PHSCI 310 Exam 2 Latest Update
Depression - ANSWER Major depressive disorder and related conditions,
Chronic and recurring
4th most disabling disease worldwide
Worsens health of people with other diseases and increasingly disabling over time
70% psychiatric hospitalizations, 40% suicides, only 21% adequately treated
Altertions in emotion and mood, presence of at least 5 symptoms involving energy,
sleep, mood, self-concept, etc.
Also associated with anxiety
Major Depressive Disorder - ANSWER Combination of symptoms that interfere with
person's ability to work, sleep, study, eat, and enjoy pleasurable activities
Prevents normal functioning, May occur only once, but often occurs throughout a
lifetime
Other types of depression - ANSWER Dysthymic disorder, psychotic depression,
postpartum depression, seasonal affective disorder,
bipolar disorder
Pathophysiology of depression - ANSWER Current theories focus is on the long-term
effects of antidepressants on second messenger systems (neuron protection from
damage from injury or trauma, promote and maintain health of new neurons and
synapses that connect neurons)
Shrinking hippocampus (net loss of neurons)
Antidepressant drugs increase neurogenesis - timing of neurogenesis and net neuron
gain corresponds with therapeutic response, even though neurotransmitter level
increase almost immediately
Inadequate neurotransmitter activity for serotonin and/ or NE thought to lead to less
CREB (binds to DNA to regulate gene expression) and BDNF (transcriptional target for
CREB)
BDNF - brain-derived neurotrophic factor - affects normal development of nervous
system, chronic stress decreases levels, decreased in those with depression but
reversed with antidepressants
Depression Treatments - ANSWER First-line drugs - selective serotonin reuptake
,inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and
norepinephrine-dopamine reuptake inhibitor (NDRI)
SSRIs (selective serotonin reuptake inhibitors) - ANSWER Fluoxetine (prozac),
paroxetine, sertraline, citalopram, fluvoxamine, and escitalopram.
Therapeutic and side effects due to postsynaptic action of serotonin, action produces
antidepressant and anxiolytic effects, may produce adverse effcts like insomnia,
anxiety, agitation, sexual dysfunction, maybe nausea
Drugs all considered equally effective
Less side effects than older medications, not lethal in overdose
sexual dysfunction in 80% of people, reduces compliance, class switching may be
needed
Serotonin discontinuation syndrome - ANSWER syndrome caused by abrupt withdrawal
of an antidepressant drug,
onset of a few days for a couple weeks, disequilibria, GI symptoms, flulike symptoms,
sensory disturbances, sleep disturbances
Dual action antidepressants - ANSWER venlafaxine and duloxetine are SNRIs that block
serotonin and NE reuptake
may have better efficacy than SSRIs
similar delayed onset,
worse side effects and risk of overdose
Bupropion (welbutrin) is only norepinephrine-dopamine reuptake inhibitor, does not
effect SSRIs, used to treat kids with ADHD, less sexual dysfunction or enhanced sexual
function, may cause weight loss, may cause anxiety, tremor, insomnia, psychosis, and
seizures, mechanism like cocaine but not generally abused
First generation antidepressants - ANSWER Tricyclic antidepressants, and monoamine
oxidase inhibitors introduced in 50s and 60s, increase NE and serotonin in brain,
effective for depression, anxiety, as effective as second generation SSRIs, less
expensive, worse side effects, Imipramine is example
Tricyclic antidepressants - ANSWER inhibit presynaptic NE and serotonin reuptake
transporters, inhibit postsynaptic histamine, ach, and several other receptors
Anticholinergic activity can lead to confusion, memory and cognitive impairment, dry
mouth, blurred vision, increase heart rate, urinary retention
antihistaminic can cause drowsiness and sedation
, antiadrenergic can cause postural hypertension
life threatening effects are a concern especially for those who may consider suicide -
excitement and convulsions
Monoamine oxidase inhibitors - ANSWER inhibit monoamine oxidases that metabolize
dopamine, NE, and serotonin, example is phenelzine
also inhibit tyramine metabolism - tyramine increases BP, eating tyramine rich foods can
be bad for BP and can even cause death,
may also have interactions with other nasal spray stuff
Second-generation antidepressants - ANSWER trazodone is example
blocks 5-HT2 receptors, but its metabolite is a serotonin agonist
as efficacious as TCAs
Drowsiness is common, priapism is rare but can cause permanent impotence with
possible surgery\only modest effects on cognitive functioning
Clinical pharmacology of antidepressants - ANSWER most approved for acute and
long-term treatment
acute episodes usually 6-14 months untreated, goal of acute treatment is remission of
all symptoms, antidepressants may not acheive max benefit for 2 months
30-40% remission in 8-12 weeks, improved response with sequenced augmentation or
switching classes - 70-80% remission
85% have recurrence of MDD
Ketamine - ANSWER Spravato (esketamine) - depression relief within hours, for patients
that resist other treatments, can be used as anesthetic, recreational drug to cause
dissociation, and as date rape drug
Psychostimulants - ANSWER augment monoamine NT action, particularly dopamine but
also serotonin and NE,
Increase dopaminergic activity in brain's central reward pathway
Cocaine history - ANSWER 5000 years ago was coca leaves first use, 1850s cocaine
identified and purified, used as local anesthetic, combined with wine, in coca-cola, etc.
