NUSC 3P14 Pharmacology

Donepezil (Aricept)

acetylcholinesterase inhibitor/anticholinesterase inhibitor

Rivastigmine (Exelon)

acetylcholinesterase inhibitor/anticholinesterase inhibitor

Galantamine ER (Reminyl ER)

anticholinesterase inhibitor

Memantine (Namenda)

NMDA receptor antagonist
- allows Ca to enter cells to prevent excessive neuronal stimulation

Donepezil & Memantine (Namzaric)

cholinesterase inhibitor and NMDA receptor antagonist

Anticholinesterase inhibitors

- prevent breakdown of AcH (NT important for learning and memory)
- supports communication among nerve cells by keeping AcH high

NMDA receptor antagonist

decreases activity of glutamate (NT has role in information processing, storage and retrieval)

Alzheimer's Disease

decreased AcH (alters learning, memory, mood)
increased glutamate (overexposure of Ca)

SSRIs (selective serotonin reuptake inhibitors)

- selectively inhibits serotonin reuptake into the presynaptic neuron
- greater tolerability, ease of dosing and safety in OD
- DON'T prescribe with MAOI/other serotonin drugs
- Side effects: GI upset, insomnia, drowsiness, anticholinergic effects, sexual dysfunction, weight gain(longterm) /loss (short)

Citalopram (Celexa)

SSRI

Escitalopram (Cipralex)

SSRI

Fluoxetine (Prozac)

SSRI

Fluvoxamine (Luvox)

SSRI

Paroxetine (Paxil)

SSRI

Sertaline (Zoloft)

SSRI

SNRIs (serotonin-norepinephrine reuptake inhibitors)

- inhibits the reuptake of serotonin and norepinephrine into the presynaptic neuron
- first-line agents
- similar side effects as SSRIs
- HTN can occur @ high doses (sympathetic increase) - HTN crisis

Venlafaxine (Effexor XR)

SNRI

Duloextine (Cymbalta)

SNRI

Desvenlafaxine (Pristiq)

SNRI

Serotonin Syndrome

With any drug that increases 5-HT (e.g., MAO inhibitors, SNRIs, TCAs)
- life threatening
- confusion, hallucinations, uncoordinated movements, agitation, headache, tremors, fever, coma
-Treatment: cyproheptadine (5-HT2 receptor antagonist) and symptomatic treatment

Bupropion (Wellbutrin)

- Norepinephrine and dopamine reuptake inhibitor (NDRI)
- first-line agent
- insomnia, dry mouth, agitation, constipation, increased risk of seizure (contra head injury, epilespsy)
- LESS sexual dysfunction
- smoking cessation ****

Trintellix (Vortioxetine)

- serotonin modulator & stimulator
- thought to inhibit the reuptake of serotonin and causes receptor antagonism
- N+V, constipation

Tricyclic Antidepressants (TCAs)

- first generation
- start low dose, gradually increase, slow taper off
- anticholinergic effects, sweating, seizures, sedation
- orthostatic hypotension (slow position changes)
- urinary retention
- NEVER take with MAOI/ other antidepressants
- e.g., amitriptyline, Imipramine
- Fatal overdose

Monoamine Oxidase Inhibitors (MAOIs)

- first-generation
- start low, go slow
- increase the availability of NT
- massive HTN crisis risk (headache)
- avoid tyramine - NO fermented alcohol (wine, cheese), fruits/veggies (pickled), processed meats, sausage, salami), chocolate ---> MI, Stroke
- avoid OTC drugs (NSAIDs, acetaminophen, antacids) ---> HTN crisis
- watch salt intake
- monitor suicide
- DON'T combine with other antidepressants
e.g., phenelzine, selegiline, isocarboxazid

Lithium Carbonate

- bipolar disorder
- monitor drug levels regularly - start low dose
- 0-6-1.2 meq/L GOOD
- low therapeutic index
- TOXIC - > 1.5 meq/L (diarrhea/twitching/tremors/vomiting)
- effects may take 1-3 weeks
- side effects: GI upset, fine hand tremor, weight gain
- renal failure, toxic to thyroid
- cautions with other drugs: diuretics, ACE inhibitors, ARBs, NSAIDS can increase lithium levels
- salt restricted diet*

Anticonvulsants

- bipolar disorder
- decreases neuronal excitability
- inhibition of Na and Ca channel, glutamatergic NT and enhances GABA
- e.g., carbamazepine, valporate and lamotrigine

Carbamazepine (Tegretol)

- Anticonvulsant
- agitation with acute mania with lithium
- SE: anticholinergic effects (orthostatic hypotension), bone marrow suppression, hematologic diseases (leukopenia...)
- increases liver enzymes... increases hepatic metabolism
- *Monitor liver function and CBC

Valporate (Epilim)

- anticonvulsant
- acute mania
- common: drowsiness, weight gain, tremor, hallucination
- rare: thrombocytopenia, hepatotoxicity, pancreatitis, hepatic failure
- Monitor LFTs, drug serum level

Lamotrigine (Lamictal)

