Pharma MT 2 (not all-inclusive)

Psychosis

- describes symptoms of mental illness that result in strange/bizarre thinking, perceptions (sight, sound), behaviors, & emotions

- can be affected by environmental factors

- Treatment: Major Tranquilizers

Psychosis symptoms

- hallucinations

- delusions

- Schizophrenia

- Schizoaffective Disorder

- Bipolar Disorder

- Substance Abuse

Hallucinations

- hearing voices (auditory hallucinations)

- Having strange sensations / unexplainable feelings

- Seeing glimpses of objects / people not there / experiencing distortions

Delusions

- Believe external forces are controlling thoughts, feelings and behaviors

- Believe trivial remarks, events or objects have personal meaning or significance

- Thinking one has special powers / is on a special mission

Schizophrenia

- Serious mental illness that interferes with ability to think clearly, manage emotions, make decisions and relate to others

- Complex, long-term medical illness

Schizoaffective Disorder

Chronic mental health condition with schizophrenia and a mood disorder

Bipolar Disorder

- Dramatic shifts in mood, energy, & ability to think clearly.

- Experience highs & lows (mania and depression) differ from the typical ups-and-downs most people experience

Schizophrenia Symptoms

- Positive: hallucinations, delusions, suspicion, disorganized thinking (inc DA)

- Negative: stereotyped thinking, apathy, poor rapport (dec NMDA)

- Cognitive: poor working memory, attention deficit, executive dysfunction

- Affective: depression, eleation, suicidal ideation

Serotonin Hypothesis of Schizophrenia

- Hallucinogens (LSD, Mescaline) are serotonin agonists

- 5-HT2A-receptor blockade is mechanism of action for atypical antipsychotic drugs (CLOZAPINE, QUETIAPINE)

- 5-HT2A-receptor modulates the release of dopamine in the cortex, limbic region, & striatum

dopamine hypothesis of schizophrenia

- Repeated administration of stimulants like amphetamines & cocaine (dopamine potentiators) can cause psychosis resembling positive symptoms of schizophrenia

- Some early studies with post-mortem tissue show increased numbers of DA receptors (D2-like) in schizophrenic patients

- High dopamine in mesolimbic pathway, low dopamine in mesocortical

Glutamate Hypothesis of Schizophrenia

- Problem appears to relate partially to deficient glutamate activity

- Schizophrenia is associated with: lower release of Glu, fewer receptors in the prefrontal cortex & hippocampus

Antipsychotics/Neuroleptics

- Dopamine (D2) Blockers

- atypical/2nd gen also block 5-HT2a receptors

Typical Neuroleptics (First Gen)

- CHLORPROMAZINE (Thorazine)

- HALOPERIDOL (Haldol)

H-HT DA Antagonist (2nd gen neuroleptics)

ARIPIPRAZOLE (Abilify)

ClOZAPINE (Clozaril)

LURASIDONE (Latuda)

OLANZAPINE (Zyprexa)

QUETIAPINE (Seroquel)

RISPERIDONE (Risperdal)

ZIPRASIDONE (Geodon)

Antipsychotic Drug Effects

- Parkinsonism: rigidity, bradykinesia, tremor

- Tardive dyskinesia: involuntary painless movements of face & upper limbs

- Acute dystonia = spasms

- akathesia

Clinical Effects of Anti-Psychotics

- Sedative

- Extrapyramidal effects (Parkinsons-like symptoms)

- lower seizure threshold

- Antiemetic

- endocrine disorders, weight gain

- autonomic (antimuscarinic) = blurry vision, constipation, dry mouth,

- cardiovascular: orthostatic hypotension

Haloperidol (Haldol)

- Selectively blocks dopamine D2 receptors

- SE: dry mouth, extrapyramidal symptoms, orthostatic hypotension, nasal congestion, reduced seizure threshold, sexual disorders

- Tardive dyskinesia most frequent extrapyramidal symptom

Clozapine (Clozaril)

