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2022 Anesth s1t8 Intravenous Anesthesia and Opioids
2022 Anesth s1t8 Intravenous Anesthesia and Opioids
2022 Anesth s1t8 Intravenous Anesthesia and Opioids
OUTLINE PHARMACOKINETICS
I. INTRODUCTION IV. OPIOID AGONISTS Primarily metabolized by the liver and subsequently its inactive
II. INTRAVENOUS A. Morphine and water- soluble metabolites are excreted by the kidneys
ANESTHETICS B. Meperidine Clearance rate: 20-30mL/kg/min (approx.1.5L/min)
A. Propofol C. Fentanyl
B. Etomidate D. Sufentanil
Initial distribution half- life: 1-8 min
C. Ketamine E. Alfentanil Secondary slow distribution half- life: 30-70 min
D. Dexmedetomidine F. Remifentanil Elimination half- life: 2-24 hrs
E. Benzodiazepines G. Codeine Infusion duration of up to 8hrs maintains a reliable context-
F. Barbiturates H. Hydromorphone
G. New Intravenous I. Oxymorphone sensitive half- life of 40 min or less.
Anesthetics J. Oxycodone
III. OPIOID AGONISTS AND K. Hydrocodone PHARMACODYNAMICS
ANTAGONISTS L. Methadone Primary mechanism: GABA- A receptor agonist
A. Introduction M. Tramadol
B. Terminologies N. Heroin (Diacetyl Alteration of the central cholinergic transmission by propofol may
C. Classification morphine) also play a role in achieving a state of unconsciousness.
D. Mechanism of Action V. OPIID AGONISTS- Initial low doses: sedation
E. Opioid Receptors ANTAGONISTS
F. Common Opioid Side A. Pentazocine
Increased doses: state of paradoxical excitation may occur
Effect B. Butarphanol o Disinhibition
C. Nalbuphine o Unpredictable movement
VI. OPIOID ANTAGONISTS o Broken speech
A. Naloxone
o Not readily arousable
B. Naltrexone
Further increase: loss of consciousness, apnea, relative
relaxation of muscles, necessitates airway support
I. INTRODUCTION
General Principles: SYSTEMIC EFFECTS
Intravenous anesthetics are now a key component of modern CNS
anesthesia practice. o Lower sedative doses may cause changes in EEG
pattern
Properties of the Ideal Intravenous Anesthetic o Induction dose:
Pharmacodynamic/ Pharmacokinetic Properties Initial stages of genera; anesthesia are
Hypnosis and amnesia reached
Rapid onset (time of one arm – brain circulation) β-wave activity decreases, with simultaneous
Rapid metabolism to inactive metabolites increase in α and δ activity
Minimal cardiovascular and respiratory depression Burst suppression: commonly employed as
No histamine release or hypersensitivity reactions neuroprotective measure prior to aneurysm
Non- toxic, nonmutagenic, noncarcinogenic clipping, attained at concentrations of 8ug/mL
No untoward neurologic effects, such as seizures, o Lower cerebral metabolic oxygen consumption rate
myoclonus, analgesia, neurtoxicity (CMRO2)
Other beneficial effects: analgesia, antiemetic, o Decreased intracranial pressure primarily by lowering
neuroprotection, cardioprotection cerebral blood flow
Pharmacokinetic- based models to guide accurate dosing o Cerebral perfusion pressure may also be lowered
Ability to continuously monitor delivery o Generally considered an anticonvulsant
Physiochemical Properties o Loss of consciousness
Water- soluble
Stable formulation, nonpyrogenic Cardiovascular
Non-irritating: painless on intravenous injection o Characteristic drop in systolic and diastolic blood
Small volume needed for induction pressure without the expected increase in heart rate.
Inexpensive to prepare and formulate o Decrease in cardiac output, stroke volume, and
Antimicrobial preparation systemic vascular resistance (SVR).
o Decreased sympathetic activity- indirect arterial
II. INTRAVENOUS ANESTHETICS vasodilation and venodilation.
A. PROPOFOL o Suppression of supraventricular tachycardia.
One of the most frequently used IV anesthetics on the market Respiratory
today. o Apnea is relatively common with a higher induction
Desirable rapid onset dose
Predictable context- sensitive half- time o typical maintenance dose of propofol results in
Rapid emergence from anesthesia diminished tidal volumes and increased respiratory rate.
Wide spectrum of uses: o Blunted response to hypoxia that may be a direct effect
o Induction and maintenance of general anesthesia on chemoreceptors.
o Intensive care unit sedation o Decreased respiratory response to hypercarbia
o Sedative- hypnotic in a variety of outpatient procedures o Potent bronchodilator direct effects on intracellular
The lipid emulsion comes in a familiar milky white consistency Calcium homeostasis.
and can be stored at room temperature without any significant
degradation.
