Exam 1 Study Guide Flashcards
Pharmacology:
study of the effect of chemicals on the living body
Pharmaceutics:
the FORMULATION and prep of drugs
Pharmacoeconomics:
study of economic impact of drugs
Toxicology:
study of the harmful effects of chemicals; pharm of WRONG doses
Pharmacognosy:
study of medicinal use of NATURALLY occurring compounds
Pharmacy:
the prep and dispensing of drugs
Pharmacogenetics:
genetic influences by and of drugs
Pharmacoepidemiology:
study of the use and effect of drugs on a large group of people
Pharmacokinetics:
study of absorption, distribution, metabolism, and excretion of the drug
What the body does to the drug
Pharmacodynamics:
physiological and biochemical mechanisms of action of drugs
What does the drug do to the body
Receptor Theory (pharmacodynamics)
there are receptors that recognize the presence of chemicals and postulate a response
Drug receptors are _ _ which act as the site for a drug
macromolecular complexes
Drug receptors are usually made of _ that are involved in production of normal cellular function
proteins
Drug receptors include:
carrier proteins
protein channels
ion channels
enzymes
nucleic acids
True or false: A drug can’t make the body do anything it can’t already do
TRUE
If a receptor is a lock, then the _ is the key
LIGAND; a drug becomes a ligand when it connects to a receptor
Properties of receptors:
sensitivity
selectivity
specificity
Drug response occurs from a _ _ (sensitivity) produced by _ _ chemicals (selectivity) and the response is the same bc the cell determines it. (specific)
low concentration
structurally similar
True or false: A desired response only occurs when the drug receptors are completely saturated
FALSE
Occupancy Theory:
-opposite of spare receptor theory, there is a linear relationship b/t receptors occupied and response
magnitude of a drug effect is proportional to the number of receptors occupied
-tissue response happens when sufficient receptors have been occupied
Spare-Receptor Concept:
there is a non-liner relationship between the number of receptors stimulated and the response
-max response can be stimulated by only a fraction of the receptors
Agonist:
bind to receptor and STIMULATE the function that receptor serves
The agonist _ the action of the endogenous ligand.(hormone, neurotransmitter in body)
MIMICS
In adequate concentrations, an agonist can cause max activation of all receptors and this is known as a _ _
full agonist
Antagonist have _ for a receptor but no _.
affinity for the receptor but no efficacy
An antagonist binds to a receptor and _ the endogenous function that the receptor serves.
blocks
Antagonists have a _ affinity for a receptor than agonists do.
HIGHER
Agonists and Antagonists compete with the _ _ for binding sites
endogenous transmitter
Competitive Bonding is _ for most drugs
REVERSIBLE; drug binds then wears off once conc of blood exceeds conc of drug in plasma
Noncompetitive Bonding is _ for drugs
NONREVERSIBLE; once it binds, it’s there forever until body replaces the structure the receptor is attached to
-EX) platelets and aspirin
Antagonists have receptor _ but lack intrinsic activity AKA _.
affinity, efficacy
Antagonists with weak affinity=
competetive
Antagonists with strong affinity=
noncompetetive
Antagonists cause a _ward shift in the drug-dose response curve, which means?
RIGHTWARD; more drug is needed to cause the same effect due to increased affinity; how far the shift depends on # of available receptors occupied by antagonist
The strongest type of bond is a _ bond and is _.
covalent, nonreversible
The weakest type of bond is a _ bond and is _.
