Psychiatry drugs pdf - غير معروف

Narcotic Analgesics

“Opioids”

Dr.Nasser A. H. Al-Harchan

Asst. Prof. of Pharmacology

College of Medicine

Baghdad University

introduction

Depression is one of the common

psychiatric disorders

It has been found that at every time

5-6% of population is depressed.

Types of depression

1.Reactive depression. (Exogenous).

2.Major depression. (Endogenous).

3.Bipolar depression. (Manic – depressive).

Antidepressants

Tricyclic anti-depressants (TCAs).

Imipramine, desipramine, nortriptyline,
protryptyline, amytriptiline, doxepin

. Atypical anti-depressants.

New TCAs, amoxapine, bupropion,maprotiline,
nomifensine, mianserin.

Selective serotonin reuptake inhibitors (SSRIs).

Fluoxetine, sertraline, paroxetine, trazodone

Monoamine oxidase inhibitors (MAOIs).

Isocarboxacid, phenelzine, tranylcypromine.

I.Tricyclic antidepressants(TCA)

• TCA are structurally similar to the

phenothiazine antipsychotics and share
many of their pharmacological actions.

• Include imipramine, amitriptyline,

desimipramine, nortriptyline, and
protriptyline.

1.Mechanism of Action of TCA

• TCA potentiate the actions of biogenic

amines, presumably by inhibiting reuptake of
the amines in the presynaptic neurons.

• TCA have both antihistamine H

and alpha-

adrenergic blocking actions.

• TCA possess antimuscarinic action and block

the reuptake of serotonin.

Pharmacokinetics of TCA

• TCA are well absorbed orally. They are lipid

soluble and penetrate all tissues and have
long half-lives. They are metabolized by liver
enzymes and many of the metabolites are
pharmacologically active.Excretion is via the
kidney.

Pharmacologic Effects of TCA

• 1-

Amine uptake blockade

: TCA block NE uptake

transporters in the CNS and peripherally in the A.N.S.
This increases sympathetic activity.

• 2-

Sedation:

is a common effect with TCA. Some may

have CNS stimulant effects.

• 3-

Antimuscarinic effects

: Atropine-like actions.

• 4-

C.V. effects

: postural hypotension due to alpha-

blockade, arrhythmia due to depression of cardiac
conduction.

• 5-

Seizures

: TCA lowers the convulsive threshold with

overdoses

Clinical Uses of TCA

• Major depressive disorders

: TCA are considered the

treatment of choice for major depression. The
various TCA are equivalent at appropriate doses with
regards to their overall efficacy.

• Nocturnal enuresis

: Bed wetting in children with

imipramine.

• Obsessive-compulsive neurosis

: accompanied by

depression, and phobic-anxiety syndromes, chronic
pain, and neuralgia may respond to TCA.

Adverse Effects of TCA

• Resemble those of the phenothiazines.
• 1-

Antimuscarinic effects

. Occur both centrally and peripherally.

Patients with prostatic hypertrophy and glaucoma are cautioned.
Tolerance develop to this effect.

• 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-

Seizures

ventricular arrhythmias

and death can result from

overdoses.

• 6-

combination of MAO-inhibitors

and TCA should be avoided.

Precautions with TCA use

• TCA should be used with caution in manic-

depressive patients, since they may unmask
manic behavior

• TCA have narrow therapeutic index.

Depressed patients with suicidal intents
should be given limited quantities of these
drugs.

Heterocyclics

• Venlafaxine:

• Inhibits serotonin and at higher doses inhibits NE

and dopamine reuptake. Has fewer adverse effects
than TCA.

• Duloxetine:

• Not indicated in patients with end stage renal

diseases. Can cause nausea, vomiting, diarrhea,
dizziness and somnolence, sweating and sexual
dysfunctions. It can be used for depression
accompanied by neuropathic pain.

Atypical Antidepressants

• Have actions at several sites.

Include

Bupropion, Mirtazapine nafazodone and
Trazodone

. They are not better than TCA or

SSRIs but their adverse effects are different.

1.Bupropion

•

mechanism of action unknown. It decreases

the craving for nicotine in tobacco abusers.
May produce dry mouth, sweating, tremor,
and seizures

Mirtazapine

• It can block 5-HT

and α

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-HT

presynaptic autoreceptors, and so increase 5-HT
release. They are sedating due to antihistamine
effect. Trazodone causes priapism.

