Opiates/Narcotic Analgesics (class hour 36 3/17/11)

Pharmacy 3040 with Jeffery at University of Connecticut

About this deck

By: Joshua Pruitt
Textbook:

Pharmacotherapy Handbook, Seventh Edition
Created: 2011-03-28
Size: 26 flashcards
Views: 16

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major effects

analgesia- relief of pain in absence of impairment of other sensory modalities
euphoria

sense of well being, pleasure
subject to abuse (although vast majority of patients using these drugs chronically for pain do so without abuse or dependance)

opiates vs opioids

opiates = natural or semi-synthetic
opioids = synthetic

general effects of opiates

tend to relax the user
when injected, user feels imediate "rush"

sudden surge of pleasure and euphoria; warmth; heaviness in extremities

other initial and unpleasant effects include restlessness, nausea, and vomiting
user may repeatidly go back and fourth from feeling alert to drowsy
with lare doses the use can't be awakened, pupils become smaller. and the skin becomes cold, moist and bluish; breathing slows down and death may occur

endogenous compounts and their precursers

PDMC ⇒ endorphins
prepro-enk ⇒ enkephalins
prepro-dyn ⇒ dynorphins

opiate receptors

3 main receptors = Mu, Kappa and Delta

distributed in CNS and PNS(esp. in areas associated with pain and reward)

Epsilon (not as well known, won't talk about much)
Sigma (not officially an opiate receptor, although some opiates do bind)

many kappa mixed agonists

Mu receptor functions and affinities

supraspinal and spinal analgesia
sedation
inhibition of respiration
slowed GI transit
modulation of hormone and neurotransmitter release

endorphins>enkephalins>dynorphins

Delta receptor functions and affinities

supraspinal and spinal analgesia
modulation of hormone and neurotransmitter release

enkephalins>endorphins and dynorphins

Kappa receptor functions and affinities

supraspinal and spinal analgesia
slowed GI transit
psychotomimetic effects

dynorphins>endorphins and enkephalins

synaptic location of action for Mu, Delta and Kappa

presynaptic (primary afferent neuron)
reduces calcium influx, which causes reduction of transmitter release

Mu
Kappa

postsynaptic (secondary afferent neuron)
increase potasium conductance which hyperpolarizes cell, reducing excitability(action potential)

Mu
Delta

Mu analgesia: spinal and supraspinal

simultaneous administration of morphine at spinal and supraspinal sites results in synergy with a tenfold decrease in needed total dose of morphine at either site alone
supraspinal effect of opiates seem to be more responsible for dulling the appreciatation of pain

Mu: respiratory depression

reduces sensitivity of CO₂ sensory receptors in medulla
problem with OD (tends to correlate to mu activity>kappa activity)

Mu: anti-diarrheal

are located and act in GI tract

decrease ACh release
decrease sensory info from GI tract (food is here!)

anti-diarrheal drugs that don't cross BBB have been developed

Diphenoxylate (lomotil)
Loperamide (imodium)

opiate antagonists

primarily used to treat overdose of an opiate
can cause/precipitate severe withdrawal
prevent or abolish excessive respiratory depression caused by opiates
also used to block rewarding effects for addicts

Naloxone
Naltrexone

Kappa receptor

produce less respiratory depression as analgesics
morphine live withdrawal but less severe
high doses produce dysphoria and hallucinogenic effects
many drugs are partial agonists and may be antagonist to Mu in some areas leading to less analgesic effects or anti-analgesic effects

drugs could precipitate withdawal in people using Mu receptor agaonists at the same time...
Talwin (pentazocine)
Stadol (butorphanol)

Heroin

heroin(inactive) crosses BBB(heroin>morphine) where it's deacetylated in the brain to morphine(active)
no recognized medical uses

Orphanin receptor(NOP receptor)

most opiates lack affinity, but Naloxone and Lofentanil do bind
signal transduction nearly identical to opiates (dec. cAMP and inh. N-Ca channels)
may reduce opiate tolerance

Ultram (tramadol)

novel analgesic
weak Mu agonist(naloxone) combined with NE/5HT reuptake inhibitor
low affinity for Mu receptor but metabolite has much higher affinity
enantiomer's affinity differ

R(+) higher affinity for 5HT receptor
S(-) higher affinity for NE <-- *higher risk of cardiovascular effects

Mu receptor subtypes and functions

Mu₁

supraspinal analgesia
euphoria
physical dependance

Mu₂

repiratory depresion
spinal analgesia
dec. GI motility

Ziconotide

novel analgesic
blocker of voltage-gaited N-type calcium channels
recently approved for intrathecal analgesia in patients with refractory chronic pain

Gapapentin

novel analgesic
an anticonvulsant analog of GABA
is an efective treatment for neuropathic pain
blocks pain associated with inflammation
potential site of action includes calcium channels

novel analgesics

Ziconotide
Gabapentin
NMDA antagonists
THC analogs
nicotine, serotinin, histamine antagonists
TRPV-1 receptor antagonists

responds to temperature related pain
sensitivity inc. by bradykinin

cough

antitussive effects of opiates do not correlate with analgesia or respiratory depression
complex mechanism responding to sensory pathways (mechanical and chemical)

i.e. obstruction, mucus and edema; tachykinins and bradykinins

dextromethorphan

cough suppressant in>120 OTC cold medications
acts centrally on the cough center in the medulla and nucleus tractus solaris to increase cough threshold
NMDA antagonist
metabolite (detrorphan) has higher affinity for NMDA receptor
only at high doses has euphoric effects ⇒ abuse

effects of opiates with high degree of tolerance development

analgesia
euphoria, dysphoria
sedation
respiratory depression
antidiuresis
nausea and vomiting
cough suppression

effects of opiates with moderate and low degrees of tolerance development

moderate

bradycardia

miosis
constipation
convulsions

drugs to treat opiate dependence

methadone
suboxone (mu and kappa partial agonist)
clonidine

About this deck

By: Joshua Pruitt
Textbook:

Pharmacotherapy Handbook, Seventh Edition
Created: 2011-03-28
Size: 26 flashcards
Views: 16

About StudyBlue

“I have been getting MUCH better grades on all my tests for school. Flash cards, notes, and quizzes are great on here. Thanks!”
Kathy