Psychopharmacology

Psychotropic medications

-Sedative-hypnotic

-Anti-anxiety

-Antidepressants

-Antipsychotics

-Dementia medications

Sedative-hypnotic and anti-anxiety drugs’ primary goal

-Relax the patient and promote “normal” sleep

-decreased anxiety

-included benzodiazepine and non-benzodiazepines

Benzodiazepines

-cause sedation

-used as “sleeping pills”

-included sedative hypnotic and anti-anxiety drugs

Benzodiazepines MOA

-Increase the effects of GABA

→GABA is inhibitory neurotransmitter that decreases excitation throuhgout CNS

-Benzodiazepines and GABA bind to a specific receptor (GABAa) in the brain

→Therapeutic effects- sedation, hypnosis, decreased anxiety

-GABAa- subunits: alpha, beta, gamma, with subsequent subdivisions

Non-benzodizepines - newer seddative hypnotics

-Barbiturates

→When used at sedative-hypnotic doses function similar to benzodiazepines to potentiate the inhibitory effects of GABA

→At higher doses may also directly reduce effects of glutamate ans also depress neuronal excitability in other areas of the brain and spinal cord

-Non benzodiazepines sedative-hypnotics

→bind preferentially to GAGAa receptor

-These ARE NOT benzodiazepines, but still bind to GAGA (alpha1 subunit) receptors in the brain

→DO NOT bind at the same place as benzodiazepines

-May produce fewer problems when discontinued

Newer sedative hypnotics

Other non-benzodiazepines

-Alcohol (ethanol) and substances with alcohol-like properties

→work through mechanisms poorly understood

→May act on protein receptors and activates GABAa receptors increasing inhibition in CNS

-Certain antihistamines, antidepressants, antipsychotics, anticonvulsants, and opioid analgesics also have sedative properties and may be used in limited situations to promote sleep

Sedative-hypnotic pharmacokinetics

-Highly lipid soluble and absorbed easily from the GI tract

-Systemic distribution with the ability to reach the CNS

-Termination by hepatic enzymes or storage in non-CNS tissues

Newer anti-anxiety drugs

-used to treat generalized anxiety disorders, possible panic disorder, OCD, and PTSD

-May decrease anxiety with less sedation, ;ess physical dependence, and addiction

-Drawbacks: slow onset, moderate efficacy

Use of antidepressants as anxiolytics

-Anxiety often occurs with depression

→patients may need both types of drugs

-Antidepressants can have direct effects- affect either serotonin or serotonin-norepinephrine balance in brain

-May alc0 have fewer side effects; less chance for addiction

sedative-hypnotic drugs: Adverse effects

-residual (hangover) effects

-retrograde amnesia

-complex behaviors (sleep walking/driving, especially with Ambienn)

sedative hypnotic and anti-anxiety drug adverse effects

-Rebound effect (insomnia, inc anxiety)

-FALLS

-Tolerance and dependence

-Benzodiazepines: possible link to Alzheimer's disease

sedative-hypnotic and anti-anxiety drugs rehabilitation concerns

-These drugs treat sxs, not the cause of the insomnia or anxiety

-Consider the trade-offs: benefits versis sedation

-There appears to be a trend toward the use of non-benzodiazepine sedative-hypnotics and axiolytics

Depression

-loss of the ability to enjoy life

-most common mental illness (characterized by feelings of sadness and despair)

-sadness that is incapacitating

-There is a neurochemical basis for depression

depression drug strategy

-increase or prolong the effect of one or more of the amine neurotransmitters

Types of antidepressants

-SSRI

-SSNRI

-Tricyclics

-MAO inhibitors

-Others

Selective serotonin reuptake inhibitors (SSRI)

-block reuptake of serotonin in the presynaptic terminal to allow serotonin to remain in the synaptic cleft and continue to exert effects longer

-if primary problem related to serotonin, may experience greater efficacy compared to other categories

selective serotonin-norepinephrine reuptake inhibitors (SSNRI)

