Final Exam Weng (Cumulative+ New)

The Cholinergic Hypothesis in AD —> _______ in _______, so we need _______

decrease, ACh, more ACh

Cholinesterase Inhibitors (ChEIs)

• MOA: reversibly _______ centrally-acting _______ (and butyrylcholinesterase for rivastigmine) to _______ of _______ at the synaptic gap

• Prevents breakdown of _______ in the brain

• Acetylcholinesterase inhibitors (ACheIs)

inhibits, AChE, increase concentration, ACh, ACh

• _______ (Aricept®) MOA: _______ (_______) in the _______

Donepezil, inhibits AChE, brain

_______ (Exelon®) MOA: _______ and _______ by _______ binding to respective enzyme active sites in the _______

Rivastigmine, inhibits AChE, BChE, covalent, brain

_______ (Razadyne®) MOA: _______ and _______ to _______ more _______ in the brain

Galantamine, inhibits AChE, stimulates nicotinic receptors, release, acetylcholine

Glutamate-Induced Calcium-Mediated Excitotoxicity in AD:

• _______ glutamate —> persistent _______ of _______ receptors —> lethal influx of _______ —> _______ and _______

excess, activation, NMDA, extracellular calcium, excitotoxicity, cell death

N-methyl-D-aspartate (NMDA) Receptor Antagonist

• Protects brain from _______ levels of _______, which can overstimulate _______ and result in _______

• MOA: binds to NMDA receptors, acting as a _______ that _______ the activity of _______ —> decrease _______-induced _______-mediated excitotoxicity

excessive, glutamate, neurons, neuronal death, non-competitive antagonist, blocks, glutamate, glutamate, calcium

_______ (Namenda®) MOA: _______ toxic effects associated with _______ and regulates _______

Memantine, blocks, excess glutamate, glutamate activation

_______ (Namzaric®) MOA: Same as memantine MOA + _______ in the _______

Donepezil + Memantine, inhibits AChE, brain

What is Parkinson’s Disease (PD)?

• Neurodegenerative disease that results in progressive loss of _______ and _______

coordination, movement

Dopamine is _______ in PD

severely reduced

DA _______ freely cross blood-brain barrier (BBB)

• _______ crosses BBB (with some help) and is used by brain to synthesize more _______ —> improvement in _______ symptoms

However, only a _______ of L-DOPA actually makes its way across BBB into neuron.

does not, L-DOPA, DA, motor, small percentage

_______ (Sinemet) MOA: _______ (_______) to _______ peripheral metabolism of _______ (DA precursor) to DA_______

• Carbidopa _______ in peripheral tissues

Carbidopa/Levodopa, inhibits dopa decarboxylase, DDC, prevent, levodopa, DA, inhibits DDC

_______ (Zelapar) and _______ (Azilect) MOA: selectively _______ to block _______ to _______

Selegiline, Rasagiline, inhibits MAO-B, DA breakdown, DOPAC

Antiepileptic drugs (AEDs) work by:

• Blocking _______ channels

• Blocking/altering _______ channels

• Increasing _______

• Decreasing _______

Sodium, Calcium, GABA, Glutamate

Suppression of Na+ Influx

• Neuronal action potentials are propagated by _______ though _______

• After depolarization, _______ is _______ (_______) and returned to resting “standby” state

sodium influx, sodium channels, sodium, inactivated, closed

Suppression of Na+ Influx: Na+ Channel Blockers

• Reversibly _______ to _______ in _______ state

• _______ return to active state

• Decreases/suppresses high frequency _______

binds, sodium channels, inactive, delays, excitation

_______ (Lamictal) MOA: _______

• _______ increases lamotrigine concentrations

• Oral _______ reduces lamotrigine

Lamotrigine, sodium channel blocker, Valproic Acid, estrogen-containing contraceptives

