1st test anasthesia Flashcards
Who is in charge of controlling all physiological and physiopathological functions of the organism, administrating drugs to produce desired effects and avoid undesired effects or toxicity, as well as control renal function, hepatic function, temperature etc?
anesthesiologist
owner of px controlling all biological and fisiopathological functions during times in OR
therapeutic objective = give and maintain a dose in determined places for a desired effect
analgesia, amnesia
art of anesthesiology
must adjust dose and velocity of administration depending on clinical response of px
- (a lot of drugs have to be adminstered slowly)
want desired effect while avoiding undesired side effects/toxicity
what is succinilcoline?
it is a depolarizing relaxer
what happens if succilycholine is rapidly administrated?
px will present fasciculations or involuntary movements
px se retuerce
increases gastric , intraocular and incracraneal pressure –> broncoaspiration if px ate
3 pillars of anesthesiology
physiology, pharmacology, anatomy
ej of how to block a nervous transmission
local anesthetic like lidocaine to interrupt transmission of pain sensation
side effects of lidocaine
hipotension
role of amnesia in this subject
elimination of all memory for a 6-12 hr period is important
The point of general inhaled anesthesia?
- Maintain a central depression or an anesthetic coma for surgeon to operate
What are the 3 aspects/principles of anesthetics?
pharmacological
pharmacokinetic
pharmacodynamic
pharmacological principal
○ Professional has knowledge of drug (precipirates in sun? pH? Needs to be in cold? Best administration, disolvent)
liposoluble vs hydrosoluble
drug known to irritate a lot veins , painful
propofol
pharmacodynamics vs pharmacokinetics
Pharmacodynamics is the study of how a drug affects an organism, whereas pharmacokinetics is the study of how the organism affects the drug. …
what are the 4 aspects/parameters of Pharmacokinetics
Absorpion
distribution (volume)
metabolization (velocity ,time , etc)
elimination
absorption depends on what 4 aspects?
Biodisponibilidad/Bioavailability)
Perfusion grade where it is administered (Plasma concentration of drug is greater when deposited somewhere with a lot of irrigation)
Velocity of administration
Route of administration (determines velocity of absorption)
what does distribution depend on?
○ Depends on physical chemical cx of drug, CO, and regional blood flow
Different types of metabolization?
oxidation in liver
Reduction
Hydrolysis
types of elimination
through kidney or hepatobiliary, pulmonary
info about drug metabolism
Drug metabolism is the metabolic breakdown of drugs by living organisms, usually through specialized enzymatic systems.
The study of drug metabolism is called pharmacokinetics.
The metabolism of pharmaceutical drugs is an important aspect of pharmacology and medicine. For example, the rate of metabolism determines the duration and intensity of a drug’s pharmacologic action.
The metabolism of xenobiotics is often divided into three phases:- modification, conjugation, and excretion. These reactions act in concert to detoxify xenobiotics and remove them from cells
Biotransformation occurs only for the agents at physiological pH, having low molecular weight and less complex. Biotransformation is a process specifically to make agents more polar and excretable. If biotransformation does not occur, drugs may have longer duration of action, and undesired effects are observed along with desired ones. Biotransformation, in fact, is the inactivation of pharmacological action of drugs.
Cytochrome P450:
Cytochromes are the heme proteins, present abundantly within the living kingdom. They have about thousand known kinds. Only 50 of these heme proteins are found within the humans, which are divided into 17 families and sub-families. Name is derived because it is a heme protein (abbreviation cyp) and 450 because it reacts with carbon monoxide and during the reaction absorbs light at 450 nm.
NADPH
NADPH is a flavoprotein, less abundant than cyp 450.
For every 10 molecules of cytochrome P450, only one NADPH cytochrome reductase is present
Biochemical Reactions:
Phase I reactions
Phase II reactions
Phase I reactions:
Phase I reactions are non-synthetic catabolic type of chemical reactions occurring mainly within the ER. They are the reactions in which the parent drug is converted into more soluble excretable agents by introduction or unmasking of functional component.
Example includes phenobarbitone, aromatic hydroxylation of which abolishes its hypnotic activity. Similarly, metabolism of azathioprine produces 6-mercaptopurine.
Drug products, which are water soluble are excreted by the kidneys. Sometimes this is not true and phase I compounds do not result in true inactivation and may act as functional components of phase II reactions.
Phase I reactions include:
Oxidation
Reduction
Hydrolysis
ej , reduced, hydrolisized
Reduction
Chloramphenicol, dantrolene, clonazepam
Hydrolysis
Esters: procaine, suxamethonium and aspirin
Amides: procainamide, lidocaine
oxidation vs reduction
Oxidation is a reaction in which an atom, molecule or compound loses anelectron. OIL = Oxidation Is Lost; RIG= Reduction Is Gain LEO = Lose Electron in Oxidation; GER = Gain Electron in Reduction (LEO the lion says GER)
oxidation in the liver/ types
Types of Biotransformation:
Biotransformation taking place due to different enzymes present in the body/cells is known as enzymatic elimination.
- Enzymatic
a. Microsomal
Microsomal Biotransformation:
Enzymes responsible are present within the lipophilic membranes of endoplasmic reticulum. After isolation and putting through homogenization and fractionation, small vesicles are obtained, known as microsomes. They possess all functional, morphological properties of endoplasmic reticulum i.e. smooth and rough. Smooth ER is concerned with biotransformation and contains enzyme components while the rough ER is mainly concerned with protein synthesis.
Enzymes isolated from ER possess enzymatic activity termed as microsomal mixed function oxidase system.
Components:
Cytochrome P450 (ferric, ferrous forms)
NADPH (flavoprotein)
Molecular oxygen
Membrane lipids
b. Non-microsomal
Non-Microsomal Biotransformation:
The type of biotransformation in which the enzymes taking part are soluble and present within the mitochondria.
- Non-enzymatic (Hofmann Elimination)
Non Enzymatic Elimination:
Spontaneous, non-catalyzed and non-enzymatic type of biotransformation for highly active, unstable compounds taking place at physiological pH. Very few drugs undergo non-enzymatic elimination. Some of these include:
Mustin HCl converted into Ethyleneimonium
Atracurium converted into Laudanosine and Quartenary acid
Hexamine converted into Formaldehyde
Chlorazepate converted into Desmethyl diazepam
Hydrolysis
is a reaction in which a molecule or compound is broken down, by the addition of a water molecule (usually with an acid to catalyze the reaction)
atracurium and Cisatracurium are ?
non polarizing relaxers
different routes of administration of drugs
oral = enteral sublingual rectal subcutaneous intramuscular Intravenous Intratecal, BSA, BPD Pulmonary
cx of enteral administration
most comfortable economical commonly used needs px cooperation ambulatory rare in anesthesia tho
80-90% of drugs absorbe where
in second part of SI
but some in stomach
cx of sublingual administration
○ Allows you to reach greater hematic concentration due to lecho venoso, big irrigations under tongue allows greater absorption than in gastric mucous
used in urgency situatins
cx of rectal administration
○ Fast absoprion ○ Causes nausea and vomit ○ Analgesics, antiinflammatories Common for analgesics in pediatrics when irritating
cx of subcutaneous administration
○ Slow and regular absorption drugs
○ Heparin
○ insulin
cx of IM administration
○ Slow absorption for sustancias oleosas
○ Fast for hydric substances (much more irritating)
rare in anesthesia
cx of IV administratin
○ Fast start allowing exact dosification
Adequate when administrating large volumes of drug
common in anesthesia - 90%
cx of intratecal, BSA, BPD
○ can be subarachnoid or epidural
fast, local
○ Can have effects without affecting CNS/SNS
common in anesthesia - 5-10%
cx of pulmonary administration
○ Only used in urgent cases especially when we have px with cardiac arrest that isnt canalized
○ Drugs can be applied through orotraqueal tube § Atropine Adrenaline - > 90% effectivity
ph with irritation?
alkaline irritates a lot –> flebitis(trombo)
use a high flow big vessel
anesthesiologist discharges after what time
24hr
theraupetic objective of pharmacodynamics
maintain an adequate oncentration of a drug in a specific locations with a determined desired action
pharmacokinetics teacher wants
absorption - EV
volume of distribution
metaboliation (velocity, time
bioavailability
In pharmacology, bioavailability (BA) is a subcategory of absorption and is the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokineticq properties of drugs. By definition, when a medication is administered intravenously, its bioavailability is 100%.
other route
topica, contacto, through dermis
monitorization of px in OR depends on
clinical case, severity of px status
minimal monitorization
EKG echo continuous thru whole process
non/invasive continuous systemic BP monitoring
saturation - pulse oximetry
monitor temperature
start before putting them to sleep
need pressure oygen source and hemodynamic monitor
continuous suction
laryngoscope , intubation equipment, orotraqual tube
CV evlautation
echo, prueba de fuerza, EKG
What is an anesthesia Machine?
machine that give px gases
high risk monitorzation
measure depth of coma anesthesico invasive pressure - arterial pressures CO NM relaxation gasometry continuous electrolye measurement balances
hemodynamic monitor vs ventilation monitor
HD - BP, HR, CO, etc
Ventilation - ventilator parameters in qx - rate, tidal volume, and oxygen content etc
parts of laryngoscope
…
types of laryngoscope
- 2 types: curved and straight (in px with laynx anterior and elevated)
must have equipment by anaesthesiologist
need pressure oygen source and hemodynamic monitor
continuous suction
laryngoscope , intubation equipment, orotraqual tube,nasotraqual
have a EV route ready/venous access
what are traqueal tubes?
