First Pass Miss Exam 3 Flashcards
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)
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
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 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 are the best described effects mediated by opioid signal transduction at the cellular level?
- Closing of voltage gated Ca channels on presynaptic nerves -> prevent release of NT
- Opening of K channels on postsynaptic neurons -> hyperpolarize
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)
After CYP2D6 metabolism, it is made into morphine
- > rapid metabolizers at risk for OD, do not give to children
- > CYP2D6 inhibitors like fluoxetine can also interfere
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
Tramodol, Codeine, and Fentanyl all rely on CYPs to some degree
What is naloxegol and what is it used for?
Pegylated naloxone metabolite used for treatment of opioid-induced constipation in chronic pain patients
What is the PD profile of dextromethorphan?
Very strange
- > NDMA antagonist - NMDA camel
- > Sigma-1 receptor antagonist
- > SNRI
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
How are benzodiazepines metabolized?
The majority must first be oxidized in the liver by CYP450, and then ALL will be conjugated with glutathione and excreted in the urine
What drug is a partial agonist of 5-HT1A receptors and what is its primary indication? How long is its effect?
Buspirone
Takes weeks to manifest the effects -> used for long-term anxiety treatment, especially generalized anxiety disorder of patients with substance abuse (not dangerous like benzos)
What is one drug which can be used for both sleep onset and sleep maintenance insomnia? Does it have abuse potential? What are its side effects?
Suvorexant -> orexin receptor antagonist
- > no abuse potential
- > daytime drowsiness and suicidal ideation
-> ramelteon CANNOT help with sleep maintenance, causes increased prolactin, decreased testosterone, and doing things will asleep
How can benzos have varying specificities, aside from their halflife?
Each has two alpha, two beta, and 1 gamma subunit, each with different isoforms -> different areas of the brain will have different receptor isoforms depending on gene expression
-> some alpha subunits of receptors are only expressed in the basal ganglia, for instance, and thus would be targeted in muscle relaxants
What is the most common side effect of benzos/barbs and who is at greatest risk? What should be done to mitigate risk?
Psychomotor dysfunction - including cognitive impairment, decreased psychomotor skills, and unwanted daytime sedation. Worse in drugs with long-lived active metabolites
Greatest risk: elderly patients, dose should be reduced by at least 50% since it increases the risk of falls and fractures. This is due to changes in brain function with aging (not liver)
What are the two primary indications for carbamazepine?
Trigeminal neuralgia and bipolar disorder
- > can also treat focal seizures or generalized tonic clonic
- > make absence and myoclonic seizures worse
What are the most common and most severe toxicities of carbamazepine? what should be done to limit toxicity?
Most common: Ataxia (pancake stack falling) and diplopia (crossed headlights of car)
Most severe - Steven-Johnsons syndrome - predicted by presence of a certain HLA-B allele most often seen in Asian patients
Screen for this allele and give with divided doses
What a final broad spectrum AED which can be used against all seizures? What is its mechanism of action?
What are the common adverse effects of levetiracetam and why is it used over the others?
Levetiracetam (think elevator)
Mechanism of action - binds SV2A glycoprotein in synaptic vesicles, modifying neurotransmitter release
Other than the typical ataxia and diplopia: causes somnolence
Used over the others for its clean PK profile - secreted unchanged by the kidney or nonhepatic metabolism to inactive metabolite (does not interact with CYP450).
What is the primary side effect of ethosuximide? When would you want to use the second line drug and what is it?
Dose-related GI stress
Second line drug: Valproic acid -> used when they may also have generalized seizures of different types, or focal seizures (ethosuximide only good for absence)
What benzo might be good to give in an ambulence for status epilepticus and why?
IM midazolam -> IM injection easier to give than IV lorazepam (or IV diazepam, followed by phenytoin or phenobarbital)
What is Lennox-Gastaut syndrome and what is the best treatment?
Multiple seizures of different types, coupled with some mental disability.
Best treatment is ketogenic diet -> high fat, low carb, medium protein.
Secondary treatments include lamotrigine, levetiracetam, and valproate
What is RNS and how does it work?
Response neurostimulator device - electrical stimulation in brain foci for drug-refractory seizures -> works about as well as vagal stimulation
Vagal stimulation also used in treatment of anxiety / depression
What is one broad spectrum anticonvulsant most commonly used for offlabel treatment of refractory migraine and bipolar disorder? How does it work?
Topiramate! - Toupee -rimate from sketchy
Works by inactivation of Na+ , agonism to GABA-A allosteric site, and inhibition of carbonic anhydrase