Drugs Flashcards
Levodopa
Dopaminergic Agent
Class: Dopamine (DA) precursor
MOA: Crosses BBB and is converted to dopamine–> improves nigrostriatal functioning
Given with carbidopa (as Sinemet);
Use: firstline treatment for Parkinson’s unless patient is young (want to delay as long as possible)
SE: Dyskinesias; hypotension, nausea, anxiety, fatigue
Psychoses of dosed too high
MAO-A inhibitors are contraindicated
(except MAO-B, which only hits DA)
Carbidopa
Dopaminergic Agent
Class: Aromatic amino acid decarboxylase inhibitor
MOA: Inhibits peripheral conversion of L-DOPA to dopamine; does not cross BBB
Use: Parkinson’s (given with Levadopa to
lower side effects)
SE: Dyskinesias, on-off phenomenon, —
MAO-A inhibitors are contraindicated
(except MAO-B, which only hits DA)
Buproprion
Dopaminergic Agent
Class: Norepinephrinedopamine reuptake inhibitor (NDRI)
MOA: Blocks dopamine transporter (DAT) ->
increased dopamine in synapse
Use: Parkinson’s (and depression, smoking cessation, weight loss)
SE: Insomnia, anxiety, agitation, nausea, dry mouth, sweating, palpitations, Mild increase in BP
dextroamphetamine
lisdexamfetamine
Dopaminergic Agent
Class: Stimulant
MOA: Blocks dopamine transporter (DAT); also increases VMAT2
Use: ADHD
Norepi and dopamine side effects; weight loss; addictive Psychosis at high doses
Modafinil; Armodafinil
Dopaminergic Agent
Stimulant
Increases histamine activity in the tuberomammilary nucleus; may block DAT
Fatigue due to narcolepsy, apnea, shiftwork disorder
SEs are Similar to, but less severe, than amphetamines, Addiction possible
Selegiline
Dopaminergic Agent
MAO-B inhibitor
Prevents breakdown of DA
Early Parkinson’s; depression
Hypotension, dizziness, insomnia, weight gain Nausea, vomiting
For depression it comes in a patch called EMSAM
Rasagiline
Dopaminergic Agent MAO-B inhibitor Prevents breakdown of DA Early Parkinson's Hypotension, dizziness, insomnia, weight gain Nausea, vomiting
Tranylcypromine
Isocarboxazid
Phenelzine
Dopaminergic Agent
MAOI
Irreversibly inhibit both MAO-A and MAO-B
Depression
Hypotension, dizziness, insomnia, weight gain
Hypertensive crisis (with tyramine-rich foods); serotonin syndrome (MAOI + SSRI)
Entacapone
Dopaminergic Agent COMT inhibitor Prevents breakdown of DA Parkinson's Nausea, fatigue DA side effects Short-acting (2 hours)
Tolcapone
Dopaminergic Agent COMT inhibitor Prevents breakdown of DA Parkinson's Nausea, fatigue; liver failure, DA side effects Use only if entacapone fails.
Bromocriptine
Dopaminergic Agent Ergot D2 receptor agonist Increases DA activity Mild Parkinson's; Restless Leg Syndrome hyperprolactinemia Mania, nausea, dizziness, fatigue Peripheral DA-like effects
Must be titrated slowly due to hypotension
Pramipexole ;
Ropinerole
Dopaminergic Agent Selective D2 receptor agonist Increases DA activity Mild Parkinson's; Restless Leg Syndrome Syndrome Mania, nausea, dizziness, fatigue Peripheral DA-like effects
Less effective with motor symptoms of PD
Apomorphine
Dopaminergic Agent
D2 receptor agonist
Increases DA activity
Mild Parkinson’s; Restless Legs Syndrome
Mania, nausea, dizziness, fatigue Peripheral DA effects
Injectable only; serotonin receptor antagonists contraindicated (e.g., ondansetron)
Aripiprazole
Dopaminergic Agent D2 & D3 receptor (partial) agonist I ncreases DA activity Schizophrenia; depression Less side effects than other DA agonists; akathisia
Amantadine
Dopaminergic Agent Anti-viral Stimulates D2 receptors, blocks DAT Mild Parkinson's (2nd-line); influenza Nausea, dizziness, psychosis, insomnia, seizures ---
Contraindicated in elderly with dementia (anticholinergic effects)
Reserpine
Dopaminergic Agent Synapse depleter Blocks VMAT (no release of monoamines into synapses) Use: Hypertension SE: Depression
Tetrabenazine
Dopaminergic Agent Synapse depleter Blocks VMAT (no release of monoamines into synapses) Huntington's Chorea, Depression is a SE
Benztropine;
Trihexiphenidyl
Dopaminergic Agent
Anticholinergics
Antagonize the ACh muscarinic receptor
Early Parkinson’s; reduce EPS parkinsonian side effects
Typical anticholinergic (dry mouth, blurred vision, racing heart, constipation, confusion, delirium, hallucinations)
Contraindicated in demented Parkinson’s; abrupt discontinuation exacerbates symptoms
Diphenhydramine
Dopaminergic Agent
Antihistamine Anticholinergic properties Reduce EPS Parkinsonian side effects
Typical anticholinergic (dry mouth, blurred vision, racing heart, constipation, confusion, delirium, hallucinations)
Chlorpromazine;
Thioridazine
Dopaminergic Agent
First-generation antipsychotics (Low Potency)
Non-selective D2 receptor antagonism
Use: Psychosis (schizophrenia)
SE: EPS; fatigue and weight gain (H1 antagonism); anticholinergic effects; orthostasis (alpha1 antagonism)
Tardive dyskinesia with chronic use
Little effect on negative symptoms of Schizophrenia
Fluphenazine;
Thiothixine ;
Haloperidol
Dopaminergic Agent
First-generation antipsychotics (High Potency)
Non-selective D2 receptor antagonism
Use: Psychosis (schizophrenia); movement disorder in Huntingtons
SE: EPS; NMS
Tardive dyskineasia with chronic use
Little effect on negative symptoms
Clozapine
Dopaminergic Agent
Second-Generation Antipsychotic
D2 (& D1, D4) receptor antagonist; 5HT2a receptor antagonist
Use: Refractory shizophrenia
Side effects similar to other “pines”,
but also agranulocytosis (NMDA receptor antagonism?)