-decrease serotonin and norepinepherine reuptake, but not dopamine

-beneficial in treating other conditions (chronic pain associated with OA, peripheral neuropathy, and fibromyalgia)

Tricyclics

-Non selective

-Affects synapses using all 3 primary amine neurotransmitters- serotonin, norepinepherine, dopamine

-Less used in favor of newer agents

MAO inhibitors

-Monoamine oxidase (MAO)- enzyme on amine synapses that removes released transmitters through the enzymatic destruction

→inhibit enzyme and more transmitter remains in synaptic cleft to exert effect

-More of a last resort drug vs a drug of choice

Other antidepressants

-These drugs are usually more complex, but are an option for some patients

→drugs that block serotonin receptors AND serotonin reuptake

→drugs that are norepinepherine-dopamine reuptake inhibitor

→drugs that may block presynaptic norepinephrine and serotonin receptors

Mechanism of antidepressant drugs

-Antidepressants prolong the effects of amine neurotransmitters by either:

→inhibiting of one or more amine neurotransmitters (SSRI; SSNRI; tricyclics; others)

→Decreasing neurotransmitter breakdown (MAO inhibitor)

Mechanism of MAOIs

-monoamine oxidase breaks down norepinephrine, serotonin, and dopamine

-when monoamine oxidase is inhibited, norepinephrine, serotonin, and dopamine are not broken down, increasing the concentration of all 3 neurotransmitters in the brain

-the transmitter is recycled and can be used over again

-20-40% of the transmitter is destroyed by the enzyme

Why might increased amine neurotransmitters decrease depression

-antidepressant drugs increase the activity of amino amine neurotransmitters

-increased neurotransmitter activity increases the brain-derived neuropathic factor (BDNF)

-BDNF stimulates growth (neurogenesis)in the hippocampus

Antidepressants: adverse effects - tricyclics

-sedation

-anticholingeric effects (dry mouth, confusion, urinary retention, constipation, tachycardia)

-Cardiovascular effects (arrhythmias and OH, especially in elderly

-seizures

-increased risk of a fatal overdose

Antidepressant adverse effects: MAOI

-CNS excitation

-increased BP (especially with other drugs/foods that cause catecholamine release)

Antidepressant adverse effects: SSRI & SSNRI

-generally better tolerated

-may increase risk of seizures

-some GI problems

other adverse effects: Serotonin syndrome

-possible with use of any antidepressant

-occurs when the CNS serotonin receptors are overstimulated

-Sxs: increased HR and BP, confusion, hallucinations, agitation, sweating, shivering, dystonia, dyskinesia, muscle pain, GI problems

-Usually reversible if addressed immediately. can be fatal if left unchecked

Antidepressants prescribed for off-label use

-common syndromes: fibromyalgia, neuropathic pain, HA, LBP, Raynaud’s phenomenon, other chronic pain syndromes

Antidepressants: rehabilitation concerns

-time lag before the beneficial effects are realized

-chance of increased depression during initial tx

-need to recognize/acknowledge mood changes

bipolar syndrome

-may be referred to as “manic-depressive” disorder

=associated with mood swings from one extreme (mania_ to another (depression)

-depressive episodes are similar to those in previous slides

-Manic episodes: euphoria, hyperactivity, talkativeness

bipolar syndrome - Lithium

-Antimanic

-Prevents manic episodes

-considered the best tx for bipolar syndrome

-MOA unclear: may stabilize neurons, may be neuroprotective

Lithium ion itself and pharmacokinetics

-is in the same category as sodium

-is an element not degraded in the body- not metabolized

-eliminated intact by the kidneys

-can accumulate rapidly

-Lithium toxicity

Sxs of lithium toxicity

Ranges of lithium effects

other meds used to treat bipolar syndrome

-Antiseizure drugs

-antipsychotics

Bipolar disorder rehab concerns

-Be alert for behavior changes that may indicate that the drug is reaching toxic levels

