Dr Iwan Sahrial Hamid MSi Drh

SEDATIF-HIPNOTIC

Reduce Stimulation CNS

CNS STIMULANT

Increase Stimulation CNS

A stimulant is a drug that speeds up activities of the CNS

A depressant is a drug that slows brain and body reactions

Stimulants increase Depressants decrease

HR

BP

RRRelax muscle tensionLower alertnessCause drowsiness

Increase Motor ActivityIncrease AlertnessDecrease need for Sleep

Mild CNS

Moderate CNS

SevereCNS

bull Inability to focusbull Decreased interest in

surroundings

bull Decreased perception of heat or cold

bull Sleepbull Drowsiness

bull Respiratory failurebull Coma loss of reflexesbull Unconsciousness

bull Decreased fatiguebull Mental alertness bull Wakefulness

bull Insomniabull Nervousnessbull Excessive talkingbull Hyperactivity

bull Cardiac dysrhythmiasbull Seizures bull Confusion

Low dose

Over dose

Higher dose

increase dose

bull SEDATIVES ndash reduce anxiety and exert a calming effect

bull HYPNOTICS - produces drowsiness and facilitates the onset and maintenance of a state of sleep

Increase Sedative-hypnotic Dose

CN

S ef

fect

s

Possible selective anticonvulsant and muscle-relaxing activity

Sedation

Hypnosis

(Benzodiazepines) Anesthesia

Medullary depression

(Barbiturates) Coma

Relationship between dose of benzodiazepines and barbiturates and their CNS effect

Why prescribed

1048698 Anxiety

1048698 Short term problems (performance)

1048698 Long term problems (panic GAD PTSD)

1048698 Sleep problems

1048698 Muscle relaxants

1048698 Depression

1048698 Only 20 of prescriptions done by

psychiatrists

1048698 Benzodiazepine is in top 10 of all medical

prescriptions

SEDATIVE - HIPNOTIC

Generalized anxiety

disorder (GAD)

Posttraumatic stress

disorder (PTSD)

General Function

1048698 Decrease CNS responding

1048698 Lower anxiety

1048698 General sedation

1048698 Some cognitive slowing

1048698 Major therapeutic use is to relieve anxiety

(anxiolytics) or induce sleep (hypnotics)

1048698 Hypnotic effects can be achieved with most

anxiolytic drugs just by increasing the dose

1048698 All of the anxiolyticssedative-hypnotics should

be used only for symptomatic relief

1048698 All the drugs used alter the normal sleep cycle and

should be administered only for days or weeks

never for months

Classifications

1048698 Barbiturates (BARBs)

1048698 Benzodiazepines (BZDs)

BENZODIAZEPIN

Appear Effects

Hypnotic Sedation Muscle Relaxation

Anxyolitic and decrease convultion with different

Potention

Effects of benzodiazepinebull On increasing the dose sedation progresses to

hypnosis and then to stupor

bull But the drugs do not cause a true general anesthesia because

-awareness usually persists

-immobility sufficient to allow surgery cannot be achieved

bull However at preanesthetic doses there is amnesia

Mechanism of action

Benzodiazepines (BDZs) bind to the gamma

sub-unit of the GABA-A receptor Their binding

causes an allosteric (structural) modification of

the receptor that results in an increase in GABA

A receptor activity BDZs do not substitute for

GABA which bind at the alpha sub-unit but

increase the frequency of channel opening

events which leads to an increase in chloride ion

conductance and inhibition of the action

potential

Figure 1 Figure and tables index

A stimulant is a drug that speeds up activities of the CNS

A depressant is a drug that slows brain and body reactions

Stimulants increase Depressants decrease

HR

BP

RRRelax muscle tensionLower alertnessCause drowsiness

Increase Motor ActivityIncrease AlertnessDecrease need for Sleep

Mild CNS

Moderate CNS

SevereCNS

bull Inability to focusbull Decreased interest in

surroundings

bull Decreased perception of heat or cold

bull Sleepbull Drowsiness

bull Respiratory failurebull Coma loss of reflexesbull Unconsciousness

bull Decreased fatiguebull Mental alertness bull Wakefulness

bull Insomniabull Nervousnessbull Excessive talkingbull Hyperactivity

bull Cardiac dysrhythmiasbull Seizures bull Confusion

Low dose

Over dose

Higher dose

increase dose

bull SEDATIVES ndash reduce anxiety and exert a calming effect

bull HYPNOTICS - produces drowsiness and facilitates the onset and maintenance of a state of sleep

Increase Sedative-hypnotic Dose

CN

S ef

fect

s

Possible selective anticonvulsant and muscle-relaxing activity

Sedation

Hypnosis

(Benzodiazepines) Anesthesia

Medullary depression

(Barbiturates) Coma

Relationship between dose of benzodiazepines and barbiturates and their CNS effect

Why prescribed

1048698 Anxiety

1048698 Short term problems (performance)

1048698 Long term problems (panic GAD PTSD)

1048698 Sleep problems

1048698 Muscle relaxants

1048698 Depression

1048698 Only 20 of prescriptions done by

psychiatrists

1048698 Benzodiazepine is in top 10 of all medical

prescriptions

SEDATIVE - HIPNOTIC

Generalized anxiety

disorder (GAD)

Posttraumatic stress

disorder (PTSD)

General Function

1048698 Decrease CNS responding

1048698 Lower anxiety

1048698 General sedation

1048698 Some cognitive slowing

1048698 Major therapeutic use is to relieve anxiety

(anxiolytics) or induce sleep (hypnotics)