Van Der Waals, reversible
The bonds of receptors are as follows in order of strongest to weakest:
covalent, ionic, hydrogen, hydrophobic, van der waals
A _ _ activates a receptor but can’t elicit max response
Partial Agonist
A partial agonist may not elicit max response because:
-it may partially block effects of the full agonist
-possess both agonist and antagonist properties
-has lower efficacy than full agonist
_ _ are drugs that bind to a receptor causing an opposite reaction to an agonist
Inverse Agonists
NOT antagonists
Inverse Agonists bind with inactivated receptors and could be more beneficial than antagonists in disease states that occur from _ of receptor activity
upregulation
Dose Response Curve is the relationship among _, _, and _ _ as they relate to a typical sigmoidal dose or concentration versus response curve
efficacy, potency, and individual variability
Affinity/Potency is used to differentiate between different agonists that activate the same receptor and produce the same _ _ but at _ concentrations
max response (efficacy), different concentration;
-most potent drug required smallest dose
Efficacy is its ability to produce the desired response _ by _ of a receptor
expected, stimulation
-The magnitude of response with respect to the given dose
There will always be some _ in the dose response curve
variability
Intrinsic Activity is the _ _ effect obtained when comparing compounds in a series
relative max
Quantal Drug Response=
quantifies the actions of the drugs and expresses them as the effective dose (ED50), toxic dose (TD50), and lethal dose (LD50)
ED50=
effective dose in 50% of the population
TD50=
toxic dose in 50% of the population
LD50=
lethal dose in 50% of the population
LD50/ED50=
Therapeutic Index (bigger the better)
TD50/ED50=
Therapeutic Window (pharmaceutical window)
Therapeutic Index=
LD50/ED50, safety measure of a drug; how much it takes to kill someone
Therapeutic Window=
TD50/ED50; index used to estimate drug dose to treat disease effectively WHILE IN SAFETY RANGE and not causing significant adverse effects
Therapeutic Range ( Margin of Safety)=
range of doses that produce concentrations between toxicity and subtherapeutic thresholds
The top end of the therapeutic range is the toxic threshold which is the _ _ _ which is derived from _
minimum toxic concentration, TD50
The bottom end of the therapeutic range is the subtherapeutic threshold which is the _ _ _ which is derived from _
minimum effective concentration, ED50
Receptors not only initiate regulation of physiological and biochemical functions but themselves are also subject to many _ and _ controls
regulatory and homeostatic
Down Regulation AKA Desensitization=
diminished response
Effects of down regulation on cell:
-receptors decrease in number
-each receptor is less stimulated (decreased sensitivity -> tolerance)
Increased doses of a drug are needed to achieve same effect is the result of _ _
down regulation
Down regulation is caused by:
continued stimulation of the cell by AGONISTS
-Ex) bronchodilators for asthma
Up Regulation=
number and sensitivity of receptors increase
Effects of up regulation on cell:
-increase in number of receptors
-receptors are more sensitive to a drug
A patient developing tolerance requiring higher doses of an antagonist to counteract the increased receptor number is the result of _ _.
up regulation
Up regulation is caused by:
chronic administration of an ANTAGONIST
-Ex) beta adrenergic receptors up regulating in presence of antagonists and down regulate in presence of agonist
Tolerance=
increased concentration of a drug is needed for a response
Drug Tolerance (pharmacodynamic tolerance)=
a change in tissue sensitivity due to an adaptive mechanism
Dispositional Tolerance (pharmacokinetic tolerance)=
a change in the drug level due to an adaptive change in absorption, distribution, metabolism, or excretion of the drug
-Ex) enzyme induction or inhibition
Tachyphylaxis=
rapid development of tolerance with acute drug administration
Ceiling Effect=
dose beyond which there is no increase in effect, additional dosing leads to adverse effects
Interaction=
alteration in the therapeutic action of a drug by concurrent administration of other exogenous chemicals
Addition=
the combined effect of 2 drugs acting via the same mechanism is EQUAL to that expected by simple addition of their individual actions;
1+1=2
Synergism=
The combined effect of 2 drugs is GREATER than the algebraic sum of their individual effects
1+1=3
Potentiation=
The enhancement of the action of 1 drug by a second drug that has no detectable action of its own
1+0=3
Ex) penicillin (1) + probenicin (0) = prevents drugs from being excreted but has no effect on infection
Antagonism=(in terms of reactions)
action of one drug opposes the action of another
1+1=0
Ex) opioids + narcan, protamine + heparin, NMBD + suggamadex
Pharmacokinetics (4 things)
absorption
distribution
metabolism
excretion
The effect of size on pharmacokinetics:
the smaller a molecule is the more able it is to cross membranes
Degree of Ionization/ Lipid Solubility:
drugs are either weak acids or bases;
-higher the ionization the less likely a drug will pass thru a membrane
-measured with pKa
Ionized drugs are:
-charged
-water soluble
-unable to pass thru cell membranes
Non-ionized drugs are:
-non-charged
-lipid soluble
-able to diffuse across cell membranes
Bioavailability=
% of a drug that enters the systemic circulation in an unchanged form after administration of the product
The extent to which a drug reaches its effect after its introduction into the circulatory system is its _.
bioavailabiliity
The rate at which the systemic absorption occurs establishes a drug’s _ and _.