-may need to alert the physician/healthcare practitioner 

Antipsychotic medications - psychosis definition and cause

-psychosis: more severe forms of mental illness

-Cause: increased dopamine activity in specific CNS pathwaysan

antipsychotic meds - other neurotransmitters that may be involved (other than dopamine)

-5-HT

-Glutamate

-Acetylcholine

Antipsychotics MOA

-BLOCK CNS dopamine receptors, especially D2 receptors in mesolimbic pathways

-D2 antagonist blocks enough of the receptors so that when the dopamine is released, it doesn’t over-stimulate the post-synaptic terminal

Antipsychotics traditional vs “atypical” 

-Traditional: original antipsychotic meds

-” Atypical”: newer than traditional and may be preferred because of fewer/milder side-effects

Traditional antipsychotics

-tend to bind to several types of CNS dopamine receptors, including those that influence motor function in basal ganglia

-less predictable

-more patient-to-patient variability

-side effects and potential for long-term implicationsA

Atypical antipsychotics

-weak blockers of dopamine type 2 (D2) receptors

-Strong blockers of specific serotonin receptors (5-HT2 receptors)

-Clinical significance

→better at treating psychosis ?

→fewer, less serious side effects

-Less incidence of relapse due to improved tolerance and patient compliance

Antipsychotic adverse effects

-traditional agents: OH, sedation, anticholinergic effects

-Atypical agents: weight gain; disturbed lipid/glucose metabolism

-Primary concern with all antipsychotics: extrapyramidal (motor) side-effects

Extrapyramidal side-effects

-tardive dyskinesia

-pseudoparkinsonism

-akathisis

-other dystopias, dyskinesias

extrapyramidal effects - tardive dyskinesia

-prevalence: 25% of patients on long-term traditional antipsychotics

-cause: denervation super-sensitivity?

-Risk factors: advanced age; genetic predisposition; affective mood disorders; diabetes; hx of alcohol abuse (>6 months of continuous use)

-best tx: early recognition and change in type or dose of the antipsychotic drug

antipsychotics - Neuroleptic malignant syndrome (NMS)

-can occur with all antipsychotics

-Sxs: catatonia, rigidity, tremors, fever

-Increased risk if the dose is high, the patient is agitated, or has impaired mental function

-Can be fatal: critical need to detect NMS early and discontinue the drug

-REFER IMMEDIATELY

antipsychotic - Non-motor effects

-Metabolic effects: substantial weight gain; increased plasma lipids; DM

-Risk varies with drug

Antipsychotics rehab concerns

-must consider the options: benefits versus sedation

-be alert for OH

-recognize extrapyramidal side-effects

Dementia definition

-degenerative changes in the neuronal structure and function

-irreversible dementia: alzheimers disease

goals of drug therapy for dementia

-improve cognitive and intellectual function

→neuronal changes lead to decreased ACh activity in the brain

→cholinergic stimulants: increase ACh activity either directly or indirectly

-Improve/modify behavior

Indirect cholinergic stimulants: effect in dementia

-drug inhibits cholinesterase enzyme

-ACh breakdown is inhibited

=ACh activity/effects are prolonged

cholinergic stimulants - indications and efficacy

-Indications: improve cognition; behavioral function

-Efficacy: help patients retain more cognitive/intellectual function in the early stages of AD

Memantine (Namenda)

-blocks NMDA-glutamate receptors in the brain

→glutamate: excitatory amino acid, important in memory and learning

-glutamate activity disrupted in AD: drug therapy normalized glutamate influence

-provides another strategy to slow AD progression; sustain memory, and intellect

FDA approved monoclonal antibody drug AD that was eventually discontinued

-Aducanumab (Aduhelm)

→first to target fundamental pathophysiology of disease (amyloid plaques and neurofibrillary tangles)D

Drugs used to improve or modify behavior

-antidepressants

-antianxiety drugs

-antipsychotics

Behavior modification in AD and rehab implications

-government regulations instituted to curb the use of antipsychotics

-more emphasis on using sx-specific meds

-consider non-pharm interventions

-Rehab implications: following commands, participation, VCing, impact on safety