CNS Drugs: Opioids and Drugs of Abuse Flashcards
Exam 4
What are the 3 types of endogenous ligands?
- Endorphins
- Enkephalins
- Dynorphins
What are the 2 types of neurons in hierarchical systems?
Relay neurons – relay signal to other parts of CNS
Circuit neurons – local, control
Relay neurons are _______. Which neurotransmitter(s) are included in this neuron type?
Excitatory (EPSP) - Glutamate and tachykinins
Circuit neurons are ________. Which neurotransmitter(s) are included in this neuron type?
Inhibitory (IPSP) – GABA, glycine, dopamine, and opioid peptides
What are the neurons included in the nonspecific (diffuse) systems?
NE, Dopamine, 5-HT, ACh
Diffuse activation is conducted by small, ___________ fibers
unmyelinated
ACh-secreting neurons have cell bodies located in the ______ and the _____, that project to the ______, _______, and _______
ventral telencephalon; pons
cerebrum, hippocampus, and thalamus
ACh secreting neurons can be linked to what 3 functions?
- Learning and memory
- Sleep wake cycles
- Arousal and sensory information
What are the two components of pain?
Sensory and emotional
What are the 3 stimuli of pain?
- Noxious chemical
- Thermal
- Mechanical
What are the 3 pathways of sensation transmission?
- Non-noxious mechanical stimulus (A beta) - all cutaneous mechanoreceptors, highly myelinated
- Noxious heat, mechanical stimuli (A delta) - sharp pain, initial reflex, highly myelinated
- Noxious chemical, heat, mechanical stimuli (C) - slow, burning pain, unmyelinated
What are the 2 methods of pain suppression?
- Opioids – block pathway
- Anti-inflammatory – suppress nociceptor signaling
What are the 2 pain pathways that respond to noxious chemicals?
Tissue damage – bradykinin
- Receptors – B1 (inflammatory) and B2 (constitutive)
- Activate PLA and PLC
AA Cascade – COX and LO - Prostaglandins
What is the most common opioid receptor subtype in the CNS?
μ (mu)
What are the 3 opioid receptor subtypes?
μ (mu), δ (delta), and Κ (kappa)
What is the medication that is a μ (mu) receptor antagonist?
naloxone (Narcan)
What are the 2 medications that are μ (mu) receptor full agonists?
morphine, fentanyl
What are the 2 medications that are μ (mu) receptor partial agonists?
codeine, oxycodone
What are the 5 functions of the μ (mu) opioid receptors?
Spinal analgesia, sedation, inhibition of respiration, slowed GI transit, modulation of hormone/NT release
μ (mu) receptors have the highest affinity to which endogenous opioid peptide?
endorphins
δ (delta) receptors have the highest affinity to which endogenous opioid peptide?
enkephalins
Κ (kappa) receptors have the highest affinity to which endogenous opioid peptide?
Dynorphins
What are the three pain tracts in the CNS? What are their main focuses?
Spinothalamic → primary pain pathway
Spinoreticular → emotional pain sensation
Spinomesencephalic → mu-opioid receptors
Pharmacokinetics of opioids: absorption
Well absorbed (IM, SQ, Oral)
- Nasal, patch – avoid first pass effect
- Codeine: low 1st pass metabolism
Pharmacokinetics of opioids: distribution
Highly perfused tissues – accumulation
- Brain, heart, kidney, liver
- Skeletal muscle – reservoir
Pharmacokinetics of opioids: metabolism
Varied:
- Morphine – Phase II to active forms (M3G, M6G)
- Esters (heroin) – tissue esterases to morphine
- Other – Phase I (CYP3A4, CYP2D6)
Pharmacokinetics of opioids: excretion
Mainly in urine
What are the 3 opioid peptides?
enkephalins, endorphins, and dynorphin
What is the MOA of opioids?
