Narcotics Flashcards by rina ng

How is analgesic different from anesthetics

Analgesics - relief from pain
Anesthetics - eliminates all sensation including pain

How well did you know this?

Not at all

Perfectly

What determines choice of analgesia

Type of pain eg neuropathic pain responds better to TCAs/AEDs, migraine responds better to triptans and NSAIDs
Severity of pain
Response to other analgesics

How well did you know this?

Not at all

Perfectly

What are the endogenous opioid receptors

Mu, kappa, delta

How well did you know this?

Not at all

Perfectly

What are endogenous opioid peptides

endorphin, enkephalins, dysnorphins

How well did you know this?

Not at all

Perfectly

Types of opioid analgesics

Full agonist, partial agonist and antagonists

How well did you know this?

Not at all

Perfectly

Central and peripheral location of receptors do what?

Modulates pain
Inhibit respiration
Slows GIT transit
Modulate NT and hormonal release
Psychomimetic effects

How well did you know this?

Not at all

Perfectly

Describe the absorption and distribution of opioids

Good absorption SQ, IM and oral
High interpatient variability in first pass effect
Rapidly distributed to highly-perfused organs (brain, kidney, liver, lungs)
Accumulates in fatty tissues

How well did you know this?

Not at all

Perfectly

Morphine metabolized to what compounds?

M3G - neuroexcitatory (GABA/glycinergic)
M6G - more potent analgesic

How well did you know this?

Not at all

Perfectly

Route of elimination of morphine, and effects when impaired

Excreted by kidney
Renal failure may lead to M3G-induced seizures
M6G - enhanced opioid effects

How well did you know this?

Not at all

Perfectly

Explain metabolism of codeine

Metabolized to active compounds by P450 CYP2D6 - demethylation to morphine
Genetic polymorphism linked to variation in analgesic response

How well did you know this?

Not at all

Perfectly

MOA of opioids

Binds to GPCR that:
1) closes voltage-gated calcium channel on presynaptic terminals, reduces NT release:
- glutamate
- ach
- NE
- seotonin
- substance P

2) open potassium channel - K efflux = hyperpolarised and inhibit post-synaptic neurons and nerve activity

How well did you know this?

Not at all

Perfectly

Opioids act on multiple synapses, transmitters and receptors, such as in

Inflamed/damaged peipheral tissue
spinal dorsal horn where pain fibers are
Descending inhibitory neurons (periaqueductal grey, rostral ventral medulla)
Release of endogenous ligands

How well did you know this?

Not at all

Perfectly

Define tolerance

Gradual loss of effectiveness with frequently repeated doses of opioid analgesics
To reporduce original response, larger dose must be given

How well did you know this?

Not at all

Perfectly

Mechanism of development of tolerance

Concepts:
1) upregulation of secondary messenger system (CAMP)
2) Failure of receptor recycling - normally activation leads to endocytosis followed by resensitisation and recycling of receptor to cell surface
3) Receptor uncoupling: dysfunction of structural interactions between mu receptor, G proteins, 2nd messenger system and target ion channel

How well did you know this?

Not at all

Perfectly

CNS effects of opioids

analgesia
euphoria
sedation without amnesia
respiratory depression
cough suppression
NV
miosis
temperature dysregulation
trunchal rigidity

no effects on cerebral blood flow and ICP UNLESS resp depression = increase PCo2

How well did you know this?

Not at all

Perfectly

Effects of opioids of CVS

Bradycardia (except meperidine - antimuscarinic actions = tachy)
Hypotension

Effects of opioid on GIT

constipation due to actions on enteric and CNS - reduced motility, increased tone
biliary colic

Effects of opioid on urinary system and kidneys

Urinary retention due to:
increased sphincter and detrusor tone
decreased awareness of bladder stimuli

Renal dysfunction from decreased renal blood flow

Other effects of opioids

Release of ADH, prolactin, somatotrophin
Pruritus
Modulation of immune system

Opioids are part of management plan for what type of pain on the WHO ladder

Moderate to severe pain

Common errors in analgesic prescription

Failure to assess pain severity
Failure to match severity to appropriate level of therapy
Failure to monitor effectiveness and modify plans if response inadequate/excessive
Failure to distinguish between acute and chronic pains - rolerance and physical dependence

Clinical uses of opioids

Analgesia
Adjuvant analgesia added to less-than-satisfactory opioid regime
Anesthetic

What type of pain does opioid works best on

Opioid works best on severe constant pain (sharp intermittent less effectively controlled)

Pain a/w cancer requires continuous use of potent opioids. How to administer?

Fixed interval administration rather than PRN use
Slow release form - longer and more stable level of analgesia
Transdermal patches if GI function prevents oral use
Buccal and nasal prep can be effective

Use of opioids in obstetric labour results in

neonatal respiratory depression Safer alternative is meperidine

Types of adjuvant analgesiics

Multipurpose (antidepressants, corticosteroids, alpha2 adfrenergic, neuroleptics) Neuroleptic pain (AEDs, LA, NMDA antagonists) Bone pain (calcitonin, bisphosphonates, radiopharm) MSK (muscle relaxants) Painr from bowel obstrction (octreotide, anticholinergics)

Clinical use of opioid as anesthetic

preop - premed as sedative, anxiolytic, analgesic intraop - adjuncts to other anesthetic agents high dose used as primary component of anesthetic regime regional analgesia by administration into epidural or subarachnoid space to act on spinal cord dorsal horn superficial neurons epidural has less SE (resp depression, pruritus, NV) GOOD for post op pain control

When does tolerance manifest

2-3 weeks of frequent exposure to ordinary therapeutic doses Develops mores readily in more potent opioids, when large doses given at short intervals

Degree of tolerance depends on

1) Opioid - more common in mu Cross tolerance may be partial or incomplete agonists 2) Effects: - marked tolerance to analgesic, sedative, respi depressant, antidiuretic, emetic and hypotensive effects tolerance does NOT develop to miotic, convulsant and constipating actions

How is tolerance managed

Opioid rotation - change to another opioid Use of adjuvant non-opioid to allow recoupling of opioid receptors - ketamine shown to reduce post-op pain and opioid requirement in tolerant patients

Symptoms of physical dependence

rhinorrhea lacrimation yawning hyperthermia piloerection hypervenetilation mydriasis muscular aches vomiting diarrhea anxiety hostility

Time of onset, intensity and duration of symptoms of physical dependence related to

DRUG and half life morphine/heroin withdrawal starts 6-10h, peaks 36-48h, ends aft 5 days methadone - less severe but last up to 2 wks

Psychological dependence such as?

euphoria, sedation, pleasurable sensation promote compulsive use

How to minimize risk of tolerance

- establish therapeutic goals before starting opioid - limit dosage at lowest effective level (no early refills, no multiple prescrtibers) - consider alternative eanalgesics - frequently re-evaluate need for opioids

Contraindications of opioids

1) Combining full agonist (morphine) with partial agonist (pentzocine) = reduce analgesia and induce withdrawal 2) HI - resp depression = cerebral vasodilation = raised ICP 3) Pregnant women - fetus develops dependent, early postpartum w/drawal 4) Avoid/reduce dose in hepatic/renal dysfx 5) Avoid combination with sedative-hypnotics (resp depression) antipsychotics (sedation, CV effects) MAOi (hyperpyrexic coma)

Contraindications of opioids