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Flashcards in First Pass Miss Exam 3 Deck (124):

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?

1. Closing of voltage gated Ca channels on presynaptic nerves -> prevent release of NT
2. 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


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?


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


What are the two clinically important MAO inhibitors? What is their mechanism of action?

1. Tranylcypromine - try a sip of wine
2. Phenelzine - funnel leading into bottle of wine

They nonselectively bind and irreversibly inhibit MAO-A and MAO-B


What is the mechanism of action of TCA's? What other receptors do they inactivate?

Imipramine, Desipramine, Clomipramine (OC!!D)

Blockage of NE and 5-HT reuptake, and blockade of 5-HT2 subtypes

Secondary: "Dirty drugs" - blockade of:
H1 receptor - swatting bee dodgeball
alpha1 receptor - alpha1 cupcake candle
M1 receptor - anticholinergic tea party
Na channels - peanut stand, heart effects


What are the contraindications of TCA's and why?

Prostatism / narrow angle glaucoma - anticholinergic effects
Post-MI and heart block - anticholinergic effects
Bipolar disorder -> can lead to a switch syndrome (mania after depressive episode)


What are the features of TCA overdose?

Other than craziness from anticholinergic effect:

3 C's

Convulsions - seizures, antagonist to GABA-A receptor?
Cardiotoxicity - Na channel interference can cause prolonged QRS and QT -> leads to TdP arrhythmia


What are the adverse effects of TCA's not in overdose?

1. Weight gain
2. Anticholinergic effects
3. Cardiovascular effects - tachycardia (M1), orthostatic hypotension (alpha 1), conduction delay and arrhythmias (Na channel)
4. CNS - drowsiness / lethargy (H1), lowers seizure threshold - shaking kid


What are the clinical indications of TCA's?

Major depressive disorder - second line due to toxicity

Chronic pain syndromes - i.e. migraine bell, diabetic neuropathy diasweeties

OCD - kid compulsively sorting marbles


Other than depression, what are SNRI's good for treating?

Neuropathic pain (diasweeties machine with broken cord) as well as fibromyalgia (fiber bars)


What are the adverse effects of bupropion? How does this relate to contraindication?

Can cause insomnia, nightmares, anxiety, and seizures

Contraindicated (seizure risk) for patients with history of CNS tumor, seizures, head trauma, or **eating disorders** - think of girls having a seizure with their eating disorders on the basketball court in sketchy


What drug class is trazodone in? Mechanism of action?

Trazodone trombone

In the SARI class - Seratonin antagonist / Reuptake Inhibitor

Antagonizes the 5-HT-2 receptors in specific (basketball number 52), also the alpha 1 receptor (burnt out alpha1 lighter) and H1 receptor (bee being swatted on head of player)

Low dose hypnotic, high dose antidepressant
-> augmentation therapy for insomnia


What is the mechanism of action of Mirtazapine?

Alpha-2 antagonist -> increases NE and serotonin in the synapse

H1 antagonist: relieves insomnia at night but possible daytime sleepiness

Antagonizes 5-HT-2 and 5-HT-3: Less nausea, GI, insomnia, and anxiety

Net effect is boosted 5-HT to 5-HT-1 receptor: decreased depression


What class of drugs is Nefazodone in and what does it share all its characteristics with?

SARI - like trazodone


What are the clinical features of serotonin syndrome? When does this most often occur?

Hyperpyrexia (high temp), hyperreflexia, hypertension, agitation, tremor, tachycardia, and myoclonus

Any serotonin reuptake blocking agent (including drugs of abuse like cocaine, and dextromethorphan / linezolid) + a MAO-Inhibitor


What SSRI's are safest and most dangerous in pregnancy?

Safest - Fluoxetine and citalopram

Dangerous - Paroxetine, particularly ASDs and VSDs of the heart


How long does it take for lithium action to be seen? What should be done to treat acute episodes of mania in light of this?

Halflife is 24 hours -> onset of action is around 10-14 days

Thus, in acute episodes, start lithium and acutely treat with an antipsychotic or benzodiazepine (i.e. valium)


What are the most common dose-related effects of lithium toxicity and when are these worse?