1048698 Hypnotic effects can be achieved with most

anxiolytic drugs just by increasing the dose

1048698 All of the anxiolyticssedative-hypnotics should

be used only for symptomatic relief

1048698 All the drugs used alter the normal sleep cycle and

should be administered only for days or weeks

never for months

Classifications

1048698 Barbiturates (BARBs)

1048698 Benzodiazepines (BZDs)

BENZODIAZEPIN

Appear Effects

Hypnotic Sedation Muscle Relaxation

Anxyolitic and decrease convultion with different

Potention

Effects of benzodiazepinebull On increasing the dose sedation progresses to

hypnosis and then to stupor

bull But the drugs do not cause a true general anesthesia because

-awareness usually persists

-immobility sufficient to allow surgery cannot be achieved

bull However at preanesthetic doses there is amnesia

Mechanism of action

Benzodiazepines (BDZs) bind to the gamma

sub-unit of the GABA-A receptor Their binding

causes an allosteric (structural) modification of

the receptor that results in an increase in GABA

A receptor activity BDZs do not substitute for

GABA which bind at the alpha sub-unit but

increase the frequency of channel opening

events which leads to an increase in chloride ion

conductance and inhibition of the action

potential

Figure 1 Figure and tables index

Mild CNS

Moderate CNS

SevereCNS

bull Inability to focusbull Decreased interest in

surroundings

bull Decreased perception of heat or cold

bull Sleepbull Drowsiness

bull Respiratory failurebull Coma loss of reflexesbull Unconsciousness

bull Decreased fatiguebull Mental alertness bull Wakefulness

bull Insomniabull Nervousnessbull Excessive talkingbull Hyperactivity

bull Cardiac dysrhythmiasbull Seizures bull Confusion

Low dose

Over dose

Higher dose

increase dose

bull SEDATIVES ndash reduce anxiety and exert a calming effect

bull HYPNOTICS - produces drowsiness and facilitates the onset and maintenance of a state of sleep

Increase Sedative-hypnotic Dose

CN

S ef

fect

s

Possible selective anticonvulsant and muscle-relaxing activity

Sedation

Hypnosis

(Benzodiazepines) Anesthesia

Medullary depression

(Barbiturates) Coma

Relationship between dose of benzodiazepines and barbiturates and their CNS effect

Why prescribed

1048698 Anxiety

1048698 Short term problems (performance)

1048698 Long term problems (panic GAD PTSD)

1048698 Sleep problems

1048698 Muscle relaxants

1048698 Depression

1048698 Only 20 of prescriptions done by

psychiatrists

1048698 Benzodiazepine is in top 10 of all medical

prescriptions

SEDATIVE - HIPNOTIC

Generalized anxiety

disorder (GAD)

Posttraumatic stress

disorder (PTSD)

General Function

1048698 Decrease CNS responding

1048698 Lower anxiety

1048698 General sedation

1048698 Some cognitive slowing

1048698 Major therapeutic use is to relieve anxiety

(anxiolytics) or induce sleep (hypnotics)

1048698 Hypnotic effects can be achieved with most

anxiolytic drugs just by increasing the dose

1048698 All of the anxiolyticssedative-hypnotics should

be used only for symptomatic relief

1048698 All the drugs used alter the normal sleep cycle and

should be administered only for days or weeks

never for months

Classifications

1048698 Barbiturates (BARBs)

1048698 Benzodiazepines (BZDs)

BENZODIAZEPIN

Appear Effects

Hypnotic Sedation Muscle Relaxation

Anxyolitic and decrease convultion with different

Potention

Effects of benzodiazepinebull On increasing the dose sedation progresses to

hypnosis and then to stupor

bull But the drugs do not cause a true general anesthesia because

-awareness usually persists

-immobility sufficient to allow surgery cannot be achieved

bull However at preanesthetic doses there is amnesia

Mechanism of action

Benzodiazepines (BDZs) bind to the gamma

sub-unit of the GABA-A receptor Their binding

causes an allosteric (structural) modification of

the receptor that results in an increase in GABA

A receptor activity BDZs do not substitute for

GABA which bind at the alpha sub-unit but

increase the frequency of channel opening

events which leads to an increase in chloride ion

conductance and inhibition of the action

potential

Figure 1 Figure and tables index

bull SEDATIVES ndash reduce anxiety and exert a calming effect

bull HYPNOTICS - produces drowsiness and facilitates the onset and maintenance of a state of sleep

Increase Sedative-hypnotic Dose

CN

S ef

fect

s

Possible selective anticonvulsant and muscle-relaxing activity

Sedation

Hypnosis

(Benzodiazepines) Anesthesia

Medullary depression

(Barbiturates) Coma

Relationship between dose of benzodiazepines and barbiturates and their CNS effect

Why prescribed

1048698 Anxiety

1048698 Short term problems (performance)

1048698 Long term problems (panic GAD PTSD)

1048698 Sleep problems

1048698 Muscle relaxants

1048698 Depression

1048698 Only 20 of prescriptions done by

psychiatrists

1048698 Benzodiazepine is in top 10 of all medical

prescriptions

SEDATIVE - HIPNOTIC

Generalized anxiety

disorder (GAD)

Posttraumatic stress

disorder (PTSD)

General Function

1048698 Decrease CNS responding

1048698 Lower anxiety

1048698 General sedation

1048698 Some cognitive slowing

1048698 Major therapeutic use is to relieve anxiety

(anxiolytics) or induce sleep (hypnotics)

