Opioid specific drugs Flashcards
▪ Gold standard or prototype for opioid agonists
-naturally occuring
morphine
-what is duration of action for morphine and why?
about 4 hours
-Comparatively low lipid solubility
▪ Moves slowly across the blood brain barrier
dose of morphine for anesthetic purposes?
0.1 – 0.2 mg/kg used IM as
premedication and IV
what mac level does morphine decrease with ceiling effect?
65%
why does only <0.1% of morphine administered enter the CNS at peak plasma
concentrations? (4 reasons)
– Low lipid solubility
– High degree of ionization at physiologic pH
– Protein binding
– Rapid conjugation with glucuronic acid
is morphine taken up by lungs?
no
morphine clearance?
Hepatic clearance is high and dependent on liver blood flow.
what are the two metabolites of morphine?
Morphine 3-glucuronide (75-85%) and
morphine 6-glucuronide (M6G) (5-10%)
Metabolites of morphine excreted..
renally, so renal failure causes accumulation of M6G and prolonged effect
in women, what are 4 differences to consider when giving morphine?
▪ Greater analgesic potency
▪ Slower offset
▪ No effect on apneic threshold
▪ Hypoxic sensitivity decreased
why should you Pretreat morphine with H1 and H2 blockers
histamine release is common, wont decrease the release but will block the decrease in SVR and BP
Discovered during search for synthetic atropinelike drug
demerol (meperidine)
Causes increase in heart rate, some large airway bronchodilation
really not used for anesthesia in adults
demerol
why does demerol cause an increase in N/V?
Sensitizes the labyrinthine apparatus
demerol is metabolized by demethylation in the liver to
normeperidine (90%) which is excreted by
the kidneys
Dose of demerol used for peds
0.5 to 1 mg/kg
Normeperidine side effects
- cns stimulant - seizures
- hallucinations
- delirium
Meperidine duration is
typically 2-4 hours
(Demerol dose of
> 5 mg/kg) or renal failure can cause
seizures
why does demerol suppress postoperative shivering?
– May represent stimulation of kappa receptors or
decreased shivering threshold
– May also be related to the alpha2 receptor stimulation
– Hypertension, tachycardia – Diaphoresis, hyperthermia – Confusion, agitation – Neuromuscular changes – hyperreflexia – Severe – coma, seizures, coagulopathy, metabolic acidosis
Serotonin syndrome may be caused by
interaction of meperidine with MAOIs, tricyclics
Opioid designed for anesthesia
fentanyl
how much more potent is fentanyl than morphine?
100x
High lipid solubility of fentanyl explains
the rapid onset and greater potency
clinical duration of fentanyl
20-40 minutes
___ initial IV dose of fentanyl is taken up by the lungs
75%
Repeat doses of fentanyl accumulate in
muscle (large compartment) and fat (high lipid solubility)
with Repeated doses or an infusion of fentanyl, drug is stored in
the lungs, fat, and muscle causing
prolonged analgesia and respiratory depression
how is fentanyl metabolized
N-demethylation
Norfentanil most common in humans
3 metabolites of fentanyl
– Norfentanyl
– Hydroxyproprionyl-fentanyl
– Hydroxyproprionyl-norfentanyl
Elimination t ½ life of fentanyl is
3.1-6.6 hrs
Longer t ½ life of fentanyl is due to
o larger volume of distribution as fentanyl can move into tissues more rapidly than morphine.
what 3 reasons do the Elderly have prolonged elimination t ½ life with fentanyl?
– Decreases in hepatic blood flow
– Microsomal enzyme activity
– Decreases in albumin production (highly protein bound 79-87%)
what type of surgery is fentanyl duration prolonged with and why?
abdominal aortic surgery involving infrarenal aortic cross-clamping.
doses for fentanyl?
▪ 1 – 2 mcg/kg IV for analgesia
▪ 2 – 20 mcg/kg IV as a balanced technique to blunt circulatory responses
dose of fentanyl that dependably blunts the sympathetic response of larygoscopy?
– 5-8 mcg/kg
dose of fent that significantly reduces the dose of propofol for placement
of an LMA
▪ 0.5 mcg/kg
Large doses of fent (50-150 mcg/kg) can reduce MAC by up to
80%
Single dose of 3mcg/kg 25-30 minutes prior to incision can reduce iso or des MAC by
50%
Small doses (1mcg/kg) reduce MAC by
40%
Advantages of Fentanyl (3)
▪ No direct myocardial depression
▪ No histamine release
▪ Suppresses stress response to surgery
Disadvantages of Fentanyl
▪ Sympathetic stimulation in response to pain, especially with good LV function
▪ Unreliable amnesia
▪ Post-op respiratory depression
▪ Cardiovascular effects of fent
– Heart rate decreases more than morphine
▪ Occasional decreases in BP and CO
– No histamine release
▪ Muscular effects of fent?
– Myoclonus related to depression of inhibitory neurons – seizurelike with no EEG changes
neuro effects of fent?
moderate increases in ICP (6-9) even
with unchanged PaCO2 bc of vasodilation and an increase in cerebral vascular resistance
synergist of fent?
benzos, increased resp depression
prop
what is a weird side effect caused by fent pre op?
reflex coughing
Most potent opioid currently available
sufentanil
what is pulmonary uptake of sufentanil?
60%
Elimination t ½ life sufentanil?
