencyclidine PCP derivative
Inhibits reflexes in the spinal cord as well as excitatory neurotransmitter effect in brain
‘Dissociates’ the thalamus = eyes open, swallowing, muscle contracture but unable to process sensory input (nystagmic gaze)
Ketamine binds non-competitively to the phencyclidine site on N-methyl-D-aspartate (NMDA) receptors
Comes at 10 mg/ml in 10 ml syringe or high dose 50mg/ml and 100 mg/ml multidose vials
Concentrated for IM use, 3 ml is upper limit of IM volume
Induction of Anesthesia
IV: 1-2 mg/kg
IM: 4-8 mg/kg
Ketamine: Clinical Considerations
BENZODIAZEPINES
Principal pharmacologic effects:
Reduce Anxiety
Sedation (“sleeping pill”)
Mild muscle relaxation
Anterograde amnesia
Cardio: ↓SVR, ↓BP
Resp: ventilatory depression at higher doses
CNS: ↓CMRO2, ↓CBF, ↓ICP
Other:
Work synergistically with opioids to depress respirations, especially in the elderly
MIDAZOLAM (VERSED)
Comes as 1 mg/cc in either 2 or 5 cc bottle
1-2 mg is standard premedication/block sedation dose
Up to 5 mg in patients on chronic benzos or with severe anxiety
0.5 mg/kg PO pediatric dosing
Can be given via Nasal, Oral, and IV…
Nasal Dose - 0.2-0.3 mg/kg
Diazepam (Valium)
Highly lipid soluble with a large Vd
Hepatic P450 metabolism
Highly active metabolite nordiazepam
Clinical Considerations
Cardio: mild ↓BP
Resp: minimal depressant effects
CNS: sedation, anticonvulsant
Commercial preparation
5-10 mg/cc
5-10 mg IV standard dose for muscle spasm
Flumazenil (Romazicon)
Specific and exclusive benzodiazepine antagonist
Short DOA re-sedation is possible
Commercial preparation
0.05 – 0.1 mg/cc flumazenil hydrochloride
Dosing
0.2 mg every 60 sec. up to 1 mg
Opioids
Opioids
Morphine at high doses can lead to hallucinations
Opioids
Pharmacokinetics of Opioids
Oral, IV, IM, IN, transmucosal, rectal, spinal, and epidural
Distribution: uptake depends on solubility
Fent/Sufent rapid, morphine is slower
Metabolism: Liver by CYP 450
Except Remifent (ester structure) to hydrolysis
Meperidine to normeperidine (active metabolite)
MSO4 to Morphine 6-glucuronide (greater activity)
Elimination: Excreted as metabolites in urine
Opioid Effects on Organ Systems
Need to look at M+M for this (had a duplicate slide)
Opioid Side Effects
See Chest Wall Rigidity with Fentanyl during induction without a muscle relaxant
OPIOID ANTAGONIST
We try to avoid Narcan as much as possible due to how will block all opioids blocking the pain
NEUROMUSCULAR BLOCKING AGENTS
Succinylcholine
Dose: 1-2 mg/kg Rapid Sequence Induction dose to produce optimal intubating conditions in 30-60 seconds.
Mimics acetylcholine
Clinical sign of onset- fasciculations
Duration: Usually 5-10 minutes
Metabolism- Rapid hydrolysis by plasma pseudocholinesterase
Increased plasma K+ concentration due to potassium release from muscle (if patient has high K+ preop, could be a contraindication to the operation)
Transient increase in IOP/ICP/ intragastric pressure
Myalgia after fasciculations
Triggering agent for Malignant Hyperthermia
PSEUDOCHOLINESTERASE DEFICIENCY
Rocuronium
Dose- 0.6-1.2 mg/kg
Duration of action- 30-90m
HIGHLY VARIABLE especially after redosin
Onset: 60-90 seconds making it usable for RSI
Metabolism- not really. Is excreted primarily by liver but by kidneys as well
Reversal agents- neostigmine (competitive antagonist) and sugammadex (binds to rocuronium and inactivates it)
Cisatracurium (Nimbex)
Onset 3-5 mins and the duration of action is about 20-40mins
Hoffman elimination 80% and plasma esterase 20%
Hoffman elimination is a spontaneous nonenzymatic chemical breakdown that occurs at physiological pH and temperature
2mg/cc standard concentration
0.08 – 0.12mg/kg dose
Primarily used for pts that have decreased kidney function
Laudanosine metabolite of nimbex can decrease a pts seizure threshold.
Vecuronium (norcuron)
Onset 3-5 min, DOA 30-60 min
10 mg lyophilized powder with 10 mls (1mg/1ml)
0.08-0.12 mg/kg
Metabolized to a small extent by the liver
Primarily biliary excretion 75% and renal excretion 25%
Not widely used
Pancuronium (pavulon)
Was used for pediatric hearts
Vagolytic properties raised HR
(Easy Test Question)
Longest acting NMBA
Metabolized somewhat by the liver
Primarily renal excretion 40% with some bile 10%. (not good for renal pts)
Dose is 0.08-0.12mg/kg
Achieves adequate relaxation for intubation in 2-3 mins, would not be used if trying to secure an airway quickly
Neuromuscular blocking reversal agents
Chemicals in this family can act either directly by stimulating the nicotinic receptors or muscarinic receptors, or indirectly by inhibiting cholinesterase.
