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Antidepressants
Al-Mehdi
122
Pharmacology
Graduate
04/04/2010

Additional Pharmacology Flashcards

 


 

Cards

Term
Definition of mental disorders
Definition

 

-A behavioral or psychological syndrome that occurs in an individual

-  The consequences of which are clinically significant distress (e.g. a painful symptom) or disability (e.g. impairment of function)

-  Must NOT be merely an expectable response to common stressors and losses (e.g. loss of a loved one) or a culturally sanctioned response to an event (e.g. trance states in religious rituals)

- That reflects an underlying psychobiological dysfunctions

-          That is not primarily the result of social deviance or conflict with society (referring to the communist countries where all dissenters are considered to have neurosis) 

 

Term
Mood disorders
Definition

-Major depressive Disorder & Dysthymia, Bipolar disorder

Term
Cognitive disorders
Definition
Delerium, Dementia, AD, Amnesia
Term
What are the five mental domains?
Definition

  • Negative Emotionality
  • Positive Emotionality
  • Cognitive Processes
  • Social Processes
  • Arousal/regulatory systems

Term
Fear is caused by a dysfunction in what part of the brain?
Definition
Amygdala
Term

Stress and anxiety are caused by a dysfunction in what part of the brain?

Definition
HPA axis (Hypothalamus, pituitary, adrenal)
Term

Aggression is caused by a dysfunction where?

Definition
Amygdala, hypothalamus, testosterone and vasopression
Term
The Perisylvan network is associated with what?
Definition
language
Term

The Parietofrontal network is associated with what?

Definition
spatial cognition
Term

The occipitotemporal network is associated with what?

Definition
face and object recognition
Term

The limbic network network is associated with what?

Definition
retentive memory
Term

The prefrontal network is associated with what?

Definition
attention and behavior
Term

What are the 4 functions of the association cortex?

Definition

  •    Emotion- most altered component in mood disorders
  •    Cognition-recognition of self
  •    Thought
  •    Behavior

Term
What is the function of Ach?
Definition
Attention and memory
Term
What is the function of Serotonin?
Definition
Mood and Anxiety
Term
Function of NE
Definition
mental arousal and mood
Term
Function of glutamate, GABA
Definition
Learning and Long-term memory
Term
Function of Dopamine
Definition
Arousal levels and physical motivation
Term
Function of Enkephalins
Definition
Sense of calm
Term

What NT changes in Alzheimer's disease and in what way?

Definition
Ach, decreases
Term

What NT(s) changes in Huntington's disease and in what way?

Definition
Ach and GABA, both decrease
Term

What NT changes in Anxiety and in what way?

Definition
Serotonin, NE, and GABA, all decrease
Term

What NT changes in depression and in what way?

Definition
Serotonin and NE, both decrease
Term

What NT changes in Parkinson's disease and in what way?

Definition
Dopamine, decrease
Term

What NT changes in Schizophrenia and in what way?

Definition

dopamine, INCREASE 

*Only disease caused by an increase in NT

Term
What tonic substance do clotting platelets release into serum?
Definition
Serotonin
Term
In carcinoid syndrome, what cells cause an overproduction of serotonin?
Definition
enterochromaffin cells
Term

4 sites of serotonin in the body

Definition

 

Enterochromaffin cells (90% of all 5-HT)-          found in the gut

Platelets (actively transport and store    serotonin).

