Midterm 2

What is depression?

• Persistent sad or irritable mood

How is depression diagnosed? General symptoms?

Must have 1 of the following

• Depressed mood most of the day

• Diminished interest or pleasure in all life activities

Must have 4+ of the following symptoms

• Weight loss

• Insomnia / hypersomnia

• Fatigue / loss of energy

• Pscyhomotor agitation or retardation

• Worthless / guilt

• Can’t concentrate / indecisive

• Suicidal ideation

Must occur in same 2 week period

Diagnosis symptoms can’t be from

→ Drugs

→ Bereavement

Whats the etiology of depression?

• Abnormalties in neurotransmitters (Down N Sad)

• Genetics (Race/ethinicity/gender)

  • Women ↑

• Catastrophic life events

• Environmental factors (professions, living situation etc)

How is depression treated?

Goals of treatment

• Reduce and remove signs and symptoms

• Restore occupational and psychosocial function

• Reduce/prevent relapse and recurrence

• Pharmacological therapy (drugs)

  • TCAs

  • MAOIs

  • SSRIs

Types of depression

• Major depressive disorder (MDD)

  • Impairs activity of daily living

• Dysthymic disorder

  • Chronically mildly depressed — part of personality

• Bipolar disorder

  • Manic

  • Cyclothymic

    • Mild bipolar

• Substance induced disorder

• Seasonal affective disorder

• Postpartum depression

  • Within 1—6 weeks after baby

• Premenstrual dysphoric disorder

  • 1—2 weeks before menstrual cycle

4 pharmacological therapy drug classes for depression

• Tricyclic Antidepressants (TCAs)

• Monoamine Oxidase Inhibitors (MAOIs)

• Selective Serotonin Reuptake Inhibitors (SSRIs)

• New Generation Antidepressants

Choice of drug is multifactorial, it depends on 2 things…

• Patient profile

• Drug profile

What’s the mechanism of action for Tricyclic antidepressants (TCAs)?

What are the TCA Drugs?

• Inhibit reuptake of norepinephrine and serotonin

Drugs

• Amitriptyline

• Nortriptyline

• Imipramine

• Doxepin

• Protriptyline

What’s the mechanism of action for Monoamine Oxidase Inhibitor (MAOIs)?

What are the MAOI Drugs?

• Inhibit MAO that degrades down dopamine, norepinephrine, serotonin — increases levels

• Also blocks metabolism of tyramine → leads to hypertensive crisis risk

Drugs

• Phenelzine

• Isocarbozazid

• Tranlcypromine

Last line of antidepressant therapy — too many side effects/ disadvantages

What’s the mechanism of action for Selective Serotonin Reuptake Inhibitors (SSRIs)?

What are the SSRI Drugs?

• Selectively blocks reuptake of serotonin

• 4—6 weeks for therapeutic effect

• Low compliance rate

Drugs

• Fluoxetine — Treat eating disorders/ safe for pregnancy

• Sertraline — Diarrhea

• Paroxetine — Most sedating / weight gain

• Citalopram — minimal side effects, sexual dysfunction

What’s the mechanism of action for New generation antidepressants?

What are the New generation depressant Drugs?

• Inhibits reuptake of serotonin and norepinephrine (SNRI)

How different from TCAs?

• TCA — Tricyclic chemical structure

Drugs

• Trazodone

  • Inhibit reuptake serotonin and NE

  • Sedation, priapism (prolonged erection), orthostasis (LBP)

• Nefazodone

  • Inhibit reuptake serotonin and NE

  • Calming antidepressant — less sedating

• Bupropion

  • Inhibit reuptake of dopamine

  • Smoking cessation at low levels

Venlafaxine drug does what

• Inhibits reuptake of dopamine, norepinephrine, and serotonin

Mirtazapine drug does what

• Stimulates increased release of serotonin and norepinephrine

  • High dose — less sedating, for depression

  • Low dose — more sedating

Problems with antidepressants drug therapy

• recommended for 6—12 months

• Recurrent episodes

Why not stop a drug suddenly?

• Withdrawals; need to taper off

How are antidepressants chosen?

• Patient profile

• Drug profile

What is anxiety?

Fear or apprehension

• Activation of sympathetic and limbic system (Regulate emotion and behavior)

• Leads to neurosis prolonged

2 components of anxiety?