Most metabolic risk of all
antipsychotics, but little EPS/TD;
must monitor WBC bc of agranulocytosis
Olanzapine ;
Quetiapine ;
Asenapine
Dopaminergic Agent Second-Generation Antipsychotics D2 receptor antagonist, 5HT2a receptor antagonist Use: Psychosis, mania, agression SE: Suicide risk in ages
Risperidone; Ziprazidone; Paliperidone; Iloperidone; Lurasidone
Dopaminergic Agent Class: Second-Generation Antipsychotics MOA: D2 receptor antagonist; but various other receptor agonism/antagonism Use: Psychosis, mania, agression SE: Suicide risk in ages
Pilocarpine HCl
Ocular Drug
Class: Direct muscarinic agonist
Use: Pupillary constriction, increased aqueous outflow
Treatment of glaucoma (both open angle and acute closed angle); cataract surgery
SE: Decreased vision when patient has cataracts due to miosis and headache, Bronchospasm, salivation, nausea, vomiting, diarrhea, abdominal pain, tenesmus, lacrimation, sweating
Used less frequently today due to side effects (SLUDGE)
Echothiophate
Ocular Drug Indirect muscarinic agonist Irreversibly binds cholinesterase Use: Treatment of glaucoma --- SE: Bronchospasm, salivation, nausea, vomiting, diarrhea, abdominal pain, tenesmus, lacrimation, sweating
Used less frequently today due to side effects
Atropine
Ocular Drug
Antimuscarinic
Pupillary dilatation; paralysis of ciliary body
Use: Improve discomfort during active eye inflammation (ueveitis)
SE: Ataxia, nystagmus, restlessness, mental confusion, hallucination, violent and aggressive behavior, insomnia, photophobia, urinary retention
Very long acting so not used unless severe inflammation
Scopolamine
Ocular Drug
Antimuscarinic
Pupillary dilatation; paralysis of ciliary body
Improve discomfort during active eye inflammation (ueveitis) (also used to treat motion sickness)
SE: Ataxia, nystagmus, restlessness, mental confusion, hallucination, violent and aggressive behavior, insomnia, photophobia, urinary retention
Tropicamide
Ocular Drug
Antimuscarinic
Pupillary dilatation; paralysis of ciliary body
Most commonly used cycloplegia for eye exams
SE: Ataxia, nystagmus, restlessness, mental confusion, hallucination, violent and aggressive behavior, insomnia, photophobia, urinary retention
Edrophonium
Ocular Drug
Nm agonist
Destroys acetylcholinesterase
Use: Diagnose myasthenia gravis
Epinephrine
Ocular Drug
Direct adrenergic agonist
Dilation of episcleral vessels –> increased aqueous outflow
SE: Extrasystoles, palpitation, hypertension, myocardial infarction, trembling, paleness, sweating
Hydroxyamphetamine
Ocular Drug
Class: Indirect adrenergic agonist
MOA: Release NE
Use: Separates 1st and 2nd from 3rd order neuron dysfunction in Horner’s syndrome; positive dilation means 1st or 2nd order, an ominous sign
Cocaine
Ocular Drug
Indirect adrenergic agonist
Prevent reuptake of NE
Use initially to confirm diagnosis of Horner’s Syndrome
Phenylephrine
Ocular Drug
Direct α1-agonist —
Use: Dilate pupil for eye exam and cataract surgery —
Extrasystoles, palpitation, hypertension, myocardial infarction, trembling, paleness, sweating
Caution in elderly patients: at 10% can cause cardiac side effects
Brimondine tartrate
Direct α2-agonist Suppresses aqueous humor production through action of cAMP in non-pigmented ciliary epithelium Primary agent for treatment of glaucoma --- --- May cause follicular conjunctivitis; use with MAOi can cause fatigue/drowsiness
Timolol
Ocular Drug
β-blocker
Reduce intraocular pressure by reducing aqueous production at the ciliary process
Use: Second line treatment of glaucoma —
Bradycardia, hypotension, syncope, palpitation, congestive heart failure, bronchospasm, mental confusion, depression, fatigue, lightheadedness, hallucinations, memory impairment, sexual dysfunction, hyperkalemia
Contraindicated in CHF, asthma; bradycardia over time may produce tachyphylaxis
Levobunolol
Ocular Drug
β-blocker
Reduce intraocular pressure by reducing aqueous production at the ciliary process
Use: Second line treatment of glaucoma —
Bradycardia, hypotension, syncope, palpitation, congestive heart failure, bronchospasm, mental confusion, depression, fatigue, lightheadedness, hallucinations, memory impairment, sexual dysfunction, hyperkalemia
Betaxolol
β1-blocker
Reduce intraocular pressure by reducing
aqueous production at the ciliary process Second line treatment of glaucoma
Latanoprast
Prostaglandin analog Increase uveoscleral outflow Primary agent for treatment of glaucoma Eyelash growth, change in iris color, intraocular inflammation May cause cystoid macular edema in cataract surgery and activate herpes
Travoprost
Prostaglandin analog Increase uveoscleral outflow Primary agent for treatment of glaucoma Eyelash growth, change in iris color
May cause cystoid macular edema in
cataract surgery; more effective in
African Americans
Bimatoprost
Prostaglandin analog Increase uveoscleral outflow Primary agent for treatment of glaucoma Eyelash growth, change in iris color
May cause cystoid macular edema in
cataract surgery and activate herpes
Unoprostone isopryl
Prostaglandin analog Increase uveoscleral outflow Glaucoma Eyelash growth, change in iris color Least effective overall
Nifedipine
Ca-channel blocker Increases ocular perfusion at nervehead Low-tension glaucoma Not widely used.
Dorzolamide HCl
Carbonic anhydrase
inhibitor
Reduce aqueous production via interfere
with the active transport of Na through Na-
K-ATPase pump Second line glaucoma therapy Red eyes, lid allergies
Contraindicated in sulfonamide
allergies
Acetazolamide
Carbonic anhydrase inhibitor Reduce aqueous production via interfere with the active transport of Na through Na- K-ATPase pump Oral agent used for advanced glaucoma and with cataract surgery Paresthesia, fatigue, drowsiness, depression, diarrhea, metaboliv acidosis, electrolyte changes Anaphylaxis, blood dyscrasias Used only if other topical therapy fails.
