antidepressants & neuroleptics lesson 20. unipolar depression n major depressive disorder n...
Post on 30-Dec-2015
215 Views
Preview:
TRANSCRIPT
Antidepressants & Neuroleptics
Lesson 20
Unipolar Depression
Major Depressive Disorder Extreme sadness & despair
extent & duration important Prevalence
females 9-26% males 5-12%
2:1 females ~
MAOIs Monoamine oxidase inhibitors
tranylcypromine (Parnate), phenelzine, (Nardil) NE, DA, 5-HT
Dietary restrictions (Cheese Effect) avoid foods containing tyramine metabolism amphetamine-like
risk of cerebral hemorrhages Many drug interactions Overdose risk ~
Nonselective Cyclic Antidepressants
Reuptake inhibitors DA, NE, & 5HT Tricyclic Antidepressants (TCA)
Imipramine, Desipramine Tetracyclic
Maprotiline Risk of many drug interactions (e.g.,
alcohol, neuroleptics, etc. ~
NSCA: Main Side Effects
Risk of overdose Mania or psychosis Sedation Anticholinergic syndrome
tremors, dry mouth, weakness, constipation, blurred vision, confusion
Impotence
Second GenerationAntidepressants
SSRIs Selective serotonin reuptake inhibitors
fluoxetine (Prozac, Sarafem) sertraline (Zoloft) paroxetine (Paxil) citalopram (Celexa) escitalopram (Lexapro) fluvoxamine (Luvox)
Fewer fx on NE & DA ~
SSRIs: Side Effects Fewer than TCAs
lower sympathetic arousal no anticholinergic fx
Serotonergic syndrome GI discomfort, anxiety, restlessness,
insomnia, etc. Sexual dysfunction Low risk of overdose Equally effective as TCAs ~
SSRIs: Pharmokinetics
All similar to fluoxetine (prozac) lipid soluble high protein binding
Half-life 2 - 3 days active metabolite 7 - 15 days
norfluoxetine ~
Other Selective Reuptake Inhibitors Norepinephrine Dopamine Reuptake
Inhibitor (NDRI) bupropion (Welbutrin) Also tx bipolar & Smoking cessation
(Zyban) Side fx
less sexual dysfuntion than SSRI Insomnia seizures - 150 mg/dose limit no subjective euphoria, abuse ~
Selective Serotonin Norepinephrine Reuptake Inhibitor (SNRI) venlafaxine (Effexor)
Serotonin-2 Antagonists/Reuptake Inhibitors (SARI) 5HT2 –R: autoreceptor Anxiety disorders, bulimia
Noradrenergic/Specific Serotonergic Antidepressant (NaSSA) Mirtazapine (Remeron)~
Other Selective Reuptake Inhibitors
Schizophrenia
Disordered thoughts & bizarre behavior 1 percent of population equal among sexes
Progressive can only manage symptoms ~
Symptoms
Positive Symptoms Thought disorders Delusions Hallucinations
Negative Symptoms Poverty of speech Poverty of emotion Social withdrawal ~
Neuroleptic Drugs
Also called antipsychotics All Effective
No abuse liability Low overdose liability
Major side Effects: Motor impairments Agranulocytosis ~
Patient Populations: Mental Institutions
Thousandsof patients
400
300
200
100
1900 1930 1960 1975
600
500
YEAR
1956
First Generation Neuroleptics
Relieve only positive symptoms Chlorpromazine (Thorazine)
phenothiazines primarily blocks D1 & D2
Haloperidol (Haldol) butyrophenones primarily blocks D2
D2-R affinity and clinical potency ~
Strength of D2 binding
Therapeutic effects
Hi
LoChlorpromazine
Haloperidol
Spiroperidol
1st Generation: Pharmacokinetics
Administration Primarily p.o.; im for rapid effects
90-95% depot binding liver, lungs, adrenals, spleen
Long half-life Some metabolites active up to 3 mo.
No symptoms during this period compliance problems ~
Major Side Effects
Movement Effects (Extrapyramidal) Parkinsonism Akathisia Tardive Dyskinesia
Agranulocytosis white blood cells (WBC) Not frequent, but 50% mortality ~
Atypical Neuroleptics
Relieve negative & positive symptoms Lower M-PAT risk
tardive dyskinesia Atypical neuroleptics
affinity for D2-R 5HT antagonism ~
Clozapine Clozaril Agranulocytosis
Risperidone Risperdal agranulocytosis; M-PAT
Aripiprazole (Abilify) depression ~
Atypical Neuroleptics
top related