PCOL MIDTERMS TOPIC: GENERAL ANESTHETICS

3RD YEAR 2ND SEMESTER

TOPIC: General Anesthetics Use Specific Drugs for Each Component
• Reversible loss of consciousness and insensibility • Sensory: N20, opioids, ketamine for analgesia.
to painful stimuli. • Cognitive: Produce amnesia, and preferably
• Act on the brain, medulla, and spinal cord. unconsciousness, with N2O, .25-.5 MAC of an
• Major surgery, sedate na ung px. inhaled agent, or an IV hypnotic (propofol,
midazolam, diazepam, thiopental).
Adjuncts (dinadagdag): • Motor: Muscle relaxants as needed.
1. Muscle relaxants - to facilitate intubation &
ventilation. Balanced Anesthesia
2. Anticholinergics - to decrease body secretions. 1. Monitored Anesthesia Care (MAC)
3. Benzodiazepines & ultra-short-acting • Aka Conscious Sedation or Twilight
barbiturates - for induction of anesthesia. Sleep
4. Opioids - post-operative pain. • For minor superficial surgery or for
invasive diagnostic procedure.
5 Primary Effects • Sedative + Local Anesthetic
• Unconsciousness • Gising pero parang wala pa sa wisyo
• Analgesia
• Skeletal muscle relaxation Medications used during MAC include +
• Amnesia LA:
• Inhibition of autonomic reflexes ➢ Midazolam (Versed)
➢ Fentanyl
➢ Propofol (Diprivan)
Ideal Properties of General Anesthetic Drug
1. Induce rapid, smooth loss of consciousness.
2. For Extensive Procedures
• Rapid and pleasant anesthetic
• Preoperative drug: BZD
induction and recovery.
2. Be rapidly reversible upon discontinuation. • Induction: IV agent (Thiopental or
Propofol)
• Induce anesthesia smoothly and rapidly
• Maintenance: Combination of inhaled
while allowing for prompt recovery
(nitrous oxide, vol liquids) or IV drugs
after its administration is
(propofol, opioid).
discontinued.
• Once inistop ung pag gamit nung drug
wala na agad effect. Depth of Anesthesia – aka Guedel Signs
3. Possess a wide margin of safety (aka • Stage 1 – Analgesia Stage (CORTICAL STAGE)
therapeutic index) • Stage 2 – Excitement
• When we say “Narrow Therapeutic • Stage 3 - Surgical anesthesia
Index” it means ung space between MEC • Stage 4 – Medullary depression
& MTC is maliit so unting adjust lang ng
dose Toxic agad, so dito ang gusto natin Stage I – Analgesia Stage
wide ung margin of safety para kahit • Cortical Stage
itaas ung dose hindi magiging toxic • Analgesia without amnesia.
4. Rapid changes in anesthetic depth. • Later in stage I, both analgesia and amnesia are
5. Adequate relaxation of skeletal muscles. produced.
6. Absence of toxic effects or other adverse
properties in normal doses. Stage II – Delirious & Excited
• Delirious/Delirium
Balance Anesthesia • Have amnesia
• Combination of IV and inhaled drugs. • Respiration is rapid, and heart rate and blood
• Neuroleptics and Opioids. pressure increase.
▪ Augments (pinapaganda ung effect) the • Retching (movement of vomiting/parang
action of GA. nasusuka pero wala) and vomiting may occur.
• Skeletal muscle relaxants.
• Anticholinergics.
Stage III - Surgical Anesthesia
• Slowing of respiration and heart rate and
extends to complete cessation of spontaneous
respiration (apnea).
• Kapag nag normal ung breathing & hindi na
nagalaw ung eyes it means we achieved this
stage. Eto ung stage na dapat lang ma-achieve.
• 2 most reliable indication:
1. Loss of Eyelash reflex
2. Establishment of Regular Respiratory
Pattern

Stage IV – Medullary Depression

• Severe depression of the CNS (Without
circulatory and respiratory support, death would
rapidly ensue).