A tracheal tube is a catheter that is inserted into the trachea for the primary purpose of establishing and maintaining a patent (open and unobstructed) airway. … An endotracheal tube is a specific type of tracheal tube that is nearly always inserted through the mouth (orotracheal) or nose (nasotracheal).
cxof difficult intubation
prominent maxilar?
macroglosia
naso traqual
canula de mayo
at inhalatory or IV with difficult intubation cx and ventilation difficult
An oropharyngeal airway (also known as an oral airway, OPA or Guedel pattern airway) is a medical device called an airway adjunct used to maintain or open a patient’s airway. It does this by preventing the tongue from covering the epiglottis, which could prevent the person from breathing. When a person becomes unconscious, the muscles in their jaw relax and allow the tongue to obstruct the airway.
In respiratory physiology, ventilation is the movement of air between the environment and the lungs via inhalation and exhalation. Thus, for organisms with lungs, it is synonymous with breathing.
what is traqueal intubation
placeent of a tube in the traqueal cavity
can be any px
parts of tube
balon(cuff?) –> to trap air and keep all gases in alveolos and not eliminated by air
some low pressyre others high pressure
balloons in sondas are to fixate them
first person to intubate`
1880 qx sir William macowen
inventor of laringoscope
1895 kerstein
formulated scienctific base for intubation
1910 Cahavallier
different types of intubation
orotraqueal - most frequent,
naso traqueal - Levin in nose
endotraqual - directly in traquea
cricodetomy
indications for intubation
To administrate OXYGEN/VENTILATION = #1
- Administration of inhalatory gases (nariz o boca)
- Px in respiratory arrest
- Px that present airway prolems (tumor, burn, FB, secretions)
- Px in cerebral coma
- Px that cant manage secretions (fibrocystic disease, no strength, need aspirations , fibroscopy)
different calibres for tubes
\Adult male = 7.5ml wide - 9ml wide
Woman - 6ml-7.5ml - wide,d
Kids < 5 = age + 16 divded by 4 (plus 4 dived by 5 he said?)
Selecitve intubation tubes = doble lumen
when is nastraqueal canulla CI
§ CI in <2yr px due to high incidence of adenoides in this age group
double lumen tubes
used in selective pulmonary intubation for example in thoracic qx, can block one lung at a time while working
more expensive
consequences of intubation
- Bleed
- Perforation of traquea is common and –> emphysema
- Orotraqueal edema
- Dentary rupture
- Gastric colocation is common
- Vocal cord lesions (wrong tube side)
what does tube size depend on
sex and age
Principle function of larynx?
- Protection of low airways against entrance of anything (liquid, solid, bacterial)
- Contain essential fonation organ = vocal cords (Mobile organ that elevates @ deglution and when making sound)
- Labor (increases pressure –> increasesa abdominal pressure)
Defecation
Topographic location of larynx?
- Medial and anterior neck in front of pharnxy and below hyoide bone and above traqueal rings
(pharynx is continuation of esophagus)
- Relation with spine depends on age and sex ○lower border More elvated in woman - C4 ○ In man - lower border of larynx - C6 ○ RN C2
can palpate with finger
Dimensions of larynx?
- 7cm long x 4cm wide - adult male
- Woman - 4.6cm long x 2.6 wide
Cartilage of Larynx
- 6:
○ Impair epiglottis (search for first in direct larginoscopey), thyroid, cricoid
Pairs arytenoid (also very visible), corniculados (morgani), cuneiforms
classification of larynx muscles
extrinsic (depressors and elevators) - movement and fixation of larynx - §one Insertion in larynx and another outside
intrinsic
extrinsic depressor muscles - takes to original position after elvation
□ Sternohiodeo
□ Tirohiodeo
□ homoiodeo
extrinsic elevator muscles (in second deglution time and during acute sound)
□ Geniohiodeo □ Digastric □ Milohiodeo □ Stilohiodeo □ Medial constricor and inferior of pharynx
intrinsic muscles of larynx -
both insertions inside larynx - responsible for vocal cord movement
§ Cricotiroideo... § Cricoaritenoid posterior muscle - □
irrigation of larynx
- Superior larynx artery
venous drainage of larynx
- Superior laryngeal vein –> internal post. Yugular
- Infeiror –> superior thyroid vein
- Posteiror –> inferior thyroid vein
superior innervation of larynx
○ 2 branches
○ Internal = sensitive to all internal larynx
○ External = motor to cricoide muscle
inferior innervation of larynx = recurrent
○ Purely motor –> 2 branches
○ Internal - motor to internal config of larynx
○ External - extrinisic muscles
tension of vocal cords - must know where it is in qx - irreversible
both innervation of larynx are branches of
vagus
other cartilages not really seen
sesamoid ant, post - not really seen
cx of cricothyroid muscle
originates in lateral side of anterior arc of cricoid cartilage. some fibers go up to post inf border of thyroid lamina an dother go behind and lateral to inferior part of thyroid cartilage. - only muscle of larnx that is innervated by superior laryngeal nerve; lengthens and tenses vocal cords to take them to paramedian line
cx of cricoaritenoid posterior muscle
only one that causes apertura of vocal cords (others close)
□ Originates in posterior part of lamina of cricoids
fibers pass up and out to insert in muscular process of arytenoid cartilage
abducter of vocal cords
innervated y recurrent laryngeal nerve
first anesthetic gases used
chloroform (serial killers)
used to be with compressa
now we use tube to administrate all gases
definition of general inhalatory anesthesia
absence of all painful stimuli induced by an anasthehtic gas
depression or anesthetic coma for a qx produce induced by inhaled agent
anesthesia a la reina
a la reina - no monitrozation of anesthesic points, higher mortalithy
why no balon in kids
no ballon in kids because sublglottic is thinnest part (<5yr) - should have some escape of gas
orotraqueal intubation px needs to be
asleep (EV resp depression or irregular) and relaxed of orofrangeal muscles (paralysis of muscles) assisted ventilatationo, then intubate and control then mark parameters
which agent depends all on px cx
vs edtraq px can be awake
how many needles
4
halothane causes
anesthetic gas
bradycardia - give atropine b4
arrhythmias - lidocaine buffer
narcotic for analgesia
how can ventilation be
spontaneous
assisted
controlled
Characteristics of an ideal inhalatory agent?
- Shouldn’t be toxic
○ El éter, cloroformo, halotano (Hepatotoxicidad), el ciclopropano, el metoxiforano (Nefrotoxicidad y Hepatotoxicidad).- should be a good NM relaxer
○ Si lo hace la necesidad de utilizar un bloqueador neuromuscular será menor - sevorane best - should have a Wide margin of security
○ no importa la cantidad de horas o posiciones que el paciente tenga frecuentemente ante un gas no afecte la función de la vida. - Induction and recuperation should be fast
○ Que necesitamos que el gas duerma rápidamente al paciente pero que también se metabolice rápidamente para que despierte rápido. - Few cardiac alterations
○ BP, HR, CO MAP variables should be maintained
○ Maintain perfusion - not reduce blood flow to organs
§ Halotano
○ Al principio provocaban muchos cambios cardiacos, hoy en día los gases de usos diarios como el Isoflurano y Sevoflurano tienen mínima acción sobre la función cardiaca. - Should not liberate histamine
○ Used to have a lot of anaphylactic reactions which would further complicate hemodynamic situation - high mortality rate
put blocker beta H1, H2 - antihistamines before - Shouldn’t not cause nause and vomit
○ Before we used to think px wasn’t recovered until they didn’t vomit cuz they all used to cause it
- should be a good NM relaxer
monitor position in anesthesiologist
in front
Inhalatory agents currently used?