- Selectively blocks dopamine D2 receptors

- α-blockade, H1 blockade, anticholinergic

- Strongly blocks 5-HT2 receptors in cortex which then acts to modulate some dopamine activity

- Extrapyramidal side effects are minimal

- SE: orthostatic hypotension, sedation, weight gain, inc HR, dry mouth, dizziness, inc risk for SEIZURES (2-3%), AGRANULOCYTOSIS (1%)

RISPERIDONE (Risperdal)

- Fewer side effects than Clozapine

- Blocks selective D2, NE, & 5-HT2

- Effective for positive and negative symptoms

- Extrapyramidal side effects low (except at high doses)

- SE: sedation, weight gain, inc HR, orthostatic hypotension, dizziness

- elevated prolactin

- No agranulocytosis risks

OLANZAPINE (Zyprexa)

- Improved negative symptom reduction

- better than Risperidone in extrapyramidal issues

- Relieves nausea (Used in chemotherapy)

- Does not cause prolactin elevation

- SE: weight gain, postural hypotension, movement disorders, dizziness, constipation, dry mouth (anticholinergic at high doses)

Memantine (Namenda XR)

Class: Dementia

Mechanism: NMDA glutamate receptor antagonist, blocks excessive extrasynaptic activity of NMDA glutamate receptors

Usage: underlying symptoms of dementia

SE: GI disturbances (N/V, diarrhea), headaches

Donepezil (Aricept)

Class: Dementia

Mechanism: cholinesterase inhibitor, decrease breakdown of ACh

Usage: underlying symptoms of dementia

SE: GI disturbances (N/V, diarrhea), headaches

Amitryptyline (Elavil)

Class: Antidepressant

Mechanism: TCA, non-specific blockers of transmitter reuptake

Usage: resistant depression

SE: A LOT! anti-cholinergic effects, sedation, weight gain, postural hypotension

Nortriptyline (Pamelor)

Class: Antidepressant

Mechanism: TCA, non-specific blockers of transmitter reuptake

Usage: resistant depression

SE: A LOT! anti-cholinergic effects, sedation, weight gain, postural hypotension

Mirtazapine (Remeron)

Class: Antidepressant

Mechanism: TECA, blocks H1, alpha2, 5-HT receptors

Usage: depression

SE: CV, sedation

Fluoxetine (Prozac)

Class: Antidepressant

Mechanism: SSRI, selective serotonin reuptake inhibitors, allows for serotonin to remain in the synaptic cleft for longer periods of time

Usage: depression

SE: nausea, anxiety, agitation, insomia (early)

weight gain, weakness, sexual dysfunction (late)

withdrawal syndrome

Sertraline (Zoloft)

Class: Antidepressant

Mechanism: SSRI, selective serotonin reuptake inhibitors, allows for serotonin to remain in the synaptic cleft for longer periods of time

Usage: depression

SE: nausea, anxiety, agitation, insomia (early)

weight gain, weakness, sexual dysfunction (late)

withdrawal syndrome

Paroxetine (Paxil)

Class: Antidepressant

Mechanism: SSRI, selective serotonin reuptake inhibitors, allows for serotonin to remain in the synaptic cleft for longer periods of time

Usage: depression

SE: nausea, anxiety, agitation, insomia (early)

weight gain, weakness, sexual dysfunction (late)

withdrawal syndrome

Citalopram (Celexa)

Class: Antidepressant

Mechanism: SSRI, selective serotonin reuptake inhibitors, allows for serotonin to remain in the synaptic cleft for longer periods of time

Usage: depression

SE: nausea, anxiety, agitation, insomia (early)

weight gain, weakness, sexual dysfunction (late)

withdrawal syndrome

Escitalopram (Lexapro)

Class: Antidepressant

Mechanism: SSRI, selective serotonin reuptake inhibitors, allows for serotonin to remain in the synaptic cleft for longer periods of time

