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Buprenorphine
Codeine
Oxycodone
Methadone
Naloxone
Intro
Synthetic derivative of the
alkaloid thebaine
Semisynthetic phenanthrene
derivative
Synthetic mu opioid antagonist
propionnanilide
1st Pure opioid antagonist
N-alkyl derivative of oxymorphone
Use
Rx of moderate to severe
pain. More common for
outpatient use due to safety
profile
Naturally occurring
phenanthrene derivative.
Methyl substitution.
Weak affinity andlow potency
50%.
Rx of mild to mod pain.
Antitussive, antimotility agent
and traditionally for head
injury patients (no evidence –
lack resp and neuro
depressive effects)
Rx of mild, mod, severe pain,
Treat addiction to opioid/weaning
programs
Neuropathic pain
Opioid resistant pain states
For the rapid reversal of the effects of
opioids.
Resp depression.
Has been used in animal studies to
reverse hypotension 2ndary to
hypovolaemic/septic shock.
MOA
Partial agonist at mu opioid
receptors, with high affinity
and potency. It has igh
affinity but low intrinsic
activity at kappa receptors
Mu
kappa receptors (spinal)
Mu
NMDA antagonist
R- more potent, 10xhigher affinity to
opioid receptor. (most of analgesic
effect)
S – NMDA antagonist. Inhibits
reuptake of 5Ht and NAdr
Mu kappa and delta R competitive
antagonist
Pharmace
utics
CCS. 300mcg/ml and
200/400mcg tablets
Low affinity for opioid
receptors. (10x less potent)
Antitussive effect via specific
high affinity codeine
receptors
10% of drug metabolised to
morphine  analgesia and
constipating effects
15/30/60mg tablets. Syrup
5mg/ml. CCS fo injection
60mg/ml. and in fixed dose
preps with paracetamol,
ibuprofen and aspirin.
5mg tablets capsules
5mg/ml solutions
SR 10,20,40,80mg tablets
And now IV formulation
Pure and combined with Tylenol or
aspirin
Racemic mixture of 2 enantiomers
5, 10 tablets.
40mg dispersible tablets
crushed or dissolvable (NG admin)
1,2,10mg/ml solutions
10mg/ml for injection
CCS or iv/im
20mcg/ml or 400mcg/ml naloxone HCl
30-60mg 4-6hrly im or o.
70% bio (peak in 1hr)
1mg/kg rectal for paeds.
Nt for iv due to hypotension
High O bioavailability
75% o bio
Hi absorption from GIT (90%) but high
1st pass = 2% 0 bio
1-4mcg/kg incremental doses
or 0.4-2.0mg for known overdose.
Onset 2min Lasts 20-40mins
Infusion 5mcg/kg/hr
46% PB, 2L/kg higly lipd sol/
Pharmacokinetics
Absorptio
Im/iv 0.3-0.6mg 6-8hrly im
n
bio 40-90%
o bio significant 1st pass effect
SL 0.2-0.4 6-8hrly
sl
bio 44-94%
Distributio
n
Metabolis
m
96%PB 3.2L/kg
7%PPB VD 5.4l/kg
Liver. Dealkylation then
glucuronidation.
Excretion
Unchanged in faeces and
renal.Clearance decreased
30% with GA
T1/2 = 5 hrs
Methyl group reduces hepatic
conjugation.
C6G (active). Ndemethylation(norcodeine)
and O-demethylation to
morphine (via CYP2D6).
Genetic polymorphism (10%
UK pop and 30% hong kong
Chinese poor metabolisers)
10%unchanged renal.
23ml/kg/min
t1/2 = 3 hrs
90% PB. high lipid sol.
Extensive hepatic conjugation and
oxidative degradation to a variety of
metabolites main excreted in urine.
Active metabolites
Glucuronidation to noroxycodone
(1% activity)
CYP2D6 (interact pot.) to
oxymorphone.
Liver (and intestinal)
CYP3A4 both enantiomer
CYP2D6 for R enan.
Nil active metabolites
Hepatic
N3G
T1/2 2.5-3hrs
T1/2 12-150hrs (35hrs)
Excreted almost exclusively in faeces
Cl = 25ml/kg/min
T1/2 1-1.5 hrs
Pharmacodynamics
CNS
25x as potent as
morphine
sedation, analgesia,
respiratory depression
euphoria, meiosis, NV.
Headache, confusion,
dizziness
CVS
Minimal CVS effects
Bradycardia (25%) SBP
↓10%
RESP
GIT
GUT
SKIN
Other
Respiratory depression
Antitussive
Bronchospasm
(histamine)
↑PVR
Emesis. Delayed gastric
emptying
Decreased urine output
Histamine release
Decreases release of
luteinising hormone and
increases release of
prolactin
Respiratory depressant
effects not completely
reversed by naloxone.
Doxapram will however.
Severe resp dep. with
benzos.
Complicated pain
management intraop.
(preadm cease,
nonopioid MM mx,
regional, or HDU)
10x less potent than
morphine
few central effects
Analgesia
Less sedation than morphine
CC if overdose or IV.
Prolongs QT Torsades
(congenital prolonged QT,high
doses 60mg, conditions that
increase QT –hypoK and
hypoMg)
Antitussive
Some resp depression
and ↓response to O2 and
CO2
Resp. depression
Rapid reversal of opioid effects:
Resp depression and sedation
Also antagonises analgesia of
other opioids
Drowsiness at high doses
Decreases pain threshold and
antagonises placebo effect
↑SNS activity
↑HR, BP pulm edema at high
doses
a/w arrhythmias (even VF)
used in animal sudies to reverse
hypotension of septic/hypovol
shock
Reverses sphincter of Oddi
spasm
NV with rapid iv admin.
Marked decrease in GI
motility. NV
Low propensity for
dependence
Withdrawal in opioid addicts
Also crosses placenta and may
ppte withdrawal in foetus or
neonate.
Naltrexone
Similar drug to naloxone for
opioid withdrawal and
alcoholism
50mg tablets
100mg dose will block effects of
heroin for 48hrs
better oral bioavailability
T1/2 10hrs