• Mental symptoms

  • Worry, fear, thinking

• Physical symptoms

  • Sweating, rapid heart beat, pacing

Types of anxiety disorders

• Situational

  • Short term 2—3 weeks

  • Situation (Exam, deadline, work etc)

• Generalized anxiety disorder (GAD)

  • Unrealistic worry

• Panic disorder

  • Short episodes panic attack

• OCD

  • Obession (persistent thoughts)

  • Compulsive (Intrusive behaviors)

• PTSD

  • Traumatic event impacts ADL

How is anxiety diagnosed?

• Unrealistic worry about 2+ life circumstances

Must have 3 out of 6 symptoms

• Restlessness

• Fatigue

• Irritability

• Muscle tension

• Difficulty concentrating

• Disturbed sleep

6 months or longer

2 treatment approach for anxiety?

• Non—pharmacological approach

  • Psychotherapy (therapist)

  • Meditation

  • Exercise

  • Stress relieving activities

• Pharmacological approach

  • Drugs

2 pharmacological drug classes for anxiety?

• Benzodiazapines (BZD)

  • Anxiolytics and enhances GABA neurotransmitter in brain

  • Binds to GABA receptors — slows down brain

• Non—benzodiazapine

What is GABA?

Gamma aminobutyric acid (GABA)

• Inhibitory neurotransmitter

• Slows down brain

What are the long acting and short acting benzodiazapines?

Long acting

• Diazapam

• Chlordiazepoxide

• Clonazepam

Short acting

• Temazepam

• Alprazolam

• Lorazepam

What are the non—benzodiazapine drugs?

• Azapirones

  • Bind to serotonin — decrease serotonin activity, calming anxiety

• Buspirone

  • No relaxation

  • Mild antidepressant

beta blocker

• Propanolol — nonselective (B1 and B2) — Treats physical symptoms of anxiety

What is psychosis?

• Impaired reality, bizarre behaviora and deterioration of personality

How is psychosis diagnosed?

Must have 2+ of the following for 1+ month

• Impaired sense of reality

• Thought and emotion disturbances

• Hallucinations

• Delusions

• Confusion

• Disorganized speech or behavior

• Negative symptoms (5 A’s)

Schizophrenia requirements?

• Males more common

• Symptoms 6+ months

What are the 5 A’s (Negative symptoms) of psychosis?

• Alogia — Poverty of speech

• Avolition — Lack of motivation

• Anhedonia — Lack of interest / pleasure in activities

• Affective blunting — Lack of emotional expression

• Attention impairment — Can’t focus / easily distracted

What neurotransmitter is involved in psychosis?

• Excess dopamine transmission cause psychosis

Etiology of psychosis? (Cause)

• Teens —> early 20s

Prodromal symptoms (early signs)

• Social withdrawal

• Loss of interest in school / work

• Deterioration in hygiene

Outcome of psychosis?

• Remission cycle

• Incomplete recovery

• Episodes treated early = better outcome

How do antipsychotics work?

• Block postsynaptic dopamine receptors

What are the 2 types of dopamine receptors?

• D1 receptors

  • Block D1 = partial antipsychotic activity

  • Cause EPS (Extrapyramidal symptoms)

• D2 receptors

  • Block D2 = Complete antipsychotic activity

  • Most effective — desired therapeutic effect

3 classes of antipsychotic drugs

• Phenothiazine

• Non—phenothiazine

• Atypical antipsychotic

How do phenothiazine work? What are the drugs?

• Block dopamine receptors —Specifically D2 (main)

  • Also block serotonin, epinephrine, norepinephrine

Low dose

• Treat nausea, vomitting, hiccups

High dose

• Treat anxiety, agitation, psychosis

Drugs

• Chlorpromazine

• Thioridazine

• Trifluoperazine

What is EPS (Extra pyramidal symptoms)?

• Parkinson—like side effects

• Caused by blocking D1 receptors

  • Tremors, drooling, rigid body movements

How do Non—phenothiazines work? What are the drugs?

• Block D1 receptors

• High incidence of EPS

• Similar to phenothiazines, but more potent

Drugs

• Thiothixene

  • Low sedation, cause EPS

• Haloperidol

  • More sedation, cause EPS

How do Atypical antipsychotics work? What are the drugs?

• Block both dopamine receptors and serotonin

• MOA not understood

• Drug of choice, low EPS

• Best for negative symptoms (5 A’s)

Drugs

• Clozapine

  • Agranulocytosis (low white blood cell)

• Olanzapine

  • Weight gain

• Risperidone

  • Suicidal ideation

• Quetiapine

  • Effective in young patients

  • Control negative symptoms

What neurotransmitter is responsible for nausea and vomitting?