- Bind to receptors in brain and spinal cord
- Modulation of pain
- Receptor effects
- Reduce neurotransmitter release (Glutamate, ACh, NE, serotonin, substance P)
- Hyperpolarize postsynaptic neurons
What are the 6 CNS effects of opioids?
- Analgesia – sensory and emotional aspects
- Euphoria (dysphoria)
- Sedation
- Respiratory depression - brainstem
- Cough suppression
- Miosis (always – marker)
What are the CV effects of opioids?
- Most have no direct effects
- Bradycardia (CNS)
- Meperidine (Demerol) - tachycardia
What are the GI effects of opioids?
Constipation (ENS) – marked, no tolerance
Which of the 2 side effects of opioids don’t change with tolerance?
miosis and constipation
______ is an opioid antidiarrheal that only has CNS effects when given with _______
Loperamide (GI ABCB1)
Quinidine (ABCB1 inhibitor)
List the 7 applications of opioids
- Analgesia
- ACS -MONA
- Acute pulmonary edema
- Cough
- Diarrhea
- Shivering
- Anesthesia
What are the symptoms of opioid toxicity?
- Dysphoric Reactions – Restlessness, tremor
- Respiratory depression
- Nausea and Vomiting
- Increased intracranial pressure
- Postural hypotension (worsened with hypovolemia)
- Constipation
- Urinary retention
- Itch (parenteral)
Differentiate between opioid tolerance, dependence and withdrawal
Tolerance - fairly rapid
Dependence - continuation despite negative effects, withdrawal symptoms if d/c’d
Withdrawal - Stems from Physical and Chemical dependence
What are the symptoms of opioid withdrawal?
- Rhinorhhea
- Lacrimation
- Yawning
- Chills
- Piloerection
- Hyperventilation
- Hyperthermia
- Mydriasis
- Muscle aches
- N/V/D
- Anxiety
- Hostility
______ is given for drug overdose
Naloxone (Narcan)
_____ is given for alcohol withdrawal
Naltrexone
Why should opioids be given sparingly in head injuries?
Opioids may enhance respiratory depression (lethal)
Define Opioid Induced Hyperalgesia (OIH) and explain the mechanism
Increase pain sensation, distinct from original pain complaint that occurs in 30% of chronic use patients
Sensitization of muOR - MOR-1K (increases cAMP in cell)
What is the treatment for Opioid Induced Hyperalgesia (OIH)?
- Taper off opioids
- Switch to alternative pathway (GABA analogs)
What are the 3 structural classes of opioids?
- Phenanthrenes
- Phenylheptylamines
- Phenylpiperidines
What are the 3 Phenanthrenes that are strong opioid agonists?
- Morphine, hydromorphone (Dilaudid)
- Heroin (diacetylmorphine)
What is the Phenylheptylamine that is a strong opioid agonist?
Methadone
What are the 2 Phenylpiperidines that are strong opioid agonists?
Fentanyl and Meperidine (Demerol)
Which opioid is the only opioid that causes tachycardia? How?
Meperidine (Demerol) - Antimuscarinic effects (tachycardia)
What is the main use for Meperidine (Demerol)?
Post-op shivering
What are the 2 cautions in administration of Meperidine (Demerol)?
- Serotonin syndrome
- Seizures - potentiate seizures for already exposed patients
What are the 2 treatments for post-operative shivering?
Meperidine (Demerol) and Ondansetron
What are the 3 Phenanthrenes that are moderate opioid agonists?
- Codeine, oxycodone
- More effective as combinations
- Oxycodone + acetaminophen = Percocet
- Oxycodone + Aspirin = Percodan
What is the Phenylpiperidine that is a moderate opioid agonist?
Tramadol
What are the 3 opioid antagonists?
Naloxone, naltrexone, naloxegol
Buprenorphine (Buprenex) is a ______ agonist
partial
Which partial opioid agonist can be used for post-op shivering?
Butorphanol (Stadol)
What opioid can be used for cough suppression?
Dextromethorphan