1048698 Hypnotic effects can be achieved with most

anxiolytic drugs just by increasing the dose

1048698 All of the anxiolyticssedative-hypnotics should

be used only for symptomatic relief

1048698 All the drugs used alter the normal sleep cycle and

should be administered only for days or weeks

never for months

Classifications

1048698 Barbiturates (BARBs)

1048698 Benzodiazepines (BZDs)

BENZODIAZEPIN

Appear Effects

Hypnotic Sedation Muscle Relaxation

Anxyolitic and decrease convultion with different

Potention

Effects of benzodiazepinebull On increasing the dose sedation progresses to

hypnosis and then to stupor

bull But the drugs do not cause a true general anesthesia because

-awareness usually persists

-immobility sufficient to allow surgery cannot be achieved

bull However at preanesthetic doses there is amnesia

Mechanism of action

Benzodiazepines (BDZs) bind to the gamma

sub-unit of the GABA-A receptor Their binding

causes an allosteric (structural) modification of

the receptor that results in an increase in GABA

A receptor activity BDZs do not substitute for

GABA which bind at the alpha sub-unit but

increase the frequency of channel opening

events which leads to an increase in chloride ion

conductance and inhibition of the action

potential

Figure 1 Figure and tables index

Increase Sedative-hypnotic Dose

CN

S ef

fect

s

Possible selective anticonvulsant and muscle-relaxing activity

Sedation

Hypnosis

(Benzodiazepines) Anesthesia

Medullary depression

(Barbiturates) Coma

Relationship between dose of benzodiazepines and barbiturates and their CNS effect

Why prescribed

1048698 Anxiety

1048698 Short term problems (performance)

1048698 Long term problems (panic GAD PTSD)

1048698 Sleep problems

1048698 Muscle relaxants

1048698 Depression

1048698 Only 20 of prescriptions done by

psychiatrists

1048698 Benzodiazepine is in top 10 of all medical

prescriptions

SEDATIVE - HIPNOTIC

Generalized anxiety

disorder (GAD)

Posttraumatic stress

disorder (PTSD)

General Function

1048698 Decrease CNS responding

1048698 Lower anxiety

1048698 General sedation

1048698 Some cognitive slowing

1048698 Major therapeutic use is to relieve anxiety

(anxiolytics) or induce sleep (hypnotics)

1048698 Hypnotic effects can be achieved with most

anxiolytic drugs just by increasing the dose

1048698 All of the anxiolyticssedative-hypnotics should

be used only for symptomatic relief

1048698 All the drugs used alter the normal sleep cycle and

should be administered only for days or weeks

never for months

Classifications

1048698 Barbiturates (BARBs)

1048698 Benzodiazepines (BZDs)

BENZODIAZEPIN

Appear Effects

Hypnotic Sedation Muscle Relaxation

Anxyolitic and decrease convultion with different

Potention

Effects of benzodiazepinebull On increasing the dose sedation progresses to

hypnosis and then to stupor

bull But the drugs do not cause a true general anesthesia because

-awareness usually persists

-immobility sufficient to allow surgery cannot be achieved

bull However at preanesthetic doses there is amnesia

Mechanism of action

Benzodiazepines (BDZs) bind to the gamma

sub-unit of the GABA-A receptor Their binding

causes an allosteric (structural) modification of

the receptor that results in an increase in GABA

A receptor activity BDZs do not substitute for

GABA which bind at the alpha sub-unit but

increase the frequency of channel opening

events which leads to an increase in chloride ion

conductance and inhibition of the action

potential

Figure 1 Figure and tables index

Why prescribed

1048698 Anxiety

1048698 Short term problems (performance)

1048698 Long term problems (panic GAD PTSD)

1048698 Sleep problems

1048698 Muscle relaxants

1048698 Depression

1048698 Only 20 of prescriptions done by

psychiatrists

1048698 Benzodiazepine is in top 10 of all medical

prescriptions

SEDATIVE - HIPNOTIC

Generalized anxiety

disorder (GAD)

Posttraumatic stress

disorder (PTSD)

General Function

1048698 Decrease CNS responding

1048698 Lower anxiety

1048698 General sedation

1048698 Some cognitive slowing

1048698 Major therapeutic use is to relieve anxiety

(anxiolytics) or induce sleep (hypnotics)

1048698 Hypnotic effects can be achieved with most

anxiolytic drugs just by increasing the dose

1048698 All of the anxiolyticssedative-hypnotics should

be used only for symptomatic relief

1048698 All the drugs used alter the normal sleep cycle and

should be administered only for days or weeks

never for months

Classifications

1048698 Barbiturates (BARBs)

1048698 Benzodiazepines (BZDs)

BENZODIAZEPIN

Appear Effects

Hypnotic Sedation Muscle Relaxation

Anxyolitic and decrease convultion with different

Potention

Effects of benzodiazepinebull On increasing the dose sedation progresses to

hypnosis and then to stupor

bull But the drugs do not cause a true general anesthesia because

-awareness usually persists

-immobility sufficient to allow surgery cannot be achieved

bull However at preanesthetic doses there is amnesia

Mechanism of action

Benzodiazepines (BDZs) bind to the gamma

sub-unit of the GABA-A receptor Their binding

causes an allosteric (structural) modification of

the receptor that results in an increase in GABA

A receptor activity BDZs do not substitute for

GABA which bind at the alpha sub-unit but

increase the frequency of channel opening

events which leads to an increase in chloride ion

conductance and inhibition of the action

potential

Figure 1 Figure and tables index

General Function

1048698 Decrease CNS responding

1048698 Lower anxiety

1048698 General sedation

1048698 Some cognitive slowing

1048698 Major therapeutic use is to relieve anxiety

(anxiolytics) or induce sleep (hypnotics)

