Meperidine
Receptor
Mu
Kappa
Structure
Phenylpiperidine derivative
Clinical Use
Post op pain
Post op shivering
Primarily for labor pain
Fentanyl
Sufentanil
Alfentanil
Selective Mu receptor
agonist
Phenylpiperidine derivative
Analgesia
Adjunct to IA
Blunt circulatory response:
Laryngoscopy
Sudden change in surg.
stimulation
Analogue of fentanyl
Analogue of fentanyl
Greater receptor affinity
Structurally unique – ester
linkage susceptible to
hydrolysis by non-specific
plasma and tissue esterases
**fastest elimination**
Potency 5-10 > fentanyl
1/5 – 1/10 potency of
fentanyl
**most potent**
Potency = fentanyl
Analgesia
Induction
Heart room
Blunt response to brief
single stimulus:
Intubation
Retrobulbar block
Blunt response to brief
single stimulus
Intubation dose = 15
mcg/kg
Analgesic infusion during
GA = 0.05 – 2.0
mcg/kg/min
Blunt circ response to high
Des. = 10-20 mcg/kg
Blunt catechol = 30 mcg/kg
Pharmacokinetics 1/10th as potent as morphine
75x more potent that MSO4
100 mg = 10 mg morphine
Onset IV = 10 min
DOA = 2-4 hrs
Similar to atropine and
possesses some antispasmodic
qualities
Remifentanil
Onset = 30 sec
Effect-site equil time = 6.8 min
Short DOA d/t rapid
redistribution to inactive
tissue sites
>potency and rapid onset d/t
> lipid solubility
Lungs = large inactive storage
site,1st pass Pulm uptake –
75% of initial dose
E1/2 x > than any other
opioid; context sensitive ½ x
increases w/duration
12xs more potent than
fentanyl
Sufenta 5mcg = Fent 50 mcg
Rapid redistribution to
inactive tissue sites
High tissue affinity d/t > lipid
solubility
Alfentanil 500 mcg = Fentanyl
50 mcg = Sufentanil 5 mcg
Onset = rapid; redistributes to
inactive tissue sites
Need long acting opioids
before infusion is stopped
Fastest elimination d/t rapid
metabolism by blood nonspec. esterases
Accumulates less than other
opioids
Highly non-ionized at
physiological pH
Effect site equil time = 1.1 min
Effect-site equil time =1.4 min
E ½ x = 6 min
Renal Fail. Does not alter E ½ x
or clearance
Small Vd
Effect-site equil time = 6.2 min
1st pass pulm uptake = 60%
Longer E ½ x in Elderly &
obese
Short E ½ x = 1.5 hrs
Longer E ½ x w/Cirrhosis
Highly protein bound 92.5%
Highly protein bound 92%
Small Vd
Longer E1/2 x in Elderly
Induction dose= 1 mcg/kg
Small Vd = low lipid sol
Highly Protein bound 79-97%
Large Vd
**Potency from least to greatest: Demerol < Morphine<Alfentanil <Fentanyl = Remifentanil < Sufentanil**
Meperidine
Metabolism
Extensive Hepatic metabolism
90% demethylated to active
metabolite Normeperidine
Normeperidine
-hydrolyzed to an acid and
excreted in urine
Normeperidine E ½ x = 15 hrs
*Seizure Activity*
Fentanyl
Extensively Metabolized by:
N-demethylation
Inactive metabolite =
norfentanyl
Excreted by kidneys
Detected in urine 72 hrs after
single dose
Sufentanil
Rapidly metabolized by:
N-dealkylation
O-demethylation
Inactive and active
metabolites formed
<1% unchanged in urine
Alfentanil
2 independent Pathways:
Noralfentanil major
metabolite
Efficiently cleared by liver
metabolism within 60 min
Redistributes to inactive
tissue sites
Remifentanil
Unique among the opioids –
rapid metabolism
Not affected by
Pseudocholinesterase
Deficiency
Can be used in renal and
hepatic disease
High lipid solubility -> max
renal tubular reabsorption
E ½ x of Meperidine = 3-5 hrs
Clearance sensitive to hepatic
blood flow
60% Protein Bound
Use Cautiously in Elderly and
Renal Disease
Side Effects
Causes Histamine Release
No Histamine release
No Histamine release
No Histamine release
No Histamine release
Orthostatic ↓ BP
Marked Bradycardia
Hypotension
Hypotension
Hypotension
↑ HR and Mydriasis- modest
atropine like effect
Possible seizure activity
Bradycardia
Bradycardia
Bradycardia
↓ Myocardial contractility
w/large doses
Chest wall and skeletal
muscle rigidity
Itchy nose
Delirium and Seizures
***Life threatening
interaction w/MAOIs =
Serotonin Syndome***
Type I Rxn:
Hypertension
Agitation
Skeletal Muscle Rigidity
Headache
Hyperpyrexia
Type II Reaction:
Hypotension
Respiratory Depression
Coma
Acute Opioid tolerance
Skeletal muscle rigidity with
large doses
Codeine
Hydromorphone
Methadone
Heroin
Structure
Made from Morphine
Derivative of Morphine
Synthetic Opioid with prolonged
duration of action (24 hrs)
Synthetic Opioid produced by
Acetylation of Morphine=
Diacetylmorphine
Pharmacokinetics
E ½ x with PO = 3.5 hrs
Onset IV almost immediate
E ½ x = 35 hrs
