Exam 1 Flashcards
Anesthesia
artificially induces loss of ability to feel pain
Anesthesia purpose
to permit the performance of surgery or painful procedures. not ANS, no movement, not aware
GA
drug induces loss of consciousness
patient is not arrousable event to painful stimuli
don’t have to intubated/ vent or on volatile anesthetics
independent ventilatory function often impaired; airway, ventilation, cv support
Regional/ peripheral anesthesia
Insensibility caused by interrupting the sensory nerve conduction of a particular region of the body
Peripheral
spinal
epidural
LOC is unchanged (unless sedatives are used)
ventilatory/airway protection is maintained
Sedation
3 levels
spectrum of consciousness between awake and unconscious
minimal sedation
anxiolysis
ex; 2mg of versed
“I dont care” meds
responsive to verbal commands
airway, spont ventilation, cardiac function are unaffected
moderate sedation
ex; 5mg of versed
responsive to verbal/touch
no assistance needed with the pts airway
spont ventilation is adequate
cardiac function is usually maintained
Deep sedation
responsiveness after repeated or painful stimulations
assistance might be required for airway
spont ventilation is possible inadequate
cardiac function is usually maintained
What methods were used between 4000BC and 400 BC
Poppy, cocoa leaves
acupuncture
ethylene fumes from geological fault lines beneath apollos temple
cannabis vapor
carotid compression
Hippocrates
accommodate the operator/ surgeron
avoid sinking down and turning away
1st Pharm book
Materia medica
written by Discorides - surgeon in Neros army
5 volumes; plants, animal and mineral products
360 medical properties; antiseptic, anti-inflammatory, mental cramps, psych problems
Mandragora (mandrake) and wine
used in the early days as hallucinogenic, human shaped, considered to have magical properties
soporifices
liquid on sponge- inhalations/ smell and breathe it in
in the middle agest they used;
1/2 ounce of opium
juice of mandrake leaves
juice of hemlock
3 oz of hyposycamus
sufficient water
reversal for soporifics
vinegar
hyposcyamus
L- isomer of atropine
1st inhalation anesthetic
Diethyl ether
made from sulfuric acid and ethyl alcohol
named ether; greek for ignite/ explode
tested on chickens
recreation d/t whiskey tax
Valerius Cordus
made the first inhalational anesthetic, diethyl ether
German botanis/ physician
Sir christopher Wren and Robert Boyle
Created IV therapy using a good quill and bladder as bag
administered alcohol into a dogs vein
witnessed metabolism of drugs
was a member of the royal society of London
Joseph priestly
English chemist
discovers oxygen and nitrous oxide
discovered photosynthsis
Humphry Davy
British chemist
discovered the elements; k, na, ca, mg
Suggested to use N2O for surgical pain control (not appreciated)- didn’t help with movement
Horace wells
dentist
noticed that a man under the influence of N2O had no recall of pain/ injury
self administered for tooth extraction and uses on several dental patients
Public demonstration at mass general for arranged administration of N2O for amputation but pt moved “humbug?”
Andrews
Chicago surgeon
N2O and oxygen anesthesia without cyanosis= dec mortality
Hewitt
1st anesthesia machine with N20/ O2
Crawford long
delivered Ether for a pt with 2 vascular neck tumors
continued use of whiskey
William morton
Dentist
needed anesthesia for denture fitting (made of wood at the time)
1st public demonstration of ether
1846
called it Letheon….made it to england in 60 days
didnt have; iv access, prolonged emergence, variable quality, proper filling mask
Dr Robinson squibb
developed process for pure ether
founded squibb pharmaceuticals…leading manufacturer
disadvantages of ether
flammable
prolonged induction (long on and off set)
unpleasant, persistent odor
high incidence of N/V
Sir James simpson
OB in scotland
experimented w/ chloroform following dinner parties
defined pain; actual or potential tissue damage
religious opposition
Bible quote used against religious opposition
Genesis 2;21
John snow
Fill time anesthetist
used chloroform for queen victory; prince leopold and princess beatrice
disc epidemiology when he traced London cholera outbreak to water sources
Hyderbad commissions
said chloroform was safe with their methods
respiratory and cardiac paralysis convinced them chloroform might not be safe
430 cases w/o recording devices + 157 cases with recording devices
Guthrie
Discovered delayed chloroform hepatotoxicity in children
Levy
light chloroform anesthesia and adrenaline, fatal vf in adults, half awake; sleep->ans->NE-> vf
What was cocaine used for
sinus/nasal surgeries-> local anesthetic
Dr Koller
Viennese opthamologist (colleague of Sigmund Freud)
Used cocaine for anesthetic for eye surgery
dr Halsted
first regional (mandibular) nerve block w/ cocaine
dr august bier
1st spinal anesthetic with cocaine
developed Bier block
sister mary bernard
low pay
intelligent
focus/ attentive
Alice Magaw
Mother of anesthesia
14,000 open drop ether cases w/o death
Agatha Hodgins
worked for crile brothers
opened on of 1st nurse anesthesia schools
taught in france during WW1
developed N2O/ O2 techniques
founded AANA
Cyclopropane
violently explosive/ hospital explosions
Halothane
developed Hepatitis
slow onset
Isoflurane
Relatively safe/ cheap
Less N/v
Quicker onset than Halothane.