Brinzolamide
Carbonic anhydrase
inhibitor
Reduce aqueous production via interfere
with the active transport of Na through Na-
K-ATPase pump Second line glaucoma therapy Red eyes, lid allergies
Tranylcypromine;
Phenelzine
Antidepressant
Class: MAOI
MOA: Irreversibly inhibit both MAOa and MAOb
Use: Depression, anxiety, PTSD, chronic pain, enuresis, bulimia, alcoholism
Hypertensive crisis (with tyraminerich foods); serotonin syndrome (MAOI + SSRI); agitation (rare), delerium --> seizures Anticholinergic, orthostatic hypotension, sexual dysfunction, weight gain, sedation
Desipramine;
Imipramine;
Amitriptyline;
Nortriptyline
Tricyclic Antidepressant
Block reuptake of NE or 5-HT at varying potencies and selectivity; also variably block muscarinic, a-adrenergic, dopamine, and histamine receptors
Depression, anxiety, PTSD, chronic pain, enuresis, bulimia, alcoholism
Sympathomimetic (cardiac arrhythmias and conduction defects, especially at OD)
Antimuscarinic, orthostatic hypotension, sedation (additive
with alcohol), seizures
Not very safe; rarely used anymore
Fluoxetine; Paroxetine
SSRI
Inhibit reuptake of 5-HT (and NE to lesser extent)
Depression, anxiety, PTSD, chronic pain, enuresis, bulimia, alcoholism; premenstrual dystrophic disorder
Serotonin syndrom (with MAOIs)
Fewer than tricyclics; mostly nausea, decreased sexual
function
Fluoxetine and Paroxetine are Potent P450 inhibitors;
Fluoxetine forms active metabolite (norfluoxetine)
Paroxetine
SSRI
Inhibit reuptake of 5-HT (and NE to lesser extent)
Depression, anxiety, PTSD, chronic
pain, enuresis, bulimia, alcoholism Serotonin syndrom (with MAOIs)
Fewer than tricyclics; mostly
nausea, decreased sexual
function Potent P450 inhibitor
Sertraline
SSRI Inhibit reuptake of 5-HT (and NE to lesser extent) Depression, anxiety, PTSD, chronic pain, enuresis, bulimia, alcoholism Serotonin syndrom (with MAOIs) Fewer than tricyclics; mostly nausea, decreased sexual functio
Escitalopram
SSRI Inhibit reuptake of 5-HT (and NE to lesser extent) Depression, anxiety, PTSD, chronic pain, enuresis, bulimia, alcoholism Serotonin syndrom (with MAOIs) Fewer than tricyclics; mostly nausea, decreased sexual function
Citalopram
SSRI Inhibit reuptake of 5-HT (and NE to lesser extent) Depression, anxiety, PTSD, chronic pain, enuresis, bulimia, alcoholism Serotonin syndrom (with MAOIs) Fewer than tricyclics; mostly nausea, decreased sexual function
Duloxetine
SNRI Inhibits reuptake of 5-HT and NE
Depression, anxiety, PTSD, chronic
pain, enuresis, bulimia, alcoholism
Venlafaxine
SNRI Inhibits reuptake of 5-HT and NE
Depression, anxiety, PTSD, chronic
pain, enuresis, bulimia, alcoholism
Bupropion
Atypical Blocks DA and NE reuptake Depression, anxiety, PTSD, chronic pain, enuresis, bulimia, alcoholism; maintain nicotine abstinence in quitting smokers Lowers seizure threshold
Mirtazapine
Atypical 5HT2a antagonists; also inhibit 5HT reuptake Depression, anxiety, PTSD, chronic pain, enuresis, bulimia, alcoholism
Lithium
Unknown; lithium depletes secondary messengers IP3 and DAG, important in aadrenergic and muscarinic-cholinergic transmission Anti-manic/mood-stabilizing (bipolar); long-term cluster headache prevention If elevated levels: neurotoxicity, cardiac toxicity, renal dysfunction Drowsiness, weight gain, tremor, polydipsia, polyuria Nausea and vomiting early sign of lithium OD; indomethacin and Nadepleting diuretics should be avoided (increase [Li])
Nalmefene
Opiod antagonist — —
May produce a prolonged
withdrawal state (nausea, vomiting,
piloerection, yawning)
N-acetylcysteine
Antioxidant
Supplies sulfhydryl groups to glutathione;
improves microcirculation, provides antiinflammatory
effect Acetaminophen overdose
Fomepizole
Blocks alcohol dehydrogenase Methanol & ethylene glycol poisoning — — Very expensive
Cocaine
CNS stimulant Blocks reuptake of dopamine, norepinephrine, and serotonin Topical anesthetic, combined vasoconstrictor and local anesthetic Sympathetic effects; paranoia, aggression --- Rapidly hydrolyzed by plasma cholinesterase; crack is the free base form
LSD
Schedule I Hallucinogen Agonist at 5HT2A receptors on Raphe cell body --> inhibition of Raphe Nuclei firing --> increased sensory input; partial dopamine agonist Schedule I hallucinogen; model hallucinogen against which all others compared; limited studies in psychoanalysis, alcoholism, autistic children, and terminal cancer patients Bad trips (anxiety attack, panic attack), flashbacks, "street drug" lifestyle; no overdoses, birth defects, or chronic psychoses linked to LSD --- Oxidized in liver; cross tolerance with mescaline and psilocybin
Mescaline
Schedule I Hallucinogen Agonist at 5HT2A receptors on Raphe cell body --> inhibition of Raphe Nuclei firing --> increased sensory input; partial dopamine agonist --- --- Cross tolerance with LSD and psilocybin
Psilocybin
Schedule I Hallucinogen Agonist at 5HT2A receptors on Raphe cell body --> inhibition of Raphe Nuclei firing --> increased sensory input; partial dopamine agonist --- --- --- Cross tolerance with mescaline and LSD
Phencyclidine
Dissociative (PCP) anesthetic Antagonist of ion channel associated with NDMA receptor; agonist at mu opioid receptors --- Violent behavior, coma, seizures, arrest; inexplicable psychoses Dissociation, confusion, ataxia, marked nystagmus Long half-life due to being highly lipid soluble and having active metabolites
Amphetamines
Indirect sympathomimetic (release biologic amines from nerve terminals in periphery and in CNS); dopamine most important Narcolepsy, ADHD Vasospasm leading to possible stroke or MI, arrhythmia, weight loss (anorectic effect) Tremor, anxiety, irritability, confusion, possibly paranoid state Others: dextroamphetamine (Dexedrine), methamphetamine (Desoxyn), methylphenidate (Ritalin)
Marijuana
Cannabinoid Hits cannabinoid receptors (CB1, CB2: Gprotein coupled receptors) Schedule I hallucinogen; anti-emetic, anti-nausea, and appetite stimulate for cancer chemotherapy and AIDS patients; analgesic for neuropathic pain; potentially: glaucoma, asthma, anxiolytic, migraine, and multiple sclerosis treatment Vasodilation --> tachycardia, dilation of conjunctival vessels, bronchodilation, decreased intraocular pressure, hunger May impair reproductive function in adolescents; heavy use may impair development of very young users; possible respiratory damage due to tar Active ingredient is delta-9- tetrahydrocannabinol; metabolized by P450, with chronic use inducing enzyme; highly lipid soluble