1048698 Hypnotic effects can be achieved with most

anxiolytic drugs just by increasing the dose

1048698 All of the anxiolyticssedative-hypnotics should

be used only for symptomatic relief

1048698 All the drugs used alter the normal sleep cycle and

should be administered only for days or weeks

never for months

Classifications

1048698 Barbiturates (BARBs)

1048698 Benzodiazepines (BZDs)

BENZODIAZEPIN

Appear Effects

Hypnotic Sedation Muscle Relaxation

Anxyolitic and decrease convultion with different

Potention

Effects of benzodiazepinebull On increasing the dose sedation progresses to

hypnosis and then to stupor

bull But the drugs do not cause a true general anesthesia because

-awareness usually persists

-immobility sufficient to allow surgery cannot be achieved

bull However at preanesthetic doses there is amnesia

Mechanism of action

Benzodiazepines (BDZs) bind to the gamma

sub-unit of the GABA-A receptor Their binding

causes an allosteric (structural) modification of

the receptor that results in an increase in GABA

A receptor activity BDZs do not substitute for

GABA which bind at the alpha sub-unit but

increase the frequency of channel opening

events which leads to an increase in chloride ion

conductance and inhibition of the action

potential

Figure 1 Figure and tables index

Classifications

1048698 Barbiturates (BARBs)

1048698 Benzodiazepines (BZDs)

BENZODIAZEPIN

Appear Effects

Hypnotic Sedation Muscle Relaxation

Anxyolitic and decrease convultion with different

Potention

Effects of benzodiazepinebull On increasing the dose sedation progresses to

hypnosis and then to stupor

bull But the drugs do not cause a true general anesthesia because

-awareness usually persists

-immobility sufficient to allow surgery cannot be achieved

bull However at preanesthetic doses there is amnesia

Mechanism of action

Benzodiazepines (BDZs) bind to the gamma

sub-unit of the GABA-A receptor Their binding

causes an allosteric (structural) modification of

the receptor that results in an increase in GABA

A receptor activity BDZs do not substitute for

GABA which bind at the alpha sub-unit but

increase the frequency of channel opening

events which leads to an increase in chloride ion

conductance and inhibition of the action

potential

Figure 1 Figure and tables index

Effects of benzodiazepinebull On increasing the dose sedation progresses to

hypnosis and then to stupor

bull But the drugs do not cause a true general anesthesia because

-awareness usually persists

-immobility sufficient to allow surgery cannot be achieved

bull However at preanesthetic doses there is amnesia

Mechanism of action

Benzodiazepines (BDZs) bind to the gamma

sub-unit of the GABA-A receptor Their binding

causes an allosteric (structural) modification of

the receptor that results in an increase in GABA

A receptor activity BDZs do not substitute for

GABA which bind at the alpha sub-unit but

increase the frequency of channel opening

events which leads to an increase in chloride ion

conductance and inhibition of the action

potential

Figure 1 Figure and tables index

Mechanism of action

Benzodiazepines (BDZs) bind to the gamma

sub-unit of the GABA-A receptor Their binding

causes an allosteric (structural) modification of

the receptor that results in an increase in GABA

A receptor activity BDZs do not substitute for

GABA which bind at the alpha sub-unit but

increase the frequency of channel opening

events which leads to an increase in chloride ion

conductance and inhibition of the action

potential

Figure 1 Figure and tables index

Figure 1 Figure and tables index

Hypothetical model for the excitatory and neurotoxic action of

uremic retention solutes on the central nervous system The model

focuses on reported effects on GABAA receptor (GABAA-R) NMDA-

type glutamate receptor (NMDA-R) and voltage-gated Ca2+ channel

(VGCC) but may include other neuroexcitatory effects of these solutes

The excitatory neurotransmitter L-glutamate is released from presynaptic

terminals and binds to AMPA and NMDA receptors GABAergic

interneurons provide synaptic inhibition through activation of GABAA-R

and chloride influx (resulting in inhibitory hyperpolarization of the

membrane) In the presence of GSA or other excitatory uremic retention

solutes GABAA-Rs will be blocked and NMDA receptors (NMDA-Rs)

activated lifting the voltage dependent block from NMDA-Rs Ca2+

influx through NMDA-R ionophores and VGCCs activates postsynaptic

Ca2+-triggered events These may include activation of nitric oxide

synthase (NOS) and postsynaptic density-95 (PSD-95) protein leading

to nitric oxide (NO) synthesis and anterograde NO diffusion Presynaptic

effects of NO and activation of presynaptic VGCC could increase

excitatory glutamate release

Benzodiazepin Aktivasi GABA a

Aktivasi Reseptor GABA a

Pembukaan kanal Cl- Membran Sel Saraf

Masukknya Ion Klorida Ke Dalam Sel Saraf

Peningkatan Potensial Elektrik Sepanjang Membran Sel

Hiperpolarisasi Hambatan Eksitasi

BDZ (Benzodiazepin) Pharmacodynamics

1048698 Benzodiazepines act on GABAa

receptors

GABA receptor

A pentameric protein

Forms an ionotropic receptor complex

Consists of several subunits designated

Alpha (mainly responsible for the

pharmacology of the receptor)

Beta

Gamma (required for high affinity

benzodiazepine binding)

Anxiolytic and

Sedative-hypnoticsGeneric Name Trade Name

Chlordiazepoxide Librium

Clonazepam Klonopin

Diazepam Valium

Flurazepam Dalmane

Lorazepam Ativan

Oxazepam Serax

Temazepam Restoril

Triazolam Halcion

Non-

Benzodiazepine

anxiolytics

and hypnotics

Buspirone BuSpar

Chloral hydrate Noctec

Zolpidem tartrate Ambien

Medication

Dose (mg)