1914 narcotic act banned it in medicines and beverages, 1918 procaine (novicaine)
developed as synthetic anesthetic
Cocaine mechanism of action - ANSWER Actions in central and peripheral nervous
system
Depression - ANSWER Major depressive disorder and related conditions,
Chronic and recurring
4th most disabling disease worldwide
Worsens health of people with other diseases and increasingly disabling over time
70% psychiatric hospitalizations, 40% suicides, only 21% adequately treated
Altertions in emotion and mood, presence of at least 5 symptoms involving energy,
sleep, mood, self-concept, etc.
Also associated with anxiety
Major Depressive Disorder - ANSWER Combination of symptoms that interfere with
person's ability to work, sleep, study, eat, and enjoy pleasurable activities
Prevents normal functioning, May occur only once, but often occurs throughout a
lifetime
Other types of depression - ANSWER Dysthymic disorder, psychotic depression,
postpartum depression, seasonal affective disorder,
bipolar disorder
Pathophysiology of depression - ANSWER Current theories focus is on the long-term
effects of antidepressants on second messenger systems (neuron protection from
damage from injury or trauma, promote and maintain health of new neurons and
synapses that connect neurons)
Shrinking hippocampus (net loss of neurons)
Antidepressant drugs increase neurogenesis - timing of neurogenesis and net neuron
gain corresponds with therapeutic response, even though neurotransmitter level
increase almost immediately
Inadequate neurotransmitter activity for serotonin and/ or NE thought to lead to less
CREB (binds to DNA to regulate gene expression) and BDNF (transcriptional target for
CREB)
BDNF - brain-derived neurotrophic factor - affects normal development of nervous
system, chronic stress decreases levels, decreased in those with depression but
reversed with antidepressants
Depression Treatments - ANSWER First-line drugs - selective serotonin reuptake
,inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and
norepinephrine-dopamine reuptake inhibitor (NDRI)
SSRIs (selective serotonin reuptake inhibitors) - ANSWER Fluoxetine (prozac),
paroxetine, sertraline, citalopram, fluvoxamine, and escitalopram.
Therapeutic and side effects due to postsynaptic action of serotonin, action produces
antidepressant and anxiolytic effects, may produce adverse effcts like insomnia,
anxiety, agitation, sexual dysfunction, maybe nausea
Drugs all considered equally effective
Less side effects than older medications, not lethal in overdose
sexual dysfunction in 80% of people, reduces compliance, class switching may be
needed
Serotonin discontinuation syndrome - ANSWER syndrome caused by abrupt withdrawal
of an antidepressant drug,
onset of a few days for a couple weeks, disequilibria, GI symptoms, flulike symptoms,
sensory disturbances, sleep disturbances
Dual action antidepressants - ANSWER venlafaxine and duloxetine are SNRIs that block
serotonin and NE reuptake
may have better efficacy than SSRIs
similar delayed onset,
worse side effects and risk of overdose
Bupropion (welbutrin) is only norepinephrine-dopamine reuptake inhibitor, does not
effect SSRIs, used to treat kids with ADHD, less sexual dysfunction or enhanced sexual
function, may cause weight loss, may cause anxiety, tremor, insomnia, psychosis, and
seizures, mechanism like cocaine but not generally abused
First generation antidepressants - ANSWER Tricyclic antidepressants, and monoamine
oxidase inhibitors introduced in 50s and 60s, increase NE and serotonin in brain,
effective for depression, anxiety, as effective as second generation SSRIs, less
expensive, worse side effects, Imipramine is example
Tricyclic antidepressants - ANSWER inhibit presynaptic NE and serotonin reuptake
transporters, inhibit postsynaptic histamine, ach, and several other receptors
Anticholinergic activity can lead to confusion, memory and cognitive impairment, dry
mouth, blurred vision, increase heart rate, urinary retention
antihistaminic can cause drowsiness and sedation
, antiadrenergic can cause postural hypertension
life threatening effects are a concern especially for those who may consider suicide -
excitement and convulsions
Monoamine oxidase inhibitors - ANSWER inhibit monoamine oxidases that metabolize
dopamine, NE, and serotonin, example is phenelzine
also inhibit tyramine metabolism - tyramine increases BP, eating tyramine rich foods can
be bad for BP and can even cause death,
may also have interactions with other nasal spray stuff
Second-generation antidepressants - ANSWER trazodone is example
blocks 5-HT2 receptors, but its metabolite is a serotonin agonist
as efficacious as TCAs
Drowsiness is common, priapism is rare but can cause permanent impotence with
possible surgery\only modest effects on cognitive functioning
Clinical pharmacology of antidepressants - ANSWER most approved for acute and
long-term treatment
acute episodes usually 6-14 months untreated, goal of acute treatment is remission of
all symptoms, antidepressants may not acheive max benefit for 2 months
30-40% remission in 8-12 weeks, improved response with sequenced augmentation or
switching classes - 70-80% remission
85% have recurrence of MDD
Ketamine - ANSWER Spravato (esketamine) - depression relief within hours, for patients
that resist other treatments, can be used as anesthetic, recreational drug to cause
dissociation, and as date rape drug
Psychostimulants - ANSWER augment monoamine NT action, particularly dopamine but
also serotonin and NE,
Increase dopaminergic activity in brain's central reward pathway
Cocaine history - ANSWER 5000 years ago was coca leaves first use, 1850s cocaine
identified and purified, used as local anesthetic, combined with wine, in coca-cola, etc.
1914 narcotic act banned it in medicines and beverages, 1918 procaine (novicaine)
developed as synthetic anesthetic
Cocaine mechanism of action - ANSWER Actions in central and peripheral nervous
system