- Anticonvulsant
- First-line treatment for bipolar depression and is approved for acute and maintenance therapy (preventing future episodes)
- Stevens-Jhonson Syndrome (life-threatening)
- ** drug interactions with Valporic acid and carbmazepine

Bipolar Disorder Med Classes

- Mood stabilizers (lithium)
- anticonvulsants (carbamazepine, valproate, lamotrigine)
- antipsychotics; sedation & mood stabilizing effects (olanzapine, risperidone)
- anxiolytics (short-term acute mania; calming effects) (diazepam, lorazepam, clonazepam) *risk for dependency

Typical Antipsychotics

- 1st generation
- treat schizophrenia and related psychotic disorders primarily by blocking dopamine receptors - particularly D2 receptor
- SE: sedation, constipation, dry mouth, weight gain, EPS, urinary retention, hyperprolactinemia (can cause menstrual irregularities and sexual dysfunction)
- SE result from blocked cholinergic, histaminergic, adrenergic receptors
- don't cure but decrease symptoms

Atypical Antipsychotics

- 2nd & 3rd generation
- block dopamine & serotonin
- work on moderate to high D2 antagonism and high serotonin antagonism
- glutamate receptors?
- don't cure but decrease symptoms
- SE: weight gain, sedation, dizziness, constipation, dry mouth, urinary retention, orthostatic hypotension, fall
- increased appetite, weight gain and risk of DM
- higher doses; EPS

EPS in schizophrenia

- 77% or more of D2 receptors blocked will create EPS
- more likely with typical antipsychotics

Pseudoparkinsonism

rigidity, mask-like face, shuffling gate

acute dystonia

acute, progressive stiffness and twitching of muscles

akathisia

motor restlessness (pt unable to sit/stand)
- often misdiagnosed as psychotic agitation

Clorpromazine (Thorazine)

- typical antipsychotic
- weight gain ++

Loxapine

- typical antipsychotic

Haloperidol (inj q 4 weekly)

- typical antipsychotic
- weight gain +

Apriprazole (Abilify) (3rd gen)

- atypical antipsychotic
- weight gain +
- LAI

Olanzapine (Zyprexa)

- atypical antipsychotic
- weight gain +++

Clozapine (Clozaril)

- atypical antipsychotic
- weight gain +++
- positive, negative and cognitive symptoms
- treatment-resistant SZ
- SE: agranulocytosis
- Monitor WBC
- sore throat, malaise, mouth ulcer, fever
- not given unless blood test done

Quetiapine (Seroquel)

- atypical antipsychotic
- weight gain ++

Risperidone (Risperdal)

- atypical antipsychotic
- weight gain ++
- LAI

Ziprasidone (Zeldox)

- atypical antipsychotic
- weight gain +

LAIs

First Generation (Zuclopenthixol, Flupentixol, Haloperidol)
Second Generation
(Aripiprazole, Paliperidone, Risperidone)

dangerous responses to antipsychotics

- tardive dyskinesia: persistent EPS/ long treatment of APs (repetive, involuntary movements)
- anticholinergic activity c (induced delrium, dry mucous membrane, non reactive pupils, hot and dry red skin)
- NMS: reduction in brain dopamine activity (reduced LOC, muscle rigidity, hyperthermia, increase HR, RR, diaphoresis, drooling)
- agranulocytosis: absence of granulocytes (fever, malaise, flu like symptoms)

Adjuncts to Antipsychotic Drug Therapy

- Antidepressants
- Mood stabilizing agents
- Anticonvulsants
- Antiparkinsonian drugs
- Antianxiety- affective symptoms/agitation
- ECTs
- CBT

cognitive-behavioral therapy (CBT)

- integrative therapy that combines cognitive therapy (changing self-defeating thinking) with behavior therapy (changing behavior)
- identify, reality test and correct distorted belief & thoughts, challenge negative thinking and replace with positive & rational thoughts

Benzodiazepines

- enhance inhibitory effects by targeting GABAa receptors
- GABA = calming
- underactivity of GABA = anxiety
- SE: drowsiness, dizziness, reduced concentration, retrograde amnesia, physical dependence
- high addiction potential
- falls risk
- sedation
- D/C slowly avoid D/C symptoms (rebound anxiety, insomnia, seizures)

Clonazepam (Rivotril)

Benzodiazepine

Lorazepam (Ativan)

Benzodiazepine

Diazepam (Valium)

Benzodiazepine

Zoplicone (Imovane)

- short-acting sedative-hypnotic sleep agent
- fast onset; take @ bedtime

Buspirone hydrochloride (Bustab)

- melatonin receptor agonist/nonbenzodiazepine
- short-term relief
- less sedation

Treatment of Anxiety

- Benzodiazepines
- short-acting sedative-hypnotic sleep agent
- melatonin receptor agonist/nonbenzodiazepine
- antidepressants
- anticonvulsants
- antihistamines
- beta blockers (atenolol)

Amitriptyline (Elavil)

tricyclic antidepressant

Imipramine (Tofranil)

tricyclic antidepressant

Phenelzine

MAOI

Selegiline

MAOI

Isocarboxazid

MAOI