Usage: depression

SE: nausea, anxiety, agitation, insomia (early)

weight gain, weakness, sexual dysfunction (late)

withdrawal syndrome

Venlafaxine (Effexor)

Class: Antidepressant

Mechanism: SNRI, selective serotonin-norepinephrine reuptake inhibitors

Usage: depression, anxiety disorders, chronic nerve pain

SE: dry mouth, insomnia, blurred vision, increase BP

Desvenlafaxine (Pristiq)

Class: Antidepressant

Mechanism: SNRI, selective serotonin-norepinephrine reuptake inhibitors

Usage: depression, anxiety disorders, chronic nerve pain

SE: dry mouth, insomnia, blurred vision, increase BP

Duloxetine (Cymbalta)

Class: Antidepressant

Mechanism: SNRI, selective serotonin-norepinephrine reuptake inhibitors

Usage: depression, anxiety disorders, chronic nerve pain

SE: seizures (dry mouth, insomnia, blurred vision, increase BP)

Buproprion (Wellbutrin)

Class: Antidepressant

Mechanism: NDRI, norepinephrine-dopamine reuptake inhibitors

Usage: anti-smoking

SE: dry mouth, nausea, insomnia

Trazadone (Desyrel)

Class: Antidepressant

Mechanism: 5-HT2 antagonist, blocks and inhibits serotonin receptor reuptake

Usage: insomnia

SE: dry mouth, nausea, fatigue, sedation

Phenelzine (Nardil)

Class: Antidepressant

Mechanism: MAOI, monoamine oxidase inihibitor, non-selective and irreversible, oxidizes epinephrine, serotonin

Usage: depression

SE: drowsiness, low BP, sleep disturbances, weight gain, blurred vision

Selegiline (Emsam/Eldepryl)

Class: Antidepressant

Mechanism: MAO-B, oxidizes dopamine

Usage: Parkinson's

SE: drowsiness, low BP, sleep disturbances, weight gain, blurred vision

Chlorpromazine (Thorazine)

Class: Antipsychotic

Mechanism: first generation, selectively block D2 receptors

Usage: mood disorders

SE: dry mouth, extrapyramidal symptoms, tardive dyskinesia

Haloperidol (Haldol)

Class: Antipsychotic

Mechanism: first generation, selectively block D2 receptors

Usage: mood disorders

SE: dry mouth, extrapyramidal symptoms, tardive dyskinesia

Clozapine (Clozaril)

Class: Antipsychotic

Mechanism: selectively block D2 receptors, strong block for 5-HT2

Usage: ?

SE: seizures, agranulocytosis

Risperidone (Risperdal)

Class: Antipsychotic

Mechanism: blocks NE, D2, 5-HT2

Usage: positive and negative symptoms

SE: sedation, weight gain, elevated prolactin

Olanzapine (Zyprexa)

Class: Antipsychotic

Mechanism: blocks NE, D2, 5-HT2

Usage: positive and negative symptoms, negative symptom reduction, anti-nausea

SE: weight gain, dry mouth

Ziprasidon (Geodon)

Class: Antipsychotic

Mechanism: blocks NE, D2, 5-HT2, structural analog of risperidone

Usage: positive and negative symptoms

SE: less weight gain, but other similar SE (sedation, elevated prolactin)

Quetiapine (Seroquel)

Class: antipsychotic

Mechanism: blocks NE, D2, 5-HT2

Usage: positive and negative symptoms

SE: sedation, orthostatic hypertension

Lurasidone (Latuda)

Class: antipsychotic

Mechanism: blocks NE, D2, 5-HT2

Usage: positive and negative symptoms

SE:

Aripiprazole (Abilify)

Class: antipsychotic

Mechanism: acts as agonist in areas of dopamine deficit, antagonist in areas of hyperactivity

Usage: schizophrenia

SE: nausea, vomiting, constipation, dizziness

Lithium Carbonate (Lithonate)