Anandamide
Endogenous
cannabinoid
Hits cannabinoid receptors (CB1, CB2: Gprotein
coupled receptors) Endogenous cannabinoid
Dronabinol
Synthetic THC
Hits cannabinoid receptors (CB1, CB2: Gprotein
coupled receptors)
Schedule III drug; anti-emetic, antinausea,
and appetite stimulate for
cancer chemotherapy and AIDS
patients
Nabilone
Synthetic THC Hits cannabinoid receptors (CB1, CB2: Gprotein coupled receptors) Schedule II drug; treatment-resistant nausea and vomiting, weight loss and anorexia in AIDS patients --- --- Less psychoactive side effects than marijuana
Morphine
Opioid Mu-opioid receptor agonist Severe analgesia, mood alteration, antitussive, sedation Miosis, constipation, respiratory depression Dry mouth, nausea/vomiting, sedation, sweating; dreams, dysphoria, delerium, myoclonus, seizures, pruritis, urticaria, urinary incontinence 2 major active metabolites: M6 (more potent/active), M3 (little affinity); intraspinal administration possible
Codeine
Opioid Mu-opioid receptor agonist (low receptor affinity); demethylated to form morphine (10% of oral ingestion, via CYP2D6) Moderate analgesia, antitussive (found in many cough medicines) Miosis, constipation, respiratory depression Dry mouth, nausea/vomiting, sedation, sweating; dreams, dysphoria, delerium, myoclonus, seizures, pruritis, urticaria, urinary incontinence 10% of Caucasians unable to convert codeine to morphine (can still experience side effects, though)
Tramadol
Opioid Mu opioid receptor agonist (weak); some NE/5HT uptake inhibition (leading to analgesia); synthetic codeine analog Moderate (not severe) analgesia Miosis, constipation, respiratory depression Dry mouth, nausea/vomiting, sedation, sweating; dreams, dysphoria, delerium, myoclonus, seizures, pruritis, urticaria, urinary incontinence 1 metabolite: demethylated, more potent analgesic
Fentanyl
Opioid Mu-opioid receptor agonist (strong); highly lipid-soluble Severe analgesia after identification of dose level via other opiod (e.g., morphine) Miosis, constipation, respiratory depression Dry mouth, nausea/vomiting, sedation, sweating; dreams, dysphoria, delerium, myoclonus, seizures, pruritis, urticaria, urinary incontinence IV, transdermal; do not change dose more than 1/week (long half-life); intraspinal administration possible
Methadone
Opioid Mu-opioid receptor agonist Chronic, severe pain; treatment of heroin and opiod addicts Miosis, constipation, respiratory depression Dry mouth, nausea/vomiting, sedation, sweating; dreams, dysphoria, delerium, myoclonus, seizures, pruritis, urticaria, urinary incontinence 90% bound to plasma protein, accumulates in tissues (thus, extended duration of action); do not change dose more than 1/week (long half-life
Oxycodone
Opioid Mu-opioid receptor agonist Moderate to severe analgesia Miosis, constipation, respiratory depression Dry mouth, nausea/vomiting, sedation, sweating; dreams, dysphoria, delerium, myoclonus, seizures, pruritis, urticaria, urinary incontinence Oxycontin is extended release
Meperidine
(Demerol) Opioid Mu-opioid receptor agonist Don't use this Miosis, constipation, respiratory depression; mental status changes and seizures (normeperidine) Dry mouth, nausea/vomiting, sedation, sweating; dreams, dysphoria, delerium, myoclonus, seizures, pruritis, urticaria, urinary incontinence 1 metabolite: normeperidine
Propoxyphene
(Darvon) Opioid Mu-opioid receptor agonist (weak) Don't use this Miosis, constipation, respiratory depression; CNS toxicity (norpropoxyphene) Dry mouth, nausea/vomiting, sedation, sweating; dreams, dysphoria, delerium, myoclonus, seizures, pruritis, urticaria, urinary incontinence 1 metabolite: norpropoxyphene (has long half-life)
Loperamide
(Imodium) Opioid Slows peristalsis via opioid receptors in intestine, and possibly decreased GI secretion Diarrhea Miosis, constipation, respiratory depression Dry mouth, nausea/vomiting, sedation, sweating; dreams, dysphoria, delerium, myoclonus, seizures, pruritis, urticaria, urinary incontinence Meperidine congener
Diphenoxylate
(Lomotil) Opioid Slows peristalsis via opioid receptors in intestine, and possibly decreased GI secretion Diarrhea Miosis, constipation, respiratory depression Dry mouth, nausea/vomiting, sedation, sweating; dreams, dysphoria, delerium, myoclonus, seizures, pruritis, urticaria, urinary incontinence Meperidine congener
Naloxone
Opioid antagonist Competitive mu-, delta-, and kappa-opioid receptor antagonist Acute opioid toxicity (depressed RR best predicts reponse) Can precipitate withdrawal (flu-like symptoms of nausea, vomiting, diarrhea; piloerection, yawning, irritability) --- Continuous parenteral infusion, as lasts only 15-30 minutes (oral almost completely metabolized by liver); patient has normal mental status
Naltrexone
Opioid antagonist Mu-opioid receptor antagonist Alcoholism
May produce a prolonged
withdrawal state (nausea, vomiting,
piloerection, yawning
Diazepam
Benzodiazepine GABAa agonist; binds between a1 and y2 subunits; half-life of 43 hours (active metabolites up to 100 hours) Short-term depression treatment; maintenance of bipolar; severe bipolar; anticonvulsant; muscle relaxant --- Daytime sedation and drowsiness, anterograde amnesia, synergistic depression of CNS with other drugs, pyschologic and physiologic dependence (chronic use) "Ceiling effect" due to augmenting action of GABA
Chlordiazepoxide
(Librium) Benzodiazepine GABAa agonist; binds between a1 and y2 subunits; half-life of 10 hours (active metabolites up to 100 hours) Short-term depression treatment; maintenance of bipolar; severe bipolar --- Daytime sedation and drowsiness, anterograde amnesia, synergistic depression of CNS with other drugs, pyschologic and physiologic dependence (chronic use) "Ceiling effect" due to augmenting action of GABA
Lorazepam
(Ativan) Benzodiazepine GABAa agonist; binds between a1 and y2 subunits; half-life of 14 hours Short-term depression treatment; maintenance of bipolar; severe bipolar; sedation; anticonvulsant; prevent withdrawal symptoms in alcoholics --- Daytime sedation and drowsiness, anterograde amnesia, synergistic depression of CNS with other drugs, pyschologic and physiologic dependence (chronic use) "Ceiling effect" due to augmenting action of GABA; directly conjugated into inactive metabolite