ARAO 1 of 10
Midterms (1st Sem) Intravenous Anesthesia and Opioids
Dr. Jayber L. Tagacay
ANESTHESIOLOGY· December 5, 2020
B. ETOMIDATE C. KETAMINE
Introduced into anesthetic practice as an induction agent Emergence from Ketamine anesthesia was associated with:
Gained much popularity because of its safe hemodynamic o Emergence delirium
profile. o Hallucinations
Increased reports of adrenal suppression, pain on injection, o Alterations in mood and affect
thrombophlebitis, PONV, myoclonus, and hiccups. NMDA receptor has been found to play a key role in nociception.
The use of Etomidate is the result of a risk/benefit analysis. o Low dose Ketamine has an opiate sparing effect in the
management of acute pain.
PHARMACOKINETICS Effects of Ketamine related to pain can be best described as
Imidazole derivative (the D(+) enantiomer) and is not stable in antihyperalgesic, antiallodynic, or toleranceprotective.
neutral pH solutions Has gained interest I the treatment of major depression, however
Quick onset of action (“vein to brain”) its clinical effects are of short duration.
Fast resolution of effect secondary to redistribution
Metabolized in the liver and excreted predominantly by the PHARMACOKINETICS
kidneys (approx. 80%) and in bile (approx. 20%) Analog of Phencyclidine that is a chiral compound and is a
Largely protein bound (approx. 75%) racemic mixture of S and R enantiomers.
Initial distribution half- life 2.7 mins Routes of administration (Bioavailability)
Redistribution half- life 29 mins o Intramuscular (93%)
Elimination half- life 2.9 – 5.3 hrs o Transnasal (25-50%)
Volume of Distribution 2.5 – 4.5L/kg o Rectal or Oral (16%)
Induction Dose 0.2 – 0.3mg/kg High lipid solubility and low protein binding (20%)
o Allow for a rapid uptake of Ketamine in the brain, as
PHARMACODYNAMICS well as a fairly rapid redistribution.
Binds as an agonist to the GABA-A receptors and thus has an IV onset 30 – 60 sec
inhibitory influence on the brain Duration 10 – 15 mins
Neurodepressant properties IV induction dose 0.5 – 2 mg/kg
Potent vasoconstrictor that reduces CBF, ICP, and CMRO2. IM induction dose 4 – 6 mg/kg
Peak plasma levels 0.75 mg/mL
CSF levels 0.2 mg/mL 1hr after dosing
ARAO 2 of 10
Midterms (1st Sem) Intravenous Anesthesia and Opioids
Dr. Jayber L. Tagacay
ANESTHESIOLOGY· December 5, 2020
ARAO 3 of 10
Midterms (1st Sem) Intravenous Anesthesia and Opioids
Dr. Jayber L. Tagacay
ANESTHESIOLOGY· December 5, 2020
o Omitting the loading dose decreases the incidence o Manufactured as an acidic formulation that may
Hypotension produce mild local tissue and vein irritation.
o After a 1ug/kg bolus, blood preassure decreases at Benzodiazepines bind to specific receptor sites that are part of the
23%. GABA-A receptor complex
ARAO 4 of 10
Midterms (1st Sem) Intravenous Anesthesia and Opioids
Dr. Jayber L. Tagacay
ANESTHESIOLOGY· December 5, 2020
ARAO 5 of 10
Midterms (1st Sem) Intravenous Anesthesia and Opioids
Dr. Jayber L. Tagacay
ANESTHESIOLOGY· December 5, 2020
Efficacy k - Receptor
o Range in magnitude of an effect produced by a drug o k - Receptor–mediated analgesia may be less effective
receptor combination relative to the maximum possible for high-intensity painful stimulation than µ-opioid–
effect mediated
Potency o Opioid agonist–antagonists often act principally on k-
o The relative dose required to achieve an effect, and is receptors
related to receptor affinity
C. CLASSIFICATION
ARAO 6 of 10
Midterms (1st Sem) Intravenous Anesthesia and Opioids
Dr. Jayber L. Tagacay
ANESTHESIOLOGY· December 5, 2020
ARAO 7 of 10
Midterms (1st Sem) Intravenous Anesthesia and Opioids
Dr. Jayber L. Tagacay
ANESTHESIOLOGY· December 5, 2020
ARAO 8 of 10
Midterms (1st Sem) Intravenous Anesthesia and Opioids
Dr. Jayber L. Tagacay
ANESTHESIOLOGY· December 5, 2020
during monitored anesthesia care in otherwise healthy adult Compared with morphine, parenteral heroin has a
patients a. more rapid onset
b. less opioid-induced nausea
SIDE EFFECTS c. greater potential for physical dependency
The short recovery period may be considered a disadvantage if
the infusion is stopped suddenly V. OPIOID AGONIST- ANTAGONISTS
Nausea and vomiting, depression of ventilation, and mild These drugs bind to receptors, where they produce limited
decreases in systemic blood pressure and heart rate responses (partial agonists) or no effect (competitive antagonists)
Hyperalgesia The side effects are similar to those of opioid agonists, and, in
o Patients receiving large doses of remifentanil addition, these drugs may cause dysphoric reactions
intraoperatively are often surprisingly high, suggesting The advantages of opioid agonist–antagonists are the ability to
remifentanil may be associated with acute opioid produce analgesia with limited depression of ventilation and