Rapid penetration into the brain
Peak = 5 – 20 min
DOA = 2-5 hours
5x as potent as Morphine
2 mg = 10 mg Morphine
Uses
Effective antitussive at 15 mg PO
Same as morphine
Heroin addiction
Good for mod to severe pain
Side Effects
Histamine Release with IV dosing
No histamine release
Similar SE to morphine
Same SE as morphine
Metabolism
Limited 1st pass hepatic metabolism
– effective when given PO
Demethylated to:
Morphine and Norcodeine
Shorter DOA than morphine 4-5
hours
Lack nausea
Great potention for physical
dependency
Metabolized in Liver to inactive
metabolites
Hydrolyzed in brain to active
metabolites
Opioid Agonists-Antagonists
drugs
∙ Pentazocine (TTalwin)
∙ Butorphanol (SStadol)
∙ Nalbuphine (N
Nubain)
∙ Buprenorphine (BBuprenex)
receptor
effects
side
effects
∙ Bind to MU receptors and act as a partial Agonist OR Antagonist
∙ Provide weaker analgesia than opioid agonists – good for mild – moderate pain
∙ Produce analgesia without respiratory depression
∙ Antagonist quality creates a “C
CEILING” effect for analgesia (only first dose effective)
∙ Low potential for physical dependence
∙ Side effects similar to Opioids
∙ May cause Dysphoric Reactions
Opioid Agonists-Antagonists
Pentazocine
(Talwin)
Butorphanol
(Stadol)
Nalbuphine
(Nubain )
Buprenorphine
(Buprenex)
∙ Opioid agonist
∙ Weak antagonist
∙ Similar to
- Pentazocine
∙ Related to
- Oxymorphone
- Naloxone
∙ Derived from Opioid Alkaloid:
- Thebaine
? Delta
? Kappa
∙ MU  low affinity
∙ Kappa  moderate affinity
∙ Sigma  minimal affinity
∙ MU  Antagonist effects
∙ MU  high affinity 50x > MSO4
- Slow dissociation =  action
- Resistant to Antagonism of
Naloxone (Narcan)
∙ Agonist effects  Antagonized by
Naloxone (Narcan)
∙ Antagonist effects  Withdrawal
∙ Agonist effects  20 x > than
Pentazocine
∙ Antagonist effects 10 - 30 times
greater
∙ Equal potency Analgesia to MSO4
∙ Analgesia Onset and Duration
- Similar to Morphine (MSO4)
- Nubain 10mg IM
? Very Potent
- 0.3mg IM = 10mg Morphine
uses
Treatment of:
∙ Chronic Pain
∙ Relieves Moderate Pain
∙ Good for:
- Acute Pain rather than Chronic
∙ 10-20mg IV reverses the respiratory
depression of Fentanyl postop
- But maintains Analgesia
∙ Good for:
- Moderate to Severe Pain
dose
∙ Dose 10-30mg IV or 50mg PO
∙ 50mg PO = 60mg Codeine
∙ Available in parenteral form
∙ 2 -3 mg IM = 10mg Morphine
∙ > 30mg  “C
CEILING EFFECT” d/t
antagonist activity
∙
∙ Extensive 1st-Pass Hepatic
Metabolism
∙ Metabolized to an inactive metabolite
∙ Excreted in Urine
∙ E ½ x = 2- 3 hours
∙ Hepatic metabolism to inactive
metabolites
∙ Excreted in Urine
∙ E ½ x = 2.5 - 3.5 hours
∙ Rapidly &Completely absorbed
after IM
∙ Metabolized in the Liver
∙ Morphine-like Drugs Inactive
∙ E ½ x = 3 - 6 hours
∙ Onset = 30 min
∙ Duration 8-10 hours
∙ Highly Lipid Soluble
Sedation
Diaphoresis
Dizziness
Dysphoria
Crosses the Placenta  Fetal
Depression
∙  Catecholamines 
-  HR
-  BP
-  PAP
-  LVEDP
∙
∙
∙
∙
∙
∙ Abuse potential LOW
∙
∙
∙
∙
moa
receptors
effects
pharm.kinetics
and
metabolism
side effects
∙
∙
∙
∙
∙
Sedation
Diaphoresis
Nausea
Respiratory Depression
Attenuates Opioid Agonist Activity**
? Does NOT cause
-  HR
-  BP
-  PAP
Opioid Antagonists
Drowsiness
Incidences of Pulmonary Edema
Nausea/Vomiting
Respiratory Depression
structure
∙ Minor changes in structure of Opioid Agonist changes the Drug to an ANTAGONIST
∙ Substitute an Alkyl Group for a Methyl Group
receptor
∙ Displaces Opioid agonist from the MU receptors
∙ Pure Antagonist DOES NOT activate the receptor  Antagonism
Naloxone (Narcan)
receptor
pharm.kinetics
∙ ANTAGONIZES Mu Receptors ***
∙ Short Duration of Action = 30 - 45 min
dose
∙ 1 - 4mcg/kg  Reverses Opioid-induced Respiratory Depression and Analgesia
uses
∙ Detect suspected physical dependence
∙ To avoid abrupt reversal of analgesia give 40 mcg (0.1 mL)
∙ Used as continuous infusion to prevent respiratory depression and itching from neuraxial opioids
∙ Neonatal Depression - Given at Delivery (this is with moms that are NOT addicts)
∙ Opioid-Induced Depression of Ventilation
∙ Treatment of deliberate opioid overdose
metabolism
∙ Metabolized in the liver
side effects
∙ Side effects are due to reversal of analgesia and sudden perception of pain:
∙ E ½ x = 60 -90 minutes
∙ Nausea / Vomiting
∙ Increased SNS activity 
- Tachycardia
- Pulmonary Edema
- HTN
- Cardiac Arrhythmias (VF)
∙ Crosses Placenta  Acute Withdrawal of neonate of Opioid-Dependent mom (can lead to baby’s demise)