nitrous oxide- expensive - y halothane - not really anymore, cheap enflurane isoforane- y sevorane- expensive desflurane-y - not in this country
CAM of halotane
0.74
Vapor pressure of halotane
243
PE of halotane
50.2
metabolis of halothane
10-20%
inorganic metabolites
took longer to wake up
CAM of enflurane
1.68
VP of enflurane
175
PE of enflurane
56.2
metabolism of Enflurane
3-5%
CAM of isoflorane
1.40
VP of isoflorane
250
PE of isoflorane
46.5
metabolism of isoflorane
2-3%
CAM of NO2
105
VP of NO2
1atm
PE of NO2
-89.5
CAM of Sevorane
1.7-2
VP of Sevorane
160
PE of Sevorane
55
Metabolism of Sevorane
2-3%
CAM of Desfloranes
7.2-9
VP of Desfloranes
664
PE of Desfloranes
23.5
Metabolism of Desfloranes
0.02-0.04%wh
what are organic compounds
any element that contains a carbon atom inside its molecular structure
99% of pharmacological compounds
potency of any organic element depnds on
number of carbon atoms in molecular chain (more carbon, more liposoluble)
also on any halogenated elements in molecular structure
good vapor pressure (the higher the better, start with it high and with increasing breathing rate)
ebullition point < 60 (boiling point)
low blood/gas participation
the more potent the thinner the line between therapeutic and toxic
toxicity dpends on?
more carbon means more toxic
how many carbon atoms until toxicity surpases therapeutic effect
> 7 C
the only inorganic compound used in medicine today
NO2
DONT HAVE CARBON IN molecular structure
the only anesthetic agent that is found in gas form in nature and of organic origen
el ciclo propane
why did ciclo propane stop being used
super flammable
anesthetic agents used today are made up of what
hydrocarbon, carbon and hydrogen
also they are all aliphatic compounds
receive name based on how many carbons are in their structure or depending on form in which Carbon atom is in the structure
1 = methane 2= ethane 3=propane 4=butane 5=pentane
aliphatic = lineal - ALL FARMACOS INALATORIOS
cyclic (ej ciclopropane)
H atom can be substituted for other elements suchs as
iodine (126)
fluor (18)
cloro (35.5)
Bromo (80)
gives potency
iodine (126)
cloro (35.5)
gives stability
fluor (18/)??
bromo (80) - audio/?
decreases inflammation - halogenated elemends
Bromo (80)
A halogenated compound is a combination of one or more chemical elements that includes a halogen; halogens are a group of elements that include fluorine, astatine, chlorine, bromine and iodine
what is the objective of modern anesthesia
to maintain a cerebral concentration of anesthetic that is enough to carry out qx and allow rapid recuperation
what do we want out of general anesthesia
amnesia analgesia LOC inhibition of sensorial reflexes and autonomous reflesxes muscular relaxation
how can we divide general anesthesia based on its goals
MONITOR PX
induction to sleep for intubation
maintenance (BIS and hemodynamic observation)
recuperation
first anaesthetics used that were inhaled and were used for a long time
NO (only one still used today)
ether
clorform
later came halothane, methoxiflurane, enfflurane, isoflurane, desflurane, sevoflurane
balanced anesthesia
when we combine inhalaed and IV anesthetics
or opiods with neuroleptic
stages of general inhaled anesthesia by Guedel (dietileter)
I analgesia from administration to sleep amnesia - w/ benzo opiod - therefore less need for inhaled agent
II excitement and delirium irregular respiration, arcada vomit increased muscle tone, HR, BP, midriasis finishes when px loses muscle tone moves around ends when px chills out
III
qx anesthesia, coma anesthetic qx
respiration controlled, miotic pupuls, decreased ocular reflexes, no ocular movements
40-60%
IV medular depression deep coma depression of vasomotor center bradycardia, severe hypotension extreme miosis
what is anesthesic potency
the alveolar concentration at 1atm that achieves abolition of motor response to a painful stimulus in 50% of px
need 1.3 cam to abolish this response in 99% of px
why can CAM vary
px condition
meds
factors that intervene in potency of inhaled anesthetics (DONT??)
type of stimulus
duration of anesthesia
circadian rhythm
sex
factors that increase potency in anesthetics inhaled are
hypoxia anemia hypotension hypothermia preqx use of an opiod use of ketamine previous use of diazepam or other benzos (lowers CAM of inhaled anestetics) pregnancy (endorphins that act like opiods)
factors that decrease potency of inhaled anesthetic
age (mostly decreased/resistance between 1-6 months, little mass)
hyperthermia
chronic ingestion og alcohol, drug addicts on antidepressants
only gas used from past siglos that is seen in gas form in nature
NO
current uses of NO
analgesic during labor
odontology
given with another agent
doesn’t irritate airway when given through mask inhaled
history of NO
used to be used as laughing gas
first time used as anesthetic was in 1844 by Horace wells in Harvard to extract a wisdom tooth, failed b/c didnt know physical properties
physical properties of NO
colorless
odorless
dulzon
not irritative
EL MENOS POTENTE
oil/gas coefficient is 1.4 = poorly soluble
blood/gass particion coefficient = 0.46 = induction and recuperation are fast (34x > nitrogen) - passes through alveolo to artery fast - this is why its used with other gasses because since it is faster = FASTEST it also has the ability to drag other anesthetics and accelerate its action
usually inhaled
CAM of NO
104% = poor potency
pharmacokinets and dynamics of NO
inert gas
not metabolized - full elimination = inert gas
pulmonary elimination > 90%
@ > 60% @ CNS –> amnesia and analgesia
produces general anesthesia through interaction with cell membranes of CNS
@ CV exerts mild sympaticmimetic action causing discerete myocardial depression, mild increase of HR
side effects of NO
expan closed air spaces - CI in closed qx
diffusion hypoxia - large V exiting from blood to alveolos dilutes oxygen concentration in alveolo
oxidation of vitamin B12
depression of bone marrow after 4-5d(px with tetanus) - granulocytopenia, TCP
nausea vomiting
teratogenic
why cannot use NO in abdominal qx or long qx like liver transplant , vitrectomy, timpanoplasty, neumotorax or neumoperitoneo, dx laparoscopy
due to expansion of closed airspaces in ocluided px could increase risk for distension and perforation
in opthalmological qx can risk increased gas expansion in vitrectomys
mechanism of b12 oxidation by NO
NO inactivates metioninsintetase necessary for DNA synthesis and depends on B12
history of halotane
introduced in 1956
physical properties of halotane
volatile
colorless
good smell - rotten apple
doesn’t irritate - good for mask
decomposes with light and humidity
blood/gas - 2.4 (NO is faster)
oil /gas - 224
CAM of halotaine
0.74 = grand potency - THE MOST POTENT
why did we need alternatives to halotane
hepatotoxic
mimics viral hepatitis
elevates transaminases, fever, jaundice
massive necrosis causes acute liver failure with high mortality - diff dx - halothane removes blood flow there
necrosis of hepatocytes
factors that increase hepatotoxicity of halotane
40-70yrs, feminine, obesity, genetic factors, previous exposure to it
FD of inhaled agents @ CNS
all inhaled agents liberate excitatory NT causing central depression and maintain nerve cells depolarized by blocking ion exchange
blocks Ach liberation
FD of inhaled agents @ heart
depends on agent
halothane and enflurante reduce CO - reduce systemic vasc resistence –> central bradycardia b/c block depolarization at SA node –> liberating histamine - all this decreases precharge
isoflorane secorane and desflorane don’t really affect CO, lower it minimally - same with MAP, hardy any effect on HR
FD of inhaled agents @ BP
mostly reduced by halothane and enflurane (worse if dehydrated)
directly related to alceolar concentration
less decrease by iso, sevo, desflurane
inhaled agent that most modifies HR and depolarization velocity @ SA node
halotane
FD of inhaled agents @ kidney
decrease renal function
reduce diuresis
reduce GFR and renal BF
secondary to effects on CV system
return to normal after suspension (if persiststs there was previous renal or CV pathology, hydroelectrolitic disorder orincompatible blood administration)
renal condition depends on hemodynamic condition
was px hydrated pre qx? low BP? - low perfusion? kidney problems already? incompatible blood Methoxyflurane nephrotoxic
isoflurane history
made in 1971, commercialization began in 80s
1988 here in DR
halogenated metil-etil-eter and isomer of enflurane
isoflurane
FD/FK of isoflurane
less biotransformation/metabolism 0.2
least hepatotoxic (maintains flow) - even if lesiones
pulm elimination >80% and as metabolites (trifluoracetico, FL, Cl) thru kidney - 10%
causes a lot of resp depression
FD of isoflurane @ CV system
increases HR mild - not risky
VD - coronary (indicated in coronary bypass)
decreases vascular resistence without modifiying CO
maintains hemodynamic stability
direct depressor of myocardial contractibility
FD of isoflurane @ resp systtem
irritates. no mask, can cause laringospasms
BD
acts on medullary centers causing resp depression and depression of airway reflexes
FD of isoflurane@ CNS
depresses cortical function
decreases excitatory transmion from cerebral cortex
strengthens nondepolarizing muscle relaxers - less need for them
increases ICP slightly
physical cx of sevoflurane
98-2000 here - used alot here
volatile liquid derived from fluorado of metilisopropileter with a halogen (FLUOR) 7 atoms no color good smell doesn't irritate
can give with simple mask in kids
blood gass - 0.62 - fastested after isoflurane - sleep fast
low blood solublility
oil/gas - 53
not hepato o nephron toxic (doesnt derease flow)
CAM sevoflurane
is the one that most varies with age ( less with age and more in kids)
1.7-2%
reduced to half if with NO 60%
boiling point of sevoflurane
58.5
vapor pressure of sevoflurane
157 so you can give conventional vaporizers
elimination of sevoflurane
lungs >90%
kidney - 10%
metabolites 2-3% - in liver using cytochrome P4502E1
hemodynamic and CV effects (FD) of sevoflurane
similar to isoflurane
stable
HR same!!!
