pharm 2- antidepressant

a chemical "text message" between neurons.

Neurotransmitter

• : the gap between two neurons.

• 
  

• Synapse / synaptic cleft

• the sender, which releases the messages.

• 
  

• Presynaptic neuron:

• : the receiver.

• 
  

• Postsynaptic neuron

• : docking stations on the receiver where messages land. Only the right message fits

• Receptors

• a vacuum on the sender that sucks leftover messages back in, so the message stops and gets recycled.

• 
  

• Reuptake pump (transporter):

• an enzyme inside the sender that acts like a shredder, destroying messages.

• MAO (monoamine oxidase):

Three neurotransmitters matter for depression.

monoamines, =which include

Serotonin - 5HT

norepinephrine,

dopamine

caused by a deficit of norepinephrine, dopamine, or serotonin.

depression theroy -Biogenic amine hypothesis

synaptic dysfunction- depression

• decreased neurotransmitter release

• or impaired postsynaptic response

a stress-hormone system (HPA axis) gets out of balance, and inflammation markers in the blood run high

endocrine/immune factors- depression thoery

imbalanced glutamate (a excitatory brain chemical) and low vitamin D

nutrition factors- depression theory

depression what it looks like

low energy, messed-up sleep, changed appetite/sex drive, trouble doing daily tasks, overwhelming sadness/despair /disorganization

anxiety - what it looks like

tension, nervousness, fear, overreacting to things

sedation- what it looks like

• : becoming unaware of / unresponsive to your surroundings

hypnosis- what it looks like

• extreme sedation that pushes you into sleep by further slowing down the brain

ways antidepressants work- Inhibiting MAO breakdown

1. - MAOIs block .(MAO), prevents the inactivation of NE, dopamine, and 5HT in presynaptic terminals.

• The neurotransmitter get destroyed less, so more of them pile up.

ways antidepressants work- Blocking reuptake transporters

TCAs, SSRIs, and SNRIs block the reuptake pumps on the presynaptic neuron.

• This concentrates monoamines in the synaptic cleft.

ways antidepressants work- Receptor & clearance regulation

• Atypicals (adjust sensitivity of receptor) downregulate presynaptic inhibitory autoreceptors and modulate postsynaptic site sensitivity.

• Turning down the brakes so more messages get released.

• 
  

• SSRI- reuptake blockade- normal state

serotonin is released, binds to receptors, and the excess is quickly vacuumed back into the presynaptic terminal.

antidepressant action- reuptake blockade

the drug physically blocks the serotonin transporter, "effectively capping the vacuum."

The Result- reuptake blockade

: an increased amount of serotonin stays trapped in the synaptic cleft, stimulating postsynaptic receptors for a more extended period.

Serotonin is being cleaned up more slowly, NOT MORE CREATED

it has more time to do its job.

day 1- to week 1 Energy & Side Effects of antidepressants

Physical energy improves first, and side effects start right away: insomnia, agitation, nausea.

Mood Improvement antidepressants week 1 to week 2

stays flat until about Week 2, then slowly climbs. - full effect in 4 weeks

AKA delayed onset of therapeutic efficacy,

whats dangerous from week 1-2 after taking anti depressants

patient's energy comes back but their mood hasn't. A person who was too depressed to act on suicidal thoughts may now have the physical energy to carry out a plan.

first line antidepressant

SSRI, SNRI

2nd line antiderpessant

TCAs

last resort antidepressant

MAOIs

Anticholinergic effects SSRI, SNRI

none

Anticholinergic effects TCA

High (dry mouth, retention)

Anticholinergic effects MAOI

Moderate

cardiac risk ssri , snri

low

low to high- snri

cardiac risk TCA

High (orthostatic hypotension, dysrhythmias)

cardiac risk MAOI

High

sedation risk SSRI / SNRI

low

sedation risk TCA

high

sedation risk MAOI

low

dietary restrictions SSRI/SNRI/TCA

none

dietary restrictions MAOI

severe - tyramine

• what antidepressant to start with

SSRI/SNRI

Escalate to these for neuropathic pain or treatment resistance.

TCA

strictly for unresponsive depression because of fatal interaction risks.

MAOI

come from blocking acetylcholine,

result in fight/flight

• Anticholinergic effect

anticholinergic effect ex

dry mouth, trouble urinating (urinary retention), constipation, and blurry vision.

"can't spit, can't pee, can't poop, can't see."

specifically block presynaptic reuptake of 5HT, increasing serotonin availability.

SSRIs

why are SSRI first line therapy

completely lack the anticholinergic and cardiotoxic effects of TCAs.

Broad Clinical Indications- SSRI

• 
  

• depression disorder, OCD, panic disorder, bulimia, PMDD, PTSD, social anxiety, phobias

Adverse Effects:

• SSRI

• insomnia, agitation, nausea, diarrhea, sexual dysfunction, dry mouth

what to monitor for SSRI when combined with aspirin, NSAIDs, or oral anticoagulants.

increased bleeding risk-

help form clot

serotonin

lower serotonin in platelet

SSRI

what does clacium channel blockers do

vasodilate -

they are most potent antihypertensive meds

: inhibits reuptake of both serotonin (5HT) and norepinephrine (NE).