tolerance a low potential to produce physical dependence
In general, agonist–antagonist drugs should be reserved for
G. CODEINE patients who are unable to tolerate a pure agonist.
Ss the result of the substitution of a methyl group for the hydroxyl
group on the number 3 carbon of morphine A. PENTAZOCINE
The presence of this methyl group limits first-pass hepatic Possesses opioid agonist actions (antagonized by naloxone) as
metabolism and accounts for the efficacy of codeine when well as weak antagonist actions (sufficient to precipitate
administered orally withdrawal symptoms when administered to patients who have
About 10% of administered codeine is demethylated in the liver been receiving opioids on a regular basis).
to morphine, which may be responsible for the analgesic effect
of codeine, although codeine-6-glucuronide may also exert an PHARMACOKINETICS
analgesic effect. Well absorbed after oral or parenteral administration
Effective at suppressing cough at oral doses First-pass hepatic metabolism is extensive, with only about 20%
Maximal analgesia, equivalent to that produced by 650 mg of of an oral dose entering the circulation.
aspirin, occurs with 60 mg of codeine
When administered IM, 120 mg of codeine is equivalent in CLINICAL USES
analgesic effect to 10 mg of morphine 10 to 30 mg IV or 50 mg orally, is used for the relief of moderate
Included in medications as an antitussive or is combined with pain.
nonopioid analgesics for the treatment of mild to moderate pain. An oral dose of 50 mg is equivalent in analgesic potency to 60 mg
of codeine
H. HYDROMORPHONE Useful for treatment of chronic pain when there is a high risk of
Derivative of morphine that is about five times as potent as physical dependence
morphine but has a slightly shorter duration of action
Hydromorphone is an effective alternative to morphine in the SIDE EFFECTS
treatment of opioid-responsive moderate to severe pain The most common side effect of pentazocine is sedation
Nausea and vomiting are less common than with morphine
I. OXYMORPHONE Dysphoria, including fear of impending death, is associated with
About 10 times as potent as morphine and seems to cause more high doses.
nausea and vomiting Pentazocine, 20 to 30 mg IM, produces analgesia, sedation, and
Has a great potential for physical dependence depression of ventilation similar to 10 mg of morphine.
J. OXYCODONE B. BUTARPHANOL
Commonly used orally for treating acute pain (about twice as Compared with pentazocine, butorphanol’s agonist effects are
potent as oral morphine and has a similar duration of analgesic about 20 times greater, whereas its antagonist actions are 10 to
action) 30 times greater
Abuse potential is but new, abuse-resistant formulations that are Rapidly and almost completely absorbed after IM injection
not easily solubilized for IV injection are now widely marketed In postoperative patients, 2 to 3 mg IM produces analgesia and
depression of ventilation similar to 10 mg of morphine.
K. HYDROCODONE
A commonly used oral opioid for treating acute pain and is similar SIDE EFFECTS
in potency to oral morphine and has a similar duration of Common side effects include sedation, nausea, and diaphoresis
analgesic action (high abuse potential) Dysphoria is infrequent
L. METHADONE C. NALBUPHINE
Synthetic opioid agonist that produces analgesia in the setting of Phenanthrene opioid derivative
chronic pain syndromes and is highly effective by the oral route The most common side effect was drowsiness
The efficient oral absorption, prompt onset of action, and Used to antagonize the ventilatory depressant effects of µ opiod
prolonged duration of action render this an attractive drug for receptor agonist while still providing analgesia by K receptor
suppression of withdrawal symptoms in physically dependent stimulation.
persons such as heroin addicts
VI. OPIOID ANTAGONISTS
M. TRAMADOL Minor changes in the structure of an opioid agonist can convert
A centrally acting analgesic that is 5 to 10 times less potent than the drug into an opioid antagonist at one or more of the opioid
morphine in volunteers receptor sites
Naloxone antagonized only an estimated 30% of the effect of Naloxone, naltrexone, and nalmefene are pure opioid receptor
tramadol. antagonists with no agonist activity
N. HEROIN (DIACETYLMORPHINE) A. NALOXONE
A synthetic opioid produced by acetylation of morphine Nonselective antagonist at all three opioid
There is rapid penetration of heroin into the brain,where it is 1 to 4 g/kg IV reverses opioid-induced analgesia and depression
hydrolyzed to the active metabolites monoacetylmorphine and of ventilation
morphine
ARAO 9 of 10
Midterms (1st Sem) Intravenous Anesthesia and Opioids
Dr. Jayber L. Tagacay
ANESTHESIOLOGY· December 5, 2020
ARAO 10 of 10