Stage III (Surgical Anesthesia)

Divided into 4 planes:
• Plane 1: Roving eye balls. This plane ends when Current Levels of Anesthesia
eyes become fixed. 1. Induction
• Plane 2: Loss of corneal and laryngeal • This level encompasses the
reflexes. administration of preoperative
• Plane 3: Pupil starts dilating and light reflex is medications, adjunctive drugs to
lost. anesthesia, and the anesthetics required
• Plane 4: Intercostal paralysis, shallow for surgery.
abdominal respiration, dilated pupil. 2. Maintenance
• This level begins when the patient has
Stage IV (Medullary Depression) achieved a depth of anesthesia
sufficient to allow the surgery to
• This stage of anesthesia includes severe
begin and ends upon the completion of
depression of the vasomotor center in the
the surgical procedure.
medulla as well as the respiratory center.
3. Recovery
• Without full circulatory and respiratory support,
• The recovery phase begins with the
death rapidly ensues.
termination of the surgical procedure
• Stop brain, lungs & heart.
and continues throughout the
postoperative recovery period until the
Signs of Stage 4:
patient is fully responsive to his or her
• Cessation of breathing to failure of circulation
environment.
and death.
• Pupil is widely dilated
Types/Routes of Administration of General
• Muscles are totally flabby
Anesthetics
• Pulse is thready or imperceptible
1. Inhalational
• BP is very low.
2. Intravenous
3. Rectal (rare)

• We use neuromuscular blocker para marelax

and mabilis mailagay ung tubo or
maintubate.
Inhalational Anesthetics So dito ung blood natin low solubility therefore mas
• Gas mabilis ung effect. Since mababa lang ung solubility sa
▪ Nitrous oxide, Xenon blood kaya tatagos lang. Yung airway tapos alveoli so
▪ High vapor pressures & low boiling ngayon pag di natunaw sa dugo dadaan lang siya sa blood
points. and tatagos na sa brain kaya tulog aga dung px, kaya fast
• Volatile liquids onset of action, and also quick removal kasi after sa
▪ Halothane, enflurane, isoflurane, brain babalik ulit sa dugo and babalik ulit sa lungs/alveoli
desflurane, sevoflurane, and then airway mabilis ung effect. Remember magkakaiba
methoxyflurane ung effect ng gamot depending on dosage form.
▪ Low vapor pressures & high boiling
points Kapag ang gamot ay gas we have to consider the blood gas
partition kung saan kapag hindi soluble sa blood
Pharmacokinetics therefore mabilis ang effect and removal.
• Depth of anesthesia is dependent upon the
concentration of anesthetic in the central
nervous system.
• Gaano kadami ung binigay na dose sa px.

Induction
Factors To Consider:
1. Blood: Gas Partition Coefficient
Blood: Gas Partition Coefficient
2. Inspired Air Concentrations
• In terms of the extent of hepatic metabolism,
3. Breathing Rate
the rank order for the inhaled anesthetics:

Blood: Gas Partition Coefficient Halothane (pinakamabilis) > Enflurane >

• Useful index of solubility. Sevoflurane > Isoflurane > Desflurane > Nitrous
• Relative affinity of an anesthetic for the blood Oxide (pinakamabagal)
compared with that of inspired gas.
• Ilang % or parts ng gas ung nassoluble sa blood, Oil: Gas Partition Coefficient
dito masasabi if soluble ba ung drugs sa blood.
This is also an important determinant kung
High Oil: Gas Coefficient
gaano kabilis ung induction & recovery ng drug.
• Cause quick redistribution into adipose tissue.
• Redistribution into fat causes the recovery of
Blood Gas Partition Explanation:
consciousness.
Iba ung gamot pag inhaled and oral, pero diba
• Kapag ung drug soluble sa fat ibig
commonly sa drugs kapag mataas ung solubility mas
sabihin napupunta sa fat and if nasa fat
mabilis ma-absorb kasi nasa blood kaagad, fast solubility
ung drug mawawalan ng effect therefore
fast absorption therefore fast effect.
if walang effect babalik ung
consciousness.
Pero iba kapag GAS ung gamot, dapat hindi masyadong
natutunaw sa blood dahil na-aabsorb sila sa lungs and • Higher the coefficient the more potent the
hindi sa blood kasi sa air sila. agent.