SNRI

ex drug SNRI

venlafaxine, desvenlafaxine, duloxetine, levomilnacipran.

special indication milnacipran (SNRI)

fibromyalgia (a condition of widespread chronic pain and fatigue).

adding norepinephrine reuptake inhibition of SNRI can

but monitor for

boost energy and focus

stimulant-like effects,(elevated heart rate or blood pressure

inhibits presynaptic reuptake of 5HT and NE

TCA

soluability of TCA

highly lipid soluable

peak and onset TCA

2-4 hr

10-14 days

TCA uses

depression, neuropathic pain (nerve pain), fibromyalgia, anxiety disorders.

TCA contrainidcatations

recent MI (heart attack),

myelography (e dye is injected around the spinal cord), concurrent MAOI use, and pregnancy.

Anticholinergic adeverse effects TCA

dry mouth, urinary retention, constipation, blurred vision.

Cardiovascular adverse effect TCA

orthostatic hypotension, dysrhythmias, sedation.

A patient on amitriptyline reports severe, work-impairing sedation. The provider may switch them

desipramine (Norpramin). -

This is a secondary amine with fewer sedating effects compated to a tertiary amine with marked sedation

ex of tertiary amine what it do

amitriptyline

heavily sedating,

ex of secondary amine

desipramine

barely sedates at all,

permanently blocks the enzyme (MAO) that normally breaks down norepinephrine, dopamine, and serotonin

PREVENT TYRAMINE BREAKDOWN

last resort

MAOI

foods to avoid with MAOI

fermented, or cured foods- aged cheese, wine, cured sausages, and beans-

tyramine rich foods

what can tyramine rich foods cause woth MAOI

massive norepinephrine release → hypertensive crisis.

• Triggered by prevented tyramine breakdown./

hypertensive crisis

• Symptoms: of hypertensive crisis

• Severe occipital headache (the back of the head)

• Massive BP spike

• Palpitations

• Neck stiffness

MAOI drug interactions

(strengthen) sympathomimetics ,TCAs, SSRIs, insulin, and oral antidiabetic agents.

treiggered when combining SSRIs/SNRIs with MAOIs, St. John's Wort, or triptans

Serotonin Syndrome

Neuromuscular signs serotonin syndorme

hyperreflexia (overactive reflexes), muscle rigidity, tremors, myoclonus (sudden jerky muscle twitches).

Autonomic instability related to serotonin syndrome

high fever, diaphoresis, tachycardia , extreme agitation.

Neuromuscular sign of hypertensive crisis

neck stiffness

cardiovascular signs, hypertensive crisis

massive BP spike, palpitations.

defining feature hypertensive crisis

severe occipital headache.

what to know about seorotnin syndorme and hypertensive crisis

both can be fatal anf need to stop med immediatly

Weak dopamine/norepinephrine reuptake inhibitor INSTEAD of serotonin

Bupropion (Wellbutrin/Zyban)

profile of Bupropion (Wellbutrin)

low side effects- Minimal sexual dysfunction,

activating profile

Also used for smoking cessation

Bupropion (/Zyban)

Inhibits 5HT/NE reuptake.

Nefazodone

profile of nefazodone

activating profile

/severe risk systemic effects

box warning for Nefazodone

potential life-threatening hepatic failure

• Blocks 5HT reuptake/receptors.

• 
  

Trazodone

profile trazodone

• low side effect

• high sedating effects

off label use Trazodone

sleep adi for insomnia

blocks Presynaptic alpha-2 antagonist,(normally inhibit release)

SO it increases 5HT/NE release.

Mirtazapine (Remeron)

what can Mirtazapine (Remeron cause

marked sedation and significant appetite and weight increase.

first line med for children/adolescents for depression

Fluoxetine- SSR

first line med for children/adolescents for ocd

sertraline or fluvoxamine- SSRI

Boxed Warning:and what to avoid for children and adolescants

increased risk of suicidal ideation and behaviors

MAOIs entirely due to toxicity.

Workup: first rule out what for adults

thyroid disease, cardiovascular, or hormonal causes. These can mimic depression.

pregnancy care

requires rigorous risk-benefit evaluation, encourage pregnancy registry enrollment. A registry tracks outcomes for babies exposed to a drug.

TCA warning:older adult

exacerbates urinary retention in BPH (benign prostatic hypertrophy

Renal/hepatic risk :older adult

start low and titrate slowly because of impaired clearance.

Toxicity vulnerability risk : older adults

high risk of CNS sedation, dizziness, and hallucinations

Baseline Assessment: before antidepressanst

liver and renal function,

baseline vitals and ECG,

evaluate suicide risk, and rule out underlying medical or thyroid illness.

Patient Education:

• -antidepressamts

• Emphasize the 2–4 week onset lag.

• Demand strict medication adherence.

• Explicitly warn against alcohol use or abrupt drug discontinuation to prevent withdrawal.