Worse 1-2 hours after oral dosing, when plasma levels are highest

Include: GI distress, fine hand tremor, and polyuria-polydipsia


Why does lithium cause polyuria and lithium-induced diabetes insipidus (LINDI)?

Polyuria - due to inhibitory effect on vasopressin -> increase in urine volume and thirst

LINDI - due to loss of responsiveness to antidiuretic hormone in the kidney (lithium is brought in principle cells and reduces the expression of aquaporin-2)
-> treated with amiloride or HCTZ


What factors predispose to lithium toxicity?

Sodium restriction / loss, dehydration, vomiting / diarrhea, and drug interaction which reduces lithium clearance

-> maintain adequate sodium and fluid intake


What three drug interactions are most likely to cause lithium toxicity and why?

1. NSAIDs - reduction of GFR increases Na / Li resorption in PCT

2. Thiazide diuretics - reduce GFR

3. ACE inhibitors - reduce GFR


What are two drugs which decrease lithium levels?

1. Caffeine / theophylline - increase diuresis and lithium clearance
2. Sodium -> high dietary sodium intake promotes renal clearance of lithium


Should lithium be used in pregnancy and why?

Probably not, especially in first trimister due to two conditions.

1. Ebstein's anomaly - downward displacement of tricuspid valve into right ventricle (think of the snowmen in sketchy)
2. Floppy infant syndrome - low apgar scores, hypotonia, lethargy, shallow respiration, hypothyroidism, and goiter


What is the treatment of lithium toxicity?

Gastric lavage + IV fluids, with monitoring of electrolyte status.

Hemodialysis may be required at very high levels


What is an important physical sign / risk factor for falling? What can induce it?

Orthostatic hypertension -> diuretics, nitrates, psychoactive drugs


What are the distribution changes that occur with age? (think of body composition changes) How does this influence halflife?

1. Decreased lean body mass -> increase plasma concentration of water soluble drugs (decreased half life)
2. Increased body fat -> higher Vd for lipophilic drugs (higher halflife)
3. Total body water decreases -> increased plasma concentration of water soluble drugs
4. Decreased serum albumin concentration -> decreased protein binding, can lead to toxicity if extra drug is given


What is the Cockroft-Gault equation?

Formula for adjusting drug doses for renal function, based on body weight parameters and creatinine concentration (Age > 75)

Creatinine Clearance = ((140-age) * wt / (Scr * 72))

Multiply by 0.85 only in women


Most of the bisphosphonates are given orally. Which is not? What do these serve to do?

Zoledronic acid is given once yearly via IV, or once every two years to prevent osteoporosis

Reduce the risk of vertebral and non-vertebral fractures


What are the common side effects of bisphosphonates? More severe?

Donate = -DRONATE ending

Upper GI side effects: esophagitis, acid reflux, esophageal ulcers (think of the rusty rod in the neck of the dino).

Also common: hypocalcemia due to antiresorptive properties (supplement with vitamin D and Ca+2)

Severe: Osteonecrosis of jaw (jaw falling off dino), esophageal cancer


What drugs are the selective estrogen receptor modulators (SERMs)?


Includes Raloxifene (think relax in Sketchy) and Bazedoxifene


What are the side effects of SERMs?

Hot flashes, peripheral edema (fluid retention like all estrogens), increased risk of venous thromboembolism (same clotting propensity increase as estrogens)

-> selectively agonize in bone but antagonize ERs in uterus and breast -> can fight cancers


What is the mechanism of action of Calcitonin and why is it rarely used for osteoporosis now?

Directly inhibits osteoclasts (reduce calcium levels) and causes excretion of Ca+2 in the kidneys (reduce calcium levels).

Mainly used in hypercalcemia
-> rarely used due to serious allergic reactions and increased risk of malignancy


What drug is a PTH analog and how does it treat osteoporosis?

Teriparatide (TA in sketchy), think Terry PARA

Once daily injections in short bursts will promote osteoblast bone formation without stimulate of osteoclast bone degradation
-> not an antiresorptive agent

Also acts in kidney to increase vitamin D production + reuptake calcium in exchange for phosphate

-> this and calcitriol are likely to cause hypercalcemia


What are the actions of active vitamin D?