Explanation:
Low Blood: Gas Partition Coefficient - mabilis
High gas so high solubility sa blood kaya ung partition ng
umeffect
blood malaki, dahil if soluble sa dugo so lahat ng blood
1. Low solubility in blood.
pupuntahan niya so lilibot pa siya sa buong body before
• Reaches high arterial tensions rapidly,
pumunta sa brain kaya matagal ung effect pero if low
which in turn results in rapid
solubility tumatagos lang sa dugo kaya mabilis effect.
equilibration with the brain.
2. Fast onset of action
Considerations: WEIGHT and FAT RATIO of a patient.
• Ex. Nitrous oxide
3. Necessary for quick removal of anesthetic
PHARMACOKINETICS
• Anesthetic potency is currently described by the
Low Solubility/Fast Onset/Removal Explanation:
MAC.
 • The alveolar concentration of an inhaled
anesthetic that prevents movement in MECHANISM OF ACTION
50% of patients in response to a • They increase the sensitivity of GABAA receptors.
standardized stimulus. This causes a prolongation of the inhibitory
chloride ion current after a pulse of GABA
(inhibitory) release. Postsynaptic neuronal
excitability is thus diminished. (pinapadami ung
GABA w/c is an inhibitory, therefore nawawalan
ng malay)
• They block the excitatory postsynaptic current
of the nicotinic receptors.

Historical Inhaled Anesthetics

• Ether: Slow onset, recovery, explosive.
• Chloroform: Slow onset, very toxic.
• Cyclopropane: Fast onset, but very explosive.

Inhalational Anesthetics

PHARMACODYNAMICS Nitrous oxide

▪ Gas at RT, liquid under pressure in metal
cylinders.
MOA OF GENERAL ANESTHETICS
▪ This is the least toxic anesthetic.
• Impaired excitatory transmission
▪ Also, the least potent.
➢ Kasi neurotransmitter excitatory effect
▪ Rapid onset of action, and recovery from its
sa brain is consciousness pero dito
effects.
impaired excitatory kaya loss of
▪ Intermittent dosing for analgesia during dental
consciousness.
procedures and the first stage of labor.
• Ach, AMPA (amino-3-hydroxy-5-methyl-
▪ Second Gas Effect
4-isoxazol-propionic acid), NMDA (N-
− causes an increase in the
methyl-D-aspartate)
concentration of the other gases.
• Potentiated inhibitory effects
− kaya si nitrous oxide ginagamit as
➢ Pinapababa ung excitatory and
combination ng ibang gamot kasi pag
pinapataas ung inhibitory effects, which
ginamit mo si nitrous oxide
is pampakalma & pampatulog.
magkakaruon ng second gas effect where
• Chloride channels (GABA and Glycine
it will increase the conc of the other
receptors)
drug.
• Potassium channels
Second Gas Effect
• Reduce the risk of myocardial depression at a
given depth of anesthesia compared to the more
potent anesthetic given alone.
• Reduce the anesthetic requirement for the more
potent anesthetic.

Nitrous Oxide Disadvantages:

• Weak agent, no muscle relaxant activity
• Danger: HYPOXIA (low oxygen in tissues) (if used
alone in large amounts)
• Bone Marrow Depression (lead to megaloblastic
anemia)
MOA Explanation:
Ginagawa ng General Anesthetic iniinhibit nila ung mga Xenon
excitatory neurotransmitter like NMDA kasi ung effect ng • An inert gas.
mga to is gising or consciousness therefore pag ininhibit • Nonflammable and nonexplosive.
mabblock ung effect and result is loss of consciousness. • A potent analgesic.
Halothane Desflurane
▪ Halogen substituted ethane. • Very fast onset and offset.
▪ Fast induction of anesthesia and recovery. • Very pungent – breath holding, coughing, and
▪ Potent anesthetic and relatively weak analgesic. laryngeal spasm.
▪ Converted to Trifluoroethanol • Not recommended for induction of anesthesia in
children.
Adverse Drug Reactions:
• Hepatic Necrosis Sevoflurane
➢ There is no specific treatment for • Rapid induction
halothane hepatitis, & liver • Low pungency
transplantation may ultimately be • Breakdown by CO2 absorbents generates heat
required. and has resulted in sporadic operating room
➢ Halothane is toxic sa liver kaya pag fires.
merong hepatitis ung px tapos ginamitan • umiinit ung drug
mo ng halothane sobra-sobrang damage
na sa liver.
Intravenous Anesthetics
• Malignant Hyperthermia – medication drug
• Thiopental
Dantrolene
• Propofol
• Etomidate Ketamine
Enflurane
• Opioids
• Rapid, smooth induction.
• Pungent odor
Intravenous Anesthetic
• causes electroencephalographic (EEG) patterns
• Several drugs are used intravenously, alone or in
consistent with electrical seizure activity
combination with other drugs, to achieve an
▪ Contraindication: seizure disorders
anesthetic state (as components of balanced
anesthesia) or to sedate patients in intensive
Isoflurane care units who must be mechanically ventilated.
• Rapid, smooth induction. • Kailangan siya for balanced anesthesia, para
• Pungent odor tulog ung patient and mamemaintain. Normally
• Structural isomer of enflurane. ang ginagamit pag iinduced para ma-unconscious
• There have been no reports of seizures. is inhalation and once tulog na saka lalagyan ng
• Bronchoirritating, laryngospasm. IV to maintain unconsciousness.
• Coronary steal syndrome
Intravenous Anesthetic
Disadvantages: 1. Barbiturates (Thiopental, Methohexital)
• May cause “steal” phenomenon 2. Benzodiazepines (Midazolam, Diazepam)
• Coronary “steal” phenomenon - diversion of 3. Opioid Analgesics (Morphine, Fentanyl,
blood flow via alternate routes or reverse flow. Sufentanil, Alfentanil, Remifentanil)
− Kunwary ung dugo papunta sa puso, 4. Propofol
pero dahil nagtake ka ng isoflurane 5. Ketamine
babalik na yung blood wala ng pupunta 6. Miscellaneous Drugs (Droperidol, Etomidate,
sa puso, nag-rreverse ung blood flow. Dexmedetomidine)

Methoxyflurane Intravenous Anesthetic

• Diffuses into fatty tissue.
• Metabolism: Methoxyflurane will metabolize to 1. Ultra-Short Acting Barbiturates
Fluoride Oxalic Acid. (Thiopental, Thiamylal, Methohexital)
• Most potent of all inhalational anesthetics ▪ Use: Pre-anesthetic agent for induction
of anesthesia.
Disadvantage: • Onset of action: 10-20 seconds.
• Metabolize to a great extent to fluoride – Renal • Peak: 40 seconds.
Dysfunction (kidneys S/E) • Recovery: 30 minutes.
• Dose: 50mg test dose given with
moderate rapidity.
 • Toxicity: Respiratory and circulatory 3. Opioid Analgesics
depression. • Mainly used as adjuncts.

Thiopental
▪ Prototype.
▪ Highly lipid soluble
• MOA: Act at GABA receptors (inhibitory),
potentiate endogenous GABA activity at the
receptor, direct effect on Cl-channel at higher
concentrations.
• Rapid Onset, short-acting.
• Others: Thiamylal, Methohexital. Neuroleptic-Opioid Combinations
• Build-up in adipose tissue. • Neurolept analgesia
• Side Effects: ▪ Droperidol + Fentanyl (Innovar)
1. Hypotension (brand name)
2. Airway obstruction ▪ Walang pain na nararamdaman
3. Apnea
Neuruleptanalgesics
2. Benzodiazepines ➢ Refers to the combination of short-acting
(Diazepam, Lorazepam, Midazolam) synthetic opioid agent (fentanyl) &
• Primary Use: Pre-medication butyrophenone (doperidol)
(pandagdag sa IV anesthetics) ➢ Very drowsy, responds to voice comman,
• MOA: Potentiate action of GABA analgesia is profound.
• Cause anterograde amnesia (loss of the ➢ Combination produces peripheral vasodilation
ability to create new memories) where it decreases in arterial blood pressure.
• Toxicity: Antagonized by Flumazenil ➢ If administered rapidly, cause skeletal muscle
• Note: Midazolam is the only water- rigidity
soluble form.
• Neurolept anesthesia
▪ Droperidol + Fentanyl + 65% N2O in
O2
• May cause neuroleptic malignant
syndrome

