Opioids Flashcards
what are the three types of opioid receptors?
mu receptor
kappa receptor
delta receptor
*all are GPCRs
what are the precursor proteins that encode for opioid peptides?
Proenkephalin → enkephalins
Prodynorphin → dynorphins
Proopiomelanocortin (POMC) → beta-endorphin
where do Enkephalins bind?
bind to delta and mu receptors in the brain, spinal cord, adrenal medulla and GI tract
what are the two forms of Enkephalin’s?
Met-enkephalin = Tyr-Gly-Gly-Phe-Met
Leu-enkephalin = Tyr-Gly-Gly-Phe-Leu
where do Dynorphins bind?
bind kappa receptors in the brain and spinal cord (dynorphin A 1-17)
what are beta-endorphins?
neuromodulator/neurohormones released in response to stress
where do beta-endorphins bind?
mu and delta receptors in cells bodies of the intermediate lobe of the pituitary and hypothalamus
what is a similarity between the structure of all the opioid peptides?
their amino acid chain all start with Tyr-Gly-Gly-Phe
what are the Cellular Mechanisms of Action for Opioid Receptors?
ALL are inhibitory G-proteins (Gi/o)
1. Inhibit Adenylyl Cyclase
2. Close Voltage-Gated Calcium (Ca²⁺) Channels (Presynaptic)
3. Open Potassium (K⁺) Channels (Postsynaptic)
what are the ways opioids can cause analgesia?
- BRAIN: central or supraspinal by activating descending pain-inhibitory pathways and modulation of the affective (emotional) component of pain
- SPINAL: Inhibition of dorsal horn pain transmission neurons
- PERIPHERAL: Activation of opioid receptors on peripheral nerve fibers (Aδ and C fibers)
what is the MOA for opioids at peripheral sites?
mu receptors found on primary afferent neurons are activated and reduce the firing of pain-sensing nerves
what is the MOA for opioids at the level of the spinal cord (dorsal horn)?
- presynaptic: block calcium channels (↓Ca²⁺) → prevents release of neurotransmitters (glutamate)
- postsynaptic: open potassium channels (↑K⁺) → hyperpolarization
what is the MOA for opioids at brainstem sites (PAG and RVM)?
inhibition of GABAergic neurons → “disinhibits” the inhibitory pain neuron (activates descending pain control)
how do opioids cause respiratory depression?
- ↓ Sensitivity to CO₂ in the brainstem
- Depress Pontine and Medullary Regions
- ↓ Tidal Volume and Rate
- Dose Dependent Effects (tolerance can occur)
how do opioids cause cough suppression?
depress the cough reflex area in the brainstem
how do opioids cause Miosis?
activate parasympathetic pathways via the Edinger-Westphal nucleus (part of the oculomotor nerve circuit)
how do opioids cause Euphoria?
stimulate the brain’s reward system, especially the ventral tegmental area (VTA) and nucleus accumbens by enhancing dopamine release
how do opioids cause Nausea and Vomitting?
initially stimulate the chemoreceptor trigger zone (CTZ) in the medulla that causes nausea and vomiting but later suppress the vomiting center due to tolerance
how do opioids cause constipation?
Increased smooth muscle tone
Decreased propulsive motility
Reduced secretions
Biliary tract spasm
No tolerance develops
how do opioids effect the bladder, uterus and bronchioles?
- cause urinary retention
- could affect uterine contractions
- slightly reduce airway tone
- tolerance develops
how do opioids cause Pruritus?
Opioids trigger mast cells to release histamine, which causes itching, redness, and warmth and stimulate neural circuits involved in the sensation of itch
what are the cardiovascular effects of opioids?
- Minor Bradycardia
- Vasodilation from histamine release may trigger orthostatic hypotension
- Cerebral vasodilation can cause increased intracranial pressure
what is opioid use disorder?
Addiction associated with significant
psychological dependence and
accompanied by compulsive drug seeking
and drug taking behaviors.
what is acute opioid toxicity (overdose)?
excessive opioid use leading to severe respiratory depression
what are the symptoms of an opioid overdose?
Stupor
Miosis
coma
hypotension
shock
death
what is the treatment for an overdose?
restore ventilation either through artificial respiration or by administration of an opioid receptor antagonist (naloxone)
what is Morphine?
natural phenanthrene alkaloid derived from the opium poppy plant that is a mu (major), delta and kappa receptor agonist
what are the pharmacokinetics of Morphine?