1. Stimulates calcium and phosphate reabsorption in the kidney and intestines
2. Increases bone turnover
3. Blocks PTH (reduces bone breakdown overall)


What is the postulated mechanism of action of lithium?

Stabilization of catecholamine receptors, altered Ca+2 mediated intracellular functions, and increased GABA activity

Second messenger system inhibition:
-> Inhibits IMP in the Gq signalling system
-> inhibits adenylate cyclase in Gs signalling system
-> Reduces glycogen synthase kinase activity signalling cascade


What is FU used to treat? Why?

Treats solid tumors with long-term low dosages, since leukemias often lack the salvage pathways required to activate it


What is the mechanism of action of temolozolomide? Its use?

Agent which has a breakdown product alkylating guanine residues (most common site for alkylating agents)

Used for brain tumors


What does Ara-C effectively treat and its high dose toxicity?

Ara-C - effectively treats acute leukemias as it is not self-limiting

High dose - irreversible CNS damage

Typical: GI tract / marrow suppression


Why is bleomycin very useful? How does it work?

Breaks and fragments DNA strands, mainly lethal to cells in the M phase, keeps cells locked in G2 phase

Useful because it is detoxified by most tissues except lung and skin (no marrow toxicity)


Which vinca alkaloid is highly toxic and what is it used to treat?

Vincristine - highly toxic to peripheral nervous system (unexpected), treats leukemias

Vinblastine - treats solid tumors, toxic to bone marrow


What drug is a Topo 2 antagonist? What drug is it similar to?


Similar to Doxorubicin -
works against solid tumors, major toxicity is GI tract and marrow, but NO cardiac toxicity


What drug is used to treat CML?

Imatinib - tyrosine kinase inhibitor for philadelphia chromosome


How does ipilimumab work?

Binds the PD-1 site on T cells to prevent PD-1 / PD-L1 interaction

->checkpoint inhibitor with same mechanism of action as nivolumab, used for treatment of melanoma and lung cancer

(there are also drugs which target PD-L1 on tumor cells)


How are all natural products excreted?

Bile / Liver

All antimetabolites excreted in kidney -> only methotrexate does not require phosphorylation


What is the primary factor which determines duration of action of local anesthetics?

Protein binding -> how well they bind the receptor

Since receptor binding site is hydrophobic, more lipophilic = higher binding = increased duration of action


When will ester LA metabolism be slowed or inactive?

1. Pseudocholinesterase deficiency
2. Esters administered into CSF -> need vascular absorption before inactivation
3. Pregnancy / parturition decreases activity -> longer recovery


What are the types of regional LA procedures (vs infiltration nondiscriminant proecdures)?

1. Epidural
2. Spinal
3. Nerve block - i.e. brachial plexus
-> remember that motor nerves are more peripheral


What are the types of A and C fibers and what information do they carry? How do they relate with respect to diameter / myelination?

A = heavily myelinated, in order of descending diameter
A-alpha - unconscious proprioception, motor
A-beta - DC-ML = fine touch, pressure
A-gamma - intrafusal spindle information
A-delta - ALS - acute pain, temperature

C= unmyelinated, small diameter
C - ALS - slow, aching and burning


How are amide LA's metabolized?

Via CYP450's in liver
-> decrease dose in newborns (contraindicated due to immature enzymes) and elderly


What are the toxic effects of LA in the CNS and what is done prophylactically?

CNS stimulation by depressing cortical inhibition pathways

-> dizziness, tremors, metallic taste, confusion, respiratory depression

-> also cause hypotension + vasodilation (except cocaine)

Premedicate with benzodiazepines


For a local anesthetic, is it easier to block a myelinated or unmyelinated nerve, and a small or large nerve?

Myelinated nerve -> only needs to block 3 consecutive nodes of Ranvier to block saltatory conduction

small diameter nerve -> electrical field travels farther on sections of larger nerve, and the nodes will be much farther apart (need a wider area of anesthetic to cover)


What is the primary clinical use of benzocaine and its adverse effects?

