P/N WENG FINAL

Opioid Use disorder

Methadone

MOA: long-acting, full μ-opioid receptor agonist → produces sustained receptor activation Gi-coupled: ↓ cAMP, ↑ K⁺ efflux, ↓ Ca²⁺ influx), thereby suppressing withdrawal symptoms and reducing cravings while blunting euphoric effects of shorter-acting opioids

Opioid Use disorder

Buprenorphine

MOA: long-acting partial μ-opioid receptor agonist (Gi- coupled: ↓ cAMP, ↑ K⁺ efflux, ↓ Ca²⁺ influx) with high receptor affinity, producing sufficient receptor activation to suppress withdrawal symptoms and reduce cravings while exhibiting a ceiling effect that limits euphoria and respiratory depression

Opioid Use disorder

Naltrexone

MOA: long-acting competitive μ-opioid receptor antagonist blocks receptor activation, preventing opioid-induced signaling (no Gi activation → no ↓ cAMP), thereby eliminating euphoria and reinforcing effects of opioids

 Alcohol Use Disorder

Naltrexone

MOA: competitive μ-opioid receptor antagonist → blocking alcohol-induced endogenous opioid signaling & blunting dopamine release in the mesolimbic reward system

• Does not alleviate withdrawal symptoms, is non-addictive

 Alcohol Use Disorder

Acamprosate

MOA: Glutamatergic modulator that resotres the balance of exitatory (glutamate) and inhibitor (GABA) nuerotransmission → reducing craving and promoting abstinence

• Does not produce euphoria or affect alcohol metabolism

• Non-addictive

Alcohol Use Disorder

Disulfiram

MOA: aldehyde dehydrongenase (ALDH) inhibitor, blocks metabolism of acetalhyde, causing acetaldehyde accumulation → deterrent to drinking alcohol

• Creates aversive reaction

• Drugs does not reduce cravings or w/d symptoms

• Non-addictive

Tobacco use disorder

Bupropion

MOA: MOA: blocks neuronal reuptake of dopamine and norepinephrine to reduce nicotine cravings and withdrawal symptoms; also acts as a nicotinic acetylcholine receptor antagonist

• NDRI

• Non-nicotine therapy for smoking cessation

• Enhance dopaminergic/noradrenic activity

• Nicotinic receptor antagonism

• Risk seizures

Tobacco use disorder

Varenicline

MOA: partial alpha-4, beta-2 α4β2) nicotinic acetylcholine receptor agonist, low-level receptor stimulation while competitively blocking nicotine binding → reducing withdrawal symptoms

Alzheimer’s

Acetylcholinesterase Inhibitors: (AChE-I)

Donpezil (Aricept)

MOA: reversibly inhibits centrally-acting acetylcholinesterase (and butyrylcholinesterase for rivastigmine) to increase concentration of acetylcholine at the synaptic gap

• MOA: inhibits AChE in the brain

Alzheimer’s

Acetylcholinesterase Inhibitors: (AChE-I)

Galantamine (Razadyne®):

MOA: reversibly inhibits centrally-acting acetylcholinesterase (and butyrylcholinesterase for rivastigmine) to increase concentration of acetylcholine at the synaptic gap

• MOA: Inhibits acetylcholinesterase (AChE) and stimulates nicotinic receptors to release more acetylcholine in the brain

Alzheimer’s

Acetylcholinesterase Inhibitors: (AChE-I)

Rivastigmine (Exelon®)

MOA: reversibly inhibits centrally-acting acetylcholinesterase (and butyrylcholinesterase for rivastigmine) to increase concentration of acetylcholine at the synaptic gap

• MOA: Inhibits acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) by covalent binding to respective enzyme active sites in the brain

Alzheimer’s

NMDA Receptor Antagonist

Memantine (Namenda)

MOA: binds to NMDA receptors, acting as a non-competitive antagonist that blocks the activity of glutamate → decreases glutamate-induced calcium-mediated excitotoxicity

Alzheimer’s

NMDA Receptor Antagonist

Donepezil + memantine (Namzaric®)

inhibits acetylcholinesterase + Regulates glutamate activation

• AChE-I and NMDA non-competitve antagonist

Parkinsons

Dopamine Replacement:

Carbidopa/Levodpa (Sinemet)

MOA: inhibits dopa decarboxylase (DDC) to prevent peripheral metabolism of levodopa (DA precursor) to DA

Parkinsons

Dopamine Replacement:

Selegiline (Zeplar) and Rasagaline (Azilect)

MOA:  selectively inhibits MAO-B to block DA breakdown to DOPAC

AED for Epilepsy

Na+ Channel Blockers

• Lamotrigine (Lamcital)

• Carbamazepine (Tegretol)

• Topiramate (Topamax, Trokendi XR)

• Oxcarbamazepine (Trileptal, Oxtellar XR)

• Lacosamide (Vimpat)

• Phenytoin (Dilantin)

MOA: Na+ channel blocker

AED for Epilepsy

Ca2+ Channel Blockers

• Pregabalin (Lyrica)

• Gabapentin (Neurontin)

MOA: Ca2+ channel blocker, decreasing synaptic glutamate release

• Binds to voltage gated Ca2+ channels at alpha-2-delta subunit → decreasing Ca2+ entry → decreasing synaptic release of glutamate

Nociceptive Pain

Centrally Acting Opioids

• Morphine

• Hydromorphone (Dilaudid)

• Oxymorphone

• Fentanyl (Sublimaze)

• Methadone

• Buprenorphrine 

• Hydrocodone

• Meperidine (Demerol)

• Oxycodone

MOA: μ-opioid receptor (MOR) agonists that inhibit pain signaling, acting on both presynaptic and postsynaptic neurons

Anxiety

Benzodiazepines (BZDs)

Short Acting (1-15 hrs)

• Alprazolam (Xanax)

• Triazolam

• Exazepam

• Midazolam

MOA: enhance inhibitory effects of GABA by binding to allosteric binding site → increasing affinity of GABA binding to GABA-A receptor → increases frequency of chloride channel opening

• short

Anxiety

Benzodiazepines (BZDs)

Intermediate-acting (15-20 hrs)

• Lorazepam (Ativan)

• Temazepam (Restoril)

MOA: enhance inhibitory effects of GABA by binding to allosteric binding site → increasing affinity of GABA binding to GABA-A receptor → increases frequency of chloride channel opening

• intermediate

Anxiety

Benzodiazepines (BZDs)

Long-acting (>20 hours)

• Clonazepam (Klonopin)

• Diazepam (Valium)

• Chlordiazepoxide

• Flurazepam

• Clorazepate (Tranxene-T)

MOA: enhance inhibitory effects of GABA by binding to allosteric binding site → increasing affinity of GABA binding to GABA-A receptor → increases frequency of chloride channel opening

• long-acting

Major Depressive Disorder

SSRI

• Citalopram (Celexa)

• Escitalopram (Lexapro)

• Fluoxetine (Prozac) - activating, take in morning

• Paroxetine (Paxil) - sedating, take at night

• Sertraline (Zoloft)

MOA: selectively inhibit reuptake of 5-HT by blocking SERT → enhance and prolong serotonergic neurotransmission

Major Depressive Disorder

SNRI

• Venlafaxine (Effexor XR)

• Duloxetine (Cymbalta)

• Desvenlafaxine (Pristiq)

• Levomilnacipran (Fetzima)

MOA: inhibit reuptake of 5-HT and NE by binding to SERT and NET increased levels of both 5-HT and NE; more affinity for SERT than NET

Major Depressive Disorder

MAOIs

• Socarboxazid (Marplan)

• Phenelzine (Nardil)

• Tranylcypromine (Parnate)

• Selegiline (Emsam- transdermal patch)

MOA: Inhibit the activity of MAO enzymes, preventing breakdown of monoamine neurotransmitters (DA, NE and 5-HT) → NT’s accumulate in neuron/synapse and cause activation of respective receptors

Insomnia

Melatonin Receptor Agonists

• Ramelteon (Rozerem)

• Tasimelteon (Hetlioz)

MOA: selective dual agonist by binding to both MT1 and MT2 melatonin receptors → promotes sleep

Insomnia

Z-Drugs (Non-BZDs)

• Fulmazenil can reverse effects

• Eszopiclone (Lunesta)

• Zolpidem (Ambien, Ambien CR, Zolpimist, Edluar, Intermezzo

• Zaleplon (Sonata)

MOA: enhance GABA by selectively binding to GABA-A receptors at the alpha-1 subunit, Non-BZD GABA agonist

Insomnia

Orexin Receptor Antagonists

• Lemborexant (DayVigo)

• Suvorexant (Belsomra)

MOA: blocks orexin A and B from binding to OX1R and OX2R → suppressing arousal/wakefulness → promote sleep