Narcotic and Non-Narcotic Analgesics Flashcards
Endogenous opiates regulate CNS activity of pain, thermoregulation, appetite, reward
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POMC forms
Beta Endorphins
POMC produced only in CNS in what areas
Arcuate Nucleus of hypothalamus and Nucleus Tractus Solitarius.
Conduction of afferent peripheral nerve is blocked by goltage gated Na channel blockers known as:
-caines
NMDA receptor blockers used for what?
Preemptive blockade of NMDA can prevent surgery induced wind-up.
Some NMDA receptor blockers are
Ketamine
Dextrmethorphan
Ketamine may cause
hallucinations, amnesia, hypertension
Dextromethorphan
dizziness, confusion, fatigue
Carbamezapine
voltage gated Na channel blocker used to treat Trigeminal Neuralgia and Neuropathic pain.
Interruption of the initial signal in peripheral tissues during pain signal transduction is accomplished by what kind of drugs
NSAIDS
Na channel blockers block signal conduction in nociceptive fibers.
These are local anesthetics
Why is calcium essential in promoting signal tranduction
It is necessary for the fusion of synaptic vesicles with presynaptic endplate to release neurostransmitters into the synaptic cleft
What substances can inhibit calcium entry to the pre-synaptic terminal
Norepinephrine, GABA, endorphin and encephalin (both endogenous opiates)
Post synaptically, norep, GABA, endorphin and encephalin do what?
They activate potassium channels thus hyperpolarizing the membrane and reducing the likelihoood of a depolarization threshold being reached and thus interrupting the pain signal
The simplified mechanism of opiate analgesics
They work both pre and post-synaptically by activating the mu opiate receptor which in turn leads to decreased pre-synaptic calcium influx an increased post-synaptic calcium efflux.
Central sensitization phenomenon
Sustained activation of pain pathways leads to short and long term post-synaptic changes in protein expression and function, resulting in an increased sensitivity to post-synaptic depolarization thus increasing the intensity of onward pain transmission signals
THE NMDA receptor plays a prominent role in this phenomenon.
How do Ketamine and Dextromethorphan work>
Block NMDA receptors
Phantom limb pain
neuropathic pain symtpom
Slide 21
good review
OP-1=
Opiate Receptor 1, Delta:
- Cortical and spinal analgesia, altered hormone and NT release
OP-2=
Opiate receptor 2, Kappa:
- Cortical and spinal analgesia, psychomimetic and decreases GI transit
OP-3
Opiate receptor 3, Mu
- COrtical and spinal analgesia, induces respiration, Lower Gi transit, altered hormone and NT release
Low oral to IV dose ratio means what?
That oral doses must be higher to account for losses in absorption
For all of the opioid agonists, what receptor mediates all of the effects (both beneficial and adverse?
Mu– OP-3
Transdermal patches of Fentanyl provide what length of relatively stable drug delivery?
48-72 hours of stable drug delivery
What drugs can be delivered rectally?
Occasionally Morphoine and morphones
Does Morphine have high first pass metabolism?
YES…KNOW
Codeine and oxycodone are effective how?
Orally due to low first pass effects
Opiates distribute where in the body?
Distribute to high bloodflow organs first (muscle is the bigget reservoir)
Know that opiates can distribute into adipose tissue with high continual dosing
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Opiod receptors are what type of receptors
G-PCR….Realize that binding eventually leads to internalization (desensitization of the receptor) via the GRK-2 Beta Arrestin interaction. Endogenous opioids like ENK allow receptors to eventaully recycle and thus you have re-sensitization. Exogenous opioids don’t let the receptors recycle as efficiently.
Recycling of opioid receptors facilitated by?
GRK-2 and Beta Arrestin
Know the potential adverse effects of opioid analgesics
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Which of these potential adverse effects will not go away?
Miosis (closing the eyes), constipation, convulsions
Most common adverse effect is
Constipation—-because it won’t go away you should always give a laxative.
What if a laxative doesn’t work for opiate induced constipation
Give an opioid antagonist.
Why does constipation occur
Because the presence of opioid receptors in the GI system produces anti-cholinergic actions which slows down GI movement since Ach is the major stimulatory transmitter in regards to peristalsis.
Nausea and vomitting generally occur when?
WHen the opioid dose is given too quickly.
N/V generally does not persist as tolerance develops
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Respiratory distress is really only a risk when?
- Drug given too quickly
- Given with sleep apnea
- Combined with a sedative or hypnotic
What can be given to reverse respiratory depression
Naloxene
What type of opiates cause histamine release?
morphine
Opiate Overdose triad
COMA- Decreased cortical activity , RESPIRATORY ACIDOSIS from decreased drive to breathe
, PINPOINT PUPILS- from modulation at Edinger Westphal nucleus
Sedatives + Opiates
Increased CNS depression esp respiratory depression
Antipsychotics + opiates
Sedation and CV effects
MAOIs
contraindicated with opiates because hyperpyrexic coma and HTN
All opiates are contraindicated in renal failure except
hydromorphone and fentanyl
Meperidine metabolite with CNS toxicity
Normepridine
Alcohol withdrawal looks like
Delirium, seizures, HTN, Tachycardia
Cholinergic intox looks like
SLUDGEBBB
Sympathomimetic intox?
agitation, tachycardia, HTN
