Psychopharmacology

• Blood brain barrier have capillaries that act as selective filter to protect CNS
• The non-neuronal cells (astrocytes) prevent entry into the blood brain barrier
• Nonpolar, lipid soluble drugs cross by passive diffusion
• Polar and lipophobic drugs unable to enter the CNS unless taken by carrier-mediated transport systems
• 4 neurotransmitter categories

  • Ach
  • Monoamines
  • Amino Acids
  • Peptides
• Ach plays a role in cognition and memory

  • abundant in the periphery
  • excitatory within the brain
• Monoamines

  • dopamine
  • Serotonin
  • Norepinephrine
• Monoamines

  • dopamine
  • secreted by neurons in substantia nigra
  • used with motor control, mood, and emotions
  • inhibitive and excitatory
• Monoamines

  • Seratonin
  • released by cells in pons and BS
  • Mediates pain response, controls mood and behavior
• Monoamines

  • norepinephrine
  • Secretes in the pons
  • caused general excitation of the brain
  • Inhibitory
  • inhibits other inhibitory neurons = disinhibition
• Peptides

  • substance P is an excitatory NT, synapses in SC helps to transmit pain
  • Endogenous opioids
  • excitatory peptides that can reduce pain and cause a euphoric sensations
  • endorphins
  • enkephalins
  • dynorphins
• Benzodiazepines are used to treat anxiety and sleep
• Benzodiazepines increase GABA inhibition within CNS

  • enhance relaxation t/o the body
  • Act on GABA-alpha receptor
  • Lipid soluble
• Barbiturates are used for sleep

  • small TI of 10
  • Very addictive
  • Act on GABA-Alpha receptor
  • inhibit glycine and glutamate
  • lipid soluble
• Sedative hypnotics are used for

  • anxiety
  • Insomnia
  • Sedation prior to procedures
  • Epilepsy/seizures
  • anesthesia
  • Withdrawal control for alcohol abuse
  • Muscle relaxation
  • Dx aid in psychiatry
• If taking Sedative hypnotics, you can build a tolerance to the drug and dependency

  • withdrawal can increase sleeplessness and anxiety
  • should only be for short term use
• Sleep walking and sleep driving can be an issue with Sedative Hypnotics
• Quazepam (Doral) and Daridorexant (Quiviviq) have long half-lives and can cause daytime drowsiness
• Zolpidem (ambien) have a short half life and may cause complex nocturnal behavior
• Anti-anxiety drugs are for fear or apprehension over a situation or event

  • generalized anxiety
  • Social anxiety
  • Panic disorder
  • OCD
  • PTSD
• Anti-anxiety - benzodiazepines

  • Alprazolam (xanax) - short-term
  • Diazepam (Valium) - long
  • Lorazepam (Ativan) - short
• PAM = benzo
• Buspirone (BuSpar)

  • part of the azapirones drug class
  • Increases effect of serotonin in brain
  • For GAD, OCD, PTSD
  • Less side effects than other anti-anxiety drugs
  • 2-4 weeks to work
• Buspirone side effects

  • tachycardia
  • Chest pain
  • Palpations
• Adverse effects of anxiolytics

  • sedation
  • Addiction and tolerance
  • Rebound anxiety due to meds being stopped
  • Complication with dosing in the eldery
  • Only treats the sx, not the problem
• People with depression can have somatic complaints
• 3 types of depression

  1. reactive/secondary due to situational such as grief or illness
  2. Most common
  3. Endogenous depression or major depressive disorder due to biochemical issues
  4. depression associated with bipolar affective disorder aka manic depressive disorder
• Depression hypothesis

  • monoamine hypothesis
  • Norepi and serotonin are reduced in depression
  • Neurotrophic hypothesis
  • Lack of supports for neurons in key brain areas (BDNF reduced)
  • Hormonal abnormalities
  • Overactivity of hypothalamic-pituitary-adrenal axis
• Selective Serotonin Reuptake Inhibitors (SSRI)

  • inhibit enzyme responsible for serotonin reuptake at presynaptic terminal receptor
• Tricyclics block reuptake of amine NT at presynaptic terminal
• Monoamine oxidase inhibitors (MOA)

  • MOA is an enzyme that is inhibited allowing amines to stay in synaptic cleft longer
• SSRI/SNRI Adverse Effects

  • GI upset, serotonin syndrome (overall low side effects)
  • SSRI - hypotension
• Tricyclics Adverse effects

  • sedation
  • anticholinergic effects - causes delirium, dry mouth, constipation, tachycardia, OH
  • increased seizures
  • Potential for lethal OD due to arrythmias
• MOA Inhibitor adverse effects

  • restlessness
  • Irritable
  • sleep loss
  • anticholinergic effects (less than tricyclics)
  • hypertensive crisis
  • Fermented cheese and wine
• 5-HT2 receptor antagonist adverse effects

  • sedation
  • GI disturbances
  • Dose-related OH
  • Hepatotoxicity
• Tetracyclic and unicyclic antidepressants adverse effects

  • long half-life
  • GI issues
• Tyramine with MOA inhibitors can increase catecholamine levels leading to hypertensive crisis and MI/CVA
• Depressive episodes exceed the manic episodes in duration and frequency in both subtypes
• Bipolar I disorder is alternating episodes of mania and depression
• Bipolar II disorder is depressed episodes interspersed with less severe manic symptoms