BP decreases depending on vapor pressure giving, gas flow in the moment - too high, adjust as long as px hydrated and not bleeding
decreases CO
doesn’t modify systemic vascular resistences
resp FD effects of sevoflurane
depresses respiration
dosis dependent
no irritaiton
CNS FD of sevoflurane
same as iso
potentiates nondepolarizing NMRs
depresses electroencephalograph acvity
dose dependent
no convulsions
changes in cerebral BF
discrete increase in ICP
history of desflurane
metil-etil-eter flurado
London 1988
not here in DR yet
physical cx of desflurane
volatile liquid
irritative
itchy,spicy
cough laryngeal spasms (cant ventilate - px is rigid)
blood/gass partiicion coefficient - 0.42 = sme as NO
oil/gas coefficient - 18.7 = LOWEST
not nefrotoxic nor hepatotoxic
boiling point of desflurane
23.5
vapor pressure of desflurane
at 20C is 652
no vaporization possible unless its a Tec type electric evaporizer
high
lowest bloos/gas partition coefficient and oil/gas coefficient of all inhalatory anesthetics
desflurane
CAM of desflurane
6-9% depending on age
high
metabolization of desflurane
0.02%
desflurane FD @ CV
increases HR mild and MAP
decreases systemic vasc resistence
doesn’t change CO
desflurane FD @ resp
increases BR
decreases circulating volume which is dose dependent
respiratoy complication of general anesthesia
obstruction of airways from tongue falling (put Guedel canula, Mayo canula to lift tongue) after qx
tooth/protesis out into a bronquio
gum bleeds
laryngeal edema due to diff intubation (thin laringe, couldnt hiperextend) - closes airway after removing tube
laryngospasm (give a NM relaxer)
(obesity, macroglossia, a lot of time intubates,
hypoventilation from depression of CNS resp centers…decreased costal function due to opiods (excessive stimulation …tx: flumacenil) or due to relaxation of diaphgram from use of NM blockers (tx: anticolinestaricsadministration of neostigmine or sugammadex - increase muscle tone)
neumotorax/hemotorax due to qx or barotrauma from VM, or from guiding sonda perforating traquea , too much vent pressure causing a rupture
atelectasia from accumulated secretions, smoker - if orotraq tube is introduced too deep and only one lung ventilates (tx: bronquial lavage with saline solution)
broncoaspiration of gastric content (SNG in VM) - if px ate before qx - fatal
paralysis of asccesory muscles
relax bronquial SM
tx for neumotorax/hemotorax due to qx or barotrauma from VM
chest tube
CV complications of general anesthesia
htn, taki, globo vesical if no sonda - no analsicsdone well - should put 1hr before awake
lower stress bp with sedation, if still high suspend qx- dispara at immediate post qx more dangerous than before qx
hipotension, bled too much and dint put enough liquids
arrythmia
all produce a decrease in sympathetic (dose dependent) causing VD, negative inotropism-cronotropism, blood shunting to splenic organs.
all this is less evident in hypovolemic shock or dehydration
HTA (more common) from pain (give analgesia) or urinary retenhion (globo vesical, less urine, concentrated, low PVC, verify that sonda is well placed), due to hypovolemia (tx: NS0.9% sueros), hemorrhage (concetrates of RBCs) or IC (give dobutamine, efedrine)
arrhythmias that decrease CO and can produce PCR
IAM due to arrhythmias , hypercalcemia or previous cardiopathy
PCR - cardioresp arrest
CNS complications of general anesthesia
excitation or agitation from pain, hypoxemia or hypercapnia, dehydration or urinary retention
hypothermia - if it wasn’t managed in transqx
delay of waking due to overdose of opiods or anesthetic (antidote) ,
hypoglycemia (glucosalated serum) , hyperventilation
other complications of general anethesia
nausea and vomiting from opiods and eter (give antiemetics)/GI
anyfilactic reaction (give adrenaline and corticoids)/immunological
endocrines (hypergluciemia, hypercorisolemia) - check beofre during and right after
knowledge important for understanding NM relaxers
ANS functioning
NTs of ANS
basic anatomy of striated muscle and NM union
physiology of NM union
important for intubation , bronquial relaxation = #1 indication
#2 depends on where qx is - abdominal all thru, other area not necessaary
administered with to hlep inhaled anesthetics
NOT anesthesics
dont cross BBB
act at smooth Skeletal muscle
helps ventilation, qx, intubation
help in epilaeptic , asmatic px states
second gas effect
when a gas has the ability to transport antoher gas
only one with this ability is NO
allowing less consumption with less hemodynamic effects
how to tx hypoxia by diffusion caused by NO
administer high concentration oxygen for 3-5min after interrupting N2O
CAM
min # of gas % to cause cerebral coma at 50%
isnt enough, need > 90% so for halotane 2x dose
Vapor pressure
all these gases come in liquid and are administered vapor (pressure for liquid to evaporate)
in this case, oxygen on liquid surface of an anesthetic is found in a closed recipeint
ebulittion point
- Temperature at which a substance as liquid starts evaporating
% of organic compounds in pharmacology
99%
primary - central NT
GABA
primary - peripheral NT
glycine
antiarrythmics can use with halotane
lidocaine, esmolol
sevorane and isoflurane in cardiac qx (CV stable)
which inhaled agent is best for px with emphysema, asthma, chronic bronchitis (restrictive)
CANT use enflurane
halothane is best because it BD
sevo , iso wont help but wont hurt
agent that most blocks CO2 action on resp center and also causes arrythmias
enflurane
agent that produces most irribility and when using mask can cause laringospasm
enflurane
sevoflurane doesn’t cause this - ideal to use on mask for kids
all inhaled agents are metaoblized
in liver - oxidation reaction
less in kidney and lung
agent that causes most alveolar BD
halothane
tx status asthamaticus with
halotane
tx intractable angina with
epidural local anesthesics
why we put a dose that is 2x the CAM
so dose would be around 1.5 for halothane
CAM depends a lot on state of px hemodynamically
unstable dehydrated px doesn’t tolerate minimal CAM, VD, bleedinh
if hypovolemic, in chock I put 1.5 halothane ill deepen his depressed state and px worsens
put blood, use VC
to get a good anesthetic effect should double the CAM
least metabolized inhaled gas aka mas noble
desflurane
least hepatotoxic
desflurane
least hepatotoxic after desflurane
isoflurane
lowerst oil/gas coefficient
18.7
desflurane
gas with least metabolization
desflurane
desflurane affect on CNS
- CNS decreases peripheral vasc resistence increasing CBF
desfluranes affects on non depolarizes NM relaxers
strengthens them
agent that most relaxes bronquial SM
halothane used in asma px
enflurane effect on bronquoils
BC
tx arrhythmic complications
selective Beta blocker
lidocaine
agent that most decreases hemodynamic parameters
Halotane
BP 20-25%
CO 30%
most arrythmogenic agen
Halotane
effect of halogenated agents on mocardium
sinsibilize it to sympathetic action
agents that produce most NM relaxation
sevofluranem isoflurane, enflurane
less NM relaxers needed as a result
NM relaxers should never be administered without
necessary prep to maintain open airway and ventilation
putting the px to sleep , since doesnt cross BBB px cant move breath so avoid the psychological trauma
are NM relaxers anesthetics?