Raphe magnus nuclei of brainstem (part of  endogenous analgesic system)

Around blood vessels

 

Term
What is serotonin?
Definition
an excitatory neuron that transmits depolarization
Term
name the agonist of the 5-HT1A receptor and fxn
Definition
Buspirone- anxiolytic
Term

name the agonist of the 5-HT1D/1B receptor and fxn

 

Definition
Sumatriptan- treat migraine
Term

 

name the antagonist of the 5-HTreceptor and fxn

 

Definition

  • Phenoxybenzamine
  • Cyproheptadine-carcinoid and uticaria
  • Ritanserin-reduce thromboxane, treatment of psychedelic drugs

Term

name the antagonist of the 5-HTreceptor and fxn

Definition
Ondansertron-antiemetic
Term

 

name the agonists of the 5-HTreceptor and fxn

 

Definition

  • Cispride-GE reflux
  • Tegaserod(partial)-IBS
  • Morphine-Respiratory depression in Pre-Boetzinger complex

Term
What amino acid is Serotonin produced from
Definition
Tryptophan
Term
What serotonin receptor acts through an ion channel not a GPCR?
Definition
5-HT3
Term
What is the rate limiting step in the production of Serotonin?
Definition
Tryptophan to 5-hydroxytryptophan by Tryptophan hydroxylase
Term
What enzyme converts 5-hydroxytryptophan to Serotonin?
Definition
AAD(aromatic, amino acid decarboxylase)
Term

 

Life cycle for monoamine NTs like serotonin and NE

 

Definition

  1. Synthesis
  2. Packaging
  3. release
  4. reuptake
  5. degradation

Term
What do monoamine NT reuptake inhibiting drugs target?
Definition
SERT, NET,and DAT (NT transporters)
Term
How do drugs inhibit degradation of monoamine NT
Definition
inhibition of MAO
Term

location of MAOA and MAOB

Definition

  • MAOA- brain, placenta, liver and gut
  • MAOB-  brain, platelets, lymphocytes, and liver

Term
Overall goal of depression treatment
Definition
Inc Serotonin and NE
Term

5 classes of antidepressants

Definition

1.     Selective Serotonin Reuptake Inhibitors (SSRIs) Block SERT

2.     Serotonin-Norepinephrine Reuptake Inhibitors

a.     Selective serotonin-norepinephrine reuptake inhibitors (SNRIs) Block SERT + NET

b.     Tricyclic Antidepressants (TCAs) Block SERT + NET + M + alpha1+ H1- block muscarinic, histamine, & α1 receptors

3.    5-HT2A Antagonists  

4.     Tetra-/Uni- cyclic Block SERT + NET + 5-HT2/3 + alpha2 + H1- also block non CNS serotonin receptors, α2 receptors, & histamine

5.   Monoamine oxidase inhibitors (MAOI).

Term
How long does a patient have to have symptoms before it is diagnosed as Major Depressive disorder? Dysthymic disorder?
Definition

Major Depressive- 2 months

Dysthymic- 2 years (chronic)

Term
Symptoms of Seasonal Affective Disorder
Definition
hypersomnia, hyperphagia and lethargy
Term
How do you diagnose depression?
Definition

•≥Five symptoms nearly every day over 2-weeks

•At least one is  depressed mood or apathy /anhedonia.

1.Depressed mood (irritable in children) most of the day

2.Apathy or anhedonia

3.Weight loss/weight gain or anorexia/bulimia.

4.Fatigue or loss of energy

5.Insomnia or hypersomnia

6.Feelings of worthlessness /guilt  (DDx Normal grief)

7.Suicidal ideation

8.Impairment in functioning  (social or occupational)

9. Psychomotor agitation /retardation

10.Diminished ability to think or concentrate, or indecisiveness

±  Psychotic features : (suspiciousness, delusions, hallucinations)

Term
List the SSRI drugs
Definition

Fluoxetine (Prozac);

Fluvoxamine (Luvox)

Paroxetine (Paxil)

Sertaline (Zoloft)

Citalopram (Celexa)

Escitalopram (Lexapro

Term
 Mechanism of action of SSRIs
Definition
Block SERT- Elevates mood
Term
Indications for use of SSRIs
Definition

 

  • Mental disorders
  • Major Depression
  • Anxiety
  • Panic
  • Obsessive Compulsive
  • Posttraumatic Stress
  • Eating (Bulimia)
  •  
  • Perimenopausal vasomotor symptoms 

