Opioid Drugs Flashcards Preview

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Flashcards in Opioid Drugs Deck (50):

What receptor is the site of most opioid drug action in the CNS? Where do the endogenous opioids bind?

Mu receptor

Most endogenous opioids bind delta and kappa receptors


What are the functions of the delta and kappa receptors?

Delta - site of enkephalin binding, mediate analgesia, but less so than mu receptors

Kappa - analgesia with psychotomimetic effects -> partial agonist drugs can bind this strongly


Why are there such diverse effects of opioid receptors?

They use alternative splicing, they have many possible combinations due to receptor dimerization, and they undergo biased agonism


What is biased agonism?

Activation of the receptor via one ligand mediates different effects than activation by another opioid (slightly different signalling pathways and cascades carried out by binding the same receptor)


What are the best described effects mediated by opioid signal transduction at the cellular level?

1. Closing of voltage gated Ca channels on presynaptic nerves -> prevent release of NT
2. Opening of K channels on postsynaptic neurons -> hyperpolarize


How is morphine absorbed and why is it not taken orally?

Absorbed well by all routes, not taken orally due to extensive first pass metabolism


What is the purpose of sustained-release morphine formulations and what is the safeguard? What is this called?

They are long-acting. Safeguard is typically naltrexone in a capsule, which if crushed would lead to free opioid antagonist. This is called a diversion system.


How is morphine eliminated and what condition should it be avoided in?

Eliminated via kidneys and bile, most often by glucuronidation to an active metabolite.

Avoid in patients with renal insufficiency -> can lead to decreased clearance and possible OD


What are the analgesic effects of morphine? When is it used surgically, and can you get tolerance?

Pain relief without loss of general sensory. The pain is still reported but it affects people less.

Surgically -> used in combination with other drugs for multimodal analgesia

Can get tolerance with chronic use, and even hyperalgesia can develop


How does morphine affect mood / cognition? Where does it act?

Euphoria and tranquility, acts in locus coeruleus, mesolimbic dopamine pathway, and nucleus accumbens which all mediate pleasure and awakeness


How do the effects of morphine differ between normal, pain-free individuals and combat-injured soldiers?

Normal people: often unpleasant, causes difficulty thinking, drowsiness, nausea

Combat-injured: reduced risk of PTSD


What is a classic sign of morphine OD / abuse which does not develop tolerance, and why?


Due to excitation of parasympathetic innervation to the pupil


How does morphine inhibit cough?

Depresses cough reflex mediated by medullary cough center, at levels much lower than what would cause respiratory depression


How does morphine-mediated respiratory depression occur? Who is this important in?

Morphine decreases the response to CO2 via brain stem, which is important in patients with COPD on other CNS depressants


Why should morphine be avoided in head trauma?

Increased pCO2 can cause to cerebrovascular dilation and subsequent increased intracranial pressure


Who is most likely to vom from morphine?

Patients who are new to morphine and standing up (vestibular component to this).

Effect is mediated via area postrema chemoreceptor, and tolerance develops rapidly


What are the cardiovascular effects of morphine usage? How does this relate to one of its usages?

Peripheral vasodilation / reduced peripheral resistance. This can cause orthostatic hypotension and thus
fainting upon standing

Used for patients with dyspnea due to acute pulmonary edema associated with LV heart failure. Good in a palliative care setting.


What is the biggest quality of life concern with chronic opioid use and how is this combatted?

Constipation, due to decreased propulsive contractions and increased water reabsorption

-> proactive use of stool softeners and laxatives


What do opiates do to urinary output and labor?

Urinary output - decreased, a problem in the elderly
Uterus - prolongs labor


What systemic skin effect do opiates cause?

Itching -> not completely understood


What is heroin?

The potent, rapid-acting morphine, made into morphine rapidly by deacetylation in vivo


What painkiller is used in opioid tolerant cancer patients? How does it differ from morphine? What else is it indicated for?

Oxycodone -> more orally active than morphine

Also indicated in combination with NSAIDS for moderate-severe acute pain, but NOT chronic back pain


What is done to prevent oxycodone being used a drug of abuse?

Crush resistant, forms a viscous gel which is hard to inject or snort when crushed


What is the most widely prescribed opioid in the US and its indications?


Severe pain, also as an anti-tussive (cough)


What is the controversy surrounding hydrocodone?

FDA approved a long-active hydrocodone without tamper resistance, and also in combination with an antihistamine for coughing. Easily abused.

New formulations which are tamper-resistant have been approved


How does fentanyl differ from morphine, and why might it be preferable?

It is 80-100x more potent, and it has NO active metabolites so it is better in renal failure

-> also a short duration of action, control via IV infusion


What are the indications for fentanyl?