no
not hypnotic either
need co-use with hypnotics, sedatives or anesthetics
who was savarese Kitz
described criteria for ideal relaxer (neither completes all of them)
election depeedns on clinical situation
Kitz criteria (el hidonio?) - ideal
whixh depends on px and experience
non depolarinzing mechanism best
rapid initation of action
adequate duration - 1hr
rapid recuperation
no accumulative effects @ psuedosis ,o rredosis
no CV effects
don’t liverate histamine
easy rapid reversion with neostigmina o sugammadex
no meds interaction
don’t produce active metabolites - elimate in different organs
excretion independent of kidney and liver
without effect on CNS (in ICU) - some metabolites do, none themselves do
without muscular effect in crifical state
pharmacological presenation in stable solutions
FK of NM relaxers
this references distribution, metabolism, elimination in organisms so plasma concentration is the result of a specific dose administrated
act at NM union NOT plasma
EV (not oral or IM) - ONLY - absorption
union to protein influences distribution, hipoproteinima and rug with hugh union grade to protein (AINES) can increase free fraction of relaxer
the alteration of EC liquid volume
derived as: nephropathy and cardiopathy bodify the distribution volume of relaxers
no obstante , FK of relxers presents individual variations in px with renal failure, liver failure and px taking steroid
NMRs act where
in the NM union
not in the plasma
meanwhile block starts becoming insaturated, plasma concentration stars decreasing
distribution of NMRs
are very polarized molecules with escasa diffusion and very hydrofilica
edema, steroids, nefropatiea, too much water - dosis has to be much larger, IC, hepatopathy excess body water
volume distributes EC liquid
don’t pass BBB
and in small quantities placentary barrier without evidence of clinical effect
metabolization of NMRs
90-95% nondepolarizing at liver- recuronioi vecuronio
other group in plasma
anotther biotrasnform at plasma of sucinilcoline is eliminated in plasma, mivacuruin,(iwth acetilcolinesterasa)
cisatracuruin, and atracuriun
are cleared in plasma through biotransformation (autodestruction)
sucinilcoline and mivacuruin are hydrolyzed by plasma clinerterasic while cisatracuruin and atracuriun are degraded by elimination of Hoffman (autodestruction and temp. and body pH) besides Atracuriun is decomposed by hydrolysis of ester in 20%
steroid relaxers or metabolize mostly in liver
elimination of NMRs
relaxers that least depend on liver elimination are cistracuruin , atracuriun, mivacuruin, the first two are indicated in px with liver failiure while mivacuruin triples its duration due to decrease of colineterasic
asteroid relaxers that don’t completely degrade are eliminated thru kidney and bile
mivacuruin , atracuriun, cisatracuruin, and sucinilcoline are of election in px with renal failure
Depolarizing NMRs
these have a chemical structure similar to Ach competes with liberation in synaptic hendidura of the motor plaque por nicotinic post synaptic rec of motor plque
also acting on cholinergic muscarinic receptures they induce bradycardia and increase salivary secretions
history of sucinilcoline
disvocered in 1951 - Bovet
thought to be ideal relaxer cuz there was no others
most associated with anafilaxis
at 80s othr types were discovered and was used less and less
only used to compare effeects of others and fast intubation
iniciode accion rapida after 60seg 95%
only depolarizing relaxer with clinical use
sucinilcoline
all are EV
most popular relaxer used and critizzied even today after 50yr
same affect as Ach but longer time - depolarize
limited after the 80s but still in medical arsenal for endotraqual intubation (incierta) and emergency for kids and adults esides some contraindications
secondary effects of sucinilcoline
fasciculations - more in muscly adults less in kids, muscle contractions
myalgia, post qx pain (worse if muscular px)
increased intragastric pressure
increases intraocular pressure > 10% - CI in glaucoma px
arrythmmia - more common in kids (vagar , transitory) - massive K+ liberation from IC
malignant hyperthermia
bradychardia possible but less common
skin irritation
px with ccolinesterasa atpica - hepatopata - block takes longer
in px with extense burns or neurological disorders (paraplejic, myopathy, reynales? already with kalemia issues CI) can present severe arrhythmia in ventricles mediated by a massive hyperkalemia
alot of anafilactic reaction > 37%
, intolerance to other drugs after this one
increases IC pressure - CI in px with brain pressure increassed
why does sucinilcoline cause fasciculations
depolarization of presynaptic cholinergic rec
how to prevent bradycardia by sucinilcoline
with previous use of atropine 3min before
structure of sucinicoline, formula
formed by 2 Ach molecules united by a metil-acetic group
FORMULA (2 Ach molecules united by metilacetate bridge) very similar to Ach - acts like it but longer, elements(glucometilico, oxygen, nitrogen sufre?? etc)
cx of sucinilcoline
hydrosoluble
degraded by heat , light and alkaline pH
sould be kept in fridge between 4-10 degrees
ultrashort duration of sucinilcoline is due to what
metabolism - rapidly hydrolyzed by pseudocolinestearasic plasma enzyme which is made by the liver
much slower than Ach and is in 2 stages
half life of eliminiation of SC
7-10 min = duration of action destroyed by enzymes, longer in certain types ofpx
initation of action - 60sec
2 stages of SC metabolism
1 - produces sucinilmonocoline and coline a
2 - produces succinic acid and choline
which stage of SC metabolism is faster
wst is 6-7x faster than second
potency of block of sucinilmonocoline compared to sucinilcoline and coline
cuadragesima of sucinicolina
colina only has centesima part
are metabolites of SC toxic?
no
male vs female SC metabolism
male - 35% faster than in women
becomes slower with age
clinical use of SC
RM desp of election for endotraqueal entubation emergency (laryngospasm and full stomach real or virtual)
in PEDS only in urgency
if kid does not have permeable veins can use IM in low dose in electroconvulsive tx
clinical dosis of SC/intubation
adult of 0.5mgxkg??? - not what he said
pediatrics - 2mg x kg or in px with increased volume, edematized
intubation dose = 1mg/kg
so in qx
bollus every 10min or continous infustion (preffered)
if convulsing also useful
initation time of SC
30-60 sec (he said 60seg)
clinical duration of SC
3-10min (he said 7-10)
IM routes initation and duration of SC
IM - 5mgxkg with
3min initiation
30min duration
NM recuperation based on age
NM recuperation is faster in kids < yr
SC effects on skin
rash and gral eritema
atypical pseudocolinersterasic
SC can cause prolonged block in px ith atypical pseudocolinersterasic -
duration of block varies of 30min - 13hr
drugs most associated with anafilactic reaction
NM relaxers
Sucinilcoline most commonly
37% of accidents
CI of SC
K+ > 5
px with family history of malignant hyperthermia
px with severe burns > 7 d
px with IC HTN
px with high IOP
what determines FC and FD of NMRs
FD = potency, initiation of action, duration, and recovery
physicochemical cx like sterospacial structures
how is potency of NMR reresneted, measuresd
D051 - OR65 curve
valora effective dose DE50 and DE95!
minimal dose that can cause deprecaccion de impulso electrico a nivel nervioso (DE95)
DE50
dosis that causes 50% depressio/block of transmissionn of response to unique response
DE95
dosis which causes depression of 95% of respective to simtulus and is the most vital because en cuanto necessity of ideal qx relaxation
DE50 and DE95 of doxacuruin
DE50 - 0.012
DE95 - 0.024
MOST POTENT at most minimal dosis causes deprecacion muscular
DE50 and DE95 of vecurunio
DE50 - 0.027
DE95 - 0.043
DE50 and DE95 of cisatracuruin
DE50 - 0.029
DE95 - 0.048
DE50 and DE95 of mivacuruin
DE50 - 0.039
DE95 - 0.075
DE50 and DE95 of atracuruin
DE50 - 0.120
DE95 - 0.210 (0.5mg to intubate) multiply by 3
DE50 and DE95 of sucinilcoline
DE95 - 0.260
DE50 and DE95 of rocuronio
DE50 - 0.147
DE95 - 0.305 (0.295mg/kg????)