 

 

 

 

 

 

 

Term
Adverse effects of SSRIs
Definition

 

Drug interactions occur when an MAOI is given with an SSRI or after recently stopping SSRI – fluoxetine requires 1-3 month delay before initiating treatment with an MAOI

•Relatively well tolerated

• Adverse effects of SSRI mediated via 5-HT3

    • GIT (nausea/ diarrhea)

    • Sexual dysfunction (anorgasmia)

•Adverse effects of SSTI mediated via 5-HT2C

 Restlessness, Insomnia

 

Term
Pharmacokinetics of SSRIs
Definition

Beneficial effects may require 2-3 weeks

•May work when TCA’s fail

• In general, all have long t ½

• All are metabolized by CYP405 enzymes in the liver 

Term
What is the adverse affect that is unique to the SSRI fluoxetine?
Definition

CYP2D6 metabolizes fluoxetine→ norfluoxetine( inc t1/2)
•CYP 2D6 metabolizes codeine → morphine
Concomitant administration of fluoxetine and codeine decreases the analgesic effect of codeine

Term

Mechanism of action of Serotonin-NE Reuptake Inhibitors (SNRIs)

and 

Selective Serotonin-NE reuptake Inhibitors

(SSNERIs)

Definition
Block SERT and NET
Term
What two drugs are SSNERIs?
Definition

Venlafaxine (Effexor)

Duloxetine (Cymbalta)

Term
Indications for use of SSNERIs
Definition

• Major Depression

• Perimenopausal vasomotor symptoms

• Chronic Pain

• Fibromyalgia

Term
Adverse affects of SSNERIs
Definition

• Venlafaxine: Sedation, Hypertension

• Duloxetine: minimal

Term
Name the TCA drugs
Definition

  • Amitryptaline-prototype drug
  • Imipramine

Term
Mechanism of Action of TCAs
Definition
Blocks SERT and NET +M+alpha1+H1
Term
Indications for use of TCAs
Definition

• Major depressive disorder not responsive to other drugs

• Enuresis (bed-wetting)

• Panic disorder and agoraphobia

• Anxiety

OCD (Cloipramine)-drug of choice

• Neuropathic pain (chronic pain) – by working on the endogenous analgesic pathway to increase NE and serotonin

Term
Adverse affects of TCAs
Definition

 

•Potent    anti - M

•Weak     anti α1

•Weak     anti - H1

•Anti-M effects

   •Xerostomia

   •Decreased sweating

   •Constipation

   •Increased intraocular pressure

   •Blurred vision

   •Memory dysfunction (CNS)

 

•Anti-H1 effects

   •Sedation

   •Potentiation of CNS depressants

 

•Anti-alpha1 effects:

 •Hypotension

Cardiovascular effects:

•Elevated NE: Tachycardia

•Anti-α1 effects

TCA contraindicated in:

MI

• Congestive heart failure

• Orthostatic hypotension

• Advanced Cardiovascular disease 

 

Term
List the 5-HT2A antagonists
Definition

Nefazodone (Serzone) and Trazodone

 

Term
List the Tetra/Unicyclic Antidepressants
Definition

Bupropion (Wellbutrin)

and

Mirtazapine (Remeron)

Term
What is Bupropion's mechanism of action
Definition

 

• Block SERT + NET + 5-HT2/3 + alpha2 + H1

 

• Increased NE and Dopamine activity

 

Term

Indications for Bupropion

Definition

 

  • Major Depression
  • Smoking cessation

 

Term

Adverse affects of Bupropion

Definition

 

  • Seizures 
  • Agitation
  • Insomnia

 

Term
Mirtazapine's mechanism of acton
Definition

 

• Block SERT + NET + 5-HT2/3 +alpha2 + H1

• Increased NE & 5-HT release 

 

Term
Indications for Mirtazapine use
Definition
Sedation
Term
Adverse affects of Mirtazapine
Definition

