Category Drug Characteristics Clinical Use ADRs

ANTIDEPRESSANTS

300-3000 fold greater selectivity for serotonin transporter

Citalopram ● Allosterically inhibit transport ● Depression (primarily) ● Serotonin syndrome

● Take ≈ 2 wks to produce ● Sedation ○ Must discontinue fluoxetine for 4+ wks
Escitalopram significant improvement (can ○ Moreso for fluoxetine and before starting an MAOI
take up to 12 wks) paroxetine ○ Sx → hyperthermia, muscle rigidity,
SSRI Fluoxetine ● Potent CYP2D6 inhibitors ⇒ ● OCD in children sweating, myoclonus, changes in mental
fluoxetine and paroxetine ○ Fluoxetine, sertraline and status and vital signs
Specifically inhibit 5-HT Fluvoxamine fluvoxamine ○ Tx → cyproheptadine
reuptake ● Depression in children ● Discontinuation syndrome
Paroxetine ○ Fluoxetine and escitalopram ○ Sx → HA, malaise, flu-like sx, agitation,
nervousness, changes in sleep pattern
Sertraline ● Sexual dysfxn
● May cause QT prolongation (citalopram)
● Sz d/t lowered threshold

Affinity for SERT >>> NET. All can cause discontinuation syndrome

Venlafaxine ● Medium-high [ ] ⇒ 5-HT ● Depression ● If used in undx bipolar pts, can increase risk
reuptake inhibitor ● Chronic pain of hyomania/mania
● Minimal CYP450 inhibition ○ Diabetic peripheral ● High doses ⇒ may be an increase in HR
● Substrate for CYP2D6 neuropathy (duloxetine)
● Monotherapy ○ Postherpetic neuralgia
SNRI ○ Fibromyalgia (venlafaxine)
Desvenlafaxine ● Active, demethylated metabolite ● Insomnia/sedation
of Venlafaxine ○ Low back pain ● Constipation
Non-selectively inhibit ● Sexual dysfxn
reuptake of NE and 5-HT
Duloxetine ● Effective at ALL doses ● GI ⇒ Nausea, dry mouth and constipation
● Moderate inhibitor of CYP2D6 ● May increase BP and HR
○ May increase [ ] of drugs ● Avoid in pts w/ liver dysfxn
metabolized by these
pathways (i.e.
antipsychotics)

Levomilnacipran ● Metabolized by CYP3A4 ● Similar SNRI profile

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 Category Drug Characteristics Clinical Use ADRs

Narrow therapeutic index. Also block serotonergic, α-adrenergic, histaminic, and muscarinic receptors. Onset takes ≈ > 2 weeks
Tx chronic pain (migraine, neuralgia), tx resistant depression. Differ from SNRI in their ADRs.

Amoxapine ● Secondary amine ● Tx resistant Depression ● Discontinuation syndrome

○ Decreased cholinergic ● Cholinergic rebound effects
TCA Desipramine effects (more activating) ● ○ Blockade of muscarinic receptors ⇒
● 5-HT2 and dopamine D2 blurred vision, xerostomia, urinary
Non-selectively inhibit Nortriptyline receptors ● retention, sinus tachycardia, constipation,
reuptake of NE and 5-HT ○ Amoxapine and aggravation of angle closure
Protriptyline ● Selective NE reuptake inhibitors glaucoma
○ Desipramine (and ● Affects cardiac conduction ⇒ can
Maprotiline) precipitate life-threatening arrhythmias in
an overdose situation
Amitriptyline ● Tertiary amine ● Chest pain ○ QRS interval increase and prolonged QT
○ More sedating; can cause interval
Clomipramine AUR ● OCD tx ○ Tx → Sodium bicarbonate
● Selective NE reuptake inhibitors ○ Similar to quinidine
Doxepin ○ Maprotiline (and ● Insomnia ● Block α-adrenergic receptors ⇒ orthostatic
Desipramine) hypotension, dizziness, reflex tachycardia
Imipramine ● **be careful when using in pts ● Bedwetting in children (enuresis) ● Block histamine H1 receptors ⇒ sedation,
with BPH** weight gain
Maprotiline ● ● EtoH can cause toxic sedation
● MONITOR pts that are suicidal
Trimipramine ●

MAO fxn = safety valve” to oxidatively deaminate and inactivate excess NT.
must have dietary restrictions (b6/tyramine)

