Antidepressant Drugs

for nursing ( 2010)

Objectives Unknown
person
 List types of
antidepressants
 2-Cliniacl
pharmacology of
TCA, MAOI & SSRI
 Introduction:
What is Depression ?

 common mental disorder that presents with

depressed mood, loss of interest or
pleasure, feelings of guilt or low self-worth,
disturbed sleep or appetite, low energy, and
poor concentration (WHO def.)
 Theory are shown in (SDL ) slides
Classification√√√√
1. Tricyclic antidepressants (TCAs)*
block neuronal re-uptake of NE and 5-HT,+ other receptors
1. Serotonin/Norepinephrine Reuptake
Inhibitors
block neuronal reuptake of 5-HT & NE
1. Selective serotonin reuptake inhibitors (SSRIs)
block neuronal reuptake of 5-HT
2. Atypical Antidepressants
have varied actions.
3. MAO-inhibitors (MAOIs)
inhibit MAO type A,.
* Better name Cyclic antidepressant ( some new members are 4 rings )
I.Tricyclic antidepressants (TCA)

Imipramine
nortriptyline
TCA ( multiple effects )

 Block
 NE uptake transporters in the CNS
 serotonin Receptors (CNS).
 NE uptake transporters in ANS
 histamine H1 receptors
Adverse
 alpha-adrenergic receptors . effects

 muscarnic receptors
Pharmacologic Effects of TCA
 Antidepressant effect ( pharmacologically
desired
 most other Other effects ( usually undesired )
 increases sympathetic activity.
 Sedation & sometimes : CNS stimulant effects.
 Antimuscarinic effects: Atropine-like actions.
 C.V. effects: postural hypotension*,
arrhythmia**.
 Seizures: lowers the convulsive threshold with
overdoses

*due to alpha-blockade ** due to depression of cardiac conduction

Pharmacokinetics of TCA

 well absorbed orally.

 penetrate all tissues

 have long half-lives.

 metabolized by liver enzymes
 many of the metabolites are
pharmacologically active.
 Excretion of metabolites via the kidney.
Clinical Uses of TCA

 Major depressive disorders:

 Nocturnal enuresis:
 Bed wetting in children with imipramine.

 Obsessive-compulsive neurosis:
accompanied by depression, and phobic-anxiety
syndromes,
 Others : chronic pain, and neuralgia may
respond to TCA.
 Adverse Effects of TCA√√
1. Antimuscarinic effects. : dry mouth,
urinary retention, increase IOP etc.
2. Postural hypotension and cardiac
arrhythmias
3. Manic excitement and delirium occur in
patients with bipolar depression.
4. The elderly may suffer from dizziness
and muscle tremor.
5. overdoses : Seizures, ventricular
arrhythmias and death can occur .
Precautions with TCA use

 Patients with prostates hypertrophy and

glaucoma are cautioned.
 Patients with manic-depressive disorders
 they may unmask manic behavior
 TCA have narrow therapeutic index.
 patients with history of suicidal intents .
 Drug interactions e.g MAO inhibitors & other
CNS depressants
Serotonin/Norepinephrine Reuptake
Inhibitors (SNRIs)
 Venlafaxine and Duloxetine
 Selectively block neuronal reuptake of
5-HT & NE
 fewer adverse effects than TCA.
 May be also used in treating
neuropathic pain
4. Monoamine oxidase inhibitors (MAOIs)

 interfering
with metabolism of
brain amine in the nerve endings,
resulting in an increase in the
vesicular stores of NE and
serotonin.
Net effect enhancing the actions of
these neurotransmitters
II. Selective Serotonin Re-uptake
Inhibitors (SSRIs)