Only used TOPICALLY -> low pKa gives rapid onset. Used in creams / ointments

Adverse effects - methemoglobinemia possible


What is the primary clinical use of tetracaine and its primary adverse effect? What is the only only ester which has a long enough duration of action to be used for a spinal?

Tetracaine Used for high potency and long action in spinal anesthesia. Also for topical anesthesia of trachea, larynx, and esophagus

Adverse effect -> slowly metabolized, can cause systemic toxicity


What is the only amide LA which can be used topically? Why would the other amides be used?


Other amides are used because they are high potency and long-acting, with better sensory block than motor block
-> ropivacaine even has vasoconstrictive actions


What is the only ester LA not used topically?

- used for dental procedures, infiltration, and diagnostic nerve block


What is the new, best theory of how anesthetics work?

Dual Process Model of Anesthesia: Anesthetics bind to hydrophobic pockets of specific proteins that affect ion flux during membrane excitation. Can be presynaptic or postsynaptic. Resulting in:

1. Potentiation of inhibitory neurotransmitters
-> glycine, GABA, K+ channels


2. Inhibition of excitatory neurotransmitters
->NMDA receptors


What are the organ systemic effects of inhalation anesthetics (IA) and which one is the exception? Think CV, respiratory, brain, kidney, and liver.

Nitrous oxide is the exception

Think of the clown with deflating balloons from sketchy
CV - drop in blood pressure by various mechanism
Respiratory - decreased minute ventilation, hypercapnia
Brain - Increased blood flow (increases ICP)
Kidney - Decreased RBF / GFR
Liver - Decreased hepatic blood flow


What is the most used anesthetic in the world and why is it infrequently used in the US?

Halothane - smells gud

Aside from hepatotoxicity:
-Causes hypotension and arrhythmias in adults, sensitizes heart to catecholamines and increases cerebral blood flow
-> bad in strokes and cardiac problems


What are the practical uses of isoflurane, desflurane, and sevoflurane?

Isoflurane - Best in adults, fewest toxic effects, but smells bad for children

Desflurane - good in obese patients due to low O:G coefficient

Sevoflurane: Good in children, despite some seizure risk, nephrotoxicity, and expensive


Inhaled anaesthetics often come with a risk of hypotension and cardiac issues (especially halothane). What IV anaesthetic should be given to a patient with these conditions and why?

Etomidate - does not cause significant cardiovascular or respiratory depression
-> however it is not an anti-emetic like propofol, and can cause nausea/vomiting + give with lidocaine for pain on injection


In what "state" are patients in when they take ketamine?

Cataleptic state - it is a dissociative agent - causes nystagmic gaze with eyes open

Good as an analgestic and hypnotic as well as amnestic


What is propofol good for?

Rapid onset and recovery, anti-emetic, and can be used to sustain anesthesia in short procedures (no IAs needed)


What brain changes are associated with schizophrenia?

Decreased blood flow in frontal lobe / caudate during working memory tasks, loss of cortical interneurons and reduced hippocampal volume. Ventricles become enlarged due to atrophy


What hypothalamic issues can 1st generation APDs cause in the acute phase?

1. hyperprolactinemia, due to blockade of dopamine, which is PIH - crying tears of milk

2. neuroleptic malignant syndrome - rarely, dangerous fever + autonomic instability and muscle breakdown
Treat with dantrolene - fried chicken NMS buckets


What are the off-receptor effects of first generation APDs?

Sedation (H1 blockade - beeswatter), orthostatic hypotension (alpha1 blockade - burned out candle), anticholinergic effects (M1 blockade - tea party in van gogh painting)


What are the adverse effects of second generation APDs / how do they differ from first gen?

Likely fewer extrapyramidal effects, less tardive dyskinesia

QT prolongation
Weight gain, insulin resistance, T2 diabetes, hyperlipidemia (almost like beta blockers)


What drug is considered a "borderline atypical" and why?

Risperidone - more DA-related adverse effects than 2nd gen, but less 5HT-related weight gain


Give three other uses for APDs outside of schizophrenia?