Flurazepam
(Dalmane) Benzodiazepine GABAa agonist; binds between a1 and y2 subunits; half-life of 74 hours (active metabolites up to 100 hours) Short-term depression treatment; maintenance of bipolar; severe bipolar --- Daytime sedation and drowsiness, anterograde amnesia, synergistic depression of CNS with other drugs, pyschologic and physiologic dependence (chronic use) "Ceiling effect" due to augmenting action of GABA
Alprazolam
(Xanax) Benzodiazepine GABAa agonist; binds between a1 and y2 subunits; half-life of 12 hours Short-term depression treatment; maintenance of bipolar; severe bipolar; sedation --- Daytime sedation and drowsiness, anterograde amnesia, synergistic depression of CNS with other drugs, pyschologic and physiologic dependence (chronic use) "Ceiling effect" due to augmenting action of GABA
Midazolam
(Versed) Benzodiazepine GABAa agonist; binds between a1 and y2 subunits; half-life of 1.9 hours Anesthesia (calming effects, production of anterograde amnesia) --- Daytime sedation and drowsiness, anterograde amnesia, synergistic depression of CNS with other drugs, pyschologic and physiologic dependence (chronic use) "Ceiling effect" due to augmenting action of GABA
Triazolam
(Halcion) Benzodiazepine GABAa agonist; binds between a1 and y2 subunits; half-life of 2.9 hours Short-term depression treatment; maintenance of bipolar; severe bipolar; induce sleep --- Daytime sedation and drowsiness, anterograde amnesia, synergistic depression of CNS with other drugs, pyschologic and physiologic dependence (chronic use) "Ceiling effect" due to augmenting action of GABA
Zolpidem
(Ambien) Non-benzodiazepine receptor agonist BDZ-1 selective agonist Sedation and hypnosis without muscle relaxation or anticonvulsant activity Sleep-walking; next morning impairment
Flumazenil
(Romazicon) Benzodiazepine antagonist Competitive non-selective antagonist Benzodiazapine overdose Withdrawal (may be lifethreatening); seizures in mixed overdoses --- Non uniform in reversal of respiratory depression
Thiopental
(Pentothal) Barbiturate GABAa agonist (binds a or b subunit); highly lipid soluble, fast-on, fast-off Induce anesthesia --- Daytime sedation and drowsiness, dose-dependent depression of CNS, pyschologic and physiologic dependence (chronic use) Abrupt withdrawal life-threatening; redistribute from brain to muscle and fat, metabolized by liver; dosed based on lean body mass
Phenobarbitol
Barbiturate GABAa agonist (binds a or b subunit) Antiepileptic, anticonvulsant —
Daytime sedation and
drowsiness, dose-dependent
depression of CNS, pyschologic
and physiologic dependence
(chronic use) Abrupt withdrawal life-threatening
Buspirone
No GABAa interaction; may be partial
agonist at 5HT1A Anxiolytic without marked sedation
Nitrous Oxide
Inorganic gas NMDA receptor antagonist Mask induction in children; adjuvant to volatile anesthetics, opioids Post-operative nausea and vomiting; inactivates vitamin B (leading to abnormal embryonic development, abortion); accumulates in closed, aircontaining spaces (bowel, middle ear, pneumothoraces, air emboli) because N2O insoluble in blood --- No muscle relaxation
Isoflurane
Volatile anesthetic Most potent Gold standard for maintenance of anesthesia Pungent; dose dependent CNS depression, increase in cerebral blood flow and intracranial pressure; dose dependent decrease in systemic BP, decrease in respiratory function; relaxes skeletal muscle; increase in HR; malignant hyperthermia
Desflurane
Volatile anesthetic Least soluble, least potent (allows for rapid emergence from anesthesia) Maintenance of anesthesia Most pungent (airway irritation symptoms); dose dependent CNS depression, increase in cerebral blood flow and intracranial pressure; dose dependent decrease in systemic BP, decrease in respiratory function; relaxes skeletal muscle; increase in HR; malignant hyperthermia
Sevoflurane
Volatile anesthetic Less soluble, less potent (but not irritating) Mask induction in children and adults; maintenance of anesthesia Can form CO if not combined with CO2 correctly; dose dependent CNS depression, increase in cerebral blood flow and intracranial pressure; dose dependent decrease in systemic BP, decrease in respiratory function; relaxes skeletal muscle; malignant hyperthermia
Methohexital
Barbiturates GABAa receptor agonist, antagonist of NMDA-glutamate receptor; produce hypnosis & sedation, but is anti-analgesic Induce general anesthesia --- --- Redistribute from brain to muscle and fat, metabolized by liver; dosed based on lean body mass
Propofol
Alkylphenol (a fatty acid) GABAa receptor agonist, antagonist of NMDA-glutamate receptor; some a2 receptor activity; rapid onset and offset Anti-emetic at low doses; induction and maintenance of general anesthesia; sedation in ICU, procedural sedation Propofol infusion syndrome: being given for several days leads to metabolic acidosis, rhabdomyolysis, heart & renal failure, lowering of BP, bradycardia, and death (likely due to fatty acid oxidation) Painful injection site; supports bacterial growth Administered IV in a lipid emulsion (cause of pain); be aware of allergies (egg and soy in emulsion); no malignant hyperthermia
Etomidate
Carboxylated imidazole GABAa receptor agonist (only D-isomer) Hypnosis; no analgesic activity Pain on administration (due to solvent, propylene glycol); involuntary myoclonic movements due to subcortical disinhibition (not a seizure); post-operative nausea and vomiting; single dose inhibits cortisol synthesis --- Minimal cardiorespiratory depression (good agent in patients with minimal cardiac reserve)
Ketamine
Phencyclidine NMDA receptor antagonist, kappa opiate agonist; leads to dose-dependent unconsciousness, amnesia, analgesia Sedative/anesthetic for pediatric/developmentally delayed patients; induction in patients with reactive airway disease, hypovolemia (trauma patients), cardiac disease; with propofol for IV procedural sedation; adjuvant during and after surgery to reduce opiod use; part of multimodal pain therapy regimen; depression treatment Stimulates sympathetic nervous system outflow; increases cerebral blood flow, ICP; emergence delerium; nystagmus, lacrimation, salivation, and dissociative anesthesia --- Racemic mixture (S more potent); metabolized by P450 (norketamine, a third to a fifth as effective); great bronchodilator; contraindicated in CAD patients and those with with intracranial lesions