• Dopamine receptors (D2)

What are antiemetics?

• Drugs to treat nausea, vomitting, motion sickness, vertigo

How do antiemetics work?

What are the treatments and drugs?

• Block dopamine (D2) and serotonin receptors in CTZ (chemoreceptor trigger zone)

• CTZ = In medulla — induces vomitting / nausea

• Antihistamines can also help motion sickness

Treatment

• Remove trigger/ sensation (Ex: Get off boat/ car)

• Choose drug (patient and drug profile)

Drugs

• Prochlorperazine

• Diphenhydramine

• Scopolamine

• Dimenhydrinate (cocoa cola)

Sedatives vs hypnotics?

• CNS depressants (decrease activity)

• Sedatives

  • Reduce desire for physical activity

  • Chill

• Hypnotics

  • Induce and maintain sleep

  • Sleep

What are the 2 different STATES of sleep?

• NREM

  • Non-rapid eye movement

• REM

  • Rapid eye movement

What are the different STAGES of sleep?

NREM

• Stage 1 = 5%

  • Aware/ relaxed state

  • 60—90 mins

• Stage 2 = 50%

  • Unaware, easily awakened

• Stage 3 & 4 = 20%

  • Slow wave sleep / deep sleep

  • Important for physical rest and restoration

REM (25%)

• Dreaming

• Increased autonomic acivity

• Important for mental restoration

• 20 minutes

3 drug classes that produce CNS depression?

• Barbiturates

• Non—barbiturates

• Benzodiazepines

What are barbiturates used for?

How do they work?

What stages of sleep do they affect?

Drugs?

• Anticonvulsant, anesthesia, relaxation

Site of action

• Reticular formation

• Cerebral cortex

Mechanism of action

• Reticular activating system = keeps brain awake and alert

• Inhibit reticular activating system (RAS) = reduce excitatory stimulation of cerebral cortex

Cause

• CNS depression

• Sleepiness / sedation

Low dose

• Enhance GABA = decrease brain activity and promote sleep

• Sedation

High dose

• CNS depression

• Hypnosis

_________________________

• Increase stage 2

• Decrease stage 3 & 4

• Suppress REM = cause REM rebound

Drugs

• Secobarbital (Short)

• Amobarbital (intermediate)

• Phenobarbital (fast)

What are non—barbiturates used for?

Drugs

• Hypnosis

Drugs

• Chloral hydrate

  • Metabolite produces the effect

  • Used in children

• Zolpidem

  • Short half life

  • DOES NOT disturb normal sleep stages

What are benzodiazapines used for?

How do they work?

What stages of sleep do they affect?

Drugs?

• Anxiety

Mechanism

• Bind to BZD receptors —> increase GABA

• Lipid soluble drug

High dose

• Sleep

Low dose

• Sedative

_______________________

• DOES NOT INTERFERE WITH REM

• Stage 2 increase

• Stage 4 decrease

Drugs

• Flurazepam

• Temazepam

• Triazolam

Parkinson’s disease

• Loss of dopaminergic neurons → Decrease dopamine in basal ganglia of brain

What neurotransmitters should be in balance for control of motor muscular control?

• Dopamine

  • Inhibitory — Decrease muscle tone

• ACh

  • Excitatory — Increase muscle tone

⛔ In Parkinson’s, dopamine levels drop, but ACh levels remain unchanged, causing relative excess ACh activity, leading to:

• Tremors

• Muscle rigidity

• Bradykinesia (slowness of movement)

So, the imbalance = less dopamine, more ACh activity.

 How do anticholinergic drugs help with Parkinson’s disease?

• Anticholinergics — Blocks ACh

• Creates balance between dopamine and ACh

Drugs (Antiparkinson)

• Levodopa

  • Replenish dopamine

• Carbidopa

  • Replenish dopamine

• Bromocriptine

  • Block acetylcholine

Know the stages of anesthesia

What is the ideal stage to be in?

Be able to identify IV and inhaled anesthesia medications

Stages of anesthesia

• Stage 1

  • Cerebral cortex inhibited (no attention, no conscious, no sensory process)

  • Loss of consciousness

• Stage 2

  • Excitement phase (Jerk, muscle tense, BP up)

  • Hypothalamus control body

  • ↑BP, ↑muscle tone

• Stage 3

  • Depression of hypothalamus

  • Ideal stage for surgery (unconscious)

• Stage 4

  • Medulla paralysis

    • Breathing and heart beat stops

  • Overdose and death

Drugs to know (anesthesia)

• Nitrous oxide

  • Inhaled gas

• Halothane

  • Inhaled gas

• Thiopental

  • IV hypnotic

• Propofol

  • IV hypnotic

What are anticonvulsants?