slow onset/ slow offset-> use for icu/ not extubating pts
Turn off 20 min before bandage
Furane
Desflurane
rapid uptake and distribution (most rapid onset and offset)
High vapor pressure- almost same as atm (vaporizes quickly)
large quantitiy to achieve anesthesia
good for out pt sx
Edmund Egar
Did all of the experimentation on desflurane
developed the end- tidal concentration correlated to movement (MAC
MAC
minimal alveolar concentration; dose of volatile anesthetic
Sevoflurane
intermediate action between iso and forane
unstable in soda lime; toxic degradation product concerns (CO2 absorber Pellets)—-disproven
good for asthmatics/ kids because it doesnt cause airway irritation
Triad of anesthesia
Amnesia
analgesia
muscle relaxation
Preemptive Anesthesia/ analgesia
given before causing pain
Amnesia
Stimulation of inhibitory Transmission; ach
inhibit stimulatory transmission; GABA
Analgesia
morphine from Opium
not favored at first because of high death rate
Synthetic derivatives; demerol, fent, sufent, remi fent, hydromorphone
Todays analgesics
Narcotics (opioids)
Cox inhibitors
Gabapentins (pregaline)
Acetaminophen
Peripheral nerve blocks
Curare
muscle relaxation
from plant in south america/ blow darks
decrease amount of anesthesia due to relaxation decreased mortality
Balanced anesthesia
Muscle relaxatoin, amnesia, analgesia, homeostasis
Dr liston
3 death 1 operation (300%) mortality rate. in an attempt to quickly amputate in 2.5 minutea
hand washing, washing clothes, washing instruments
George crile
cleveland clinic
light N2O/O2 anesthesia
local infiltration of procaine/ preemptive anesthesia
helped w/ homeostasis
harvey cushing
Regional blocks prior to emergence from ether
anesthetic records, BP/HR measurements
Neolept Anesthesia
high amnestic dose, little volatile/ muscle relaxant
opiods, antiphsychotics (aldol, droperidol), nitrous
Block Autonomic and endocrine response to stressed,
high incidence of awareness, dysphoria, extrapyramidal movements
surgical stimulation produced despite lack of movement
tachycardic
htn
problem with CAD pts….Beta blockade
high dose opioid technique - had its own problems
surgical stimulation produced despite lack of movement
tachycardia
Preoperative period phase
BZD, H1 and H2 blockers, bronchodilators
Induction of anesthesia
Eomidate, ketamine, propofol, narcotics
maintenance of anesthesia
inhalation drugs, nm blockers, pressors, blockers
Emergence from anesthesia
NMB reversal, local anesthetics
Dr guedels
Reference chart for stages of anesthesia
also made oral airways
Stage 1
Beginning of induction of general anesthesia to loss of consciousness (sternal rub and no movement)
Stage 1 1st plane
no amnesia or analgesia- normal
Stage 1 2nd plane
amnestic but only partially analgesic- still remember hurting
Stage 1 3rd plane
Complete analgesia and amnesia
Stage 2
Loss of consciousness to onset of automatic breathing
eyelash reflex disappears
coughing, vomiting, stuggling to occur
irregular respirations w/ breath holding
dangerous stage
high risk for aspiration and bronchospasms- dont extubate
dont touch, dont move, be quiet
Stage 3
onset of autonmatic respiration to respiratory paralysis (surgical plane)
Stage 3 1st plane
automatic respiration to cessation of eyeball movment
Stage 3 2nd plane
Cessation of eyeball movement to beginning of intercostal muscle paralysis; secretion of tears increase
Stage 3 3rd plane
beginning to completion of intercostal muscle paralysis; pupils dilate; desired plane prior to muscle relaxants
Stage 3 4th plane
complete intercostal paralysis to diaphragmatic paralysis (apnea)
Stage 4
stoppage of respiration till death
Drug effects to the number of _______
bound receptors
greatest effect = all receptors bound
Agonists
Activates receptor by binding to receptor
Hydrogen bonding
binding to a very electronegative atom
Ion/ electrocovalent binding
Oppositely charged ions
Van der alls interactions
the sum of attractive or repulsive forces; creates orbital shift
antagonist
binds to a receptor but does not activate the receptor
get in the way of the agonist.