- well absorbed orally but large first-pass metabolism in liver (low bioavailability)
- completely eliminated through glomerular filtration in kidneys
- oral administration preferred
- t 1/2 is 2-4 hours
- lasts for 3-5 hours
- dose every 4 hours
- IV/PO ratio: 1:3
what is Morphine-6-Glucuronide (M-6-G)?
an active metabolite produced by glucuronidation metabolism in the liver with a high affinity for mu receptors
what is opioid induced hyperalgesia?
Increased sensation of pain seen with long-term use of opioids like morphine and fentanyl maybe due to spinal dynorphin overexpression, activation of bradykinin receptors and NMDA receptor activation
what are the contraindications and cautions for opioids?
- compromised respiratory function
- kidney disease
- liver disease
- head trauma
- pregnancy
- GI conditions (obstruction or paralytic ileus)
what is Codeine?
natural phenanthrene alkaloid derived from the opium poppy similar to morphine, and has a methoxy group (–OCH₃) that provides greater oral bioavailability
what are the pharmacokinetics of Codeine?
- metabolized in the liver and a small portion is converted to morphine by CYP2D6
- excreted via urine
- lasts 4-6 hours
what are the uses and doses for Codeine?
oral analgesic: 30-60 mg
antitussive: 15-20 mg
what are the side effects of Codeine?
Low incidence of nausea, dizziness, sedation, and constipation
enhanced analgesic efficacy is produced by co- administration of codeine and ?
acetaminophen
what is Heroin (Diacetylmorphine)?
semisynthetic opioid that is metabolized into morphine and made by adding two acetyl groups to morphine making it more lipid-soluble
what is Hydrocodone?
semisynthetic opioid derived from codeine. It is used mainly for moderate-moderately severe pain relief and cough suppression and last around 4-6 hours
what are the brand names for Hydrocodone?
Vicodin®
Hycet®
Lortab®
Lorcet®
what is Oxycodone?
semisynthetic opioid, equipotent to morphine used to manage moderate to severe pain that lasts 4-6 hours (8-12 in XR)
* no active metabolites
what are the brand names for Oxycodone?
Oxycontin®
Percodan®
Percocet®
Roxicet®
Endocet®
what is Dihydrocodine?
orally available semisynthetic opioid used for mild to moderate pain, lasting about 4 hours, and is often combined with aspirin or acetaminophen
what are the brand names for Dihydrocodeine?
Synalgos DC®
Panlor DC®
what is Hydromorphone?
a semi-synthetic oral/parenteral opioid used for severe pain, lasting 3-5 hours, more potent than morphine and has no active metabolites
what are the brand names for Hydromorphone?
Dilaudid®
Long-acting formulation: Exalgo®
what is Meperidine?
synthetic Mu-opioid receptor agonist (some antimuscarinic properties) structurally unrelated to morphine used for moderate to severe pain relief lasting around 3-6 hours
what are side effects of Meperidine?
- tachycardia
- metabolite produces CNS excitation - tremors and seizures
what is the brand name for Meperidine?
Demerol
what is Methadone?
mu-opioid receptor agonist and NMDA receptor antagonist used for severe pain and opioid use disorder, with good oral efficacy and a very long, variable half-life (12–120 hrs) lasting 4-6 hours
what is a major caution of Methadone?
QT interval prolongation, which can lead to dangerous heart rhythm issues
what is the brand name for Methadone?
Dolophine
what is Fentanyl?
extremely potent mu-opioid receptor agonist (80–100x more potent than morphine) with high lipid solubility, which gives it a rapid onset and very short duration of action
what is Fentanyl used for?
used in general anesthesia, severe pain, and in patients with renal dysfunction, as it has no active metabolites, but carries a high abuse potential and can cause muscle rigidity, especially of the chest wall
what are the various formulations of Fentanyl?
IV (bolus or infusion) – for acute pain or anesthesia
Transdermal patch (Duragesic®) – for chronic pain
Lozenge (Actiq®) – for breakthrough cancer pain.
what are Mixed opioid receptor agonists-antagonists?
drugs that can activate some opioid receptors while blocking others, cause less respiratory depression, have lower abuse potentials and are used as pain relievers
What is Pentazocine?
mixed opioid receptor drug structurally related to morphine that is an agonist at kappa receptors and weak antagonist at mu
receptors used for mild to moderate pain
what are the pharmacokinetics for Pentazocine?