duration and intensity
Factors that influence bioavailability:
-lipid solubility
-solubility in aqueous and organic solvents
-pH and pKa
-blood flow
-environment into which drug is introduced
-patient’s age, sex, pathology, temperature
Route of admin with HIGHEST bioavailability:
IV, 100% bioavailable, most rapid onset
Route of admin with LOWEST bioavailability:
PO and inhalation; 5-100% bioavailable,
-PO is most convenient but has SIGNIFICANT first-pass effect
-inhalation has a VERY rapid onset
Admin order of highest % of bioavailability:
IV, transdermal, IM, subcutaneous, per rectum, PO, Inhalation
Stomach pH
1-3
Duodenal pH (small intestine)
5-6
Colon pH (large intestine)
8
Ileum pH (rectum)
8
Blood plasma pH
7.4
CSF pH
7.4
Urine pH
4-8
pKa
pH at which a drug is 50% ionized and 50% nonionized; ionization constant
True or false: pKa is a measure of acid or base status
FALSE, it measures the extent of ionization
True or false: the ionized portion of the drug will stay in the blood but it sends the non ionized drug elswehere.
true
Drugs that are 100% _ will have no CNS effect because none is transferred to the brain
ionized
If any portion of the drug is _ it can pose potential for fetal harm
nonionized
_ soluble substances are excreted by the kidney at the _ _ .
water, distal tubule
The liver converts _ soluble substances into _ soluble substances most commonly with cytochrome oxidases AKA _ _ _.
fat, water, cytochrome enzyme P450.
Primary metabolizing enzymes include (4):
CYP450, microsomal enzymes, mixed function oxidase, an metabolizing enzymes
3 factors effecting liver metabolism:
-intrinsic ability of the liver to metabolize a drug
-hepatic blood flow
-extent o binding of the drug to blood components
Lipid synthesis happens with enzymes found in the _ _ _ and to some degree in the _ of the cell. (think parts of cell)
smooth endoplasmic reticulum and cytosol of the cell
Although it mostly occurs in the liver, there are still considerable levels of metabolization that happen in:
lungs, kidneys, GI and placenta
Phase 1 of metabolism in the liver includes the processes of:
oxidation, reduction, hydrolysis (more common)
Phase 1 of the liver metabolism forms products that are more _ and _ active
chemically and pharmacologically
Phase 1 of the liver metabolism often involves the _ system in which _ _ is involved
momooxygenase, cytochrome P450
CYP3A4 metabolizes about _% of clinically administered drugs
50%
CYP2D6 metabolizes about -% of clinically administered drugs
25%
Phase 2 of the liver metabolism includes the processes of:
conjugation and synthesis
Conjugation=
coupling the reactive drug molecule (from phase 1) to an endogenous group so the resulting product is more water soluble
If a drug takes too much energy to metabolize, the body will use _ _ so that when you excrete _ the drug is carried with it.
glucuronic acid, glucose
Some drugs are excreted via bile, reactivated in the _, and reabsorbed via _ circulation
intestine, enterohepatic
P450 enzymes can _ hepatic drug metabolism which increases the _ of drugs with _ metabolites
accelerate, toxicity, toxic
Enzyme Induction=
increases drug metabolizing effects in liver
- ex) alcoholics have high amts of liver enzymes and break drugs down more quickly
Enzyme Inhibition=
decreases drug metabolizing effects of liver
- ex) grapefruit juice inhibits enzyme CYP3A4 which means less if broken down and more is circulating in plasma, increasing effects
First Pass Effect AKA Hepatic Metabolism is a _-systemic metabolism in the liver or gut wall that reduces the _ of many drugs when given orally.
pre-systemic, bioavailability
True or false: upon ingestion, the drug first goes to the blood stream and from there to the liver.
False! Goes to liver first then bloodstream!
True or false: since some parts of a drug are metabolized by the liver this means there is less drug bioavailability for use
True
Drugs bind to _ _ because of their innate affinity to them
plasma proteins
Acidic drugs bind to the protein:
plasma albumin
Basic drugs bind to these 2 proteins:
B-globulin and A-acid glycoproteins
The degree of a protein binding to a drug is proportional to its _ solubility which means more _ soluble agents = more highly protein bound
lipid, lipid
True or false: A bound drug is free to act on receptors therefore protein binding doesn’t effect drug distribution
FALSE, they can’t act on receptors unless they are free
The drug-protein molecule is too large to diffuse through _ _ membranes and is trapped in the _ system which will cause high _ concentrations.
blood vessel, circulatory, plasma
Extensive protein binding can _ drug elimination via metabolism and excretion
SLOW
Clinical drug interactions rarely occur because of _ between drugs for _.
competition between drugs for proteins
When unbound drugs increase in plasma, _ increases as well, lowering the risk of toxicity
excretion
When plasma proteins are at lower level than normal, total drug concentrations are _ but unbound concentrations are _ _.