Onset of

action

(minutes)

Half-life

(hours)

Metabolic

pathway

Duration of

hypnotic

effect

Estazolam 1-2

(elderly )

05-1 mg

15-30 8-24 Oxidation Intermediate

Flurazepam 15-30 60-120 47-100

including

metabolites

Oxidation Long

Quazepam 75-15

(elderly

75 mg)

20-45 25-41

including

metabolites

Oxidation Long

Temazepam 15-30

(elderly

75-15 mg)

45-60 10-20 Conjugation Intermediate

Triazolam 0125-025

(elderly

15-30 16-54 Oxidation Short

PHARMACOKINETICS

bull A short elimination t12 is desirable for hypnotics although this carries the drawback of increased abuse liability and severity of withdrawal after drug discontinuation

bull Most of the BZDs are metabolized in the liver to produce active products (thus long duration of action)

bull After metabolism these are conjugated and are excreted via kidney

KINETIK

Absorpsi Biasanya diberikan secara peroral

absorpsinya cepat tergantung dari lipofilisitas

obat yang berbeda (Triazolam Diazepam

Lebih Cepat)

Distribusi

Lebih mudah larut lemak lebih cepat memasuki

CNS Semua Sedatif-Hipnotik menembus

Plasenta Barrier tidak dianjurkan pada masa

kebuntingan

Kloralhidrat meningkatkan efek antikoagulan

dari Warfarin

Biotransformasi

Hampir semua Benzodiazepin mengalami

oksidasi mikrosomal (Fase I) Metabolit

Aktif yang waktu Paruhnya lebih lama

Reaksi Fase II Konjugasi oleh Glucuronosyl-

Transferase ekskresi urine Glucoronide

Ekskresi

Metabolit larut air diekskresi lewat ginjal

Penurunan fungsi hepar menurunkan proses

klirens

Classification

1 Long acting barbiturates (More than 8hours) ndash Barbitone

Barbital sodium

Phorobarbital Mephobarbital

2 Intermediate acting barbiturates (4 - 8hours) ndash Allo

barbital hexobarbital

pento hexital sodium

3 Short acting barbiturates (less than 4 hours) ndash Seco

barbital hexobarbital

Pento barbital cyclo barbital

4 Ultra short acting barbiturates ( I-V anaesthetics) ndash

Thiopental sodium

Metho hexital sodium

Mechanism of action Barbiturates either have a Gama amino butyric acid

(GABA) like action or enhance the effect of GABA aninhibitory transmitter

The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters

When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation

Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration

EFEK BARBITURAT

Pada CNS

Dicapainya semua semua tingkat depresi

sedasi ansiolitik hipnosis bbrp tingkat

anestesia koma sampai dengan kematian

Efek Hipnotik dicapai 20-60 menit

Efek Anestesi umum Tiobarbital Oksibarbital

Efek Antikonvulsi Fenobarbital Mefobarbital

Menyerupai kerja Benzodiazepin dosis lebih

tinggi Agonis GABA Depresi lebih berat

MODEL STIMULASI

BLOKADE SISTEM PENGHAMBATAN

(STRIKNIN METRAZOL)

PENINGKATAN RANGSANGAN SINAP

(DOKSAPRAM NIKETAMID XANTIN

DERIVED)

Agents which remove inhibition from CNS

neurons increase synaptic excitation

or alter axonal membrane properties

Net result is CNS stimulation

Pharmacological properties

Produces CNS excitation by blocking

glycine-mediated postsynaptic

inhibition

Sequence of strychnine effects

Tightness of neck and jaw muscles

Hyperreflexia

Tonic extensor thrusts

Tetanic symmetrical convulsions

(opisthotonus)

Respiratory arrest

STRIKNIN

ACTION Kompetitif Antagonis Terhadap Inhibitor

Transmiter GLYSIN (Penghambatan

Pasca Sinap)

Konvulsan Spinal Rangsangan pada Medula Spinalis

Rangsangan pada Medula Oblongata Efek pada

Pusat Vasomotor

Peningkatan Tekanan Darah

Peningkatan Tonus Otot

Sifat Kejang

Ekstensi Tonik Seluruh Tubuh dan Ekstremitas

Kontraksi Ekstensor Simetris yang diperkuat

Rangsangan Sensorik

( Pendengaran Penglihatan dan Perabaan)

KINETIK

Absorbsi Mudah di Tempat Injeksi

Masuk Sirkulasi Masuk Jaringan

Segera Ekskresi Lewat Urine (Ekskresi

Lengkap 10 Jam)

GEJALA KLINIS

Kaku Otot Muka dan Leher

Hiperekstensi

Kontraksi Otot Diafragma Depresi Napas

Akumulasi Asam Laktat dalam Plasma

Asidosis Metabolik

PENTILENTETRAZOL (METRAZOL)

ACTION

HAMBATAN SISTEM GABA ndash ERGIC

EKSITABILITAS SSP MENINGKAT

EXCITATORY

Efeknya Lebih Kecil Dibanding Pikrotoksin

KINETIK

Absorbsi cepat Distribusi merata

Metabolisme di Hepar cepat

Ekskresi 75 di Urin dalam

keadaan Tidak Aktif

METIL FENIDAT

ACTION Efek Penglepasan Norefineprin

Simpatomimetik Berkurang

Termasuk α2 Agonis

Efek Lebih Menonjol pada Aktivitas

Mental Mirip Amfetamin

α2 AGONIS

Efek Penglepasan Norefineprin

Aktivasi Prot G(i)