  • Sedation
  • Weight gain

Term
What does MAO produce that causes damage to any available molecule? 
Definition

MAO produces the most reactive free radical, •OH, which then reacts with any available molecule causing oxidative damage

 

Term
Location of MAO in body
Definition

  • MAO is found in the outer mitochondrial membrane
  • MAOA in the gut
  • MAOB in the CNS and platelets

 

Term
MAOIs mechanism of action
Definition

Substrates for enzyme but intermediates covalently bind to and inactivate MAO

Term

Adverse effects of MAOIs

Definition

  • CNS: Pro-psychotic; proconvulsive (due to ↑dopamine)
    • Hypomania, agitation, hallucination
    • Hyperpyrexia, hyperreflexia and convulsions
  • Anti-α1
    • Orthostatic hypotension
  • Anti-M:
    • Impotence, dry mouth and constipation
  • PNS
    • Phenelzine can produce peripheral neuropathy 
  • Rx - vitamin B6

 

Term
Pharmacokinetics of MAOIs
Definition

Most inhibitors irreversible (except moclobemide)

Clinical response:

• Clinical response correlates with 85% inhibition of

   platelet MAOB. (This is a useful mechanism for           determining effectiveness of drug)

• Elevation of mood

• Suppression of REM sleep 

Term

MAOIs that inhibit MAOA and MOAB

Definition

 

  • Phenelzine
  • Tranycypromine

 

Term

MAOI that inhibits only MAOB

Adverse effects?

Definition

Selegiline

 

anxiety and insomnia

Term
MAOI that inhibits only MAOA
Definition
Moclobemide
Term

Mechanism of interaction with Tyramine and MAOA inhibitor(or non-selective MAOI)


Definition

*Tyramine Effect

  • Tyramine is a naturally occurring amine found in    cheese and other foods. 

  • Tyramine is oxidized by MAOA in the gut.

  • Tyramine induces norepinephrine release from sympathetic neurons (sympathomimetic).

  • When an MAOIA is given, there is no way to breakdown Tyramine→ uninhibitied induced release of NE from sympathetic neurons

Effect occurs within 15- 90 min of ingestion

Term

Symptoms of Tyramine effect

Definition

 

• Hypertension

• Severe occipital headache, temporal headache, neck    stiffness

• Diaphoresis, Mydriasis, Pallor

• Neuromuscular excitation, Palpitations, &/or chest pain

• Hyperthermia

 

Term
Treatment of Tyramine effect
Definition

 

Lower blood pressure

•Short-acting a1 blockers  phentolamine

•Vasodilator nitroprusside

•Ca2+ channel blocker  nifedipine

Lower body temperature

Prophylaxis:

•Advise patients not to take food containing tyramine.

•Use MAOB inhibitors (Selegiline)

•Use reversible MAOA inhibitors (Moclobemide).

 

Term
What causes Serotonin Syndrome
Definition

 

  • Serotonin syndrome occurs after a dose increase of MAOI or SSRI or after a addition of a second SSRI
  • Idiosyncratic drug-induced complication of antidepressant therapy
  • Serotonin receptors 5-HT1A & 5-HT2 are involved

 

 

 

 

Term
Symptoms of Serotonin Syndrome 
Definition

  • Akathisia-like restlessness
  • Sweating, Shivering, Tremor
  • Confusion/disorientation
  • Hyperthermia
  • Hypertension
  • Muscle rigidity in the lower extremities, Penile erection
  • Delirium, Seizures, Coma

 

 

 

 

 

Term
Treatment for Serotonin Syndrome
Definition

  • Cyproheptadine (5-HT2 and H1 antagonist) -  MOST EFFECTIVE antiserotonergic 
  • Benzodiazepines are nonspecific serotonin antagonists – decrease patient discomfort and favor muscle relaxation
  • Dantrolene- non-specific muscle relaxant (inhibits Ca2+release from SR), used occasionally in Serotonin syndrome.  Primary use in hyperthermia caused by excess Succinylcholine

Term

Symptoms seen with the drug interaction of

MAOI+L-DOPA?