LOWER, NOT AFFECTED
-ex) warfarin, phenytoin, propranolol, propofol, fentanyl, diazepam
Drug Elimination/Elimination Clearance=
ability for drug eliminating tissue to irreversibly remove drugs from the body
The kidneys eliminate _ or _ _ drugs more readily.
hydrophilic or water soluble
Elimination Half Life=
time needed for the plasma content of a drug to drop half of its prevailing concentration after a rapid bolus injection
A drug is considered fully eliminated once _% has been excreted which is usually - half lives.
95%, 4-5 half lives
First Order Kinetics or Dosage Independence states that most drugs leave the body at a _ rate.
constant
At a half life of 0, _% of drug is eliminated and _% remains
0%, 100%
At the 1st half life, _% of drug is eliminated and _% remains
50%, 50%
At the 2nd half life, _% of drug is eliminated and _% remains
75%, 25%
At the 3rd half life, _% of drug is eliminated and _% remains
87.5%, 12.5%
At the 4th half life, _% of drug is eliminated and _% remains
93.75%, 6.25%
At the 5th half life, _% of drug is eliminated and _% remains
96.875%, 3.125%
Most drugs tend to be more _ than _ so they can pass thru cell membranes to their site of action
lipophilic than hydrophilic
Highly lipophilic drugs have a _ onset of action because they _ diffuse into the highly perfused brain. They have a _ duration because of redistribution of the drug from CNS into the blood.
rapid, rapidly, short
Lipophilic drugs have _ volumes of distribtions
greater
An increase in the volume of distribution of a drug will _ its elimination half life.
increase
An increase in elimination clearance will _ a drugs elimination half life.
decrease
Distribution clearance of a drug is influenced by _ _ and regional _ _.
cardiac output and regional blood flow
The autonomic nervous system works with _, _, and _ to respond to internal and external stressors.
renin, cortisol, and hormones
Sympathetic Nervous System (SNS) =
amplification
Parasympathetic Nervous System (PNS) =
limited targeted response
_ and _ anesthetics can alter hemodynamics by influencing autonomic function
Inhaled and IV
Beta-adrenergic blockade is important for prophylaxis for _ and as a therapy for _, _, and _.
ischemia, HTN, MI, and CHF
SNS demonstrates both _ and _ adaptation to stress _ and _.
acute and chronic adaptation, pre and postsynaptically
-ex) biosynthesis, receptor regulation
Presynaptic alpha receptors play a significant role in regulating _ release
sympathetic
Many treatments for HTN target direct or indirect effects on the _.
SNS
The _ _ is the superhighway of the PNS, accommodating ~75% of CNS traffic
vagus nerve
Aging and other disease states (diabetes, SCI) come with important changes in _ function
autonomic
Symp/Parasympatholytic=
blocks SNS/PNS
Symp/Parasympathomimetic=
stimulates SNS/PNS
Parasympathetic outflow occurs with the _ _ which extends all over the body
vagus nerve
Sympathetic outflow occurs with the _ _.
Thoracolumbar region
PREsynaptically both SNS and PNS secrete _ to bind with _ _ receptors
acetylcholine, nicotinic cholinergic receptors
POST synaptically the SNS secretes _ to bind with an _ receptor and the PNS secretes _ to bind with a _ _ receptor.
SNS secretes norepinephrine, binds with adrenergic receptor
PNS secretes acetylcholine, binds with muscarinic cholinergic receptor
Types of adrenergic receptors:
-alpha
-beta
-dopamine
4 goals of anesthesia?
as stress free as possible
-amneisa
-anesthesia
-analgesia
-muscle relaxation via paralytic
Amnesia=
loss of memory
Anesthesia=
loss of consciousness
Analgesia=
freedom from pain
Muscle Relaxation via Paralytic=
relaxation or cessation of movement, certain reflexes
Deepening stages of anesthesia correlate with apparent irregular _ paralysis of the CNS
descending
-ex) cortex, subcortical areas, lower cord, upper cord, medulla
Changes in which 5 aspects define the different stages of anesthesia?