Adenilsiklase

ATP cAMP 5AMP + PI

Aktivasi Kanal K+ Hiperpolarisasi

pada Neuron Mienterik Kolinergik

Pelepasan Asetilkolin

Relaksasi Otot Polos

Aktivasi Kanal Ca2+

Sekresi Insulin

Rangsangan

Simpatis dari

CNS

KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam

Distribusi di Otak Lebih Besar

Metabolisme 80 Asam Retanilat

Ekskresi Melalui Urine

DOKSAPRAM DAN NIKETAMID

ACTION

Rangsangan pada seluruh serebrospinal

Meningkatkan derajat Perangsangan

Pada dosis kecil IV Aktivitas Kemoreseptor

karotis dan Neuron Pusat Napas Tidal Volume

Perangsangan Pusat Napas

Direct acting stimulants

Increase nueronal excitability by

decreasing neuronal recovery time or by

increasing responsiveness to excitatory

neurotransmitters eg doxapram

(Dopram)

Claimed to be a specific respiratory

stimulant and to be useful in

treatment of drug induced respiratory

depression Supportive treatment is

better Sometimes used in anesthesia

Analeptics ndash Xanthines Derived

bull Pharmacological properties

ndashMechanism of action ndash act as

antagonists at adenosine receptors

Adenosine receptors are located on

presynaptic terminals of noradrenergic

neurons and blocks NE release So

caffeine increases NE release

ndashInhibition of phosphodiesterase occurs

but only at very high doses

bull Pharmacological properties

ndashCNS ndash stimulate cortex first then

medulla and spinal cord at high doses

ndashDiuresis

ndashStimulation of cardiac muscle

ndashSmooth muscle relaxation

ndashSecretion

ndashSkeletal muscle - diaphragm

bull Adverse effects

ndashAt 1 g dose of caffeine (12 cups

coffee)

bullInsomnia excitement mild

delirium sensory disturbances

bullIncreased heart rate

bullIncreased respiration

ndashAt higher doses (10 g)

bullClonic convulsions rarr death

bull Adverse effects

ndashChronic use in pregnant women

may increase rate of spontaneous

abortion

ndashTolerance and physical dependence

can occur Withdrawal symptoms

include lethargy irritability and

headache

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

Benzodiazepin Aktivasi GABA a

Aktivasi Reseptor GABA a

Pembukaan kanal Cl- Membran Sel Saraf

Masukknya Ion Klorida Ke Dalam Sel Saraf

Peningkatan Potensial Elektrik Sepanjang Membran Sel

Hiperpolarisasi Hambatan Eksitasi

BDZ (Benzodiazepin) Pharmacodynamics

1048698 Benzodiazepines act on GABAa

receptors

GABA receptor

A pentameric protein

Forms an ionotropic receptor complex

Consists of several subunits designated

Alpha (mainly responsible for the

pharmacology of the receptor)

Beta

Gamma (required for high affinity

benzodiazepine binding)

Anxiolytic and

Sedative-hypnoticsGeneric Name Trade Name

Chlordiazepoxide Librium

Clonazepam Klonopin

Diazepam Valium

Flurazepam Dalmane

Lorazepam Ativan

Oxazepam Serax

Temazepam Restoril

Triazolam Halcion

Non-

Benzodiazepine

anxiolytics

and hypnotics

Buspirone BuSpar

Chloral hydrate Noctec

Zolpidem tartrate Ambien

Medication

Dose (mg)

Onset of

action

(minutes)

Half-life

(hours)

Metabolic

pathway

Duration of

hypnotic

effect

Estazolam 1-2

(elderly )

05-1 mg

15-30 8-24 Oxidation Intermediate

Flurazepam 15-30 60-120 47-100

including

metabolites

Oxidation Long

Quazepam 75-15

(elderly

75 mg)

20-45 25-41

including

metabolites

Oxidation Long

Temazepam 15-30

(elderly

75-15 mg)

45-60 10-20 Conjugation Intermediate

Triazolam 0125-025

(elderly

15-30 16-54 Oxidation Short

PHARMACOKINETICS

bull A short elimination t12 is desirable for hypnotics although this carries the drawback of increased abuse liability and severity of withdrawal after drug discontinuation

bull Most of the BZDs are metabolized in the liver to produce active products (thus long duration of action)

bull After metabolism these are conjugated and are excreted via kidney

KINETIK

Absorpsi Biasanya diberikan secara peroral

absorpsinya cepat tergantung dari lipofilisitas

obat yang berbeda (Triazolam Diazepam

Lebih Cepat)