Class: antipsychotic

Mechanism: unknown, low therapeutic index

Usage: bipolar disorder

SE:

Levodopa (Inbrija)

Class: Movement disorders

Mechanism: precursor molecule to dopamine

Usage: Parkinson's

SE: effect diminishes after 2-5 years

Levodopa/Carbidopa (Sinemet)

Class: Movement disorders

Mechanism: precursor molecule to dopamine, addition of peripheral DOPA decarboxylase inhibitor

Usage: Parkinson's

SE: effect diminishes after 2-5 years

Pramipexole (Mirapex)

Class: Movement disorders

Mechanism: dopamine agonist, acts on postsynaptic receptors

Usage: Parkinson's, can be used before L-DOPA to delay SE

SE: nausea, dizziness, not for use in patients with psychotic illness

Ropinirole (Requip)

Class: Movement disorders

Mechanism: dopamine agonist, acts on postsynaptic receptors

Usage: Parkinson's, can be used before L-DOPA to delay SE

SE: nausea, dizziness, not for use in patients with psychotic illness

Amantidine (Osmolex ER)

Class: Movement disorders

Mechanism: antiviral agent, antagonist of NMDA receptor

Usage: Parkinson's

SE: muscle stiffness

Benzitropine (Cogentin)

Class: Movement disorders

Mechanism: muscarinic antagonist in basal ganglia

Usage:

SE: restlessness, dry mouth, confusion

Tetrabenazine (Xenazine)

Class: Movement disorders

Mechanism: keeps dopamine out of vesicles, antagonize dopamine receptors

Usage: Huntington's

SE: ?

Diazepam (Valium)

Class: Anxiolytics and Hypnotics

Mechanism: benzodiazepine, enhance binding to GABA and GABA(A) receptors, increase Cl- conduction, long acting

Usage: generalized anxiety disorders, status elipticus

SE: Drowsiness, memory impairment, discontinued use --> rebound anxiety and insomnia

Clonazepam (Klonopin)

Class: Anxiolytics and Hypnotics

Mechanism: benzodiazepine, enhance binding to GABA and GABA(A) receptors, increase Cl- conduction, long acting

Usage: generalized anxiety disorders, status elipticus

SE: Drowsiness, memory impairment, discontinued use --> rebound anxiety and insomnia

Lorazepam (Ativan)

Class: Anxiolytics and Hypnotics

Mechanism: benzodiazepine, medium acting

Usage: generalized anxiety disorders, status elipticus

SE: Drowsiness, memory impairment, discontinued use --> rebound anxiety and insomnia

Temazepam (Restoril)

Class: Anxiolytics and Hypnotics

Mechanism: benzodiazepine, medium acting

Usage: generalized anxiety disorders, status elipticus

SE: Drowsiness, memory impairment, discontinued use --> rebound anxiety and insomnia

Alprazolam (Xanax)

Class: Anxiolytics and Hypnotics

Mechanism: benzodiazepine, short acting

Usage: generalized anxiety disorders

SE: Drowsiness, memory impairment, discontinued use --> rebound anxiety and insomnia

Buspirone (Buspar)

Class: Anxiolytics and Hypnotics

Mechanism: partial agonist at 5-HT(1A) receptors

Usage: anxiety

SE: dizziness, drowsiness, GI distress

Sympathetic Blockers

Class: Anxiolytics and Hypnotics

Mechanism: beta-blockers and alpha-2 agonists

Usage: anxiety

SE:

Eszopiclone (Lunesta)

Class: Anxiolytics and Hypnotics

Mechanism: selective for benzodiazepine site, high lipid solubility

Usage: insomnia, t(1/2) = 6 hours

SE: daytime sedation, GI upset

Zolpidem (Ambien)

Class: Anxiolytics and Hypnotics

Mechanism: selective for benzodiazepine site, high lipid solubility

Usage: insomnia, t(1/2) = 2 hours

SE: daytime sedation, GI upset

Ramelteon (Rozerem)

Class: Anxiolytics and Hypnotics

Mechanism: synthetic tricyclic analog of melatonin

Usage: insomnia

SE: ?