Competitive antagonism
Increasing amounts progressively inhibit the agonist
Shifts dose response curves to the right
inc competitive antagonism = dec agonist response
Non-competitive antagonism
Even high concentrations of agonist cannot cause the agonist effect
Partial agonist
Binding to a receptor (usually at agonist site)
causes less response than the agonist even at supramaximal doses
Inverse agonist
Compete for the same site as the agonist but produce the opposite effect
Meds that use lipid bilayer R
Opioids, bzd, b-blockers, catecholamines, nmbd
meds that use intracellular proteins
Insulin, steroids, milrinone
Meds that use circulating proteins
anticoagulants
Pharmacokinetics
Quantitative study-Of injected and inhaled drugs (and their metabolites)
ADME
Central compartment
What dilutes the drug in the first minute following injection
Venous blood in arm, inferior vena cava, right heart, pulmonary vessels, lungs, left heart, aorta
Then mix with “vessel rich group”
Acidic drugs bind primarily to
albumin
Alkalotic bind drugs primarily to
a1-acid glycoprotein
Only______drug can cross cell membranes (distribution)/ dtermine concentration available to R (potency)
free/unbound
Causes of decreased plasma proteins
Age
Hepatic disease
Renal failure
Pregnancy
Thiopental and diazepam are ____protein binding
poor
they are also lipophilic
Big volume of distribution
Warfarin is_____protein bound to plasma proteins
highly
Small volume of distribution
decreased free drug
What metabolizes drugs in the liver
hepatic microsomal enzymes
most anesthetics
Examples of drugs that have active metabolites
diazepam (valium)
propanolol (inderal)
morphine
prodrugs such as codeine
Examples of drugs that have active metabolites
diazepam (valium)
propanolol (inderal)
morphine
prodrugs such as codeine
What metabolizes drugs in the plasma
Hoffman elimination and ester hydrolysis
what metabolizes drugs in the GI tract/ placenta
Tissue esterase
Phase 1 metabolic reaction
increase polarity through; Oxidation, Reduction, or Hydrolysis
Phase 2 metabolism
covalently link with a highly polar molecule to become water soluble
Conjugation
Cyp450
10 isoforms
Membrane bound
Contains a heme cofactor
Involves oxidation and reduction
CYP2
40% homologous
CYP2A
55% homologous
Cyp2a6
the individual enzyme
Cyp3a4
most common
Up to 60% of cyP450 activity
Metabolizes > 50% of drugs: opioids, BZP, LA, immunosuppressants, antihistamines
Induction of metabolic enzymes……
Increased amount of enzyme/ metabolism
Inhibition of metabolic enzymes
Decreased activity of enzyme
Hepatic clearance
For most anesthetic drugs clearance is constant
Rate is proportional to concentration- More drug/more clearance
At some point metabolism is exceeded since liver capability is not unlimited
Rate of drug metabolism equation
R = Q (C inflow- C outflow)
CO x (concentration in - concentration out)
Flow limited hepatic clearance
Q limits metabolic rate
cardiac output?
Capacity limited
liver’s ability to metabolize is limiting factor
Glomerular filtration and renal clearance
GFR and amount of protein bound drug controls amount of drug entering tubule
Passive tubular reabsorption
Increased if drug lipid soluble, ie. thiopental (reabsorbed)
Almost zero for water soluble drugs are reabsorbed, they are excreted in urine
Active tubular secretion
From peritubular capillaries
Active transport process
penicillins
Elimination ½ time
Time necessary to eliminate 50% of drug from plasma after bolus dose
Elimination ½ life
Time necessary to eliminate 50% of drug from body.