Isocarboxazid ● MAO can be found in liver or ● For refractory depression (last-line) ● Increased tyramine → increased release of
gut ● Parkinson disease (adjunctive) stored catecholamines → HTN crisis
○ Selegiline ○ Occipital HA, stiff neck, tachycardia,
Phenelzine ○ MAO-A = DA, serotonin,
MAO-I nausea, cardiac arrhythmias, sz, stroke
NE (possibly)
Selegiline ○ MAO-B = DA ● Drowsiness, orthostatic hypotension,
● Inhibition leads to accumulation blurred vision, dry mouth, and constipation
Tranylcypromine of NT in presynaptic neuron ● Amphetamine-like stimulant effect that may
(leaks in to synaptic space) produce agitation or insomnia
● Selegiline = only transdermal ○ Selegine and tranylcypromine
option ● SSRIs should not be co-administered ⇒
○ Selective serotonin syndrome
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Category Drug Characteristics Clinical Use ADRs

Other drugs used in the tx of manic sx of bipolar disorder (antiepileptic drugs – valproic acid and carbamazepine)

● Reduces the formation of ● Acutely and PPx for managing ● Hyponatremia or NSAID administration
inositol triphosphate (IP3) by bipolar pts can increase reabsorption in PT ⇒ toxic
inhibiting enzymes in pathway ○ Effective in pts exhibiting
lithium levels
Lithium ○ Decreased IP3 ⇒ decreased mania and hypomania
neuronal response to NE ○ Produces calming effects in ○ Diuretics (especially thiazides)
and 5-HT mania pts increase reabsorption
● Inhibits the uptake of inositol ■ Other tx → Valproic acid ○ Nephrogenic DI (most common
into cell (if w/ CKD), compilation of long-term lithium)
● TI extremely low (can be toxic) carbamazepine

A variety of targets for receptors and unique ADRS (be mindful!)

Bupropion ● Weak DA and NE reuptake ● Smoking cessation ● Side effects = Dry mouth, sweating,
(Wellbutrin) inhibitor tremor
● Very LOW incidence of ● AVOID in ptz w/ risk of sz
sexual dysfxn (dose-dependent)
● Low risk of drug-drug ○ Such as pts that are bulimic, epileptic,
interactions or EtOH w/d
● Metabolized by CYP2B6

Mirtazapine ● Enhances 5-HT and NE ● Sedating b/c of its potent ● Increased appetite and weight gain
Atypicals neurotransmission by serving antihistaminic activity frequently occur
as antagonist at central ○ Shouldn’t give to pts w/ eating
presynaptic α2-receptors disorders as they may become
● No antimuscarnic effect or non-compliant
sexyal dysfxn

Vilazodone ● 5-HT reuptake inhibitor ● Depression ● Discontinuation syndrome

● 5-HT1a partial agonist ● Anti-cholinergic effects
● Weight gain

Nefazodone ● Weak 5-HT reuptake inhibitors ● Sedating (probably because of their ● Mid to moderate α1-receptor antagonism,
● Antagonists at postsynaptic potent H1-blocking activity) contributing to orthostasis and dizziness
5HT2a receptor

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Category Drug Characteristics Clinical Use ADRs

● Mid-to-moderate α1-receptor ● Increased risk of hepatotoxicity

antagonism (contributing to
Trazodone orthostasis and dizziness) ● Sedating (see above) ● Mid to moderate α1-receptor antagonism,
○ Off-label management of contributing to orthostasis and dizziness
insomnia ● Assx w/ priapism (prolonged erection of
the penis; can be painful)

Vortioxetine ● Combo of: ● Depression ● Nausea

○ 5-HT reuptake inhibition ● Constipation
○ 5-HT1a agonism ● Sexual dysfunction
○ 5-HT3 and 5-HT7
antagonism

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 Category Drug Characteristics Clinical Use ADRs

ANTIPSYCHOTICS
Neuroleptic malignant syndrome (tx w/ dantrolene or bromocriptine)
may lower the seizure threshold

Can’t reduce negative schizophrenia sx

Chlorpromazine ● Competitive inhibitors of DA ● Intractable hiccups ● Extrapyramidal symptoms (EPS),

D2 receptor ○ Particularly
Thioridazine ○ Stored in fat ● ■ Seen more in drugs w/ greater
● Low potency binding affinity (haloperidol)
○ higher risk of ■ Less often in low binding potency
anti-cholinergic + (chlorpromazine)
anti-histaminergic effects ○ Bloclomg cholinergic activity leads to
1st Generation CHarlatans and THIeves are ■ Dystonias (sustained muscle
(AKA conventional) lowlifes: CHlorpromazine and contraction causing distorted
postures)
Block D2 dopamine THIoridazine are low potency ■ Parkinson-like sx (cogwheel
receptors in brain and antipsychotics. rigidity, resting tremors)
periphery ■ Akathisia (motor restlessness)
Fluphenazine ● Competitive inhibitors of D2 ● ● Tx → B-blocker or BZ
receptor ■ Tardive dyskinesia (involuntary
Haloperidol ● High potency (can lead to ● movements – usually of tongue, lips,
akathsia) neck trunk and limbs)
Loxapine ● ● Tx → Valbenazine,
“HAL TRIed to FLy high: deutetrabenazine
Molindone HALoperidol, TRIfluoperazine, ● ● Poikilothermia
and FLuphenazine are high ● Increase PRL release d/t D2 block in
Perphenazine ● pituitary
potency antipsychotics” ● Sexual dysfxn
Pimozide ● Motor and phonic tiscs (Tourettes) ● Weight gain