2.5 hours
Volume of distribution of sufentanil 1.17 L is smaller due to?
greater protein binding than fentanyl (92% v. 79-87%)
how is sufentanil metabolized?
hepatic via N-dealkylation into inactive
metabolites which are eliminated by both the liver and kidneys
why do we not typically use sufentanil for induction?
- stiff chest syndrome
- may render patient apneic but not unconscious
- glottic obstruction
sufentanil has a longer lasting and greater analgesic effect, what other effect is preferred
less respiratory depression
what can sufentanil reduce mac by
up to 70%
dose of sufentanil?
1/10 dose of fentanyl
Fent:
▪ 1 – 2 mcg/kg IV for analgesia
▪ 2 – 20 mcg/kg IV as a balanced technique to blunt circulatory responses
Use of benzodiazepines along with iv infusion of sufentanil may necessitate
a decrease in dose of sufentanil - synergist
After infusion for 3 hours, sufentanil will decrease by
80% more rapidly than fentanyl and alfentanil.
After infusion for 8 hours, sufentanil will decrease by
50 % more rapidly than fentanyl or alfentanil.
what is sufentanils shorter context sensitive half life due to.. compared to alfent
large Vd compared to alfentanil – due to metabolism and redistribution
what medication is hard to detect an overdose during a case and why?
sufentanil, bp same even with 5x dose
why is alfentanil Volume of distribution much smaller (4-6X) than fentanyl
due to lower lipid solubility and more protein binding
Elimination t ½ life alfentanil
1.1-1.6 hrs
best choice to give for a single, brief stimulus like laryngoscopy or retrobulbar block
alfentanil
only 10% of alfentanil ionized at physiologic pH causes (onset alfent vs fent)
This causes faster onset or effect-site equilibration.
(A 1.4 mins; F-6.8 mins)
this drug is more liable to produce stiff chest and greater euphoria
alfentanil
Metabolism of alfentanil
n-dealkylation to noralfentanil and
amide N-dealkylation to N-phenylpropionamide
what makes a standard infusion and dosing regimen difficult to determine with alfentanil?
Interindividual variability related to P-450 CYP3A enzyme
when should alfentanil infusions be stopped?
15-25 mins before emergence
Direct laryngoscopy dose alfentanil
– 15 mcg/kg 90 sec before blunts SBP and HR response
– 30mcg/kg blunts catecholamine response
Induction dose alfentanil
– 150-300 mcg/kg given rapidly - unconsciousness
Infusion dose of alfentanil with inhaled agent
Infusion 25 to 150 mcg/kg/hr
difference in alfentanil and fentanyl with blood pressure response with dose given after stimulation
BP can be decreased with a dose of alfentanil after the
painful stimulation where fentanyl cannot
5X more potent than fentanyl on a mg per mg basis
remifentanil
Elimination t ½ time remifent
6-10 minutes
remifentanil Metabolized by
nonspecific plasma and tissue esterases to inactive
metabolites which are excreted by the kidneys
Context-sensitive half-time of remifent
Independent of infusion time
– Approximately 4 minutes
– Must give a longer-acting opioid to ensure analgesia when patient awakens
what drug from fent group has greatest decrease in bp
remifent
30% decrease in SBP two minutes after administration
clinical uses of remifent?
– Laryngoscopy
– Retrobulbar block
– Labor and delivery
– Desire rapid recovery – craniotomy, carotid endarterectomy
what opioid has smallest Vd?
remifent so fast equilibration and fast offset
▪ Induction dose remifent
1 mcg/kg over 60-90 sec
dose if infusing remifent before iv anesthetic dose
0.5-1.0
mcg/kg over 10 minutes
Then,
infusion 0.05 to 2.0 mcg/kg/min IV
MAC (Sedation case) with remifent dose?
0.05 – 0.10 mcg/kg/min with midazolam (2 mg IV)
– Suggests acute opioid tolerance
– Tolerance is dose dependent
hyperalgesia
seen with remifent
why do Patients receiving high doses of remifentanil require high post-op analgesics
– Possibly due to alteration in NMDA receptor
what two things block opioid tolerance?
magnesium and ketamine
a decrease in the response to a drug due to its continued administration
tolerance
an increased response to a stimulus that is normally painful.
hyperalgesia
Intermediate-acting semi-synthetic opioid
dilaudid (hydromorphone)
what opioid is best for renal patients
dilaudid bc it lacks active metabolites
1.5 mg of dilaudid is equivalent to
10 mg morphine or 100 mcg fentanyl
dose dilaudid
0.02-0.06 mg/kg
onset and duration of dilaudid
Onset: 5 minutes
▪ Duration: 4-5 hours (2-3 hrs ½ life)
Metabolism of dilaudid and what opioid is it similar to
mostly phase II via glucuronic acid (similar to
morphine)
Synthetic opioid
▪ Useful with chronic pain
methadone
elimination t1/2 of methadone
35 hours
MOA of tramadol the centrally acting analgesic
– Inhibits reuptake of NE and serotonin and inhibits release of presynaptic release of serotonin
Advantages of tramadol (3)
– Treat shivering
– Minimal ventilatory depressant
– Less likely to cause addiction –
disadvantages of tramadol
– Interaction w Coumadin, ondansetron
– Seizures
– Nausea and vomiting
-just po, iv not approved in US