LEASST POTENT
to really paralyse have multiply 3x DE95 around 0.6 to intubate
Division of NMRs
NMRs are composed of cuatenary amonio atendiendo chemical structure is divided into 2 groups
depolariizing and nondepolarinzing
Non depolarizing NMRs are divided into 2 groups
steroid amino:, pancuronio, vecuronio. pipercuronio, rocuronio - these metabolzied only at liver
benzilisoquinolina group:. D-Tubucuraina, Metocurina, mivacurio (HE SAID NO), doxacuruin, cisatracuruin, atracuruin - undergo autodestruction - dont need liver or kidney for elimination - independent
most powerful non depolarizing NMR
doxacuruin
least potent ND NMR
rocuronio
potency of vecuronio is similar to
vecuronio and cisatracuruin have similar potency
atracuruin has similar potency to
sucinil coline
dosis for NMR for idoneous intubation is
3x ED95
for maintence suggeset a dosis that is 1/3 of ED95
action initiation of NDNMRs
its the precise time to reach a decrease of 100% of contraction force
NMR time of initiation of action depends on
cx of ED50 relaxer/DE95
of dosis of inductor agent
of hemodynamic situation of px
CO, muscular blood flow
_____________________________________
time that it takes for drug to reach equilibrium between plasma and NM union,
fast eqilibruim decreases initaiotn time
increase in dose has been used to decrease action initiation times of BNM
this leads some to present adverse effects (prolonged muscular block more than desired)
decrease in CO of oldie justifies increase in intitation time
beta blocker px produces same effect
time of initiating action of NMRs competitive is propriotal to
its potency,
less potency, less initiation action time and vvice verca
administration of Rocuronio
not potent
2 dosis
ED95 = o.3mg/kg
acts fast, eliminated fast
steroid, need liver and kidney
CI hepatopand renal
administration of Doxacuruin
lower dosis ED95 = o.o25mg/kg
NDNMRs of intermediate action
vecuronio 35-45min - metabolized in liver, common here
Atracuruin - 40-50min (40)
Rocuronio - 30-40min - (30-35)50% metaobolized by now, if continuing qx have to continue, common here, metabolized by liver - 2hr to elimate completely
Cisatracuruin - 40-50min (60) $$
after in qx youll give amount thats been eliminated (half? just to maintiin abdominl paralysis?) -
NDNMRs of long duration - not really used anymore - hemodynamic problems
Doxacuruin - 85-125min
D-tubocararina - 60-100min
Pipecuronio - 80-120min
Pancuronio - 60-80min
regarding initiation time/induction to completely block , NMRs are classified into 3 groups - allow you to know when to intubate
short intiation action - 1-2min - Succinicoline and rocuronio (90sec)
intermediate - 2-5min - Atracuriun, Vecuronio, Nivacurium
Long - 4-6min - Cisatracuruin and Doxacuruin
only clinical situation that needs a brief initiation time of NMRs is in px with
full stomach
in other cases its a secondary factor and can use any NMR
NMR with shortest initaiton action time and why does that matter
sucinilcoline
useful in px with risk for broncoaspiration
duration time for succinicoline (short)
5-10min
duration time for mivacuruin (short)
15-20min
entubation dosis for atracuruin
0.5mgxkg-0.6 with duration of 50min
redosis after 30min is 0.1-0.2mg/kg with clinical duration from 20-35min
these give DE95!
dosis for continuous perfusion is 0.2-0.7mg/kg
easily antagonized by anticoineterasics
atracuruin
side effects of atracuruin?
due to histamine liberation can cause skin rash (can be buffered with previous beta blocker)
broncospasm
only seen in high dosis
slow application decreases this liberation
CV can produce arterial hypotension , takicardia
like others can be reverted with anticolinesteases??
history of atrcuriun
introduced in clinics in 1981
intermediate duration
attractive due to original elimination
which doesn’t produce active metabolites
now comes in 35mg/2ml?
FC of atracuriun
immiatley after administration plasma levels fall rapidly in a process of multiple metabolization but with one specially through Hoffman, depends on temp of body during qx and control gasometry, physioologicla ph produce 2 metabolites
action duration = 40min - prolonged if temp or desquilibrium
decomposed with heat needs refridge
metabolites of atracuriun
mono acrylate cuateranrio
laudanosine
is laudanocine relaxer?
no
high dose can produce CV depression and excitation of CNS postanesthetic
mono acrylate cuaternario
no farmacological activity - no accumulative effect so give as many redosis as you want
plasma clearance of atracuriun
5ml/k/min
farmacodinamia of atracuriun
less potency than cisatracuruin and vecuronio - 60min?
more than rocuronio - 10min more
vecuronio history
ultilized in clinic first time in 1984
FC of vecuronio
presents rapid liver capitation in 80%
excretion of vecuronio
biliar
metabolites- accumulative efffect
es el 3desacetilvecuronio
presents pharmacological activity
FD of vecuronio
potent relaxer
entubation dose of vecuronio
0.1mg/kg
initiation action of vecuronio
2-5min
duration of vecuronio
35-45min
re dosis of vecuronio and duration
0.025mgxkg (1/5)
15-20min duration
how to reverse vecuronio block and atracuruin
neostigmine
secondary effects of vecuronio
good for CV
doesn’t liberate histamine, secure
nobroncoscpasm
CI in renal hepatopathy px
indication of vecuronio
in px with CV pathologies
subit to cardiac surgery
CI of vecuronio
hepatic cirrosis and renal problems
history of cisatracuruin
introduced in 1996
most recent
cx of cisatracuruin
potent relaxer with grand security margin safe CV and metabolic
doesnt liberate histamine
ideal for px with unstable hemodynamic risk and px with hepatorenal iinsuff
only NMR that doesn’t liberate histaomine
FC = similar to atracuruin
cistracuruin
cistracuruin elimination
Hoffman - 100% biodegradation - depnds on pH and T
FD of cistracuruin
potency is 4x atracuruin
intubation dose for cistracuruin
0.1mgxkg
can be sued in continuous infusion at 0.09mgxkg in adult - redosis also
(3x DE95)
0,09
also autodestrcuts like atracuruin
initiatin action of cistracuruin
5min-6min - a bit too long, ventilate all this time
clinical duration of cistracurion
45min - prolonged
revert cistracuirin block with
neotigmina
side effects of cistacuruin
none
no histamine
no litic vagus effect
dose for kids - cistacuruin
0.02mgxkg
common cx of non opiodes anesthetic
LOC
analgesia
amnesia
first line agents in anesthetics
why use non opiod anesthetic via EV
to facilitate induction of general inhaled anesthesia
history of barbiturics
beginning of this siglo
first that produced LOC = hexobarbital - problem is that it produced too much involuntary muscular movement
thiopental was first used as anesthesia in 1930 by Walter
since then has been used EV - standard to compare other EV anesthetics - doesn’t make it the ideal
how to measure depth of coma
BIS - electric apparatus
continues EEG
depening on waves
ideal is between 40-60%
put electrodes in forehead
> 60 - awake - active
40 - sleep
used in long qx
if not use glasgow
propofol
EV sedative hypnotic non barbituric of short duration
most used these days
slow induction close to physiological sleep (inhaled can excite you before and px gets anxious and barbs)
NOT barb
mechanism unknown but we think its GABAergic - potentializes GABA, blocking excitary
FC of propofol
EV administration with fast distribution to all tissues
LOC of consciousness iafter 40sec (depends on dosis and velocity of administration) so do side effeects
intiation of action can be affected by pre-medication, dose, velocity of administration and medical condition
crosses placental barrier, -
BBB
high liposolubility so used up by most irrigated tissues - rapid sleep
joins plasma proteins 95-99%
duration of action of bolus of 2-2.5mg/kg of propofol
3-5min
odonotological px use, parto
NO - because has analgesic properties - concentrations! others don’t (just amnesia and LOC, muscle relaxer)
can accumulate in fetal blood @ C-section what do we do? do it while shes awake so right when shes out 2-3m to clamp umbilical cord
metabolism of propofol
rapid liver metabolism
20-25cc/k/min - MR
we think it clears in other places but dont know where yet
extrahepatic (clearing > liver blood flow)
18-20cc/k/min = normal flow
not necessary to adjust dose if px has renal or liver insuff
elimination of propofol, half life
urine
half life - 3-12hr (accumulates in fat tissue)
tkaes up to 10hr, can accumulate
15-20min up already
recuperation of propofol
rapid
escasa psychomotor affectation
thats why we dont modify dose in px with liver/renal problems,
inustable, VD px ADJUST DOSE, decrease peripheral vasc resistence, hemodynamic alteration
indications of propofol
general anesthesia
induction at inhalatory agent and
maintenance - sedation in critical px
superficial sedation for dx procedures or tx
presentation of propofol
ampollas of 20ml
vials of 50 and 100ml
1ml = 10mg/ml
posology , administration, anesthetic induction of propofol
adults < 55yr or /and ASA I-II - 2-2.5mg EV
oldies and weak, ASA III or IV
1-1.5mg EV ,
continuous infusion
adults < 55yr or ASA I-II (6-12mg/kg/h)
old wk, ASA III or IV (3-6mg/kg/h)
superficial sedation for dx and tx procudures
dose depends on clinic of px
avoid rapid bolus and high dosis in oldies, weak and those with CV disease
CI and precautions with propofol
CI in px with hypersensibility to propofol or any of its components
careful with cardiopathy px - higher sideeffects hemodynamic
cerebral vascular disease px or endocraneal HTN can cause decrease in CPP due to hemodynamic effects
oldies and weak might need dose adjustments - avoid bolus in them
ICHTN (even tho it decreases CPP)
REMEMBER it has no analgesic effect - use other drugs
in ppl with soy milk allergies
allergic px
asma px
overdose??
