Antianxiety drugs

Depart.Farmakologi & Terapeutik

Plenopakar Blok BMS,09

Depart.Farmakologi & Terapeutik

Fakultas Kedokteran USU

MEDAN

ANXIETY

DSM IV-TR:- Is an emotional state,unpleasant in nature,

associated with uneasiness,discomfort and

concern of fear about some defined or

undefined future threat.

Some degree of anxiety is a part of normal life

DSM IV-TR:- Is an emotional state,unpleasant in nature,

associated with uneasiness,discomfort and

concern of fear about some defined or

undefined future threat.

Some degree of anxiety is a part of normal lifeSome degree of anxiety is a part of normal life

-Some psychotics and depressed patients also

exhibit pathological anxiety

Some degree of anxiety is a part of normal life

-Some psychotics and depressed patients also

exhibit pathological anxiety

Antianxiety Drugs

= mostly mild CNS depressant

= aimed to control the symptoms of anxiety

= produce a restful state of mind without

interfering with normal mental or physical

functions.

Antianxiety (Anxiolytics);

= differ from antipsychotics;= more closely resemble sedative-hypnotics

- have no therapeutic effect to controlthought disorders in schizophrenia

- do not produce parkinsonism - do not produce parkinsonism

- have anticonvulsant property

- produce physical dependence and carry abuse liability

Terminologi

Dulu :

- anti-anxietas = anxiolitik adalah sedativa dalam

dosis minimal sehingga:

- efek antianxietas (+)

- efek sedasi minimal- efek sedasi minimal

- sedativa : bahan yang memiliki:

- efek menenangkan dan menenteramkan

- hipnotika: bahan sedativa dalam dosis lebih

besar, sehingga bersifat:

- menidurkan (sleep – inducing)

Sekarang: Buspiron: anxiolitik tanpa efek sedasi.

ANXIETY ���� Psikiatri

Penanggulangan :I - non pharmacologic approach

II - pharmacological approach

Pharmacological approach:

- benzodiazepines

- non benzodiazepines- non benzodiazepines

- buspiron

- zolpidem

- zaleptom

- older drugs

- alcohol ���� chloralhydrate

- glutethimide

- meprobamate

Classes of sedative – hypnotic drugs

1. Barbiturates

- largely obsolete, though still

occasionally prescribed.

2. Benzodiazepines

- nowadays, the most important drugs.

3. 5-HT1A – receptor agonists.3. 5-HT1A – receptor agonists.

- recently introduced, anxiolytic

activity with little sedation.

4. ββββeta - adrenergic antagonists.

- used mainly to reduce the symptoms

of anxiety

5. Miscellaneous drugs.

BENZODIAZEPINE

Masih merupakan yang terbanyak dipakai ���� why ?

Gambar 1.

Drug Peak

blood

Level

(hrs)

Elim. T

½ (hrs)

Comments

Alprazolam

( Xanax R/ ).

1 - 2 12 – 15 Rapid Oral abs Hp, S

Chlordiazepoxid 2 - 4 15 – 40 Active Met.

e

(Librium R/ ).

erratic bioavailab.from

i.m. Lp,L

Diazepam

(Valium R/ ).

1 - 2 20 – 80 idem

Lorazepam

(Ativan R/ ).

1 – 2 10 – 20 No active Met.

Hp, S

Hp = High - potency

Lp = Low - potency

S = Short half - life

L = Long half - life

PHARMACODYNAMICS

Mechanism of action

- By binding to molecular components of the

GABA receptor in CNS ���� αααα or ββββ subunits

���� opening of Cl - Channel ����

hyperpolarization ���� inhibition.

Pharmacological Effects

Efek utama BDZ adalah terhadap CNS

1. Reduction of anxiety and aggression

2. Sedation and induction of sleep.2. Sedation and induction of sleep.

3. Reduction of muscle tone and coordination

4. Anti convulsant effect.

AD. 1. Reduction of anxiety and aggression

Sedation, “taming effect”

- Tapi kadang-kadang ���� aggression (mis. triazolam) ���� ditarik dari (mis. triazolam) ���� ditarik dari peredaran di UK dll.

“dose-dependent anterograde amnesic

effects”

2. Sedation and induction of sleep���� hipnosis

All hypnotic drugs :

- Reduce REM sleep (BZD is the least)

- hang – over - irritable

- Slow wave (SW) sleep juga

Efek sedativa – hipnotika terhadap tidur

BZD Barb Zolp Zalep Busp

Onset of sleef

Duration of

NREM ( - )NREM ( - )

REM ( - )

SW ( - ) ( - )

Zolp : ZolpidemZalep : Zaleplon.

UNWANTED EFFECTS :

I. Acute Toxicity

- Jarang pada BDZ ok margin of safetyluas ���� tidur lebih lama.Hati-hati pada interaksi dengan

- CNS depressant lain seperti

alkohol, barbiturat dll.alkohol, barbiturat dll.

II. Side-effect pada dosis terapi :

- DrowsinessConfusion

- Driving skill- Job performance

-Amnesia---� retrograde amnesia---� date-rape

-Gangguan koordinasi:

III. Tolerance and Dependence

- Toleransi terjadi bukan karena metabolisme seperti pada barbiturat, tapi karena terjadi perubahan pada reseptor.Dependence terjadi ���� adalah beberapa minggu atau bulan.

���� Withdrawal effects :���� Withdrawal effects :- anxiety- tremor- dizziness, nervousness- convulsions

���� Susah menanganinya

Dependence, physiologic & psychologic

� Tergantung dari dosage, duration of therapy

and potency

Short acting, high- potency drugs like alprazolam

or lorazepam develop sooner (in 1 or 2 months)

than chlordiazepoxidethan chlordiazepoxide

Withdrawal syndrome

Gejala putus obat ( withdrawal syndroms)

- anxiety

- HR ↑↑↑↑, TD ↑↑↑↑- berkeringat - insomnia,- seizures - delirium tremens

Pada BDZ addicts ���� protracted withdrawal- anxiety - depression- insomnia- gangguan saluran cerna, neurologis danotot-otot.

Efficacy of Pharmacologic Agents in the

treatment of Anxiety disorders.

Disorder BZD SSRIs TCA Bus

Acute anxiety ++

Generalized anxiety D ++ + ++ ++Generalized anxiety D ++ + ++ ++

Panic disorder ++ ++ ++

Social phobia + ++ + +

Post-traumatic stress

D

± + + +

Obsessive-

compulsive D

++ + +

BUSPIRONE• a potent (but non-selective) agonist

at 5-HT1A – receptor

• Anxiolytic effects take days/weeks to develop

• Side effects : less than • Side effects : less than benzodeazepine, no sedation or loss of coordination

-No tolerance or dependence

-No muscle relaxant or anticonvulsant activity

ending

β-adrenergic blockers

• In case there is sympathetic overactivity:

• -palpitation

• -shaking

• -tremor• -tremor

• -gastrointestinal hurrying

Use β-blocker

BZD Receptor Ligands

Drug Peak

blood

Level

(hrs)

Elim. T

½ (hrs)

Comments

Alprazolam

( Xanax R/ ).

1 - 2 12 – 15 Rapid Oral abs Hp, S

Chlordiazepoxid 2 - 4 15 – 40 Active Met.

e

(Librium R/ ).

erratic bioavailab.from

i.m. Lp,L

Diazepam

(Valium R/ ).

1 - 2 20 – 80 idem

Lorazepam

(Ativan R/ ).

1 – 2 10 – 20 No active Met.

Hp, S

Hp = High - potency

Lp = Low - potency

S = Short half - life

L = Long half - life