Dexmedetomidine
a2 adrenergic agonist Binds a2a and a2b in locus coeruleus and spinal cord (produces sedation, sympatholysis, and analgesia) Awake intubations, awake craniotomies; adjunct to general anesthesia in patients susceptible to narcotic-induced post-op respiratory depression; withdrawal/detoxification Limited respiratory depression (wide safety margin) --- Since GABA not hit, sedation is easier to wake from and is similar to non-REM sleep; FDA approved only for ventilation of ICU patients for under 24 hours
Succinylcholine
Depolarizing NMB Divalent ACh molecule; attaches to all ACh receptors, overstimulating them (first seen as disorganized muscular contractions (fasiculations), then paralysis) Skeletal muscle relaxant (intubation) Malignant hyperthermia; cardiac dysrhythmias, hyperkalemia, increased intraocular pressure, increased intracranial pressure Increased intragastric pressure, myalgias, masseter spasm Hydrolyzed by pseudocholinesterase (in plasma); blockade cannot be reversed; only NMB with rapid onset and ultra-short duration of action
Pancuronium
Amino steroid nondepolarizing NMB Competitive blockade of ACh (no depolarization); vagolytic Skeletal muscle relaxant; avoid in patients with renal insufficiency Increase in HR --- Only long acting non-depolarizing agent; supplied as liquid; 80% excreted unchanged in liver (low metabolism in liver); reverse with AChEI
Vecuronium
Amino steroid nondepolarizing NMB Competitive blockade of ACh (no depolarization) Skeletal muscle relaxant No cardiovascular effects --- Intermediate acting; supplied as a powder (reconstitute); hepatic metabolism, hepatic and renal excretion; reverse with AChEI
Rocuronium
Amino steroid nondepolarizing NMB Competitive blockade of ACh (no depolarization) Skeletal muscle relaxant (can substitute succinylcholine in rapid sequence intubation) No cardiovascular effects --- Intermediate acting; supplied as a liquid; hepatic metabolism, hepatic and renal excretion; can speed onset with higher dose; reverse with AChEI
Sugammadex
Selective relaxant
binding agent
Complexes with rocuronium, rendering it
inactive; no effect on AChesterase Immediate reversal of rocuronium
Decrease in blood presure, nausea
and vomiting, dry mouth — Not yet FDA approved
Atracurium
Isoquinoline nondepolarizing NMB Competitive blockade of ACh (no depolarization) Skeletal muscle relaxant; use in patients with liver or renal dysfunction Histamine release (especially if given as rapid IV bolus), with resultant hypotension and tachycardia --- Undergoes spontaneous, nonenzymatic degradation (Hofman elimination); intermediate acting; reverse with AChEI
Cis-atracurium
Isoquinoline nondepolarizing NMB Competitive blockade of ACh (no depolarization) Skeletal muscle relaxant; use in patients with liver or renal dysfunction Unlike atracurium, no histamine release or downstream effects --- Undergoes spontaneous, nonenzymatic degradation (Hofman elimination); intermediate acting; reverse with AChEI
Edrophonium
AChE-I — Reversal of NMB — — Short-acting, fast onset
Neostigmine
AChE-I --- Reversal of NMB (most commonly used) --- --- More complete antagonism than edrophonium
Pyridostigmine
AChE-I — Reversal of NMB — —
Longer duration of action than
neostigmine, edrophonium
Glycopyrrolate
Anti-muscarinic —
Reversal of neuromuscular blockade’s
muscaranic effects DUMBELLS — Could also use atropine
Cocaine; benzocaine
; procaine
; tetracaine;
chlorprocaine
Ester anesthetic Binds reversibly to the intracellular portion of the voltage-gated sodium channel and inactivates it, and so blocks transmission of nociceptive nerve impulses. Local anesthesia Local: transient neurologic symptoms (basically, really bad pain), neuronal injury. Systemic (more common with longacting local anesthetics): circumoral numbness, dizziness, tinnitis, blurred vision, CNS excitation (restlessness, agitation, seizures), followed by CNS depression (respiratory arrest, unconsciousness); hypotension; cardic toxicity with higher doses. Methemoglobinemia (primarily with benzocaine), allergic reactions Used less frequently than amides; cocaine has many side effects due to action as a CNS stimulant
Lidocaine;
mepivacaine;
bupivacaine;
ropivacaine
Amide anesthetic Binds reversibly to the intracellular portion of the voltage-gated sodium channel and inactivates it, and so blocks transmission of nociceptive nerve impulses. Local anesthesia Local: transient neurologic symptoms (basically, really bad pain), neuronal injury. Systemic (more common with longacting local anesthetics): circumoral numbness, dizziness, tinnitis, blurred vision, CNS excitation (restlessness, agitation, seizures), followed by CNS depression (respiratory arrest, unconsciousness); hypotension; cardic toxicity with higher doses. Bupivicaine has highest cardiac toxicity potential; ropivicaine less potent than others (so larger therapeutic index)
IFN-beta-1a
IFN-beta-1a Many, potentially: inhibit T-cell activation, shift from Th1 to Th2, inhibit lymphocyte movement into CNS, anti-proliferative effect, apoptosis of T-cells, anti-viral, IFN-g antagonism RRMS Mild anemia, increase LFT (monitor every 6 mo.), hypothyroid; least NAB formed Flu-like, minor irritation at inject site, anemia Doesn't cross BBB; decreases relapse rate by 1/3 and reduces MRI lesions, with a trend toward decreasing disability and brain atrophy
Glatiramer acetate
Myelin basic protein analog Mixture of 4 AAs in myelin basic protein; causes T-cell apoptosis (looks like MBP), induces anti-inflammatory Th2 cells (cytokine shift from Th1), induces Treg with induction of anergy RRMS Mild: injection site reaction, anxiety attack-like reaction --- Active in CNS (not peripherally); try to use early; reduce relapse by 1/3, modest reduction in MRI lesion and reduction of atrophy, but no effect on disease progression
Natalizumab
Monoclonal antibody Binds VLA4 (integrin subunit), inhibiting leukocyte migration across BBB RRMS (2nd line) PML (JC virus); acute urticaria, systemic hypersensitivity infusion reaction Headache, dizziness, fatigue, arthralgia, rigors Decrease relapse rate by 2/3, greatly reduce MRI lesions; once/month; antibodies to natalizumab cause it to stop working; side effects more common in patients positive for neutralizing antibodies
Fingolimod