needs to be reridgerated
rich medium for bacteria
is propofol an analgesic
no
side effects of propofol
cardiopulmonary effects 1-3%: resp depression, important bradycardia, transitory apnea (use opiod or benzo before worse??) - give postive pressure oxygen hypotension 3-9% depending on dose, velocity of administration and medical state
less: arrhythmias, bigeminism, taki, ECG alterations, involuntary muscle movements,
rare: perioperatory and opistotone myoclonus, urine coloration
takicardia > bradikardia
@ recuperation: nausea and vomit
anafilactic reaction - erythematous rash superiorl thorax and above
(others are much more generalized)
severe broncospasm
NO AMNESIA
NO ANALGESIA
(anesthesia only)
vomit
local pain at infusion zone - very irritative use thick veins - can cause necrosis of tissue if leakes out (so mix it with some lidocaine)
most inhaled use
sevo, iso, des
balanced anesthesia
inhaled + EV (opiod)
depress easily - resp - lower dose, mix
neuroleptoanalgesic
opiod + neuroleptic
propofol interactions
depressor effects on CNS potentate when used with other drugs with this property
in induction can reduce the dose if px premedicated with opiaceos or sedatives
intoxication , overdose
potentiates inhaled anesthetic
why smoking affects potency of inhaled agents, asmas, chronic broncitis
thickened alvelo makes transport more difficult into arterial blood
history of opiods
have been used for 100s of years
to alleviate anxiety and reduce pain in qx
a lot not only used to supplement EV anaglesics but also as principal alone EV analgestics
morphine was isolated from opio thanks to Serturne in 1803
through needle in 1853 by Wood
allowed administration of IM morphine as a premedication
was to compliment anesthesia with Eter or cloform and obtain analgesia in post qx
at the end of siglo administrated large quantities of morphin in factioned EV dosies and IM as a complete anesthetic alone- but due to high morality rate durin 30-40yrs stopped being used during qxas anethetic and ever since co-used with analgesics in immeidate post-qx
introdcuion of barbiduritcs super short ccting as EV anesthetic and popularization of concept of balanced anesthesia revidved enthusaim for their use
classification of opiods
natural
semisynthetic
synthetic
natural opiods
morphine (madre de naturaleza)
codein (antitusino)
papaverine (VD)
tebaine (derivatives for chronic pain and to immoblize wild animals)
obtained from plant = papversomniferum
semisynthetic opiods
heroin - derived from morphine
etorphine derived from tebain - the one used to immobilize animals
synthetic opiods
morfinano - levofanol
difenilpropilamina - metadona
benzomorphine = pentazocine(sosegon)
fenilpiperidina = 4? fentanyl - sulfentalnyl. Nabulfina (nubain) meperidina (demerol) tramarol
derivatives of tebaina that are used in clinical practice to give analgesic
oxymorphine and oxicodone
anesthetic coma appropriate for qx
glasglow 7-10
reversible
when MURR rec are stimulated located at ventricular level and in greay matter will produce vs periacuedcutal vs limbic
supraspinal analgesia and resp depression
periacuedcutal produce spinal analgesia
limbic –> abolition of affective response like fear
best inhaled hat relaxes
sevo
stimulation of KAPPA rec produces
sedation, miosis, physical dependence
where are Kappa rec
gel substance , mesencefalo, brainstem
@ stimulaltion of cigma ref
psycomimetic effect
hallucinateion, disforia, takicardia, midriasis
px pueden durar…..
VN
hemato, endocrine, metabolic
etformin is
derived from tebaine
1000x potent that morphine
used to immunize wild animals
history of opiod rec
1973
murr, kappa, cigma, delta
affinity for opiod rec varies with
pH T dose cronicidad de su uso? ,via opiod affinity
MURR rec localized where
periaqueductal, - spinal analgesia
grey matter,
thalamic nuclei,
reticular substance,
limbic structures (..?respuesta afectiva@ px first time taking these)
grey and reticular central , supraspinal analgesia
location of cigma rec
lamina VI of cortex
solitary nucleo tract
spinal cord gel substsance
trigeminal nucleus
stimulation of delta rec
produces changes in affective behavior
physical dependence
person changes
localization of delta rec
lamina II, III, IV of cerebral cortex
acustic nucleo, nucleo olfative tuberculo, pontine nucleo
depending on action opiods are classified in
pure agonist - when there is direct action on MURR and KAPPA
pure opiod agnoists
these are for central or peripheral analgesia!
morphine heroin codein methadone fentanyl tramadol - useful to tx atypical pain
morphine
prototype
most used for tx
heals intense pain acute and chronic
heroine
powerful analgesic
not allowed due to adduction
codeine
potency and analgesic efficacy are less than morphine
metadone
tx of px with addictions
fentanyl
100x more active than morphine, but of fugacism effects
ellecion drug for moder anesthetic tecnniques with opiods in CV qqx and UVI
fentanyl
farmaco de primera linea en anesthesia for (long agrgressive) post qx analgesia
opiods
morphine at CV
at 1mg/kg EV no significant changes regardless of cardiopathy
in px with aortic valvulopathy can have decreased systolic volume and CO probably due to dearease in systemic vascular resistence
@ 5-10mcg/kg can decrease BP through bradikardia , vagal origin, venous VD , shunting of blood in spleen
in some px 1mg/kg liberate plama histamine cause cardiac changes, reduce BP, systemic vasc resistence
px previously tx with H1 H2 blocker, cv response attenuated
decreases venous return to herath, venous dilation - dose dependent
equipotency dosis
comparing all opiods to morphine to see potency
morphine 10mg = 0.02 levofanol, 30mg metadona. 30mg fentasucina, 10mg fentanyl, 0.2 sufentalnyl, aspirin = 600mg , AINES = 7mg
agonist-antagonist opiods
agonist accion on KAPPA
antagonist on MURR
these can block resp depression affects while maintaining analgestia
nalbuphine
pentazocina
bupenorfine - 25-30x more potent than morphine
analgesia lasts
pure antagnost
acts on MURR< KAPPA< CIGMA rec
revert desired and undesired affects
naloxone (narcan) more potent than naloxone - simila eficacyis 2altrexone ltrexone , morfinic derived
rec of analgesia
mu and kappa
today 2 opiods VO wich pH of stomach favors absorption
codein and morphine
endogenous opiods
metilencefaline
leuencefaline
B-endorphin
Di-morfine
modulate pain perception - to sorportar wound
high in plasma 24-48hr after trauma , in labor (less analgesia needed post qx trauama)
fentalnyl CV effect
much more hemodynamically accepted
unstable angina, IAM, low ejection fraction in qx use fentanyl
doesnt modify cardiac variables
besides meperidine all opdioss produce
decrease in HR (dose dependent)
meperidine INCREASES HR
half life of morphine (rapid distribution vs slow)
FC
rapid = 0.9 -2-4min to highly irrigated tissues
halflife slow - 10-20min to less irrigated tissues
plamsa clearing of morphine
10-20mI/kg/min only 10% administrated excreted in urine
morphine elimination halflife
2-4hr
via urine
fentalnyl distribution times
halflife rapid 1-3min
slow - 5-20min less irrigated
plasma clearance of fental
4ml/kg/min
clearance depends on liver metabolism
< 10% of dose is exreted unaltered thru urine
elimination halflife time = 21/2 an d 3.5hr
opiord resp efects
all that simulate MURR produce resp depression
depending on dose mostly due to direct action on resp center at brainstem
reduce sensibility of resp center to CO2 and increase APNEA threshold
opiaceos reduce hipxic stimulus and break resp stimulus that can be associated with increase in aiway resistsence causing torax lenoso
increases resp pause, delays respiration and produces irregular respiration with slow resp frequenve and reduced volume
after administration as analgesic there is intense depretsion of costal parrilala and relative stability of abdominal diaphragmatic movements
physiological factors that influence farmacology of opiods - these ppl are more sensitive to them
age - oldies more sensible
hepatopathy px (metabolism), prlong half life of elimination an dclearance
nefropathy
desequilibruim acid base
indications for oiods
pain
anesthesics in px with poor absorpcion
acute pulmonary edema
suppress cough
diarrhea- not used anymore
digestive hemorrages
t of px with adicciones (especially metadona)
CI for opiods
px with brain lesions pregnancy px with altered pulm function px with altered renal function px with alreaed liver function px with endocrinal disease others
elevated doses if oiods cause
total block of spontaneous respiration - can resond to verbal command and breath when order to
resp depression of morphine vs fentanyl
slower in morhpne but lasts longer
px more susceptible to opiods
oldies
GI effects of opisd
analgesic dose are very emetic due to stimulation of quimorec zone de disparo which is found in posttrema area of medual
also relaed to emesia in increase of trasto GI or decrease of GI activity and prolongation of emptying time
used in induction
opiods and benzos
lower concentration for maintenance
only EV anesthetic whose analgesic factor > anesthitc factorq
ketamine
why in administering inhaled anesthetics should i increase breathing rate
to get more gas exchange from alveolo to arterial blood - saturation
and to CO2 - barrida - ventilatory stimulator and inhibit resp center so you can control breathing
you can lower VP once they are sleep as well
hightest CAM - least potnet
104
NO
give enough time and in large quantities
what are the conditions necessary for halothane to produce hepatotoxicity
liver previoiusly detorated (hepatopathy, viral hepatitis)
less hepaticc blood flow (higado graso in obese)
predisposition - genetic
px exposed for long time to halothane
hard to tell if it was hepaittis (fever) or halothane produced (no fever)
methoxyflurane … off market why
caused nefrotoxicity without predisposing factors
also cloroform and ether as well were very nephrotoxic
no clincal evidence of toxicity…
isoflurane
sevorane
desflurane
inhaled anesthetic with best NM relaxing properties
sevorane
factors that can cause px to wake up later than normal after cessation of inhaled anesthetic
.can be delayed in oldies (slower metabolism, or if have previously used an opiod, hypothermia, acid-base desquilibrium, hypovolemia/acute anemia, hyperglicemia - if not should be awake by 10min after closing vaporizing
hemodynamic variables
BP, HR, CO MAP
best hemodynamic stability of inhaled anesthetic
sevorane
isoflurane
dont shunt blood away from organs
volatile
easily evaporate at normal temperature
all come in liquid form except NO
vapor pressure
the pressure of a vapour in contact with its liquid or solid form.