cant be measured
Context sensitive half-time
Time to a 50% decrease after infusion discontinued
Assumes a constant concentration
Roughly relates to ½ life
Increases the longer the infusion increases
Accumulation in peripheral tissues
When the pk (dissociation constant) and ph are identical
50% of drug ionized, 50% of drug non-ionized
Acid drugs are ionized in____ ph
Alkaline
Bases are ionized in ____ph
acid
Ionized molecules / drugs are…..
inactive
water soluble
dont cross lipid barriers
are excreted in the kidneys
and do not undergo hepatic metabolism
non-ionized drugs
active
lipid soluble (get to R)
cross lipid barriers
are not excreted in the kidney’s
and do undergo hepatic metabolism
Weak acids ionization formula (barbituarates)
pk after ph
So if a weak acid (pk 7.6) is put in a basic ph (blood 7.8)
7.8 – 7.6 = +0.2 acid drugs are ionized at basic ph
Weak bases ionization formula (LA or opioids)
pk before ph
If weak base (pk 8.0) is put in an acid ph (Blood 7.2)
8.0 – 7.2= +0.8 weak bases are ionized at acid ph
What numbers are non ionized?
nicely negative numbers are non ionized
pharmacodynamics
“what the drug does to the body”
drug effects
Potency
concentration vs response….less drug with more effect = more potent
least amount of drug needed for effect
Efficacy
the ability of a drug to produce a clinical effect
how much of the effect can I get.
ED50
dose required to produce effect in 50% of patients
LD50
Dose required to produce death in 50% of patients
Therapeutic index
ratio between (LD50/ED50 )
Stereochemistry
How drug molecules are structured In 3 dimensions
Chiral compounds
Molecules with asymmetric centers
Usually related to way carbon molecules are bonded
Usually related to way carbon molecules are bonded
Chemically identical
Mirror images
Can’t be superimposed
Right Enantiomers
Dextrorotatory
R: Rectus
Left enantionmers
Levorotatory
S: Sinister
50/50 mixture of enantiomers
racemic
Optical activity equal
Can exhibit different ADME
One enantiomer is active; other inactive or side effects
S-enantiomer of ketamine
more potent with less delirium
L-bupivicaine
less cardiac toxicity
Cisatracurium, the isomer of atracurium
lacks histamine effects
Pharmacogenetics/pharmacogenomics
How a single gene or all genes (genome) influences responses to drugs
Pharmacogenetic testing
Look for variants in genes that code for;
Drug-metabolizing enzymes
Drug targets
Immune proteins
Phenobarbital_____enzyme
induces = increased metabolism of drugs (benzos/opioid) = dec drug effect
Grape fruit juice _____ enzymes
inhibits = decreased activity of enzyme = increased concentration of drugs/ toxicity levels
Alcohol impairment requires more or less anesthesia?
Less
Marijuana requires more or less anesthesia
more
medications that do not increase half time with infusion
prop
sufentanil
alfentanil
medications that increase half time with infusion
fent
thiophental
midazolam
Relative potency
lag time between administration (plasma concentration and effect)
Enantiomers
chemically identical
mirror images
cant be superimposed
Sedatives
a drug that induces calm or sleep
Hypnotics
a drug that induces hypnosis or sleep
Sleep share what similarities with anesthesia
Both inhibits mid-brain reticular activating system in the thalamus
and reversible inhibit the CNS
EEG is related to
Cerebral Blood flow
CMRO2- cerebral metabolic requirement of oxygen (metabolic activity)
anesthesia alters these
medications with less correlation between BIS and movement
High dose narcotic
BIS < 58
not conscious
BIS < 65
had less than 5% chance of return to consciousness within 50 sec
Signal quality index
SQI
good signal or lot of artifact
EMG
are they going to move, are their muscles tightening up?
EEG
Electroencephalograms
Suppression Ration
how many seconds in the last minute has the eeg been flat. should be 0.