Selective Serotonin Re-uptake Inhibitors

(SSRIs)

• specifically inhibit serotonin re-uptake having 300-

to 3000-fold greater selectivity for 5-HT transporter
as compared to NE transporter. SSRIs have little
ability to block DA transporter. In addition they have
little blocking activity at muscarinic, α-adrenergic,
and histamine H

receptors. Therefore common

adverse effects associated with TCA such as
orthostatic hypotension, sedation, dry mouth and
blurred vision, are not seen with SSRIs

SSRIs

• SSRIs because of their relative safety and

fewer AR have largely replaced TCA and MAOI
as the drug of choice in treating depression.

• They include fluoxetine, citalopram,

escitalopram, fluvoxamine, paroxetine and
sertraline

Actions of SSRIs

• Inhibit reuptake of 5-HT leading to increased concentration

of serotonin in the synaptic cleft and increased postsynaptic
neuronal activity.

• Antidepressants, including SSRIs typically take 2 weeks to

produce improvement in mood and may require 12 weeks or
more. However none of the antidepressants is uniformly
beneficial. About 40% of patients respond well to treatment.
Patients who do not respond to one drug may respond to
another drug, and approximately 80% or more will respond
to at least one antidepressant drug. Antidepressants do not
elevate mood in normal subjects

Therapeutic Uses of SSRIs

• Used in depression,
• Obsessive compulsive disorders (fluvoxamine)
• Panic disorders
• Generalized anxiety
• Premenestrual dysphoric disorders
• Bulimia nervosa

Pharmacokinetics

• All SSRIs are well absorbed from GIT. Food has little effect on

absorption. All are well distributed with large V

Most have

long plasma half-life. Metabolized by liver and excreted in

urine.

• Fluoxetine:

Has longer half-life about 50 hours and 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 and paroxetine: are potent enzyme inhibitors
•

Paroxetine and sertraline are partly excreted in bile

•

Adverse effects of SSRIs

• Sleep disturbance:

Paroxetine and fluvoxamine are sedating,

while fluoxetine is activating causing insomnia

• Sexual dysfunction:

Loss of libido, delayed ejaculation,

anorgasmia

• Uses in children and teenagers:

one out of 50 children

becomes suicidal as a result of use of SSRIs

• Overdose:

fluoxetine may cause seizures. They cause

“serotonin syndrome” characterized by hyperthemia,muscle
rigidity, clonic muscle twitching and changes in mental status
in the presence of MAOIs

Monoamine oxidase inhibitors (MAOIs)

phenelzine (Nardil)

isocarboxazid (Marplan)

tranylcypromine (Parnate)

selegiline (Deprenyl)

MAO INHIBITORS

Mechanism of action:

Inhibit MAO enzymes (non-selective):

1) Irreversible MAO inhibitors

Phenelzine and isocarboxazid => hydrazides.

2) Reversible MAO Inhibitors.

RIMA (reversible

inhibitor of monoamine oxidase A)

Tranylcypromine => non-hydrazide,

prolonged blockade, but reversible within 4hr.

Decrease metabolism of most biogenic amines

(NE,

5HT, DA, tyramine, octopamine).

MAO INHIBITORS

Mechanism of action (con

’t):

Acute administration causes:

- NE and 5-HT in synaptic terminals in
brain but

¯NE in PNS. ¯NE synthesis.

Acute euphoria

Suppressed REM sleep.

Chronic administration causes:

¯ NE-stimulated cAMP in brain.
Down regulation of

b receptors.

Down regulation of 5-HT

receptors.

MAO INHIBITORS

MAO-A

à NE, 5-HT, Tyramine

MAO-B

à DA

Selective MAOIs:

Inhibitors MAO-A

vMoclobemide, Clorgyline

Inhibitors of MAO-B.

Deprenyl, Selegiline

MAO INHIBITORS

Wine-and-Cheese Reaction

- Fatal interaction with tyramine-

containing foods (fermented foods in
particular, such as wine and cheese).

¯ MAO-A => - Tyramine in the body

-NE in circulation => induces

hypertensive crisis => can lead to
intracranial bleeding and other organ
damage.

MAO INHIBITORS

Negative drug interactions with:

Any drug metabolized by MAOs

including

SSRIs, TCAs and meperidine, alcohol, CNS

depressants, sympathomimetics,

phenylephrine (O/C nasal decongestants),

ampetamines, and other indirect-acting
adrenergic drugs.

Interaction with drugs metabolized by MAOs (e.g.

Meperidine (opioid analgesics) => hyperpyrexia or

“hyperexcitation syndrome” involving high fever,

delirium and hypertension

MAO INHIBITORS

Other side effects:

Hypotension

Hepatotoxicity.

Sedation.