pressure gas exerts over liquid surcae in closed system
ebullition pooint
T in vapor pressure = 1atm
most noble gas
desflurane because it hardly metabolizes
meds in pain management clinic - terminal diseases, CA, dont respond to other analgsics, palliative
oxymorphine and oxicodone (10,15,25, 50mg)
if rich - fentanyl patches
onyl rec that have to do with analgesia of individual
MURR and KAPPA
how to get spinal anethesia with opiod
@ subdural level
morphine intratecal
kappa rec
produce central analgesia, miosis, all produce physical dependence,
localication of kappa rec
gelatinaous substance
mesenfalo
tallo cerebral
effect of cigma rec
produce psychomimetic symptoms - hallucinations, tachycardia, midriasis, dysphoria
(seen , efects in overdose, excitation of opiod)
all opiods.., side effects
cause physical dependence
depress respirao=tory centers by making them insensible to the command of CO2 - blocks interaction/sensibility
slow regular respiration
can cause thoracic resistance, paralysingthorax movements (rigid, cant hyperextend)
paralysis of diaphragm
nause and vomitting - reduce gastric empting, increase gastric content, stimulate zone of liparo?? - vomitting, increaseing zone sensbility,
reduce gastrointestinal transit
morphine CV effects
morphine 1mg/kg - no hemodynamic ateration even with CV problem
any effects are due to histamine liberation (massive) –> VD, less CO
in px with aortic valve problems
less volumen systolico and CO
> 1mg,kg (5-10mg/kg) - morphine itself will cause alterations
decrease BP
, vagal bradycardia,
shut bllood from splenic organs (liver, spleen)
venous VD
can use H1 H2 blocker to buffer
unstable angina, IAM, low ejection fraction in qx why not use propofol with this px
VD will kill him
anesthetic dose vs analgesic dose of fentanyl
at analgesic dose of 2-10mg/kg, - mostly used for analgsic purposes in qx
or anesthetic dose of 10-100mg/kg rarelu decreases BP even in px with poor LV function - but if have mad heart problems can use fentanyl as primary inducer
how does fentanyl come
liquid bllus
100mg/2mL
500mg
how to buffer bradicardia caused by all opiods
premedication with atropine or flicopirrolate minimizes this
who commands our ventilation
CO2 stimulates resp centers
appeal of atracuriuns elimination
biodegrades, autodilutes thru, doesnt need liver or kidney
80% Hoffman hydrolysis
hepatobiliar hydrolysis 20%
what does atracuruins elimination depend on
depends on body temperature during qx and gasometry
ej at disequilibrium or hypothermia effect is prolonged
why atracuruin needs refridgeration
decomposes with heat
px betablocked, bradicardia dont use
halothane lowers HR even more - worst fr heart - central bradi
decrease vasc resistence periferical = VD
secuersro sanguineo de organos splenicos
reduces sytoliv volume and CO
decreases MAP (worse if dehydrated or with hypovolemic shock)
can cause arrythmia - liberates massive K+
oONLY WITH ISOPROTENEROL
need anticholinergic like atropine as long as no isquemia or infart hx
GI side effects of halothane
nausea
less MAP causes direct reflux?
how to measure state of NM relaxation
toff meawsures evocated potentials, neursitimulator on peripheral nerve and depending on electirical response we see how relazed they aree
3 de 4?
how NM work
block depolarization and propagation of electrical impulse @ all nerve cells
block liberation of Na+ channels
advantages of succinilcoline
initiation action time is fast
can intubate by 60sec
4 colinesterasas enzymes
pseudocolinesterasa plasmatica - eliminaeted in plasma
when can colinesterase enzymes be low/action duration is longer
in hepatopathy px, elders, denutruitin, taking anticolesterase medications, polymorfogenetics
metabolism of succinilcoline
by colinesterase enzymes
how do NDNMRs work
these no longer work like Ach - instead work the oppsoite
acti in cholinergic rec of muscular membrane
ion channel
liberation of Ach (by stimulus mechanical or nervous) in hendidura sinaptica where acetilcolinesterase enzymes are located, unites to rec colinergic
when occupied , ion channel opens and there is ion exchange NORMALLY
NDNMRs are competitive and compete for this chol rec - ion channel doesnt open and membrane stays despolarizada
most resitant muscles of the body
those of oropharynx as well as the diaphragm
to paralyse them and well oro aperture you need to multiply x 3 dose (from abdominal muscle)
side effects increase along with this
after intubation and only want abdominal relaxaation just give original DE95 dose
first muscle to recuperate
diagphragm @ 20% reec, visceras pushed out
how many half lives
remember there are 4 half lives for any drug to be eliminated - 1st 50%, 2nd 75%, 3rd 87%, 4th 100% - we alsohav edrugs that can revert the rest of this time
NMRS he uses
vercuroniu, cistracuruin, rovuronio, atracurin
inducers of sleep ideal cx
EV anesthetics
organic compounds
also can contiain other elements like oxygen, azufre, nitrogen, methy groups
produce LOC, hipnosis - ALL - #1 reason #2 reason - can be used completely alone now, doesnt need to precede and inhaled, short qx, dx procedures, qx 15-20min, studies, ambulatory procedures, gastro, adontological
most have analgesic properties
some have more anesgelsia than anesthesia (sleep)
most cause amnesia
also are anticonvulsives
barbituric thiopental used to be most used but not anymore
metabolite of rocuronio (desmeron)
17 acteil rocuronio
advantages of rocuronio
…glucosa? not accumulative
doesnt liberate histamine,
stable - lung, cardiac
not used much due to effects at liver and kidney
4 anticolinesterases
ambenonium
neostigmina
Physostigmine
Pyridostigmine
block sction of enzyme acetilcholinesterase and so permits that more Ach reaches union plauqe
potentializes electric impulse
muescarinic effects - bradicardia and salivation
use in px with prolonged block
accelerates autodestruction
check BIS awake but paralysed, myalgia, HTN,
depends on grade of rec occupied (toff 34 - 3 de 4 electrical movemnnt)
if cant measure that measure diaragmatic movement
have to have at least 20% of rec free, not occupied
how do you know? when with electrical impulse you have 1 sole movement (25% occ)
2 movements - 50%
3 - 75%
4 movement - 100% occ ( if you give in this momentmolecules goes into ION CHANNEL - channel block, permanent tkaes 10hr to be able to intubate so need 20% free)
to block diagrphamm last one to be blocked needs 80% at least occupied @ 20% open yyou hav e diaphragmatic movment
how to revert muscarinic effects of bradicardia and salivation
with anticolinergics like atropine glicopirulato, metoclopramide
sugammaden - why beter than neostigmine
also reverts affects of NMRs
can use even at 100% rec occupied
DOESNT PRESENT muscarinic effects
hyperpolarized molecule that surrounds molecule of relxer and displaces it, doesnt give it chanve to cause channel block
neostigmine dose to use
2.5mg - unica dose can revert 80% of NMR effect
sugammaden doses
dose depends on grade of block that is present in the moment
100% block - dose - 4-6mg/kg
50% - 2mg/kg
GB miasthenia gravis px which NMR?
much less dose
and prefer non depolarizing
revertible
