Opioids - Fitz Flashcards
What channels do opioid block to have it’s effects?
Ca and K channels. Works on both pre and post synaptic neurons.
Which opioids that which binds to mu receptor are considered full agonists? which one is more potent?
Fentanyl and morphine. Fentanyl is more potent
Which mu receptor opioid drug acts as partial/mixed agonist?
Buprenorphine
Which drug that acts on the mu receptor are antagonists of the receptor?
Naloxone and naltrexone
In the pain treatment ladder, which drugs are common used for mild pain, moderate persistent or uncontrolled pain, and severe persistent or uncontrolled pain?
Mild: NSAID; acetaminophen
Moderate: Codeine; + acetaminphen, tramadol
Severe: Morphine, Fentanyl
What are the clinical effects of Mu agonists?
- Analgesia (supra-spinal)
- Euphoria
- CNS and respiratory depression
- Drug dependence
- Miosis
- GI, uterine motility
What are the clinical effects of kappa receptor agonists?
- Analgesia (spinal0
- Sedation
- Miosis
- GI uterine motility
One of the challenge with using opioids for pain relief is that tolerance varies from patient to patient. In addition, over time, for a given dose, the response deteriorates, necessitating an increase in dose or rotation to different opioids. However, which opioids clinical effects, are there no tolerance, meaning those effects do not deteriorates with change in dose, or length of use?
Miosis and constipation
Why is morphine contra indicated for brain injury and emphysema?
- Morphine depresses respiration, due to it’s depressed sensitivity to CO2. Minute volume, and tidal exchange decreases.
What are some clinical indications for morphine?
- post operative pain
- Cancer related pain
- Sickle cell crisis, trauma, severe diarrhea, dyspnea due to pulmonary edema from LVF
which full mu opioids receptor agonists drugs have a high oral/parental potency ratio indicating that they have a good oral bioavailability
Methadone, and levorphanol
Morphine undergoes extensive first-pass effect. Which metabolites are active and which ones are inactive? what enzymes are involved?
Morphine metabolism via UGT 1A1, UGT2B7 forms M-3 glucuronide and M-6-Glucuronide both of which are active. Dehydrogenase forms the active form hydromorphone.
Metabolism by CYP3A4 to form normorphine is inactive metabolite
Methadone is very similar in effect to morphine, but it’s it’s PK properties are what makes it so useful for _.
Withdrawal/maintenance and detoxification.
methadone has longer half life, better oral absorption/bioavailability than morphine.
Methadone is absolutely contraindicated in pts with what cardiac abnormality?
Long-QT syndrome. Methadone can affect cardiac electrical conduction, producing QT-interval prolongation in acute overdose or during long-term methadone treatment.
Methadone disrupts the HERG K channels
What effects of meperidine makes it different from other mu agonists?
It’s effects on the eye, causes pupil dilation. this makes it abuse difficult to detect where abuse is normally detected via pinpoint pupils.
2. Normeperidine, a toxic metabolite accumulates and causes seizures. this is different from other mu agonists in that this causes excitation whereas others causes sedation.
Which of the following can act on mu, delta and the kappa receptors. A. Fentanyl B. Sufentanil C. Alfentanil D. Remifentanil
B. Sufentanil
Which of the following is the shortest acting and is gaining popularity in childbirth use. A. Fentanyl B. Sufentanil C. Alfentanil D. Remifentanil
D. Remifentanil. Because it’s fast acting and because it’s rapidly metabolized it lowers the risk of neonatal depression.
Which of the following is MOST potent? A. Fentanyl B. Sufentanil C. Alfentanil D. Remifentanil
A. Fentanyl
_ is a partial mu agonist, and thus has less potential for drug dependence and respiratory depression. It has reliable oral absorption (about 50%) and helps relieve moderate pain. It’s also an antitussive agent, though not as safe as dextromethophan which works independent of the mu receptor and thus not addictive and not analgesic.
Codeine
There were new cases of deaths in kids being treated for sleep apnea due to use of codeine. What was causing the death?
Codeine gets converted to norcodeine (an inactive drug). But it also gets converted to morphine which is an active metabolite via CYP2D6. The problem really isn’t that it gets converted to morphine but rather how fast. These kids had evidence of being ultra-rapid metabolizer of codeine (due to gene duplication), which is an inherited ability that cause the liver to convert codeine into life-threatening or fatal amounts of morphine in the body
What two opioids are used as anti-diarrheal?
Loperamide and diphenoxylate. regular opoioids can be used for diarrhea, but these drugs have limited abuse potential and has relatively low solubility.
Which drug is a moderate mu agonist, has all the characteristics of traditional opioids, but in addition inhibits catecholamine reuptake and thus is a caution in patients on tricyclic, or SRI anti-depressants and has been associated with seizures.
Tramadol
Why has buprenorphine been used as a office-based detox/maintenance?
Buprenorphine is a partial/mixed agonist and thus has a mild analgesic effects. Thus by giving it to addicts, you’re giving a mild high, without the full effects of opioids.
patient comes to the ER with pinpoint pupils, low respiratory rate, stupor, sedation, they suspect they are an addict and has overdosed on opioids. What do you give them to reverse these effects?
mu receptor antagonist such as naloxone (IV) or naltrexone (PO). these work by displacing the agonist from the receptor.
Naloxone has 0% bioavailability if given oral and thus ONLY given IV.