_______ (Tegretol) MOA: _______

• _______ that will _______ its own levels

Carbamazepine, sodium channel blocker, autoinducer, reduce

Suppression of Ca2+ Influx

• Ca2+ influx in _______ through _______ channels

• Promotes _______

• Produces _______

axon terminals, voltage-gated, NT release, neuronal excitation

AEDs: _______ —> decreasing _______ —> decreasing synaptic release of _______

block voltage-gated calcium channels, calcium entry, glutamate

_______ (Lyrica) and _______ (Neurontin) MOA: _______, decreasing synaptic _______

• Binds to voltage gated Ca2+ channels at alpha-2-delta subunit —> _______ Ca2+ _______ —> decreasing synaptic release of _______

Pregabalin, Gabapentin, calcium channel blocker, glutamate release, decreasing, entry, glutamate

Endogenous opioids are naturally occurring _______

• Bind to opioid receptors (μ , δ and κ)

• _______ —> μ-opioid receptors

• Inhibit _______ transmission and modulate _______

peptides, endorphins, pain, mood

Role of Exogenous Opioids

• Exogenous opioids are more _______ and provide stronger, longer-lasting, and more controllable _______ compared to endogenous opioids

• Act primarily at the μ-opioid receptor

• Exogenous opioids mimic _______ at μ-opioid receptors, relieving _______ and inducing _______

potent, analgesia, endorphins, pain, euphoria

Centrally-Acting Opioid Agonists MOA: μ-opioid receptor (_______) _______ that inhibit _______

MOR, agonists, pain signaling

Drugs Used for Parkinson’s Disease (PD)

Dopamine Replacement

• Carbidopa/Levodopa (_______)

COMT Inhibitor

• Entacapone (_______)

• Entacapone + carbidopa/levodopa (_______)

• Tolcapone (_______)

Dopamine Agonists

• Bromocriptine (_______)

• Pramipexole (_______)

• Ropinirole (_______ XL)

• Rotigotine (_______)

• Apomorphine (_______, _______)

Sinemet, Comtan, Stalevo, Tasmar, Cycloset, Mirapex, Requip, Neupro, Apokyn, Kynmobi

Drugs Used for Nociceptive Pain

Centrally Acting Opioids

• Morphine

• Hydromorphone (_______)

• Oxymorphone

• Fentanyl (_______)

• Methadone

• Buprenorphrine

• Hydrocodone

• Meperidine (_______)

• Oxycodone

Dilaudid, Sublimaze, Demorol

Centrally-Acting Opioid Agonists

• Presynaptic effect: _______ channels

• Postsynaptic effect: _______ channels

closes voltage-gated calcium, opens potassium

GABA-A features:

• Pentameric structure

• Functions as _______ channel

• Major target of many _______ and _______ agents

GABA binds at _ sites between alpha and beta subunits —> triggering _______ with membrane _______

• Reduction of excessive _______ —> decrease in _______

chloride ion, anxiolytic, hypnotic, 2, chloride channel opening, hyperpolarization, neuron firing, sympathetic effect

Drugs Used to Treat Anxiety

Benzodiazepines (BZDs)

• Alprazolam (_______)

• Clonazepam (_______)

• Diazepam (_______)

• Lorazepam (_______)

• Chlordiazepoxide

• Clorazepate (_______-T)

• Oxazepam

• Temazepam (_______)

Benzodiazepine (BZD) Antagonist

• Flumazenil (_______)

Miscellaneous Drugs

• Buspirone (_______)

Beta-Blocker

• Propranolol (_______ LA/XL)

Xanax, Klonopin, Valium, Ativan, Tranxene, Restoril, Romazicon, Buspar, Inderal

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Benzodiazepines (BZDs) MOA: _______ effects of _______ by binding to an _______ binding site —> increasing _______ —> increases _______ of _______

enhance inhibitory, GABA, allosteric, GABA binding affinity, frequency, chloride channel opening

Drugs Used to Treat MDD

Selective Serotonin Reuptake Inhibitor (SSRIs)