consciousness
respiration
skeletal muscle tone
eye signs
sequential loss of reflexes
Stage 1 of anesthesia (analgesia)=
time between normal wakefulness(induction) and the loss of consciousness(hypnosis) due to an anesthetic agent
-mild analgesia; 3 planes
Planes of stage 1 anesthesia
i-no amnesia or analgesia
ii-total amnesia and partial analgesia
iii-total amnesia and total analgesia (incision is felt as a blunt instrument across skin)
Stage 2 of Anesthesia (excitatory or delirious)=
loss of consciousness to onset of automatic rhythmicity of vitals
Things you will see in stage 2 of anesthesia:
-loss of awareness and recall (amnesia)
-combativeness
-cardiovascular instability
-excitation
-deconjugate ocular movements
-emesis, vocalizations
-breath holding/retching
-nystagmus
-increased muscle tone, jaw sets
Disinhibition=
brain has both excitatory(dopamine) and inhibitory(GABA) receptors, induction drugs typically depress inhibitory receptors first
Stage 3 (surgical anesthesia); 4 planes=
a state where movement in response to pain is suppressed, initiated by the cessation of respiration
Stage 3 Plane 1=
-full regular respirations
-coordinated thoracic and diaphragmic muscular activity
-pupillary constriction
-eyes moist and slow, decreasing activity, loss of lid/lash reflex
-BP and HR normal
Stage 3 Plane 2=
-diminished and regular respirations
-mixed midline and dilated pupils
-loss of corneal and laryngeal reflexes
-BP and HR near normal
Stage 3 Plane 3=
-continued diaphragmic movement but diminished thoracic movement/intercostal paralysis
-RR increases, TV low
-further pupil dilation
-no reflexes
-hypotension and tachycardia
Stage 3 Plane 4
-respirations jerky and shallow
-thoracic paralysis, very diminished diaphragmic activity
-significant pupillary dilation
-complete muscle relaxation
-hypotension and tachycardia
Stage 4 (Medullary Paralysis or Death)
cessation of spontaneous respiration and medullary cardiac reflexes that may lead to death
-from cessation of respiration to death
-no reflexes
-flaccid paralysis, marked hypotension, weak irregular pulse
True or false: the body’s reflexes get stronger the more superficial on the body you go.
FALSE; DEEPER = STRONGER,
lungs’ reflexes are stronger than lips’
Reflexes go out in this order:
-swallowing (first air reflex)
-retching/gagging
-vomiting
-lid/lash (first eye reflex)
Nystagmus=
seen in stage 2 of anesthesia, cerebral cortex depression
Phase 1/3 of Emergence
from when anesthetic turned off and drugs reversed
-apnea-irregular breathing-regular breathing
-increased alpha and beta activity on EEG
Phase 2/3 of Emergence
where mostly everything comes back, EXTUBATE HERE IF POSSIBLE
-increased HR and BP, return of ANS and muscle tone, + pain response
- + salivation, tearing, grimacing, swallowing, gagging, coughing, defensive psoturing
Phase 3/3 of Emergence
EXTUBATE ASAP ROCKY
-eye opening
-responds to commands
-awake patterns on EEG
Uptake and Distribution of inhaled anesthetics are influenced by 4 main things:
-machine
-lungs
-blood
-tissues
Fa/Fi=
the uptake of anesthetic into lungs
Machine factors influencing uptake/distribution:
-liter flow
-absorption into plastic
Lungs’ factors influencing uptake/distribution (6 items):
-ventilation (volume)
-concentration
-blood gas solubility of drug
-V/Q problems (decrease admin rate esp. for LOW blood/gas soluble drugs)
-2nd gas effect (pulls slower anesthetics in faster)
-N20 diffusion into closed spaces (can cause expansion issues)
Blood’s factor influencing uptake/distribution:
cardiac output (decreased rate of administration especially for HIGH blood/gas soluble drugs)
Tissues’ factors influencing uptake/distribution 7 items:
-oil/gas solubility (high coefficient, slow in/slow out and vice versa)
-metabolism
-diffusion hypoxia (N20 must be washed out with 100% O2)
-pediatrics (need higher dose and affects them longer)
-pregnancy (high CO and high MV[minute vent] cancel each other out=unpregnant person during induction)
-obesity (no change in induction but more lipid mass so anesthetic stays in longer/longer to wake)
-hypothermia (faster induction from decreased MAC)
What is MAC?
minimum alveolar concentration required to achieve surgical anesthesia in 50% of patients exposed to noxious stimuli
What is MAC-Awake?
the minimum alveolar concentration that inhibits responses to commands in 50% of patients; less than regular MAC
What is MAC-BAR?
dose of anesthesia needed that blocks adrenergic and CV response to noxious stimuli in 50% of patients; blunts autonomic response (pain with incision);
-is 1.6 x MAC
Sevoflurane AKA Ultane (MAC, BG Partition Coefficient)=
2%, 0.6
50 OG, POTENT
Isoflurane AKA Forane (MAC, BG Partition Coefficient)=
1.15%, 1.4
99 OG ,VERY POTENT
N20 (MAC, BG Partition Coefficient)=
105%, 0.47
1.4 OG NOT POTENT AT ALL
Desflurane AKA suprane (MAC, BG Partition Coefficient)=
5.8%, 0.42
18.7 OG, NOT VERY POTENT
Halothane AKA fluothane (MAC, BG Partition Coefficient)=
0.75%, 2.3
224 OG, VERY POTENT
When giving anesthetic, never give less than _% O2, remaining _% is up to us.