Prochlorperazine ●

Thiothixene ● Reduce positive sx assx w/

schizophrenia by blocking D2
receptors in mesolimbic region of
brain

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 Category Drug Characteristics Clinical Use ADRs

Trifluoperazine

Have a lower incidence of EPS than the 1st-generation agents, THEREFORE used as 1st line for schizophrenia

Aripiprazole ● Partial agonists at D2 and ● Reduce positive and negative sx ● Higher risk of metabolic adverse effects:
5-HT1A ● Antiemetic (d/t blocking D2 in ○ Diabetes, weight gain,
Brexpiprazole ● Antagonists at 5-HT2A medulla) hypercholesterolemia
● Only AP approved to reduce suicide ■ Olanzapine in particular
Cariprazine risk ● Serious adverse effect ⇒ BM suppression, sz,
○ Clozapine orthostasis, severe agranulocytosis
Clozapine ● High affinity for ● Adjunctive agents w/ antidepressants ○ Clozapine
○ D1 and D4 for treatment refractory depression ● Anticholinergic ⇒ particulatry thioridazine,
○ Muscarinic ○ Aripiprazole, brexpiprazole, chlorpromazine, clozapine, and olanzapine
○ α-adrenergic receptors, quetiapine ○ Sx →
● Weak D2 antagonist ● Disruptive behavior and irritability ■ Blurred vision
secondary to autism ■ Dry mouth
2nd Generation Olanzapine ● Blocks 5-HT2A > D2 ○ Aripiprazole, Olanzapine ● Exception is clozapine, which
(AKA atypical) ● Refractory pts (minimal EPS risk) increases salivation
Risperidone ○ Clozapine ■ Confusion
Block mostly 5-HT2A but ● Psychosis associated w/ Parkinson ■ Inhibition of GI and UT smooth
also D2A receptors Pimavanserin ● Inverse agonist/antagonist at the disease muscle → constitution and urinary
5-HT2A and 5-HT2C ○ Pimavanserin retention
(-apine, -peridone, ● No appreciable affinity for ● Bipolar depression ○ Tx → benztropine
-idone) DA receptors ○ Lurasidone and quetiapine ● Blockade of α-adrenergic receptors causes
● Schizoaffective disorder orthostatic hypotension and dizziness
Quetiapine ● Weak blockade at D2 and ○ Paliperidone ● Sedation occurs with potent antagonists of the
5-HT2A H1-histamine receptor
○ Chlorpromazine, olanzapine,
Asenapine ● Typical MOA quetiapine, and clozapine
● Poikilothermia
Iloperidone ● Increase PRL release d/t D2 block in
pituitary
Lurasidone ● Sexual dysfxn
● Weight gain
Paliperidone

Ziprasidone

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 Category Drug Characteristics Clinical Use ADRs

SEDATIVES-HYPNOTICS

Lipophillic
Benzodiazepines & newer hypnotics (Z drugs) bind between α & γ subunits (called BZ site)
Synergistic binding w/ Barbs
Many converted initially to active metabolites w/ long t1/2
Cross placental barrier (danger of depression of neonatal vitals); can be found in breast milk
Flumazenil (BZ antagonist) can be used in reversing long term BZ use
BZ inferior to Z drugs for tx sleep b/c Z drugs don’t mess up sleep cycle as much
Benzodiazepines
Oxazepam ● Short acting ● Anticonvulsant effects ● Addiction potential if not used short duration
Bind to GABAA receptors ○ Rebound effects more likely ● Skeletal muscle relaxant @ high ● Tolerance frequently develops within a few
(called BZ site) → Triazolam doses (α2-GABAA receptors in SC) days; withdrawal → rebound insomnia
↑ frequency of ● Anxiety (low dosing) ○ Triazolam
GABAA Alprazolam ● Intermediate action ○ Longer acting agents ● Long T1./2 can cause daytime hangover
receptor-mediated Cl- (clonazepam, lorazepam, ● W/d sx if discontinued abruptly
channel opening Estazolam diazepam for prolonged tx) ○ Confusion, anxiety, agitation, restlessness,
● Panic disorders insomnia, tension, and rarely, seizures
(positive allosteric Lorazepam ○ Alprazolam ○ Be wary of short t1/2 because that can
modulators of GABAA) ● Insomnia (intermediate or long induce more abrupts and severe rxn
Temazepam acting) ● Ataxia at high doses
● Sleep onset (short acting – ● Alcohol and other CNS depressants have
Diazepam ● Long acting Triazolam) additive effects
-lam or -pam ● Seizures ● Used cautiously in pts with liver disease
Flurazepam ○ Adjunctive therapy –
○ Exception = Lorazepam, Oxazepam,
Clonazepam
Quazepam ○ Status epilepticus – Temazepam
Lorazepam, diazepam
Clorazepate ● Acute tx of EtOH w/d
○ Due to cross tolerance,
Chlordiazepoxide chlordiazepoxide, clorazepate,
diazepam, lorazepam, and **use carefully in pts w/ liver disease and pts w/
oxazepam are useful acute angle-closure glaucoma**
○ Long acting preferred, unless
LF issues (do short acting)
● Amnesia (short acting agent)
○ Midazolam
● Muscular disorder
○ Diazepam (good for spasms)