GA BIS range
40-60
no movement or recall
Ketamine and BIS
false high number on BIS because its a sympathomimetic and its responding to the metabolic activity on the ketamine
Beta Blockers and BIS
dec hr = dec CO = dec CBF = dec bis (false low)
Benzo effect
anxiolytics
sedation (decrease alpha activity)
anterograde amnesia (lasts longer than sedative effects)
anticonvulsant
Spinal cord mediated skm relaxation
unable to produce isoelectric state (ceiling effect)
MOA for benzos
Gamma-aminobutyric acid mediated
Facilitates action of GABA at GABAA chloride ionophore
Enhance affinity of receptor for GABA
Enhanced opening of Cl- channels
Hyperpolarization of postsynaptic membrane…more resistant to depolarization
Benzo R site
Between the gamma and alpha subunits on GABA R
Alpha 1 subunit
EFFECTS: sedative, amnestic, anticonvulsant
most abundant type
Cerebral cortex, cerebellar cortex, thalamus
alpha-2 effect and location
EFFECTS: Anxiolytic, skeletal muscle
Hippocampus, amygdala
GABA A receptor binding sites other than benzodiazepines
Barbiturates
Etomidate
Propofol
Alcohol
Benzo VOD
Highly lipid soluble (large volume of distribution)
highly protein bound (96-98%)(albumin)- not alot to cross the lipid bilayer
works and goes away quickly
Benzos and platelets
inhibits plat aggregation/ inhibits conformational change in plat membrane
(increased bleeding time)
Versed is ____ as potent as Diazepam (valium)
2-3 x
greater affinity for the R
Clearance 5x faster than lorazepam
10x faster than diazepam
Versed effects
amnesia > sedation
Midazolam is _____soluble
water
doesnt burn when injected and dont need additive
Midazolam IV solution PH
3.5
Versed imidazole ring is open when….
ph < 3.5 = water soluble/ pronated
Versed imidazole ring is closed when……
ph > 4.0= lipid soluble = unprotonated
Solubizing additive
Propylene glycol
Midazolam onset
1-2 min
midazolam peak effect
5 minutes
Why does midazolam have a short duration?
doesn’t stay on R long because lipid solubility = rapid redistribution
Midazolam elimination half time
2 hours
Doubled in elderly patients…hepatic flow/enzyme activity
Midazolam VOD
1-1.5 L/kg (large)
because its so lipid soluble
> Vd in Elderly and morbidly obese…peripheral tissues
Midazolam metabolism
CYP3A4
Active and inactive metabolites
midazolam active metabolite
1-hydroxymidazolam
½ the activity of the parent
Drugs that cause inhibition of P-450 enzymes
Decrease BZD metaolism / prolong effect
Cimetidine
Erythromycin
Calcium channel blockers
Antifungal
Fentanyl
midazolam CNS effects
dec CMRO2, CBF
Preserves vasomotor rsp to CO2
no change in ICP
vasomotor response to CO2
inc co2= vasodilation
dec co2 = vasoconstriction
Midazolam Pulmonary effect
Dose-dependent decreases in ventilation
Decreases hypoxic drive
> depression with COPD
Transient apnea if rapid IV esp. with opioid
Depresses swallowing reflex
Decreases upper airway activity
Midazolam effect on the CV system
inc hr (maintains CO)
dec bp
dec SVR
Does NOT inhibit BP/HR response to intubation
Midazolam child dose
0.25-0.5 mg/kg oral syrup
Peak 20-30 minutes
Midazolam adult dose
1-5 mg IV
Elderly require decreased doses…..Greater CNS sensitivity
Midazolam for induction
0.1-0.2 mg/kg IV over 30-60 seconds
Facilitated by preceding dose of opioid
1-3 minutes
Fentanyl 50-100 mcq
Midazolam infusion dose
1-7mg/hr IV
Markedly delayed awakening
Active metabolites accumulate
Clearance depends on hepatic metabolism not redistribution
Midazolam and SE from sedation drips
dont run for more than 2-3 days
alteration in the ability of T cells to amount an immune response (inc risk of infection)
Diazepam (Valium) VOD
Highly lipid soluble
Diazepam (Valium) preparation
Propylene glycol…pain on injection; glycol toxicity
Valium onset
1-5 min
Valium E ½ time
20-40 hours….extensively protein bound
shorter duration of action than lorazepam (Dissociates from GABAa faster)
Valium metabolism/ metabolites
CYP3A
Active metabolites
Desmethyldiazepam* (48-96 hours) and oxazepam
Nearly as potent as diazepam
Return of drowsiness 6-8 hours
Valium anticonvulsant effects/dose
Potent anticonvulsant
0.1 mg/kg IV
Abolishes DT’s, status epilepticus, lidocaine toxicity related seizures
Longer acting antiepileptic drug also administered (fosphenytoin…cerebyx)
Valium SE
Can produce isoelectric EEG
Valium effects on pulmonary system
Slight decrease in Vt
After 0.2mg/kg IV increases in PaCO2
Valium nm effects
Decreases tonic effect on spinal neuron
skeletal muscle tone decreased