Sphingosine-1- phosphate analog Prodrug; sequesters circulating lymphocytes in secondary lymphoid organs via induction of intracellular internalization of receptors on lymphocytes (no effect on lymphocyte induction, proliferation, or memory function) RRMS Bradycardia and heartblock (EKG for first 6 hours); macular edema (need opthalmology exam before and after 3 months) Reduced FEV1, increased LFTs, lymphopenia, leukopenia, asthenia, back pain, blurred vision, headache dizziness, infections Patients must be VZV immune before prescription; oral daily
Teriflunomide
Immunosuppressant Selective dihydro-orotate dehydrogenase inhibitor; blocks de novo pyramidine synthesis, reducing T- and B-cell proliferation and function against autoantigens; preserves replication and function of cells living on salvage pathway (e.g., hematopoietic cells, memory cells) RRMS Hepatotoxicity; teratogenicity (animal data) --- Oral daily
Dimethyl fumarate
Enhances Nrf2 pathway; some Th1 -> Th2
sgift —
N & V; diarrhea; stomach pain;
flushing Itching, redness, rash Oral BID
Mitoxantrone
Anthracenedione Broad immune suppression and modulation of B cells, T cells and macrophages; decreases frequency of clinical relapse, reduces disease progress, and reduces disability SPMS; RRMS (2nd line) Dose-dependent cardiac toxicity (decreased LVEF, irreversible CHF); induction of acute leukemia Nausea and vomiting, alopecia, menstrual irregularities, increased susceptibility to infection IV; once/3 months
Azathioprine;
Methotrexate;
Cyclophosphamide;
Mycophenolate mofetil
Immunosuppressant Immunosuppressive SPMS (resistant, or as combination with other therapies) Systemic toxicity: monitor blood for changes
Methylprednisone
Corticosteroid (immunosuppressant) Unclear mechanism (suppress both B and T cells, may reduce cytokine release) Acute MS attack, SPMS; shortens acute attack duration,speeds recovery --- Short-term: insomnia, mood changes, fluid retention, epigastric pain, hypertension; long-term: osteoporosis, cushingoid, secondary malignancies Given IV with oral prednisone taper
ACTH
Acute MS attack (if patient allergic to
corticosteroids, poor IV access); or if
Methylprednisone doesn’t work
Plasmapharesis
Unclear mechanism Acute MS attack not responsive to Methylprednisone
Phenytoin
Voltage-gated Na channel stabilizer Stabilize inactive conformation of Na channel Less effective for absence (particular pediatric), myoclonic, atonic seizures Rash, gingival hyperplasia, hirsutism, lupus-like reaction; can cause contraceptive failure Mild myelosuppression, increased LFT; long-term: cerebellar degeneration, peripheral neuropathy, osteoporosis IV infusion limited by hypotension; hepatic enzyme inducer (both autoand hetero-inducer), highly protein bound
Carbamazepine
Voltage-gated Na channel stabilizer Stabilize inactive conformation of Na channel More effective for complex partial seizure than primary generalized; bipolar disorder; neuropathic pain Rash (rarely, Stevens-Johnson), mild myelosuppression, mild increase in LFTs; can cause contraceptive failure --- Hepatic enzyme inducer (both autoand hetero-inducer); highly protein bound; must increase dose in 1-2 wks due to autoinduction; side effects likely due to epoxide metabolite
Oxcarbamazepine
Voltage-gated Na channel stabilizer Stabilize inactive conformation of Na channel More effective for complex partial seizure than primary generalized; bipolar disorder; neuropathic pain Rash (rarely, Stevens-Johnson), mild myelosuppression, mild increase in LFTs; can cause contraceptive failure --- Designed to bypass carbamazepine epoxide; less protein-bound, less autoinduction, fewer interactions, less toxic, longer half-life than carbamazepine
Lamotrigine
Voltage-gated Na channel stabilizer Stabilize inactive conformation of Na channel Primary generalized epilepsies, absence seizures; indicated in children; bipolar disorder; neuropathic pain Rash, (rarely, Stevens-Johnson): slow initial titration important; may lead to contraceptive failure --- May exacerbate myoclonic seizures; competes with valproic acid for excretion (potential synergy); hepatic enzyme inducer; not very protein bound
Valproate
Unknown; likely affects Na-gated channels
and GABA system
Broad spectrum: absence, myoclonic,
tonic-clonic, primary generalized, partial
onset, and secondary generalized
seizures (but not absence seizures); IV
for status epilepticus; bipolar treatment,
migraine and long-term cluster
headache prophylaxis
Weight gain, hair turnover,
hyperammonemia (which can be
mitigated with oral carnitine),
teratogenicity, blood dyscrasias Pancreatitus
Vigabatrin
GABAergic antiepileptic
GABA transaminase binder (slows down
intracellular breakdown of GABA) Anti-epileptic — — Works on GABA-A
Tigabine
GABAergic antiepileptic
GABA reuptake inhibitor Anti-epileptic — — Works on GABA-A
Benzodiazapines
GABAergic antiepileptic Bind GABA-A Status epilepticus (refractory); anesthesia Sedation --- Long-term usefulness limited by tolerance
Gabapentin
GABA analog Block presynaptic influx of Ca Adjunct for partial complex epilepsy; more commonly used for neuropathic pain Sedation --- Absorption limited by intestinal AA transporter (there is a Tm); limited protein binding; no metabolism or drug interaction in humans (so few side effects)
Pregabalin
GABA analog Block presynaptic influx of Ca
Adjunct for partial complex epilepsy;
more commonly used for neuropathic
pain
Topiramate
Glutamate Receptor Blocker Partial AMPA, Kainate Ca receptor blocker; secondary effect at voltage-gated Na channel, GABA system Partial onset seizures, secondary generalized seizures, primary generalized epilepsy; migraine prevention, long-term prevention of cluster headaches Mild metabolic acidosis, kidney stones (due to some carbonic anhydrase activity); modest weight loss; rare acute glaucoma; sedation Word-finding problems Carbonic anhydrase activity leads to mild metabolic acidosis, which leads to respiratory compensation, which leads to mild alkalosis, which leads to calcium ionization, which leads to tingling; treat with vitamin C (acidify urine)
Felbamate
Glutamate Receptor Blocker NMDA receptor blocker; secondary effect at voltage-gated Na and Ca channels, GABA system Partial onset seizures with or without secondary generalization; medically refractory epilepsy Uncommon but potentially fatal. Aplastic anemia, acute hepatic failure. Requires monitoring.