Acute post-op pain: patient controlled analgesia via transdermal iontophoresis -> press button to stimulate electrical current

Surgical anesthesia for multimodal analgesia

Acute hospitalized severe pain


What are the fentanyl delivery routes for opioid-tolerant patients?

Trandermal patch left on for 2-3 days

Also: Lozenges, sublingual tablets, and nasal sprays for breakthrough pain


What can increase and decrease the plasma levels of fentanyl?

Increase - CYP3A4 inhibitors like macrolides, azole antifungals, and grapefruit juice

Decrease - CYP3A4 inducers like carbamazepine, phenytoin


What is methadone and why does it have to be carefully titrated? Who is it used in

A long halflife full mu agonist - used in patients with opioid addiction to get their fix without the high

Needs to be carefully titrated because it can prolong the QT interval


How is methadone similar to fentanyl?

Has no active metabolites, so it can be used in patients with renal problems

It's almost like the opposite drug in terms of halflife


What is the oral bioavailability and action of codeine alone?

It has good oral bioavailability because it is not glucuronidated as easily as morphine

Before any metabolism, it is a weak agonist of opioid receptors and does have some modest analgesic effect + antitussive activity (think of codeine barcode)


How does codeine's metabolism affect its activity? When is this dangerous / what is the contraindication?

Codeine is metabolized to morphine via CYP2D6 demethylation.

Dangerous for CYP2D6 rapid metabolizers who can thus have a morphine overdose due to extra CYP2D6.

because of this fear, it is contraindicated in children


What two groups are likely to respond poorly to codeine?

1. Individuals lacking CYP2D6 - get no morphine
2. Individuals taking CYP2D6 inhibitors - i.e. fluoxetine

There are thus large individual differences in its activity


Name the drug which is a partial agonist at mu receptor, and dissociates slowly from the receptor leading to long duration of action and poor reversal via naloxone?

Buprenorphine - the blue print near the tapering flags from the pool in sketchy


What is the approved use of buprenorphine?

Opiate dependence -> less risk for OD due to partial agonist, especially in combination with naloxone

Secondarily: moderate-severe pain via injection or patch


What are the mixed agonist drugs which are not used and why not?

nalBU-PHINe, BUtor-PHanol, PENTAzocine

think of blue-phin bar (buprenorphine is also a partial agonist)

Less reversible, less analgesia, more respiratory depression, and most psychotomimetic effects


What is Tramadol and what do its parent and daughter compounds do?

A synthetic codeine derivative - think of the tram in sketchy

Parent compound: SNRI - think of the N/S compass on the tram

Daughter compound: Codeine derivative which is active

Requires metabolism from parent to daughter compound for analgesia


What are the indications for tramodol?

Less physically dependent opioid, seeing more use for chronic acute pain


What are the side effects of concern for tramodol?

1. Increased frequency of seizures
2. Serotonin syndrome


What are the contraindications for tramodol?

Other CYP2D6 / CYP3A4 inhibitors - increase seizure risk by limiting metabolism and increasing SNRI activity

Other antidepressants - serotonin syndrome

Patients with seizure history

Children - same reason as codeine


List the opioid receptor antagonists.

1. Naloxone - No lax zone -> rapid ending of effects
2. Naltrexone - No tricks zone -> cannot do heroine with this
3. Methylnaltrexone
4. Naloxegol


How does naltrexone differ from naloxone?

Naltrexone has the same receptor blocking profile, but naloxone is used acutely for OD whereas naltrexone is used to prevent relapse, especially in once monthly injection (highly politicized treatment for opiate addicts)


What is methylnaltrexone used for?

Opioid-induced constipation for patients in palliative care -> useful because it doesn't cross BBB and block analgesia


What is naloxegol and what is it used for?

Pegylated naloxone metabolite used for treatment of opioid-induced constipation in chronic pain patients


What opioid drugs are used exclusively for treatment of diarrhea?

These have poor gut absorption, local action
1. Loperamide (Imodium) - lope-eared rabbit
2. Diphenyoxylate - think dolphin-oxylate fountain


What is dextromethorphan used for? Contraindication?

An isomer of a full-agonist opiate - little orphan cough drops

used in combination with quinidine for chronic cough in lower airway, as well as pseudobulbar affect

Contraindicated in children


What is the PD profile of dextromethorphan?

Very strange
-> NDMA antagonist - NMDA camel
-> Sigma-1 receptor antagonist


Why are opioids of concern in the elderly?

Polypharmacy, poor clearance via kidneys, and many surgeries to merit their use -> constipation, balance issues (fainting upon standing), impaired cognition


Has opioid use in pregnancy changed recently? What are its potential effects?

Yes -> 5 fold increase due to drug abuse and weight gain-associated back pain

Effects: Neural tube defects, neonatal withdrawal syndrome