Definition
Agitation and Hypertension
Term

 

Symptoms seen with the drug interaction of

MAOI + TCA

 

Definition

Serotonin Syndrome

(because both drugs increase serotonin in your body)

Term
Symptoms seen with the drug interaction of MAOI + Meperidine(Demerol, shortest acting narcotic analgesic) 
Definition
  • Stupor
  • Rigidity
  • Agitation
  • Hyperthermia
  • Death 

 

 

 

 

 

Term
Symptoms seen with the drug interaction of Paroxetine(paxil SSRI) + Metoprolol
Definition
A-V block
Term
MAOIs enhance or prolong the action of:
Definition

  • General anesthetics, sedative/hypnosis
  • Antihistamines, ethanol, analgesics
  • Anticholinergics
  • TCA

Term

Adverse drug reaction that can present with the medical condition heat stroke

Definition

 

  • Malignant hyperthermia
  • cause:Inhalation anesthetics + succinylcholine

 

Term
Adverse drug reaction that can present with the medical condition hypoglycemia
Definition

Tyramine reaction

cause: Tyramine + MAOI

Term

Adverse drug reaction that can present with the medical condition hyperthyroidism

Definition

Neuroleptic malignant syndrome 

cause: Antipsychotics

Term

Adverse drug reaction that can present with the medical condition hypertensive crisis

Definition

Serotonin syndrome or tyramine rxn

causes: SSRI+MAOI or Tyramine+MAOI

Term

Adverse drug reaction that can present with the medical condition Pheochromocytoma

Definition

Serotonin Syndrome

causes: SSRI + MAOI

Term

What are the types of Manic-Depressive disorders

(Bipolar)

Definition

  • Type I: Depression with full mania
  • Type II

Term
Symptoms of Manic-Depressive disorder
Definition

  • Mania
  • Mood ranging from euphoria to irritability
  • Insomnia
  • Hyperactivity
  • Racing thoughts
  • Grandiosity
  • Variable psychotic symptoms

 
Four episodes per year is called rapid cycling 

 

 

 

 

 

 

 

• Suicidal thoughts

Term

How do you diagnose Type I bipolar disorder

Definition

  • Depression with full Mania
  • Mania
    • Persistently elevated, expansive or   irritable mood.
    • Grandiosity, decreased need for sleep, talkativeness, racing thoughts, distractibility,psychomotor agitation, excessive involvement in pleasurable activities.
  • Marked impairment of social or occupational function
  • Duration >1 week.

 

 

 

 

 

Term
How do you diagnose Type II bipolar disorder
Definition

 

•One major depressive episode

•No full manic episode

•One hypomanic episode

-Manic syndromes with mild to moderate severity

•Duration  >   4 days

 

Term

mechanism of action of Lithium in the treatment of Biopolar Disorder

Definition

• Blocks NE release

•reduces hydrolysis of inositol phosphate, blocks Protein   Kinase C

•Alters metabolism of NT’s

•Does not exert psychotropic effects in normal state, but elicits adverse effects

• No satisfactory explanation of action

Term
Indications for the use of Lithium when treating Bipolar disorder
Definition

• Acute treatment of manic phase

•6-12 month prophylactic treatement for both manic and  depression phases

• Adjunct therapy in resistant depression

Term
Adverse effects of Lithium
Definition

At therapeutic levels (.8-1.2mM)

Nephrogenic diabetes insipidus (↑serum osmolarity, ↓ urine osmolarity)- exam q.