Develop tolerance to skeletal muscle relaxant effects
No action at neuromuscular junction
Valium induction dosing
0.5-1.0 mg/kg IV
Decrease dose by 25-50%
Elderly, Liver disease, Presence of opioids
Lorazepam (Ativan) effect
More potent sedative and amnestic
lorazepam preparation
Insoluble in water
Requires solvents: polyethylene glycol
Lower lipid solubility
Lorazepam onset
Slower onset of action Then midazolam or diazepam because less lipid soluble
Ativan peak effects
20-30 min
ativan dose
1-4mg IV
Ativan E1/2
14 hours
Slower than midazolam
Ativan metabolism
Conjugated to inactive metabolites
Glucuronidation slower than oxidative hydroxylation
Not entirely dependent on hepatic enzymes
Less affected by hepatic function, age, drugs (cimetidine)
Not as affected by blood flow
Flumazenil (Romazicon)
Competitive antagonist: high affinity for BZD receptor
Prevents/reverses all agonist activity of BZD
Flumazenil (Romazicon) derivative
1,4 imidazobenzodiazepine
Flumazenil (Romazicon) metabolism
Hepatic microsomal enzymes
Inactive metabolites
Flumazenil (Romazicon) dose
0.2 mg IV and titrated to consciousness
Repeated 0.1mg q 1 minute to 1 mg total
Reversal within 2 minutes
0.3-0.6 mg to reverse sedation
0.5-1.0 mg to abolish therapeutic dose
Flumazenil (Romazicon) duration of action
Duration 30-60 minutes
Supplemental doses vs continuous infusion (0.1-0.4 mg/hr)
Flumazenil (Romazicon) contraindicated
Antiepileptic drugs
Precipitates acute withdrawal seizures
Histamine induces….
Contraction of smm in airways
increases secretion of acid in the stomach
release nt in the cns (ach, ne, 5ht)
Histamine induces….
Contraction of smm in airways
increases secretion of acid in the stomach
release nt in the cns (ach, ne, 5ht)
Drugs that induce histamine release
morphine
mivacurium (mivacron)
protamine
attacurium, (Tracrium)
H1 receptors can also activate…..
muscarinic, cholinergic, 5-HT3, and Alpha adrenergic
H2 can also activate….
5-HT3 and B-1
Histamine on H1 receptor causes
Hyperalgesia and inflammatory pain (insect stings)
Allergic rhino-conjunctivitis symptoms
Histamine on H2 receptor causes
Elevates camp (B1-like stimulation)
Increases acid/volume production
H1 and h2 receptor activation:
Hypotension (release of nitric oxide)
Capillary permeability
Flushing
Prostacyclin release
Tachycardia
H1 R location
Receptors in vestibular system, airway smooth muscle, cardiac endothelial cells etc
H1 R antagonists are used for…..
Effective for motion sickness (but cause sedation- cross bbb)
Possible protection against bronchospasm
Provides some cardiac stability (indicated in anaphylaxis)
Little tachyphylaxis
H1 receptor antagonists SE
Blurred vision
Urinary retention
Dry mouth
Drowsiness (1st generation)
Examples or H1 receptor antagonists
diphenhydramine (Benadryl)
Promethazine (Phenergan)
Cetirizine (Zyrtec)
Loratadine (Claritin)
Diphenhydramine (Benadryl) uses
Mostly used as Antipruritic
pre-treat procedure related allergies….IVP dye
Also anaphylactic indications
Stimulates ventilation- Augments relationship of hypoxic and hypercarbic drives if Administered solo
N/V
Diphenhydramine (Benadryl) E1/2
7-12 hrs
Diphenhydramine (Benadryl) and N/V
May inhibit afferent arc of oculo-emetic reflex (salt dimenhydrinate)
why its good to protect against N/V
Diphenhydramine (Benadryl) dose
25-50 mg IV
Promethazine (Phenergan) uses
anti-emetic
sedation
Effective As rescue Reduce peripheral pain levels (anti-inflammatory effects)
Promethazine (Phenergan) SE
Black box warning
children under 2yo = deaths
caustic to veins/ IV extravasation-> tissue necrosis
Promethazine (Phenergan) dose
12.5-25mg iv
Promethazine (Phenergan) onset
5 min
H2 RECEPTOR antagonists uses
duodenal ulcer disease/GERD
Decreases gastric volume
increases pH
H2 R antagonists MOA
Decreases hypersecretion of gastric fluid (h+)
From gastric parietal cells
decreased cAMP
H2 receptor antagonists SE
Diarrhea
Headache
Skeletal muscle pain
Weakened gastric mucosa d/t bacteria (prolonged administration)
HA, confusion (CNS H2 receptors; more in elderly)
Bradycardia
Increase serum creatinine
H2 receptor antagonists examples
Cimetidine (Tagamet)
Ranitidine (Zantac)
Famotidine (pepcid)
Overgrowth of what gastric bacteria is most common with a weaken gastric mucosa
candida albicans
Effect of H2 R antagonists on the kidneys
H2 compete for tubular secretion with creatinine.= increases serum creatinine by 15%
Cimetidine (Tagamet) metabolized
CYP450, cleared in urine
Cimetidine (Tagamet) inhibt CYP450 of these meds….