30%, 70%
True or false: at any point in time lung concentration = brain concentration of anesthesia
TRUE
MAC and potency are _ proportional
INVERSELY
How ventilation influences uptake/distribution
ventilation rate increases, the Fa/Fi ratio which increases more rapidly
-faster you breathe faster you go to sleep
How liter flow rates influence uptake/distribution:
higher the flow, faster gas admin; lower the flow, slower gas admin
-usually 1-2 mins for gas to get thru circuit
How absorption into plastic influences uptake/distribution:
gas can absorb into circuit tube/ machine
-VERY bad for people at high risk for to MH bc volatile anesthetics trigger MH, must do a complete washout of machine/tubes
How alveolar concentration influences uptake/distribution:
higher the dose (more you give) the faster it works
-Fa/Fi is how fast gas rises into lungs to reach inspired gas level
How blood/gas solubility of drug influences uptake/distribution:
lower the coefficient= faster anesthetic rises in lungs; faster induction + emergence
higher the coefficient= slower anesthetic rises in lungs; slower induction + emergence
How V/Q deficits influence uptake/distribution: which drugs are effected most?(3)
less than normal lungs go to sleep slower than normal lungs
-there is a decrease in onset rate especially for LOW blood/gas coefficient or more INSOLUBLE drugs-N2O, SEVO, DES
-sports care slows down much faster than old beater can
How 2nd gas effect influences uptake/distribution:
using N20 at a high concentration with another gas briefly to RAPIDLY produce effects quicker than either by themselves
-N20 is low solubility and not very potent when given with agent with higher solubility works very quickly
Implementing 2nd gas effects violate _ ‘s Law of partial pressure.
Dalton’s; gases aren’t working independently
How N20 Diffusion influences uptake/distribution:
N20 expands closed gas spaces due to difference in solubility of nitrogen it replaces and its high concentration that is required
-pressure changes at a rate dependent on perfusion of tissue around it and compliance of space it’s in
N20 Diffusion is contraindicated in bowel obstruction because:
risks perforation from obstruction blocking bowel
N20 Diffusion is contraindicated in pneumothorax because:
makes pneumothorax larger
N20 Diffusion is contraindicated in inner ear surgery because:
can make eardrum bulge and harder for surgeon to reattach it
N20 Diffusion is contraindicated in neurosurgical procedures with air injections such as:
craniotomy-too much air
N20 Diffusion is contraindicated in air embolism at the level above the heart such as:
carotid endarterectomy-worsens
N20 Diffusion is contraindicated in laparoscopy _ .
rarely, won’t be able to close belly from distention from intestines
N20 Diffusion is contraindicated within 4 weeks of use of sulfur hexafluoride gas injection into ocular surgery such as:
retinal detachment repair
How CO influences uptake/distribution:
If CO increases, onset of all anesthetics SLOW
-affects SLOW drugs more than FAST drugs bc of Fa/Fi ratio-increased CO removes drug at quicker rate
-ISO
Vessel rich group % consumption of CO and % body mass (organs)
75% of CO
10% body mass
Muscle group % consumption of CO and % body mass (skeletal, muscle, skin)
20% of CO
50% body mass
Fat group % consumption of CO and % body mass
5% of CO
20 body mass
Vessel Poor group % consumption of CO and % body mass (bone, tendons, cartilage)
0% of CO
20% body mass
How oil/gas solubility influences uptake/distribution:
describes potency; if highly potent it is slow to go in, slow to come out; halothane most potent, N20 least
-high OG solubility = more potent
-low OG solubility = less potent
How metabolism influences uptake/distribution:
certain drugs have different amounts of metabolites that are toxic so we limit those in high amounts
-sevoflurane most toxic (5-7%), N20 is the least with trace toxins
How diffusion hypoxia influences uptake/distribution:
opposite of 2nd gas effect; N20 leaves body so fast floods lungs and dilutes other gases including O2
-we give 100% O2 at end of case for ~5 mins to wash out N20 and prevent displacement of O2
How pediatrics influences uptake/distribution:
kids need higher doses but it lasts longer in them
-have factors that WOULD make onset slower but kids’ increased minute ventilation overrides the other factors
How pregnancy influences uptake/distribution:
high CO and high MV[minute vent] cancel each other out so onset is like nonpregnant person
How obesity influences uptake/distribution:
no change in induction but more lipid mass so anesthetic stays in longer/longer to wake
-longer case the longer it takes to wake bc more soluble with adipose
How hypothermia influences uptake/distribution:
decreased MAC of anesthetic from low temp requires less to fall asleep but will take longer due to decreased metabolism
-wake up more slowly from poor circulation and vasoconstriction
(3)Enzyme inhibition or activation Red Flag Drugs:
-grapefruit juice
-HIV antiretrovirals (avirs)
-certain antifungals (azoles)
Heavy Protein Bound Drugs:
-COUMADIN
-AMIODARONE
-FENTANYL
-DILANTIN
-methadone!!!