Phenytoin (Dilantin)

Class: Anticonvulsant

Mechanism: Na+ channel blocker, inhibits generation of APs

Usage: partial and generalized seizures

SE: gum thickening, increase hair production

Carbamazepine (Tegretol)

Class: Anticonvulsant

Mechanism: Na+ channel blocker, inhibits generation of APs

Usage: partial and generalized seizures

SE: rash, Steven-Johnson Syndrome, weight gain

Lamotrigine (Lamctal)

Class: Anticonvulsant

Mechanism: Na+ channel blocker, inhibits generation of APs, may also inhibit release of Glutamate

Usage: partial and generalized seizures

SE: ?

Gabapentin (Neurontin)

Class: Anticonvulsant

Mechanism: Ca2+ channel blocker, inhibits Glutamate release

Usage: partial and generalized seizures

SE: neurotoxic, dizziness, sleepy, dry mouth, blurry vision, weight gain

Pregabaline (Lyrica)

Class: Anticonvulsant

Mechanism: Ca2+ channel blocker, inhibits Glutamate release

Usage: partial and generalized seizures

SE: neurotoxic, dizziness, sleepy, dry mouth, blurry vision, weight gain

Ethosuximide (Zarontin)

Class: Anticonvulsant

Mechanism: reduces Ca2+ threshold in thalamic neurons

Usage: generalized seizures

SE: nausea, drowsiness, decreased appetite

Phenobarbital (Luminal)

Class: Anticonvulsant

Mechanism: barbituate

Usage: partial and tonic clonic seizures

SE: CNS depression

Tiagabine (Gabitril)

Class: Anticonvulsant

Mechanism: inhibits GABA transporter

Usage: partial seizures

SE: neurotoxic effects

Topiramate (Topamax)

Class: Anticonvulsant

Mechanism: targets Na+, Ca2+, GABA, AMPA

Usage: generalized seizures

SE: neurotoxic effects

Valproic Acid (Valproate, Depakote)

Class: Anticonvulsants

Mechanism: increase GABA production, decrease metabolism, Ca2+ and Na+ inhibition

Usage: partial seizures

SE: liver disease

Levetiracetam (Keppra)

Class: Anticonvulsant

Mechanism: presynaptic, bind to SV2A

Usage: 2nd line for partial seizures

SE: behavioral changes

Perampanel (Fycompa)

Class: Anticonvulsant

Mechanism: noncompetitive AMPA receptor antagonist

Usage: partial seizures

SE: serios pshychiatric changes

Vigabatrin (Sabril)

Class: Anticonvulsant

Mechanism: GABA-transaminase inhibitor

Usage: partial seizures

SE: vision loss

Zonisamide (Zonegran)

Class: Anticonvulsant

Mechanism: targets pretty much everything at once

Usage: partial seizures

SE: neurotoxic

Cannabidiol (Epidolex)

Class: Anticonvulsant

Mechanism: unknown

Usage: treatment of Lennox-Gastaut and Dravet syndrome

SE: lethargy, fatigue, increase appetite

Morphine (MS Contin [ER])

Class: Opiod

Mechanism: binds to μ receptors, blocking Ca2+ channels which decreases firing of APs and pain signal

Usage: pain treatment

SE: drowsiness, nausea, vomiting, constipation, dizziness

Hydromorphone (Dilaudid [IR])

Class: Opiod

Mechanism: morphine derivative, semi-synthetic

Usage: pain treatment

SE: drowsiness, nausea, vomiting, constipation, dizziness

Hydrocodone

Class: Opiod

Mechanism: codeine derivative, semi-synthetic

Usage: pain treatment

SE: drowsiness, nausea, vomiting, constipation, dizziness

Hydrocodone/APAP (Vicodin)