Warfarin, phenytoin, lidocaine, tricyclics, propranolol, nifedipine, meperidine, diazepam
Cimetidine (Tagamet) Adverse effects:
Bradycardia, hypotension (cardiac H2 receptors)….rapid infusions
Increased plasma levels of prolactin
Inhibits dihydrotestosterone binding to androgen receptors (impotence)
Cimetidine (Tagamet) Dose
150-300mg IV
½ dose in renal impairment
Ranitidine (zantac) dose
50mg diluted to 20cc over 2 minutes
½ dose for renal impairment
Famotidine (Pepcid) E1/2
Most potent, longest E ½ time (2.5-4 hrs)
Famotidine (Pepcid) SE
Interferes with phosphate absorption
hypophosphatemia
Famotidine (Pepcid) Dose
20mg IV
½ dose for renal impairment
Proton (H+) pump inhibitors MOA
Irreversible binding to acid secretion “pumps”
Inhibit the movement of protons (H+) across the gastric parietal cells
Up to 5 days onset (3)
Proton (H+) pump inhibitors use
Controlling gastric acidity
Decreasing volume
Healing esophagitis
Healing ulcers
Relieving symptoms of GERD
Best pharmacologic tx of Zollinger-Ellison syndrome
PPI’s SE
bone fractures
SLE
acute interstitial nephritis
C-Diff diarrhea
Vitamin B12/Magnesium deficiency
Inhibits warfarin metabolism (work too well)
Blocks enzyme that activates clopidogrel (wont work as well)
PPI’s Examples:
Omeprazole (Prilosec)
Pantoprazole (Protonix)
Lansoprazole (prevacid)
Dexlansoprazole (dexilent)
Omeprazole (Prilosec)binding
prodrug
Protonates in PARIETAL CELLS to active form
Only inhibits pumps that are present
ACID-INHIBITION INCREASES WITH REPEATED DOSING
66% maximum inhibition
Omeprazole (Prilosec) dose
Dose: 40 mg in 100cc NS over 30 minutes or
po > 3hrs prior (before OR)
Omeprazole (prilosec) SE
Ha
Agitation
Confusion
Crosses bbb
Abdominal pain
n/v
Flatulence
Small bowel bacterial overgrowth
Pantoprazole (Protonix)bioavailablility/ effect
Greater bioavailability and longer E ½ time compared to prilosec
Works as fast as ranitidine
1 hr prior to OR = decrease in gastric volume and ph
Pantoprazole (Protonix)dose
40 mg in 100ml over 2-15 minutes
PPI used for
Gerd
Gastroduodenal ulcers
Acute upper Gi hemm (infuse after egd)
NSAID ulcerations (ompeprazole)
schedule surgery
H2 blockers are used for
Aspiration pneumonitis concerns (work faster than PPI)
Intermittent symptoms/cost effective
antacids Particulate
Aluminum or magnesium based
Aspiration equals acid aspiration (dont give to full stomach)
antacids Non-particulate
Sodium, carbonate, citrate, bicarbonate base
Neutralize acid (safer to aspirate)
Ex: sodium citrate (bicitra)
Long term use of antacids
IF PH IS TOO HIGH- ACID BREAKDOWN OF FOOD INHIBITED and ACID REBOUND CAN OCCUR (when stop antacids)
MAGNESIUM BASED- COMMON OSMOTIC DIARRHEA and NEUROLOGIC AND NEUROMUSCULAR Impairment
CALCIUM BASED- HYPERCALCEMIA (concern for kidney stones)
SODIUM BASED- INCREASED SODIUM LOAD….HYPERTENSIVE PATIENTS (CHF)
Sodium citrate (bicitra) MOA
non particulate
Neutralizes acid- (base + acid = SALT, CO2 AND WATER)
Protects against aspiration pneumonia-NOT against aspiration…
Increases intra-gastric volume (adding 15-30 ml)
Sodium citrate (bicitra) length and start of effect
Work immediately…lose effectiveness 30-60 minutes
Sodium citrate (bicitra) dose
15-30 ml po
Dopamine blockers MOA
Stimulates gastric motility (prokinetic)
Increases lower esophageal sphincter tone
Stimulates peristalsis
Relaxes pylorus and duodenum- Gastric emptying and intestinal transit