-PHENYTOIN
-propranolol!!!
-diazepam!!!
-LOCAL ANESTHETIC (lidocaine)!!!
CYP3A4=
metabolizer of 50% of drugs
CYP3A4 Strong Inhibitors=
easy as 1,2,3
1)GIVEN
2) abx
3) you know
-protease INHIBITORS
-ciprofloxacin
-clarithromycin
-AZOLE ANTIFUNGALS**
-GRAPEFRUIT JUICE**
-HIV ANTIRETROVIRALS (-navir)**
CYP3A4 Strong Inducers=
-PHENYTOIN
-barbiturates
-RIFAMPIN
-CARBAMAZEPINE
-ANTICONVULSANTS
CYP3A4 Substrates=
-FENTANYL/ alfentanil
-OXYCODONE
-METHADONE
-LIDOCAINE
-dalasetron
-ONDANSETRON/ZOFRAN
-HALDOL
CYP2D6=
metabolizes 25% of drugs
CY2D6 Strong Inhibitors=
-AMIODARONE
-BUPROPION
-kava**
-goldenseal**
-FLUOXETINE**/ paroxetine
-QUINIDINE
-RITONAVIR**
-sertraline/ZOLOFT
CYP2D6 Strong Inducers=
-RIFAMPIN
-dexamethasone
-oritavancin
CYP2D6 Substrates=
-HYDROCODONE
-OXYCODONE
-CODEINE
-METHADONE
-merperidine
-dalasetron
Ultra-Rapid Metabolizers (UM)=
carry multiple copies of functional alleles leading to excessive activity (high enzyme activity)
Extensive Metabolizers (EM)=
have 2 normal or “wild type” alleles and have a normal metabolism
Intermediate Metabolizers (IM)=
carry 1 normal and 1 nonfunctional OR 2 reduced functional alleles (reduced enzyme activity)
Poor Metabolizer (PM)=
have 2 mutated alleles with very limited or completely lost enzymatic activity (reduced or absent enzyme activity)
ProDrug=
needs metabolism to activate/work
-ex) codeine
Active Drug=
metabolism inactivates drug, changes it into inactive
-ex)omeprazole, fentanyl
Prodrug + PM or IM=
-metabolizes inactive drug too slowly, doesn’t make enough active drug
-poor drug efficacy
-subtherapeutic
ProDrug (Codeine)+ UM=
-metabolizes inactive drug too quickly making too much active drug
-high drug efficacy
-accumulation of active drug increases risk of side effects
Active Drug + PM or IM=
-slow metabolism doesn’t inactivate the active drug fast enough, needs lower dosage
-high drug efficacy
-accumulation of active drug increases risk of side effects
Active Drug + UM=
- fast metabolism inactivates the active drug too quickly, needs higher dosage
-poor drug efficacy
-subtherapeutic
Fast or slow induction: Low B/G Solubility?
fast
Fast or slow induction: High B/G Solubility?
slow
Fast or slow induction: Low CO?
fast
Fast or slow induction: High CO?
slow
Fast or slow induction: High FGF rate?
fast
Fast or slow induction: Low FGF rate?
slow
Fast or slow induction: High minute ventilation?
fast
Fast or slow induction: Low minute ventilation?
slow
Fast or slow induction: High concentrations?
fast
Fast or slow induction: V/Q Disfunction?
slow
Fast or slow induction: Low concentrations?
slow
Fast or slow induction: Hypothermia?
slow
Fast or slow induction: 2nd Gas Effect?
fast
Fast or slow induction: Children?
faster
Fast or slow induction: Obesity?
no difference- SLOWER to WAKE
Fast or slow induction: Pregnancy?