1. Schizoaffective disorders - depression or bipolar with psychotic symptoms, in combination with base therapy (i.e. Papa Miller)
2. Gastroprokinetic - unlikely due to TD
3. Post-op anti-emetic - short-acting and sedating (remember the D2 receptors in area postrema)

-> think metoclopramide for 2/3


What are the adverse effects of the stimulants?

Decreased appetite / weight loss (diet pills)
Delayed sleep onset, insomnia
Anxiety / irritability
Stomach aches / headaches

metabolic, sleep, behavioral, GI


What drug was originally marked as an antidepressant but is now used less efficaciously against ADHD?


Norepinephrine reuptake inhibitor (NRI)
-> nausea, vomiting, sleeplessness
-> increases suicide risk


What drugs are used to prevent migraine currently?

1. Beta-blockers
2. Anti-epileptics
3. Antidepressants
3. Behavioral therapies (Relaxation, cognitive therapy)


What future drug target might entirely stop migraines from developing?

CGRP - either an anti-CGRP or an antagonist

Calcitonin Gene Related Peptide - Important in development of migraine


What are the functions of the anterior insular and cingulate cortexes with respect to emotional control?

Both are co-activated in response to various emotional stimuli and may play a role in fear and PTSD

Anterior Insular - more sensory in nature, control of visceral information coming in

Anterior cingulate cortex - more motor and limbic in nature - control the unpleasant experience of pain


How does increasing dopamine and the various mechanisms of addictive drugs change the brain overtime? How does this explain the inheritance of addiction?

Leads to a change in gene expression which is conserved across all addictive drugs

This is often done via epigenetic mechanisms (changes in DNA acetylation / histones) that can persist overtime long after the stimulus is gone. Some of the propensity for these epigenetic changes may even be heritable -> some people are more prone to addiction.


What is the opioid mechanism of immune-system interplay?

Opioids can actually bind the TLR4 receptors of microglia (inflammatory immune cells), and cause the release of cytokines which promote dopamine release (heightened reward).


What drug can be used to inhibit alcohol dehydrogenase? What is it used for?


Used to manage methanol and toxicity (ADH mediates toxic formic acid buildup)


What are the acute and adverse effects of poppers and snappers?


Acute: Vascular / smooth muscle dilation, increase in cerebral blood flow

Adverse: Methemoglobinemia (amyl nitrite)


What drugs can be given to blunt the withdrawal syndrome and prevent delirium tremens?

Substitutions: Benzos and Barbs
Symptomatic for seizures: Phenytoin, Gabapentin
Supportive: Thiamine (B1), NSAIDs


What are two alcohol anti-craving medications and how do they work?

Naltrexone - opioid antagonist, mechanism unclear

Acamprosate - NMDA antagonist + GABA-A agonist -> Second line due to frequent dosing


What are the two stages of ethanol dependence + ethanol removal? How do they differ?

1. Abstinence syndrome - craving, hyperirritability, anxiety, tremor, insomnia, nausea, hallucination, and seizure (NMDA /GABA are no longer being depressed)

2. Delirium Tremens - About 3 days into abstinence, does not always occur -> confusion, disorientation, agitation, hyperpyresis (fever, dehydration)


What is the triphasic withdrawal syndrome of chronic cocaine use?

1. Crash (hours) - huge depression, hypersomnolence, craving, and REM rebound

2. Subacute (weeks) - sustained depression (suicide may occur), dysphoria, lethargy, anhedonia

3. Extinction (months to years) - labile mood state, craving episodes due to personal triggers


What is the classic triad of opioid toxicity?

Coma, Respiratory Depression, Miosis

Random correlations:

TCAs are: Coma, Convulsions, Cardiotoxicity
->Doxorubicin, bupivucaine are cardiotoxic


What are the two subtypes of cannabinoid receptors and where are they present? What type of receptor are they? What is their general effect?

CB1 - Mainly in the brain
CB2 - immune cells mainly -> suppress immune system

They are GPCRs

General effect - CNS depression / decreased NT release


How do cannabinoids decrease NT release? Give an example cannabinoid that does this and what its derived from.

Anandamide - derived from arachidonic acid

Works by moving from post-synaptic to presynapic cell, inhibiting neurotransmitter release, then moving back to postsynaptic cell for degradation


What is the best drug to treat parkinsonian psychosis and how does it work?