Levetiracetam
Synaptic vesicle binder Binds synaptic vesicle protein 2, leading to less NT release Partial onset seizures, secondary generalized seizures; maybe primary generalized epilepsy Well tolerated; sedation, mostly; rarely, irritability, aphasia, thrombocytopenia
Ethosuximide
Voltage-gated Ca channel blocker Blocks T-type Ca-channels in thalamocortical circuits Absence seizures only (and neuropathic pain) Nausea (transient), sedation, irritability --- Readily absorbed, minimal first pass metabolism; not protein bound
Aspirin, acetaminophen, naproxen, indomethacin, piroxicam, diclofenac, ibuprofen
Analgesic NSAIDs Inhibition of COX-1 and COX-2
Acute treatment of moderate migraines;
acute treatment of tension headaches GI disturbances —
Excedrin (combination of aspirin,
acetaminophen, and caffeine) is
particularly effective
Butalbital
Barbiturate —
Acute treatment of migraines; use when
more traditional therapies unavailable or
contraindicated Drowsiness, dizziness — Use limited to 2-3 times per week
Codeine, meperidine,
oxycodone,
butorphanol
Opioids --- Acute treatment of migraines; patients with infrequent headaches; generally, for patients who wake up with a headache Drowsiness, constipation, respiratory depression, itching, miosis, urinary retention, euphoria Physical dependence w/ chronic use. Use less than 2 days per week; pregnant women may use codeine or meperidine with caution
Prednisone;
dexamethasone
Corticosteroids --- Acute treatment of migraines; migraine, prolonged headache syndromes (e.g., status migrainosus); rescue treatment of cluster headache --- --- Avoid chronic use
Ergotamine
Ergot alkaloid Vasoconstriction possibly; may also act as a 5HT agonist in trigeminovascular pathway Acute treatment of migraines Nausea, dizziness, paresthesia, chest pain, abdominal cramps --- Contraindicated in women planning pregnancy, uncontrolled HTN, sepsis, renal or hepatic failure, vascular disease
Dihydroergotamine
Ergot alkaloid Vasoconstriction possible; mainly act as a 5HT agonist in trigeminovascular pathway Acute treatment of migraines; less likely to cause rebound headache than ergotamine; acute treatment of cluster headaches; short-term prevention of cluster headaches (along with steroids) Nausea (less likely than ergotamine), dizziness, paresthesia, chest pain, abdominal cramps --- Contraindicated in women planning pregnancy, uncontrolled HTN, sepsis, renal or hepatic failure, vascular disease; injectable
Sumatriptan
Selective 5HT1b-d agonists; penetration of CNS, constriction of extracerebral intracranial vessels, inhibition of trigeminovascular system Acute treatment of migraines (premier option); also effective for photo/phonophobia, nausea and vomiting; acute treatment of cluster headaches Flushing, tingling, dizziness, chest discomfort (noncardiac) --- Contraindicated in vascular disease (including Prinzmetal), uncontrolled HTN, complicated migraine; injectable (suma)
Onabotulinum toxin A
Mechanisms unknown (possibly decreased afferent stimulation of trigeminovascular system, or downregulation of sensory and parasympathetic receptors) Preventive treatment of chronic migraine headaches --- Injection site pain, headache, neck weakness, ptosis FDA approved specific injection site protocol followed.
Amitriptyline,
protriptyline,
nortriptyline
Tri-cyclic antidepressants (TCA) --- Migraine prevention, tension headache prevention Dry mouth, constipation, weight gain, cardiac toxicity, orthostatic hypotension
Fluoxetine, paroxetine,
sertraline
SSRIs --- Migraine prevention, tension headache prevention; treatment for coexistant depression and chronic daily headache Weight gain, sexual dysfunction, headache
Propranolol, timolol,
nadolol, atenolol
Beta-blockers --- Migraine prevention [Only propranolol and timolol FDA approved, but nadolol and atenolol sometimes preferred for their longer half-life and tolerability.] Drowsiness, depression, decreased libido, hypotension, memory disturbance --- Contraindicated in asthma, diabetes, CHF, or Raynaud's
Verapamil
Calcium Channel Blockers --- Migraine prevention; particularly useful in prolonged or disabling aura, or complicated migraine syndromes (e.g., hemiplegic migarine); long-term prevention of cluster headaches Constipation, dizziness
Valproic acid
Antiepileptic Migraine prevention Hepatotoxicity, pancreatitis, blood dyscrasias, sedation, hair loss, weight gain, tremor, decreasing cognition
Topiramate
Antiepileptic Migraine prevention
Kidney stones, decresing cognition,
parestesias, weight loss acute angle-closure glaucoma
Oxygen
Acute treatment of cluster headaches — —
Rebound can occur when oxygen
stopped
Lithium
Alters circadian rhythm (?) Cluster headache prevention Weakness, nausea, thirst, tremor, lethargy, blurred vision & slurred speech Confusion, nystagmus Must monitor blood levels; do not use with indomethacin or Na-depleting diuretics
Tacrine
AChE inhibitor Inhibits AChE and BuChE Mild to moderate Alzheimers Transaminase elevation Nausea, vomiting, diarrhea, abdominal cramping Metabolized by P450; dosed 4/day; now obsolete
Donepezil
AChE inhibitor Inhibits AChE Mild to moderate Alzheimers; severe Alzheimers --- Nausea, vomiting, sleep disturbance Metabolized by P450; dosed 1/day
Rivastigmine
AChE inhibitor Inhibits AChE and BuChE Mild to moderate Alzheimers --- Nausea, vomiting, sleep disturbance Hydrolyzed by cholinesterases; dosed 2/day
Galantamine
AChE inhibitor Inhibits AChE; allosteric modulator of nicotinic receptors Mild to moderate Alzheimers --- Nausea, vomiting, sleep disturbance Metabolized by P450; dosed 2/day (1/day for ER strength)
Memantine
Partial antagonist of NMDA receptor Severe Alzheimers --- Dizziness, confusion, headache, constipation Excreted unchanged in urine; dosed 2/day