Class: Opiod

Mechanism: codeine derivative and tylenol, semi-synthetic

Usage: pain treatment

SE: drowsiness, nausea, vomiting, constipation, dizziness

Oxycodone (Oxyontin)

Class: Opiod

Mechanism: thebaine derivative, semi-synthetic

Usage: pain treatment

SE: drowsiness, nausea, vomiting, constipation, dizziness

Oxycodone/APAP (Percocet)

Class: Opiod

Mechanism: thebaine derivative and tylenol, semi-synthetic

Usage: pain treatment

SE: drowsiness, nausea, vomiting, constipation, dizziness

Fetanyl (Duragesic)

Class: Opiod

Mechanism: synthetic opioid, most potent

Usage: pain treatment

SE: drowsiness, nausea, vomiting, constipation, dizziness

Meperidine (Demerol)

Class: Opiod

Mechanism: synthetic opioid

Usage: pain treatment

SE: drowsiness, nausea, vomiting, constipation, dizziness

Tramadol (Ultram)

Class: Opiod

Mechanism: weak μ agonist, blocks 5HT and NorE

Usage: pain treatment

SE: drowsiness, nausea, vomiting, constipation, dizziness

Buprenorphine (Suboxone)

Class: Opiod

Mechanism: weak μ agonist, blocks 5HT and NorE

Usage: pain treatment

SE: drowsiness, nausea, vomiting, constipation, dizziness

Diphenoxylate (Lomotil)

Class: Opiod

Mechanism: slows intestinal contractions

Usage: diarrhea

SE: constipation

Loperamide (Imodium)

Class: Opiod

Mechanism: acts on μ receptors in large intestine

Usage: diarrhea

SE: constipation

Dextromethorphan (Robitussin)

Class: Opioid

Mechanism: decrease sensitivity of cough receptors

Usage: cold and flu

SE: drowsiness, nausea, vomiting, constipation, dizziness

Codeine/Guafensin (Robitussin A-C)

Class: Opioid

Mechanism: decrease sensitivity of cough receptors, thins and loosens mucus

Usage: cold and flu

SE: drowsiness, nausea, vomiting, constipation, dizziness

Naloxone (Narcan)

Class: Opiod-ish

Mechanism: opioid antagonist

Usage: opioid overdose

SE: ?

Isoflurane

Class: General Anesthetic

Mechanism: inhaled anesthetic, target multiple levels of CNS, increase GABA, increase K+ conductance, and inhibit NMDA receptors

Usage: induce and maintain anesthesia

SE: malignant hyyperthermia, nausea, vomiting, muscle spasms

Halothane

Class: General Anesthetic

Mechanism: inhaled anesthetic, target multiple levels of CNS, increase GABA, increase K+ conductance, and inhibit NMDA receptors

Usage: induce and maintain anesthesia

SE: malignant hyyperthermia, nausea, vomiting, muscle spasms

Desflurane

Class: General Anesthetic

Mechanism: inhaled anesthetic, target multiple levels of CNS, increase GABA, increase K+ conductance, and inhibit NMDA receptors

Usage: induce and maintain anesthesia

SE: malignant hyyperthermia, nausea, vomiting, muscle spasms

Enflurane

Class: General Anesthetic

Mechanism: inhaled anesthetic, target multiple levels of CNS, increase GABA, increase K+ conductance, and inhibit NMDA receptors

Usage: induce and maintain anesthesia

SE: malignant hyyperthermia, nausea, vomiting, muscle spasms

Nitrous Oxide

Class: General Anesthetic

Mechanism: inhaled anesthetic, target multiple levels of CNS, increase GABA, increase K+ conductance, and inhibit NMDA receptors

Usage: induce and maintain anesthesia

SE: malignant hyyperthermia, nausea, vomiting, muscle spasms

Propofol (Diprivan)

Class: General Anesthetic

Mechanism: IV anesthetic

Usage: induction of anesthesia

SE: CNS depression