5HT2A inverse agonist with no effect on dopamine receptors. Pure antipsychotic.


What are the nonsurgical treatments of essential tremor which are available?



Low dose primadone (or other antiseizure drugs)


What are two methods of surgical reversal of Parkinson's?

1. Ablation of thalamus or basal ganglia to restore movement

2. Deep brain stimulation - electrical stimulation of subthalamic nucleus (overactive) or GPi (overactive) to restore movement.


What are the early and chronic side effects of levodopa/carbidopa, other than longterm dyskinesia?

Early: Nausea and vomiting due to area postrema stimulation, anorexia from hypothalamic stimulation, and orthostatic hypertension

Chronic: sleepiness, and hallucinatory / dementia-related CNS effects, particularly in patients already with dementia


What drug is preferable of these three cholinesterase inhibitors for Alzheimer's and why specifically?

Rivastigmine - has no drug-drug interactions in metabolism, metabolized by cholinesterase hydrolysis

Donepezil and Galantamine are metabolized by CYP2D6 and CYP3A4


How is psychosis in Lewy body dementia treated? Why?

Clozapine or pimavanserin,

APDs have a very high risk as well -> sedation, parkinsonism, neuroleptic malignant syndrome


What is the first disease-modifying drug of Alzheimer's and how does it work?

Memantine - uncompetitive NMDA receptor antagonist, stabilizes inactive state of the NMDA channel and prevents calcium passage.

-> also helps with agitation and psychotic symptoms
-> generally treat these symptoms with antidepressants and anxiolytics
-> only for moderate to severe AD or dementia


What are the modifiable risk factors for dementia?

Everything related to CVD health (i.e. smoking and dyslipidemia), and anticholinergic burden (increases risk for MCI)


What is MSBOS?

Maximal surgical blood ordering schedule - list that predicts the number of units of blood needed for each procedure


What does CSHT mean for anesthesia and what is it for propofol?

Context sensitive half time -> how long it should take to wake up from an induction anesthetic after a procedure of a given length

Propofol - 11 minutes for a 1 hour procedure


Other than renal cell carcinoma, what other cancer is sunitinib (VEGF tyrosine kinase inhibitor) good at treating and why? Side effects?

Gastrointestinal stromal tumors -> crossreactive with platelet-derived growth factor receptor (PDGFR) and c-KIT

Hypertension and **hypothyroidism**


What cancers is cetuximab useful for?

Colorectal adenocarcinomas and head and neck squamous cell cancers


What cancer type is erlotinib used for?

EGFR-mutated non-small cell lung cancers (exons 19 and 21)


What tumors is bevacizumab used for?

Colorectal (think of colon under vegetable table and blood splattering on the chest area) and lung cancers

Adverse effects include:
Bleeding (blood on beverage lady's shirt)
Hypertension (increases peripheral vascular resistance)
Proteinuria (altered kidney blood flow)


What is nivolumab used to treat?

Melanoma, lung cancer, and kidney cancer


What drug is the prototype Antibody-drug conjugate and when is it used?

Trastuzumab (tapestry) with emtansine

Emtansine is a mitotic spindle inhibitor to breast cancer

Used in advanced HER2 positive breast cancer (her 2 kids)


How is neuropathic pain vs nociceptive pain treated?

Both are treated with opioids, non-opioids, and non-pharmacologic interventions.

For neuropathic pain, antiepileptics and SNRIs are of good value


How do neonatal phase 1 reactions compare to adult levels? Phase 2?

Phase 1: Not at full capacity until 6 months to 1 year of age

Phase 2: Not fully paced until 3 to 4 years of age, can lead to chloramphenicol toxicity


What are two drugs which are more toxic in newborns due to reduced phase 2 metabolism and why?

1. Sulfonamides - displace bilirubin from albumin. Lower levels of glucuronsyl-transferase (UGT) enzyme results in higher plasma concentrations of bilirubin, and resulting kernicterus.

2. Chloramphenicol - Lower levels of UGT resulted in accumulation of chloramphenicol which cannot be glucuronated and excreted in urine -> gray baby syndrome