• Treat seizures

2 types of seizures?

• Partial (focal) seizure

• Generalized seizures

2 subtypes of partial seizures?

• Simple partial

  • Affect single limb or muscle group

  • Conscious

• Complex partial

  • More severe than simple

  • Hallucination

  • Motor dysfunction

5 subtypes of generalized seizures? AMATT

• Absence seizures

  • Children

  • Blank staring — no shaking

• Myoclonic

  • Brief jerk of muscles

  • Contract and relax

• Atonic

  • Muscle suddenly lose strength

  • Falls (drop seizure)

• Tonic

  • Muscle suddenly stiffen

  • Conscious

• Tonic clonic (Grand Mal)

  • Abnormal electrical discharge through both hemisphere of brain

What does status epilepticus mean?

• Repeated seizure without reawakening

• Any type of seizure

Difference between anticonvulsants and antiepileptic?

• Anticonvulsants

  • Stops active seizure

• Antiepileptic

  • Prevent seizure from happening

Anti—seizure drugs

• Phenytoin

  • Anti—epileptic

  • Treat partial & tonic clonic seizures

• Carbamazepine

  • Treat partial & tonic clonic seizures

  • Bipolar

• Ethosuximide

  • Treat absence seizures

• Lorazepam

  • Treat status epilepticus

  • Drug of choice (shorter half life than diazepam)

• Diazepam (abort epilepticus)

  • Treat status epilepticus

• Valproic acid

  • Treats all types of seizures

How Narcotics (Opioids) Work?

• Narcotics bind to opioid receptors in CNS

• Receptors stimulated = reduce brain’s perception/ response to pain

• They DO NOT block sensory nerves (periphery)

• They mimic effects of endorphins = body’s natural painkillers

What are the 3 opioid receptors?

• Mu (μ)

  • Morphine like analgesia (Strong pain relief)

  • Euphoria

  • Respiratory depression

• Kappa (κ)

  • Pentazocine like analgesia (Moderate pain relief)

  • Sedation

  • Mild respiratory depression

• Sigma (σ)

  • Dysphoria (Not recc)

  • Hallucination
    Respiratory and vasomotor stimulation

What does analgesia mean?

Reduction or elimination of pain

2 components of pain recognition (Mechanism)

• Local irritation

  • Stimulate periphery nerves — pain receptors

• CNS recognition

  • Brain process and recognize pain

General side / adverse effects of narcotics

• Mental confusion

• Constipation

• Tolerance (Need higher dose)

• Dependency (reliance)

• Respiratory depression (slow breathing)

• Urinary retention

• Dysphoria (unpleasant mood, restless)

What are narcotic antagonists used for?

• Block effects of opioids

• Bind to opioid receptors — Displace narcotic analgesic

Used for

• Opioid overdose

  • Narcotic poisoning

• Respiratory depression

  • Increase

2 types of narcotic antagonists?

• Pure antagonist

  • Competitive blocking drug of opioid receptors — completely

  • No opioid activity (not agonists)

  • Naloxone (narcan)

    • For narcotic poisoning

    • No respiratory depression

• Partial antagonist

  • Partial blocking of receptors — Mild opioid activity (morphine like)

  • Bind to receptors — reverse respiratory depression

    • Good for chest pain

  • Pentazocine

Difference between narcotic and non—narcotic drugs?

Feature	Narcotic	Non-Narcotic
Site of Action	CNS (brain/spinal cord)	Peripheral (site of pain/injury)
Mechanism	Stimulates opioid receptors (Mu, Kappa, sigma)	Inhibits prostaglandins (inflammation mediators)
Addiction Risk	High (with chronic use)	Low
Used for	Moderate to severe pain	Mild to moderate pain, fever, inflammation

Narcotic drug list / Opioid analgesics and know what they’re used for?

Drug	Use
Codeine	Mild pain + antitussive (cough suppressant)
Hydromorphone (Dilaudid)	Strong opioid for severe pain
Oxycodone	Moderate to severe pain
Morphine	Prototype opioid – severe pain
Meperidine	Severe pain; can cause mydriasis instead of miosis
Methadone	Chronic pain, heroin addiction treatment
Pentazocine	Partial antagonist – used in addiction and moderate pain