Distribusi

Lebih mudah larut lemak lebih cepat memasuki

CNS Semua Sedatif-Hipnotik menembus

Plasenta Barrier tidak dianjurkan pada masa

kebuntingan

Kloralhidrat meningkatkan efek antikoagulan

dari Warfarin

Biotransformasi

Hampir semua Benzodiazepin mengalami

oksidasi mikrosomal (Fase I) Metabolit

Aktif yang waktu Paruhnya lebih lama

Reaksi Fase II Konjugasi oleh Glucuronosyl-

Transferase ekskresi urine Glucoronide

Ekskresi

Metabolit larut air diekskresi lewat ginjal

Penurunan fungsi hepar menurunkan proses

klirens

Classification

1 Long acting barbiturates (More than 8hours) ndash Barbitone

Barbital sodium

Phorobarbital Mephobarbital

2 Intermediate acting barbiturates (4 - 8hours) ndash Allo

barbital hexobarbital

pento hexital sodium

3 Short acting barbiturates (less than 4 hours) ndash Seco

barbital hexobarbital

Pento barbital cyclo barbital

4 Ultra short acting barbiturates ( I-V anaesthetics) ndash

Thiopental sodium

Metho hexital sodium

Mechanism of action Barbiturates either have a Gama amino butyric acid

(GABA) like action or enhance the effect of GABA aninhibitory transmitter

The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters

When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation

Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration

EFEK BARBITURAT

Pada CNS

Dicapainya semua semua tingkat depresi

sedasi ansiolitik hipnosis bbrp tingkat

anestesia koma sampai dengan kematian

Efek Hipnotik dicapai 20-60 menit

Efek Anestesi umum Tiobarbital Oksibarbital

Efek Antikonvulsi Fenobarbital Mefobarbital

Menyerupai kerja Benzodiazepin dosis lebih

tinggi Agonis GABA Depresi lebih berat

MODEL STIMULASI

BLOKADE SISTEM PENGHAMBATAN

(STRIKNIN METRAZOL)

PENINGKATAN RANGSANGAN SINAP

(DOKSAPRAM NIKETAMID XANTIN

DERIVED)

Agents which remove inhibition from CNS

neurons increase synaptic excitation

or alter axonal membrane properties

Net result is CNS stimulation

Pharmacological properties

Produces CNS excitation by blocking

glycine-mediated postsynaptic

inhibition

Sequence of strychnine effects

Tightness of neck and jaw muscles

Hyperreflexia

Tonic extensor thrusts

Tetanic symmetrical convulsions

(opisthotonus)

Respiratory arrest

STRIKNIN

ACTION Kompetitif Antagonis Terhadap Inhibitor

Transmiter GLYSIN (Penghambatan

Pasca Sinap)

Konvulsan Spinal Rangsangan pada Medula Spinalis

Rangsangan pada Medula Oblongata Efek pada

Pusat Vasomotor

Peningkatan Tekanan Darah

Peningkatan Tonus Otot

Sifat Kejang

Ekstensi Tonik Seluruh Tubuh dan Ekstremitas

Kontraksi Ekstensor Simetris yang diperkuat

Rangsangan Sensorik

( Pendengaran Penglihatan dan Perabaan)

KINETIK

Absorbsi Mudah di Tempat Injeksi

Masuk Sirkulasi Masuk Jaringan

Segera Ekskresi Lewat Urine (Ekskresi

Lengkap 10 Jam)

GEJALA KLINIS

Kaku Otot Muka dan Leher

Hiperekstensi

Kontraksi Otot Diafragma Depresi Napas

Akumulasi Asam Laktat dalam Plasma

Asidosis Metabolik

PENTILENTETRAZOL (METRAZOL)

ACTION

HAMBATAN SISTEM GABA ndash ERGIC

EKSITABILITAS SSP MENINGKAT

EXCITATORY

Efeknya Lebih Kecil Dibanding Pikrotoksin

KINETIK

Absorbsi cepat Distribusi merata

Metabolisme di Hepar cepat

Ekskresi 75 di Urin dalam

keadaan Tidak Aktif

METIL FENIDAT

ACTION Efek Penglepasan Norefineprin

Simpatomimetik Berkurang

Termasuk α2 Agonis

Efek Lebih Menonjol pada Aktivitas

Mental Mirip Amfetamin

α2 AGONIS

Efek Penglepasan Norefineprin

Aktivasi Prot G(i)

Adenilsiklase

ATP cAMP 5AMP + PI

Aktivasi Kanal K+ Hiperpolarisasi

pada Neuron Mienterik Kolinergik

Pelepasan Asetilkolin

Relaksasi Otot Polos

Aktivasi Kanal Ca2+

Sekresi Insulin

Rangsangan

Simpatis dari

CNS

KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam

Distribusi di Otak Lebih Besar

Metabolisme 80 Asam Retanilat

Ekskresi Melalui Urine

DOKSAPRAM DAN NIKETAMID

ACTION

Rangsangan pada seluruh serebrospinal

Meningkatkan derajat Perangsangan

Pada dosis kecil IV Aktivitas Kemoreseptor

karotis dan Neuron Pusat Napas Tidal Volume

Perangsangan Pusat Napas

Direct acting stimulants

Increase nueronal excitability by

decreasing neuronal recovery time or by

increasing responsiveness to excitatory

neurotransmitters eg doxapram

(Dopram)

Claimed to be a specific respiratory

stimulant and to be useful in

treatment of drug induced respiratory

depression Supportive treatment is

better Sometimes used in anesthesia

Analeptics ndash Xanthines Derived

bull Pharmacological properties

ndashMechanism of action ndash act as

antagonists at adenosine receptors

Adenosine receptors are located on

presynaptic terminals of noradrenergic

neurons and blocks NE release So

caffeine increases NE release

ndashInhibition of phosphodiesterase occurs

but only at very high doses

bull Pharmacological properties

ndashCNS ndash stimulate cortex first then

medulla and spinal cord at high doses

ndashDiuresis

ndashStimulation of cardiac muscle

ndashSmooth muscle relaxation

ndashSecretion

ndashSkeletal muscle - diaphragm

bull Adverse effects

ndashAt 1 g dose of caffeine (12 cups

coffee)

bullInsomnia excitement mild

delirium sensory disturbances

bullIncreased heart rate

bullIncreased respiration

ndashAt higher doses (10 g)

bullClonic convulsions rarr death

bull Adverse effects

ndashChronic use in pregnant women

may increase rate of spontaneous

abortion

ndashTolerance and physical dependence

can occur Withdrawal symptoms

include lethargy irritability and

headache

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

BDZ (Benzodiazepin) Pharmacodynamics

1048698 Benzodiazepines act on GABAa

receptors

GABA receptor

A pentameric protein

Forms an ionotropic receptor complex

Consists of several subunits designated

Alpha (mainly responsible for the

pharmacology of the receptor)