 300- to 3000-fold greater selectivity for 5-

HT transporter as compared to NE transporter.
 have little ability to block DA transporter.
 have little blocking activity at muscarinic, α-
adrenergic, and histamine H1 receptors.
 Therefore didn’t show ADE associated with TCA
SSRIs
 Became the drug of choice in treating
depression. include
 fluoxetine, citalopram,,
Therapeutic Uses of SSRIs
 depression,
 Obsessive compulsive disorders
 Panic disorders
 Generalized anxiety
 Premenestrual dysphoric disorders
 Bulimia nervosa
Pharmacokinetics
 well absorbed from GIT..
 large Vd.
 Metabolized by liver and excreted in
urine.
 √Fluoxetine: Has longer half-life about
50 h available as sustained release
preparations allowing once-weekly dosing.
 Also it is metabolized to norfluoxetine
which is active having a half-life of 10
days.
 Fluoxetine is potent enzyme inhibitors
Adverse effects of SSRIs
 Sleep disturbance:
 Paroxetine and fluvoxamine are sedating,
 fluoxetine is activating causing insomnia
 Sexual dysfunction:
 Loss of libido, delayed ejaculation, anorgasmia
 Uses in children and teenagers:
 High incidence of suicidal attempts
 Overdose: fluoxetine may cause seizures. T
 Serious Interactions MAOIs
 cause “serotonin syndrome” characterized by
hyperthemia, muscle rigidity, clonic muscle twitching and
changes in mental status
IV. Atypical Antidepressants
 Have actions at several sites.
 Bupropion, Mirtazapine nafazodone
and Trazodone + many
 They are not better than TCA or SSRIs but
their adverse effects are different.
 √1.Bupropion:. It decreases the craving
for nicotine in tobacco abusers.
2.Mirtazapine (optional )

 It can block 5-HT2 and α2 receptors. It is sedative due to

its antihistaminic activity, but has no atropine-like
actions. It does not interfer with sexual activity.
Increased appetite and weight gain can occur.
 3.Nefazodone and 4.Trazodone weak inhibitors of 5-
HT reuptake. They block 5-HT1 presynaptic
autoreceptors, and so increase 5-HT release. They are
sedating due to antihistamine effect.
 Trazodone causes priapism.
 V.MAO Inhibitors
 phenelzine, and tranylcypromine.
 Action : irreversibly inactivate the enzyme
MAO preventing oxidative deamination of
biogenic amines such as NE, EN, DA, 5-HT and
tyramine..
 Tranylcypromine: has amphetamine-like
actions.
MAOI
 PK : rapidly absorbed after
oral use and metabolized by
liver.
 √They interact with foods
containing high tyramine
contents such as cheese,
beer and chicken liver.
 The tyramine will release
CA from nerve terminals
resulting in hypertensive
crisis.
 They potentiate the actions of many drugs,
such as TCA, CA, sedative hypnotics, gen.
anesthetics, antimuscarinic, and narcotic
analgesics esp. meperidine.
 Many Adverse Effects: CNS : convulsions
and sleep disorders, agitation, headache,
hallucinations. CV blood pressure
abnormality + many other.
 Neurobiological theory of depression
 Receptor theory“ = the problem is in up-
regulation of post-synaptic receptors and
alterations in their sensitivity
The antidepressant treatment increases the
amount of monoamines in CNS and thereby
gradually normalize the density/sensitivity of
their receptors
 Recently other factors are identified.
Monoamine (catecholamine) theory (1965)

 the underlying biological or neuroanatomical basis for

depression is a deficiency of central noradrenergic
and/or serotonergic transmission in the CNS
Supported by: pharmacological effect of antidepressants (TCA,
MAOI) . reserpine induced depression
Contradiction: several drugs (e.g. cocaine) increase the amount of
these neurotransmitters in the CNS but are unable to treat
depression .the effect of antidepressants on neurotransmitter
levels is relatively quick but onset of antidepressant action is
significantly delayed
Notes TCA
 In the pediatric population, they are commonly
prescribed for the treatment of enuresis,
obsessive-compulsive disorder, attention deficit
hyperactivity disorder, school phobia, and
separation anxiety.
 TCA Blockade of fast sodium channels in
myocardial cells, resulting in quinidinelike
membrane-stabilizing effects
Signs of TCA toxicity
Anticholinergic effects may
include the following:
Xerostomia
Blurred vision, mydriasis
Urinary retention
Hypoactive or absent bowel sounds
Pyrexia
Myoclonic twitching
 Cardiovascular effects may include the
following:
 Sinus tachycardia
 Prolonged PR, QRS, and QT intervals
 Heart block
 Peripheral vasodilatation
 Hypotension
 Cardiogenic shock
 Ventricular arrhythmias
 Asystole
CNS effects may include the following:
Drowsiness
Extrapyramidal signs
Rigidity
Ophthalmoplegia
Respiratory depression
Delirium
Seizure
Coma