• Citalopram (_______)

• Escitalopram (_______)

• Fluoxetine (_______)

• Paroxetine (_______)

• Sertraline (_______)

SSRI Combined Mechanism

• Vilazodone (_______)

• Vortioxetine (_______)

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)

• Venlafaxine (_______ XR)

• Duloxetine (_______)

• Desvenlafaxine (_______)

• Levomilnacipran (_______)

Monoamine Oxidase Inhibitors (MAOIs)

• Isocarboxazid (_______)

• Phenelzine (_______)

• Tranylcypromine (_______)

• Selegiline (_______- transdermal patch)

Celexa, Lexapro, Prozac, Paxil, Zoloft, Viibryd, Trintellix, Effexor, Cymbalta, Pristiq, Fetzima, Marplan, Nardil, Parnate, Emsam

Selective Serotonin Reuptake Inhibitors (SSRI) MOA: selectively _______ reuptake of _______ by _______

• _______ has longest half-life

• _______ and _______ are potent CYP___ inhibitors

inhibits, 5-HT, blocking SERT, fluoxetine, fluoxetine, paroxetine, 2D6

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs) MOA: _______ reuptake of _______ by binding to _______

• Greater affinity for _______ than _______

• Do not have much affinity for other receptors

• Better _______

inhibit, 5-HT and NE, SERT and NET, SERT, NET, tolerability

Monoamine oxidase (MAO): degrades monoamines, such as _______

MOA: _______ the activity of MAO enzymes, _______ of monoamine _______ (_______)

5-HT, NE, and DA, inhibit, preventing breakdown, transmitters, 5-HT, DA, and NE

What Happens in Insomnia?

1. Low levels of _______ (_______)

2. Low levels of _______ (_______)

3. High levels of _______ (reticular formation _______ —> _______)

What do all three of these mechanisms have in common?

• _______ —> inhibit sleep, inability to suppress arousal/wakefulness

• _______ —> activate arousal/wakefulness and inhibit sleep

melatonin, VLPO, GABA, reticular formation, orexin and histamine, hyperactive, inactivates VLPO, inhibit VLPO, activate reticular formation

How do we treat insomnia?

1. Increase _______

2. Increase _______

3. Decrease _______

4. Decrease _______

melatonin, GABA, orexin, histamine

Melatonin Receptor Agonists MOA: selective _______ by binding to _______ receptors —> promotes sleep

dual agonist, both MT1 and MT2 melatonin

Z-Drugs MOA: _______ by selectively binding to _______ receptors at the _______ subunit

• Non-_______

enhance GABA, GABAA, alpha-1, BZD GABA agonists

Orexin Receptor Antagonists MOA: _______from binding to _______ and _______, therefore, _______ —> promoting sleep

• _______ (_______) drug

blocks orexin A and B, OX1R, OX2R, suppressing arousal/wakefulness, dual orexin receptor antagonist, DORA

Drugs Used to Treat Insomnia:

Melatonin Receptor Agonists

• Ramelteon (_______)

• Tasimelteon (_______)

Z-Drugs (Non-BZDs)

• Eszopiclone (_______)

• Zaleplon (_______)

• Zolpidem (_______ CR, _______, Edluar, _______)

Orexin Receptor Antagonists

• Lemborexant (_______)

• Suvorexant (_______)

Rozerem, Hetlioz, Lunesta, Sonata, Ambien, Zolpimist, Intermezzo, DayVigo, Belsomra

Substance Abuse

• μ-opioid receptors (MOR): MOR _______ leads to _______ cAMP, _______ K⁺ efflux, _______ Ca²⁺ influx → neuronal _______

• Inhibition of _______ interneurons in the mesolimbic pathway (reward system), leads to _______ dopamine _______ → _______ + reinforcement

activation, decreased, increased, decreased, inhibition, GABA, increased, release, euphoria

Drugs Used for Opioid Use Disorder (MBN)