They irreversibly bind to acetylcholinesterase (AchE), thereby preventing the hydrolysis of Ach and increasing the Ach concentration in the NMJ
This allows for the action potential threshold to be reached so a new impulse can be triggered in the next neuron
Reversal Agents
Anti-Cholinergic Agents
Given to counteract all the parasympathetic effects of anticholinesterase meds
Reversible binding with muscarinic cholinergic receptors
Prevents Ach binding
Effects can be overcome by increasing Ach concentrations at muscarinic sites
Effects
Antisialogogue
Inc. HR
Mydriasis
Dec. gastric motility
Naturally-occurring tertiary amines
Atropine
0.4 mg/cc
0.01-0.03 mg/kg
Potent effects on heart and bronchial smooth muscle.
Used to treat organophosphate poisoning and nerve gas exposure
Scopolamine
0.4 mg IVP for trauma amnesia
1.5 mg Transdermal Patch
Greater CNS effects than atropine, clinical doses result in drowsiness and amnesia
Synthetic= quaternary amine
Glycopyrrolate (Robinul©)
0.2 mg/cc
0.01-0.02 mg/kg
Does not cross the blood brain barrier so basically no CNS effects
Adrenergic Agonist and Antagonist
Terms we need to know relating to Heart
Alpha-1 Receptors
Vasoconstriction is the number 1 result (peripheral vascular resistance = PFR)
Alpha-2 receptors
Located Primarily on presynaptic nerve terminals
Activation of Alpha-2 receptors on presynaptic terminals causes a negative feed back loop that inhibits further norepinephrine release from the neuron.
Stimulation of Alpha-2 receptors in the central nervous system causes sedation and reduces sympathetic outflow, leading to peripheral vasodilation and decreased blood pressure.
Inhibits Insulin release
Beta-1 Receptors
Norepinephrine and epinephrine are equally as potent on Beta-1 receptors
Located on the postsynaptic membrane in the heart
Activation/stimulation of these receptors has many effects.
Positive chronotropic (increased HR)
Positive dromotropic (increased conduction)
Positive inotropic (increased contractility)
Beta-2 Receptors
Postsynaptic receptors mainly located in smooth muscle and gland cells, but also can be found in ventricular myocytes.
These receptors share a common MOA with Beta-1 receptors but despite their common MOA upon stimulation these receptors cause
Smooth muscle relaxation (bronchodilation, vasodilation)
Relaxation of the Uterus, Bladder, and GI
Glycogenolysis, Gluconeogenesis, and insulin release
Dopamine Receptors
DA Dopamine receptors– found in CNS and renal vessels
DA1 vascular relaxation
DA2 inhibit presynaptic release of NE
Sympathomimetics (Adrenergic Agents)
Why do we use them????
Cardiac stimulation
Inotropy: contractility
Chronotropy: rate
Vasoconstriction
Treatment of bronchospasm (need bronchodilation)
Management of allergic reactions
Additive to local anesthetics
Adrenergic Agonists
Phenylephrine (Neosynephrine)
Neosynephrine is a noncatecholamine with direct selective Alpha-1 agonist activity.
Main effect is vasoconstriction causing a rise in SVR and ABP.
Reflex Bradycardia is very common and can vary from pt. to pt.
DOA is very short, single dose may last 10-15 mins
Tachyphylaxis is possible with Infusions and may require titrating up the infusion as time goes on.
Syringes commonly come in 100mcg/ml concentration and vials come as 10mg/ml
Ephedrine (ephedra)
Indirect Alpha receptor agonist
Causes release of Norepi
Tachyphylaxis may occur due to depletion of Norepi stores
Vasoconstriction… Increased BP, positive chronotropic effects, increased HR
Long DOA
Is a controlled substance in some Hospitals so DO NOT throw away without knowing.
Epinephrine
Norepinephrine (levophed)
A1, A2, B1 direct receptor agonist
Intense vasoconstriction and mild inotropy
Natural mediator of sympathetic nervous system
Usually administered as an infusion due to its very short half-life
Dopamine
Big for test questions and questions in the OR
Adrenergic Antagonists (Blockers)
Get Phentolamine info from the book!!!
Mixed Antagonist
Beta Blockers
Esmolol good for when patient is waking up and don’t want their heart to increase (transient)
Metoprolol used when you tried Esmolol already (nontransient)
Hypotensive Agents (1)
Look up information in M+M!!!
Hypotensive agents (2)
Look up information in M+M!!!
Local Anesthetics (1)
Local Anesthetics (2)
Local anesthetic metabolism
Summary of nonvolatile anesthetic effects on organ systems