- Metabolized by glucuronidation in the liver
- Duration of action: 3–4 hours
- Can be administered orally or parenterally (injection).
what are the side effects of Pentazocine?
Can trigger withdrawal
High doses can cause:
- Psychotomimetic effects (hallucinations, delusions) – due to kappa receptor activation
- Dysphoria (a feeling of unease or dissatisfaction)
- Increased heart rate and blood pressure – likely due to sympathetic nervous system activation
what are the brand names for Pentazocine?
Talwin
Talwin Nx
Talacen
what is Butorphanol?
kappa receptor agonist and a weak partial agonist at mu receptors that works well for acute pain (migraines), with less risk of respiratory depression or addiction, but may cause unpleasant mood effects (dysphoria) lasting about 3-4 hours
what are the brand names for Butorphanol?
Stadol
Stadol NS
what is Buprenorphine?
partial mu-opioid receptor agonist/Kappa receptor antagonist used to treat moderate to severe pain and opioid use disorder lasting about 8 hours
what are the Forms of Administration for Buprenorphine?
Parenteral (injection) – Buprenex®
Sublingual tablets – Subutex®, Suboxone® (combined with naloxone)
Transdermal patch – Butrans® (for chronic pain)
Extended-release injectable – Sublocade® (for opioid use disorder)
What is Nalbuphine?
kappa receptor agonist/mu receptor antagonist that provides effective relief for moderate to severe pain while reducing respiratory depression risk especially useful in postoperative and anesthetic settings, but only available via injection lasting 3-6 hours
what are the low dose side effects of Nalbuphine?
sedation, sweating, headache.
- Dysphoria at high doses
what is the brand name for Nalbuphine?
Nubain
what is Tramadol?
a weak mu-opioid receptor agonist and serotonin/norepinephrine reuptake inhibitor taken orally to treat moderate pain, works for 4–6 hours, and has a low to moderate risk of abuse
what are the side effect of Tramadol?
seizures, nausea, dizziness, and risk of serotonin syndrome, especially when combined with antidepressants
what are the brand names for Tramadol?
Ultram
Ultracet
Tramadol ODT
what is Tapentadol?
modest mu-opioid receptor agonist and significantly inhibits norepinephrine reuptake taken orally for treatment of neuropathic pain and opioid-induced hyperalgesia taken every 6 hours
what is the brand name for Tapentadol?
Nucynta® IR and ER formulations
what are the side effects and contradictions for Tapentadol?
Seizures, Serotonin syndrome (especially with SSRIs, SNRIs, MAOIs) but less pruritus and GI upset than morphine
- Reduce dose in moderate liver dysfunction, avoid in severe liver disease and avoid in patients with seizure disorders
what is Naloxone?
fast-acting (1-3 min) opioid receptor antagonist used primarily to reverse opioid overdose and restore normal breathing in cases of acute toxicity lasting 1-3 hours
what are the forms of Naloxone?
Narcan® nasal spray
Evzio® autoinjector
*not effective orally
what is Naltrexone?
long-acting (48-72 hours) opioid receptor antagonist taken orally to help prevent relapse in people recovering from opioid or alcohol dependence
what are the two forms of Naltrexone?
ReVia® – oral tablet
Vivitrol® – extended-release monthly injection
what is Methylmaltrexone?
a peripherally-acting mu receptor antagonist for treatment of opioid-induced constipation or pruritus
what is the brand name for Methylmaltrexone?
Relistor
what is Alvimopan?
Peripherally-acting mu receptor antagonist for treatment of bowel recovery post surgery
what is the brand name for Alvimopan?
Entereg
what are the adverse reactions of using CNS depressants and opioids together?
Severe respiratory depression
Orthostatic hypotension
what are the adverse reactions that can occur when using MAO inhibitors (also SSRIs) with Meperidine?
Agitation, muscle rigidity, high blood pressure, hyperthermia, and even death
* can occur with tramadol, tapentadol and methadone
what are the CYP3A4 inhibitors that have adverse interactions with Buprenorphine?
- Ketoconazole (antifungal)
- Erythromycin (antibiotic)
- HIV protease inhibitors (ritonavir)
significantly increase buprenorphine levels
what are the clinical uses for opioids?
- analgesic
- anesthetic
- cough suppressant
- anti-diarrheals