Dopamine blockers contraindications/ SE
Not administered to patients with dopamine depletion/inhibition
Extrapyramidal reactions (easily crosses BBB)
Orthostatic hypotension
Some effects on chemoreceptor trigger zone- Esp cinv and s/p csection but < 5-Ht3 drugs
Dopamine blockers examples
Metoclopramide (reglan)
Domperidone
Droperidol (inapsine)
Metoclopramide (reglan) SE
Abdominal cramping (if rapid Iv)
Muscle spasms
Hypotension
sedation
Increases prolactin release
Neuroleptic malignant syndrome; High temp, muscle rigidity, tachycardia, confusion
Decreases plasma cholinesterase levels; Slows metabolism of succinylcholine, mivacurium, ester LA
Metoclopramide (reglan) dose
10-20 mg IV over 3-5 minutes (15-30 minutes prior to induction)
domperidone compared to metoclopramide
Does not cross bbb
No anticholinergic activity
Also Increases prolactin secretion by pituitary- To greater degree
domperidone SE
Dysrhythmias and sudden death
Available out of country
no FDA arrpoval
Droperidol (inapsine) SE
Strong D2 antagonist
Extrapyramidal symptoms
Neuroleptic malignant syndrome
Avoid other cns depressants: barbiturates, opioids, general anesthetics
Droperidol (inapsine) on N/v compared to other meds
More effective than metoclopramide/Equally effective to 4mg ondansetron (much cheaper)
For n/v
Droperidol (inapsine) SE
2001 Black Box Warning…prolonged QT intervals/torsades with higher doses
Lots of serious drug interactions: amiodarone, diuretics, sotalol, mineralocorticoids, calcium channel blockers
Droperidol (inapsine) dose
0.625-1.25mg IV
Serotonin Release
Released from chromaffin cells of small intestine-> Vagal afferents through 5HT3 R -> vomiting
5HT3 ANTAGONISTS Examples
Ondansetron (Zofran)
Granisetron (kytril)
dolasetron (anzemet)
ondansetron 1/2 life
4 hours
give at end of procedure
ondansetron SE
HA, diarrhea
Slight QT prolongation
ondansetron dose
4-8 mg IV
Corticosteroids MOA for CINV
centrally inhibit prostaglandin synthesis and control endorphin release
Increase effectiveness for 5HT3 antagonists and droperidol
Anti-inflammatory…less postop pain…less opioid
Corticosteroids Example
Dexamethasone (decadron)
Dexamethasone (decadron) onset / effect
Delay in onset of 2 hours
Efficacy persists for 24 hours
give at beginning of case
Dexamethasone (decadron) Side effects
Diabetic Risk of perioperative hyperglycemia- Minimal side effects with 1 dose
Perineal burning/itching
Dexamethasone (decadron) dose
4mg/8mg/
give more if airway trauma; 12, 16, 20 mg
Scopalamine patch moa
Anticholinergics
muscarinic antagonist- Competitive antagonist of Ach
Central (Cross bbb) and peripheral effects
Scopalamine patch peak concentration
concentration 8-24 hours
Apply 4 hours preop (onset)
Scopalamine patch SE
dilated pupil- mydriasis/bright lights
Scopalamine patch dose
1 patch for 24-72 hrs
Post-auricular
Priming dose (140 mcg)
1.5 mg over next 72 hours)
Bronchodilators (B-receptor agonists) MOA
Structure similar to epinephrine-Stimulatory G proteins= activate camp +decrease ca +2 entry =
decrease contractile protein sensitivity to ca+2
Actions=
Reduce inflammatory cell activation
Directly relax smooth muscle….15% increase FEV1, 6 minutes (2 puffs)
SABA repeat frequency
Q4 hr
Side effects of Beta agonists
Tremor- B2 stimulation in skeletal muscle
Tachycardia
Transient decrease in arterial oxygenation
Hyperglycemia