• _______

• _______

• _______

Drugs Used for Alcohol Use Disorder (NAD

• _______

• _______

• _______

Drugs Used for Tobacco Use Disorder (NVB)

• _______

• _______

• _______

Methadone, Buprenorphine, Naltrexone, Naltrexone, Acamprosate, Disulfiram, NCT, Varenicline, Bupropion

Methadone MOA: _______-acting, _______ that produces sustained receptor _______ (Gi-coupled: _______ cAMP, _______ K⁺ efflux, _______ Ca²⁺ influx), thereby _______ symptoms and reducing _______ while blunting euphoric effects of shorter-acting opioids

• _______, _______-acting opioid “substitute”

• _______ onset and _______ half-life → _______

long, full MOR agonist, activation, decreased, increased, decreased, suppressing w/d, cravings, safer, long, slow, long, minimal euphoria

Buprenorphine MOA: _______-acting _______ with high receptor _______, producing sufficient receptor activation to _______ symptoms and reduce _______ while exhibiting a _______ that limits euphoria and respiratory depression

• _______, _______-acting opioid “substitute”

long, partial MOR agonist, affinity, suppress w/d, cravings, ceiling effect, safer, long

Naltrexone MOA: _______-acting _______ that _______ receptor activation, _______ (no Gi activation → no _______ cAMP), thereby eliminating _______ and reinforcing effects of opioids

• Acts as a _______ therapy that _______ effects of _______ opioids

long, competitive MOR antagonist, blocks, preventing opioid-induced signaling, decreased, euphoria, non-opioid, blocks, exogenous

Alcohol Use Disorder 

Enhances _______ → _______

Inhibits _______ → _______

Increases _______ → _______

GABA, sedation, glutamate, cognitive slowing, dopamine, reward/euphoria

Naltrexone MOA: _______ that binds opioid receptors _______ them, _______ endogenous opioid signaling and blunting _______ in the _______ reward system, thereby reducing alcohol-induced _______ and _______

• Does not alleviate _______ and is _______

competitive MOR antagonist, without activating, blocking alcohol-induced, dopamine release, mesolimbic, euphoria, cravings, w/d symptoms, non-addictive

Acamprosate MOA: _______ that restores the balance between excitatory (_______) and inhibitory (_______) neurotransmission disrupted by chronic _______ use, thereby reducing _______ and promoting _______

• Does not produce _______ or affect alcohol _______, _______

glutamatergic modulator, glutamate, GABA, alcohol, cravings, abstinence, euphoria, metabolism, non-addictive

Disulfiram MOA: an _______ (_______) _______ that _______ the _______ of acetaldehyde, a toxic intermediate of alcohol, causing acetaldehyde _______ if alcohol is consumed. This results in unpleasant effects and acts as a _______ to drinking

• Creates an _______ reaction (flushing, nausea, vomiting, headache, palpitations) when alcohol is ingested

• Does not reduce _______ or _______

• _______

aldehyde dehydrogenase, ALDH, inhibitor, blocks, metabolism, accumulation, deterrent, aversive, cravings, w/d symptoms, non-addictive

Varenicline MOA: _______(α4β2) _______ that produces _______-level receptor _______ while competitively _______, thereby reducing _______ and blunting _______ surges responsible for reinforcement + reward

• May cause serious neuropsychiatric events

• _______ blockade (_______ activity)

partial alpha-4, beta-2, nictotinic ACh receptor agonist, low, stimulation, blocking nicotine binding, w/d symptoms, dopamine, competitive, antagonist

Bupropion MOA: _______ reuptake of _______ to _______ and _______; also acts as a _______

• _______ (_______), _______

• May increase risk of seizures

blocks neuronal, DA and NE, reduce nicotine cravings, w/d symptoms, nicotinic ACh receptor antagonist, norepinephrine-dopamine reuptake inhibitor, NDRI, non-competitive, seizures

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