No difference- High Vm and High CO factors cancel each other out
A high CO affects slow or fast drugs more?
Slow anesthetics
A V/Q Problem affects slow or fast drugs more?
fast anesthetics
Slow drugs have a _ B/G Solubility.
High
Fast Drugs have a _ B/G Solubility.
Low
Fast anesthetics are _ dissolved into blood and are _ ready in a gas state to bind to cells in tissues.
LESS, MORE
Slow anesthetics are _ dissolved into blood and are _ ready in a gas state to bind to cells in tissues.
MORE, LESS
Increase or Decrease MAC: Old age
decreasse
Increase or Decrease MAC: hypothermia
decrease
Increase or Decrease MAC: Giving other sedatives
decrease
Increase or Decrease MAC: Giving other anesthetics
decrease
Increase or Decrease MAC: Opiods
decrease
Increase or Decrease MAC: Acute Ethanol Consumption
decrease
Increase or Decrease MAC: Young age
increase
Increase or Decrease MAC: Hyperthermia
increase- NOT MH tho :)
Increase or Decrease MAC: Pregnancy
decrease
Increase or Decrease MAC: Hypoxemia
decrease
Increase or Decrease MAC:Hyponatremia
decrease
Increase or Decrease MAC: Anemia
decrease
Increase or Decrease MAC: Hypotension
decrease
Increase or Decrease MAC: Lithium
decrease
Most potent anesthetic:
Halothane, Isoflurane is 2nd
Least potent anesthetic/gas:
N2O, 2nd least is Desflurane
Fastest anesthetic/gas:
N20, 2nd is Desflurane
Slowest anesthetic:
Halothane, 2nd slowest is Isoflurane
True or false: The partial pressure of anesthetic stops rising in fat after halting delivery of anesthetic:
False, it continues rising for a while
Fast or slow emergence: High B/G solubility
slow emergence
Fast or slow emergence: Low B/G solubility
fast emergence
Increase or Decrease MAC: Alpha Agonists
decrease MAC
Increase or Decrease MAC: Hyperthyroidism
increase MAC
Increase or Decrease MAC: Red Headed Females
Increase MAC
Increase or Decrease MAC: Chronic Alcohol Abuse
Increase MAC
Increase or Decrease MAC: Acute Admin of CNS Stimulants (caffeine, adderall, etc.)
Increase MAC
Increase or Decrease MAC: Hypocapnia
no difference
Increase or Decrease MAC: Gender
no difference
Increase or Decrease MAC: Hypertension
no difference
Increase or Decrease MAC: Hypokalemia
no difference
Increase or Decrease MAC: Hyperkalemia
no difference
Increase or Decrease MAC: Duration of case
no difference
Need Increase or Decrease MAC: Hypercapnia
no difference
CpMax=
desired serum concentration
Equation for loading dose=
(pt’s weight x Vd of drug) x CpMax
Vd=
volume of distribution;
-degree of a drug going into tissue over plasma
-drug specific ratio, applied to pt’s specific weight
-high Vd = high amount of tissue distribution
Order of main points of anesthesia leaving during anesthesia:
-amnesia/ memory
-consciousness /awareness
-mobility/ pain response
-autonomic reactions/ reflexes
VRG (vessel rich group) is AKA=
central compartment
Parasympathetic NS involves the _ nerve
vagus
PNS and SNS secrete _ to the _ _ receptors pre-synaptically
Acetylcholine, nicotinic cholinergic
Post-synaptically the PNS secretes _ that binds with a _ _ receptor
Acetylcholine, muscarinic cholinergic
Post-synaptically the SNS secretes _ that binds with an _ receptor
norepinephrine, adrenergic
Adrenergic receptors include _, _, and _ receptors and they bind with _ secreted by the nicotinic cholinergic receptor from the SNS.
dopa, alpha, and beta, norepinephrine
Muscarinic Cholinergic receptors bind with _ that is secreted by the nicotinic cholinergic receptor from the _.
acetylcholine, PNS
Sympathetic outflow come from the _ _ region
thoraco-lumbar
Parasympathomimetic (give example)=
stimulates PNS
ex) neostigmine (for myasthenia gravis)
Parasympatholytic (give example)=
blocks PNS
ex) atropine
Sympathomimetic (give example)=
stimulates SNS
ex) catecholamines like epinephrine, dopamine, levophed
Sympatholytic (give example)=
blocks SNS
ex) beta blocker
LD=
(pt’s weight x Vd of drug) x CpMax