Propofol
• Notable Effects:
• Emulsion
• Reduction in cerebral blood flow
• Respiratory depressant
• May increase arrhythmogenicity with
epinephrine but by itself does not cause
arrhythmias or MI
• Anti-emetic effect
• Rapid onset and short duration of action.
• A sedative–hypnotic used for the induction and
maintenance of anesthesia or sedation
• An alkyl phenol
• Originally formulated in egg lecithin emulsion
▪ Anaphylactoid reactions
▪ Current formulation: 1% propofol in
10% soybean oil, 2.25% glycerol, 1.2%
egg phosphatide.
• Side Effects:
1. Pain on injection.
2. Hypotension.
3. Apnea.
Fospropofol • Similar structure with Ketoconazole
• Prodrug • Rapid induction
• Approved for sedation during monitored • Formulated in 35% propylene glycol
anesthesia care • Serious Effect:
• Metabolized to Propofol by enzyme Alkaline ▪ Depression of Steroidgenesis
Phosphatase ▪ Kasi diba similar structure siya with
ketoconazole, eh ang ketoconazole
Ketamine meron siyang mga adrenal effects, so if
• Aka Dissociative Agent same structure sila ganun din effect ni
• MOA: Noncompetitive blockade of the membrane etomidate it can also depress the genesis
effects of the excitatory neurotransmitter of formation of steroid hormones.
glutamic acid at the NMDA (N-methyl D- • Side Effect:
aspartate) receptor. 1. Myoclonic activity.
• Produces “emergence” phenomena 2. Nausea and vomiting (50%).
• Psychomimetic – “emergence reactions” 3. Cortisol suppression (steroid
• Vivid dreaming, extracorporeal hormones)
(floating "out-of-body") experience, 4. Pain on injection.
misperceptions, misinterpretations,
illusions Dexmedetomidine
• May be associated with euphoria, • Alpha 2 adrenergic agonist
excitement, confusion, fear • Hypnosis is due to stimulation of a2 receptors in
• Structure similar to PCP (phencyclidine – illegal the locus coeruleus (site of the brain that
hallucinogenic drug) principal site for NE synthesis)
• Analgesic • Use for short-term sedation of intubated and
• Dissociative anesthesia ventilated patients in ICU.
▪ Cataleptic appearance, eyes open,
reflexes intact, purposeless but
coordinated movements.
▪ Cataleptic – condition characterized by
lack of response of external stimuli and
muscular rigidity
• Stimulates sympathetic nervous system.
• Norketamine - Active metabolite
• Sensation of dissociation in 15 seconds.
• Unconsciousness in 30 seconds.
• Duration of unconsciousness = 10-15 minutes.
• Duration of analgesia = 40 minutes.
• Duration of amnesia = 1-2 hours
• Used in low doses for outpatient anesthesia in
combination with propofol and in children
undergoing painful procedures (eg, dressing
changes for burns).

“Emergence” phenomena
- Associated with postoperative disorientation,
sensory and perceptual illusions, and vivid
dreams.

Miscellaneous
Etomidate
• Potent ultra-short-acting non-barbiturate
hypnotic without analgesic property.
• Dose of 0.3 mg/kg will induce sleep that lasts
for approximately 5 minutes.
• Mechanism of Action: GABA-mimetic action