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 Category Drug Characteristics Clinical Use ADRs

Barbiturates bind within the Cl- channel (different site as BZD’s)

Lipophilic, well absorbed & distributed into the brain
Cross the placenta and can depress the fetus
Chronic use can induce CYP450 → ↑ metabolism of drugs (including themselves) and endogenous substances

Barbiturates Thiopental ● Ultra-short acting (20 min) ● Anesthetic (IV) ● Hypnotic doses → drug “hangover” after
● High lipid solubility waking
Bind to GABAA receptors ● Extensively metabolized in the ● Chronic barbiturate administration →
(different sites than BZDs) liver induction of CYP450 → diminished action of
→ many drugs
increased duration of Amobarbital ● Short acting (3-8 hrs) ● Sedative/hypnotic: ● No antidote for barbiturate overdose
GABAA ● Extensively metabolized in the ○ Used as mild sedatives to ● Respiratory depression w/ overdose
receptor-mediated Cl- Pentobarbital liver relieve anxiety, nervous tension, ● Depressed reflexes & impaired judgment →
channel and insomnia serious accidents
opening Secobarbital ● Additive CNS depression (e.g. alcohol,
antihistamines, antipsychotic, etc)
Phenobarbital ● Long-acting (1-2 d) ● Refractory status epilepticus ● Contraindivsted in porphyrias
● Long term management for
tonic-clonic sz

Hypnotics that bind to BZ sites on GABAA receptors.

Interact with GABAA receptors isoforms that contain α1 subunits
Can be antagonized by flumazenil
No anticonvulsant or muscle-relaxing properties

Eszopiclone (Lunesta) ● Quick onset and short duration ● Rapid onset of hypnosis w/ few ● Dizziness, daytime drowsiness, somnolence,
of action (Zaleplon, Zolpidem) amnestic effect or day-after ● Short-term memory loss
Zaleplon (Sonata) ○ Sleep onset issues psychomotor depression ● Lack of coordination
● Longer t1/2 (Eszopiclone) (somnolence) ● "Hangover"
Z-drugs Zolpidem (Ambien) ○ Sleep maintenance issues ● Insomnia (improve onset and ● Feeling, anxiety, dry mouth
● Rapid metabolism (short duration of sleep) ● Complex sleep behaviors (sleep-driving),
duration of action) ○ Better to use than BZ b/c less nightmares
● Interactions sleep interference, tolerance ● Hallucinations
○ Additive CNS depression less of a risk, etc
with EtOH & other drugs
○ Metabolized by CYP450

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 Category Drug Characteristics Clinical Use ADRs

Buspirone ● SLOW onset of action ( >1wk) ● Used in GAD (d/t slow onset) ● Tachycardia, paresthesias, pupillary
● Partial agonist at 5-HT1A constriction, GI distress, HA
● Selective anxiolytic w/ ● Sedation, psychomotor and cognitive
○ Minimal CNS depressing dysfunction are minimal, and dependence is
○ No antivolsing unlikely
○ No muscle relaxing ● No additive effects with alcohol
● Doesnt affect driving skill
● Metabolized by CYP3A4; prone
to drug interactions

Ramelteon ● Selective agonist at melatonin ● Induces and promotes sleep ● Dizziness

Miscellaneous receptors (MT1 and MT2) ● Has no evidence of dependence or ● Fatigue, somnolence
Tasimelteon ○ No direct effects on withdrawal effects ● Decreased testosterone and increased PRL
GABA-ergic ○ Ramelteon can be administered levels
neurotransmission in CNS long term
● Has minimal abuse liability; is
not a controlled substance
● Metabolized by CYP450; prone
to drug interactions

Suvorexant ● Blocks binding of orexins, ● Promotes sleep onset and duration ● Next-day somnolence
neuropeptides that promote ● Indicated for sleep disorders, ● Driving impairment
wakefulness especially those characterized by
● Metabolized by CYP450; prone difficulty in falling asleep
to drug interactions