• Hypothyroidism- goiter (↑TSH)

•Hyperparathyroidism

At Toxic levels (> 1.2- 1.5 mM)

• Tremor, weakness, fatigue, agitation, confusion, seizures, coma

Term
Pharmacokinetics/dosing of Lithium
Definition

• Narrow margin of safety

• Dose: Lithium carbonate 900-1500 mg/day up to 2400mg/day

• Serum level in fasting morning blood= .8-1.2mM

•Prophylactic = 0.6- 0.8 mM

Term
List the classes and drugs for treating Bipolar disorder
Definition

  • Lithium
    • As carbonate, citrate, aspartate, oroate salts 
  • Anticonvulsants
    • Valproate  (Depakote)
    • Lamotrigine (Lamictal)
    • Carbamazepine (Tegredol) 
  • Atypical Antipsycotic
    • Olanzapine (Zyprexa)

Term
Indication for electroconvulsion
Definition

  • suicidal ideation
  • depressive stupor
  • neuroleptic malignant syndrome

Term
Advantages and complications of Electroconvulsion
Definition

  • Advantage: immediate effect

  • Complications: Memory loss and Muscle pain

Term
Method of Electroconvulsion
Definition
Causes seizure(convulsion) under short-acting barbituate(Methohexital)
Term
Al-Mehdi's list of F-words
Definition

 

Fenoprofen            - NSAID

Fentanyl                - Opioid Analgesic

Flurazepam            - Sedative (GABAA receptor agonist) - benzodiazepine

Flunitrazepam        - Sedative (GABAA receptor agonist) - benzodiazepine

Flumazenil              - Antidote for benzodiazepine overdose (GABAA  receptor antagonist)

 

Fluoxetine              - Antidepressant (SSRI)

Fluvoxamine          - Antidepressant (SSRI)

Phenelzine             - Antidepressant (Nonselective MAOI)

Fluphenazine         - Antipsychotic (D2 Receptor blocker)

 

Term
Psychotic disorders
Definition
Schizophrenia
Term
Anxiety disorders
Definition
example: Generalized Anxiety disorder
Term
Sleep Disorders
Definition
Example: Primary Insomnia
Term
Substance-related disorders
Definition
example: Alcohol withdrawal
Term
Definition and examples of monoamines
Definition

A monoamine has one amino (-NH3) group connected by -CH2-CH2 to an aromatic ring

 

Examples:  Serotonin

NE

Phenylalanine

        Tyrosine

        Tryptophan 

Thyroxine (T4)

Triiodothyronine (T3)

 

Term
List the non-catechol monoamines
Definition

  • Serotonin (5-HT)
  • Histamine
  • tyramine
  • T3
  • melatonin

 

Term
List the Catecholamines
Definition

  • Dopamine
  • NE
  • Epinephrine

Term

Serotonin creates a _________ signal and

transmits __________

Definition
Depolarization and depolarization
Term
4 excitatory NTs
Definition
Glutamate, Nicotine, Serotonin, Purine
Term

Normal rate of neuronal depolariztion/repolarization

cycle

Definition
20-45 Hz(cycles/s)
Term
Neurotransmitter action must be terminated within 
Definition
22 to 55ms
Term
Which presynaptic membranes have transporters to reuptake catecholamines?
Definition
Adrenergic and dopaminergic
Term
What enzyme and cofactor are needed to go from Tyrosine to L-DOPA?
Definition

 

Tyrosine-3-monooxygenase (Tyrosine Hydroxylase)

 

 

cofactor: BH4

Term

What enzyme and cofactor are needed to go from

L-DOPA to dopamine?

 

 

 

Definition

enzyme: Aromatic L-Amino Acid Decarboxylase (AAD)

 

cofactor: Vitamin B6

Term

 

What enzyme and cofactor are needed to go from

 dopamine to NE?


 

Definition

enzyme: Dopamine hydroxylase

Cofactor: Vitamin C

Term

What enzyme and cofactor are needed to go from

NE to Epi?


Definition

enzyme: Phenylethanolamine-N-methyltransferase


cofactor: S-adenosylmethionine

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