CH 6. Psychotropic Drugs

6.1 Sedative-Hypnotics & Antianxiety Drugs

How do Benzodiazpines affect CNS when treating insomnia and anxiety

Primary drawbacks using sedative hypnotics and anxiolygics for long periods

  • Increased fall risk

  • alzheimers?

  • hangover effect

  • rebound effect

  • anterograde amnesia

explain non-drug strategies that will replace the drugs

  • Solving the root problem since drugs only solve symptoms (exercise, counseling)

Newer Sedative-Hypnotics

  • Zolpidem + Zaleplon

    • work like BZD but less rebound insomnia when discontinued

  • Eszopiclone

    • affects GABA

  • Ramelteon (NON GABA)

    • Affects melatonin receptors

Newer Anti-Anxiety Drugs

  • Azapirone: Buspirone

    • stimulates serotonin receptors in CNS

    • decrease anxiety with less sedation and less dependence

    • BUT slow onset + moderate efficacy (used for mild anxiety)

What antidepressant drugs have anxiolytic effects? —> Paroxetine and Venlafaxine

  • less chance of side effects/addiction

Adverse Effects

  • Hangover effects that is hard to time

  • Anterograde amnesia

    • short-term learning slips

  • Rebound Effect

    • stopping drug suddenly without solving problem = vengence

  • Falls

  • Tolerance and dependence

  • Avoid use in age >60

6.2 Antidepressants

Describe drugs and the neurotransmitters they effect for depression

Mechanisms of antidepressant drugs + permanent changes

  • Increase synapses which grows hippocampus

Neurotransmitters in deficit in depression —> norepinephrine, Dopamine, Serotonin

SSRIs (Selective Serotonin Reuptake inhibtors)

  • boost serotonin

SNRIs

  • boost norepinephrine

Tricyclics

  • affect all 3 (nonephrine, dopamine, serotonin)

(THESE THREE BLOCK REUPTAKE SO STAY AROUND LONGER)

Monoamine Oxidase (MAO) inhibitors (LAST RESORT)

  • (INHIBIT ENZYME THAT BREAKS DOWN)

Theory on How these drugs work

  • Drugs also growth hippocampus (brain derived neurotrophic factor)

  • increase connections

6.3 Antidepressants + Bipolar Syndrome

  • What are adverse effects with antidepressants

    • 6-8 weeks for peak weeks

  • How does Ketamine resolve depression

    • decreases excitatory amino acids and NMDA

    • blocks receptors (serotonin, dopamine, GABA)

  • Conventional vs alternative treatment for bipolar disorder

Tricyclics cause:

  • sedation

  • anticholinergic effects (dry mouth + constipation)

  • CV problems

  • Seizures + increased risk of overdose

MAO inhibitors cause

  • CNS excitation

  • Increase blood pressure (+fermented foods)

SSRI + SNRIs (First since better tolerated)

  • increase seizure

  • More GI problems

Serotonin Syndrome

  • flooding of serotonin

  • S/S: high HR/BP, confusion, hallucinations, agitation, sweating, shivering, dyskinesias

Antidepressants lag before symptoms improve with 1-2 weeks and peak at 6-8

EDUCATE PATIENTS ABOUT PEAK WEEK TIME AND WORSE S/S

Ketamine

  • Anesthetic

    • Less NMDA and decrease effect of excitatory amino acids (glutamate)

    • affects serotonin, GABA, dopamine, acetylcholine, receptors

  • Fast acting, low dose to decrease depression (LAST RESORT) via IV or nasal spray

Antidepressants for Chronic Pain

  • Cymbalta is only drug FDA approved

Treating Bipolar Syndrome

  • Lithium

    • stabilizes mood to prevent episodes

    • What organ failure should be regarded when using lithium —> kidney since element are only excreted through kidney

Antiseizure and antipyschotics used for bipolar

6.4 Antipsychotic Medications

How do antipsychotics fix neurotransmitter abnormal levels?

  • All antipsychotics block dopamine receptors; newer atypical drugs affect serotonin

Why do antipsychotic drugs cause abnormal movement patterns?

  • Basal ganglia dopamine production is disrupted

Main mechanism of antipsychotic drugs —> Block D2 mesolimbic dopamine receptors

Atypical Antipsychotics

  • Weak blockers of D2 receptors

  • Strong blockers of serotonin receptors

  • Adverse effects (ALL INCLUDE MOTOR SIDE EFFECTS AKA EXTRAPYRAMIDAL)

    • disrupted lipid/glucose metabolism

      • weight gain

both share tardive permeant dyskinesia ¼ affected (extensive face movements), akathsia (fidgeting)

  • Why do motor side effects occur when taking antipsychotics? —> drug makes its way to basal ganglia (motor control) and inhibits dopamine

  • Adverse Effects (Traditional)

    • Orthostatic hypo

    • Sedation

    • Anticholinergic efx (constipation, urinary retention)

Drugs for Tardive Dyskinesia

  • prevent storage of dopamine, norepinephrine and serotonin in pre-syn terminals

Neuroleptic Malignant Syndrome

  • Catatonia, rigidity, tremors, fever

  • Risk factors: high dose, agitated patient/impaired mental function

6.5 Treatment of Dementia

How does anti-dementia drugs extend Acetylcholine in brain

  • extend release of Ach from neurons

Why do anti-dementia lose effectiveness as dementia progresses

  • Damaged neurons no longer produce any Ach so there is nothing to prolong which is main mechanism behind the drug

Anti-dementia drugs

  • Cholinergic stimulants

    • extend Ach activity

  • Indirect Cholinergic Stimulant

    • Inhibit cholinesterase that breaks down Ach due to short half life of Ach

Memantina (Namenda; new drug)

  • Blocks NMDA-glutamate receptors (excitatory amino acid)

    • Too much in Alzheimer’s

Drug combo for AD

  • Donepezil + Memantine = Namzaric

  • slows progression + prolong effect of Ach

Aduhelm (Aducanumab; NEWEST DRUG)

  • antibody that gloms to amyloid protein to prevent plaque in brain neurons

  • Monthly IV inject; $56,000 and not even sure it works