Beta

Gamma (required for high affinity

benzodiazepine binding)

Anxiolytic and

Sedative-hypnoticsGeneric Name Trade Name

Chlordiazepoxide Librium

Clonazepam Klonopin

Diazepam Valium

Flurazepam Dalmane

Lorazepam Ativan

Oxazepam Serax

Temazepam Restoril

Triazolam Halcion

Non-

Benzodiazepine

anxiolytics

and hypnotics

Buspirone BuSpar

Chloral hydrate Noctec

Zolpidem tartrate Ambien

Medication

Dose (mg)

Onset of

action

(minutes)

Half-life

(hours)

Metabolic

pathway

Duration of

hypnotic

effect

Estazolam 1-2

(elderly )

05-1 mg

15-30 8-24 Oxidation Intermediate

Flurazepam 15-30 60-120 47-100

including

metabolites

Oxidation Long

Quazepam 75-15

(elderly

75 mg)

20-45 25-41

including

metabolites

Oxidation Long

Temazepam 15-30

(elderly

75-15 mg)

45-60 10-20 Conjugation Intermediate

Triazolam 0125-025

(elderly

15-30 16-54 Oxidation Short

PHARMACOKINETICS

bull A short elimination t12 is desirable for hypnotics although this carries the drawback of increased abuse liability and severity of withdrawal after drug discontinuation

bull Most of the BZDs are metabolized in the liver to produce active products (thus long duration of action)

bull After metabolism these are conjugated and are excreted via kidney

KINETIK

Absorpsi Biasanya diberikan secara peroral

absorpsinya cepat tergantung dari lipofilisitas

obat yang berbeda (Triazolam Diazepam

Lebih Cepat)

Distribusi

Lebih mudah larut lemak lebih cepat memasuki

CNS Semua Sedatif-Hipnotik menembus

Plasenta Barrier tidak dianjurkan pada masa

kebuntingan

Kloralhidrat meningkatkan efek antikoagulan

dari Warfarin

Biotransformasi

Hampir semua Benzodiazepin mengalami

oksidasi mikrosomal (Fase I) Metabolit

Aktif yang waktu Paruhnya lebih lama

Reaksi Fase II Konjugasi oleh Glucuronosyl-

Transferase ekskresi urine Glucoronide

Ekskresi

Metabolit larut air diekskresi lewat ginjal

Penurunan fungsi hepar menurunkan proses

klirens

Classification

1 Long acting barbiturates (More than 8hours) ndash Barbitone

Barbital sodium

Phorobarbital Mephobarbital

2 Intermediate acting barbiturates (4 - 8hours) ndash Allo

barbital hexobarbital

pento hexital sodium

3 Short acting barbiturates (less than 4 hours) ndash Seco

barbital hexobarbital

Pento barbital cyclo barbital

4 Ultra short acting barbiturates ( I-V anaesthetics) ndash

Thiopental sodium

Metho hexital sodium

Mechanism of action Barbiturates either have a Gama amino butyric acid

(GABA) like action or enhance the effect of GABA aninhibitory transmitter

The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters

When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation

Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration

EFEK BARBITURAT

Pada CNS

Dicapainya semua semua tingkat depresi

sedasi ansiolitik hipnosis bbrp tingkat

anestesia koma sampai dengan kematian

Efek Hipnotik dicapai 20-60 menit

Efek Anestesi umum Tiobarbital Oksibarbital

Efek Antikonvulsi Fenobarbital Mefobarbital

Menyerupai kerja Benzodiazepin dosis lebih

tinggi Agonis GABA Depresi lebih berat

MODEL STIMULASI

BLOKADE SISTEM PENGHAMBATAN

(STRIKNIN METRAZOL)

PENINGKATAN RANGSANGAN SINAP

(DOKSAPRAM NIKETAMID XANTIN

DERIVED)

Agents which remove inhibition from CNS

neurons increase synaptic excitation

or alter axonal membrane properties

Net result is CNS stimulation

Pharmacological properties

Produces CNS excitation by blocking

glycine-mediated postsynaptic

inhibition

Sequence of strychnine effects

Tightness of neck and jaw muscles

Hyperreflexia

Tonic extensor thrusts

Tetanic symmetrical convulsions

(opisthotonus)

Respiratory arrest

STRIKNIN

ACTION Kompetitif Antagonis Terhadap Inhibitor

Transmiter GLYSIN (Penghambatan

Pasca Sinap)

Konvulsan Spinal Rangsangan pada Medula Spinalis

Rangsangan pada Medula Oblongata Efek pada

Pusat Vasomotor

Peningkatan Tekanan Darah

Peningkatan Tonus Otot

Sifat Kejang

Ekstensi Tonik Seluruh Tubuh dan Ekstremitas

Kontraksi Ekstensor Simetris yang diperkuat

Rangsangan Sensorik

( Pendengaran Penglihatan dan Perabaan)

KINETIK

Absorbsi Mudah di Tempat Injeksi

Masuk Sirkulasi Masuk Jaringan

Segera Ekskresi Lewat Urine (Ekskresi

Lengkap 10 Jam)

GEJALA KLINIS

Kaku Otot Muka dan Leher

Hiperekstensi

Kontraksi Otot Diafragma Depresi Napas

Akumulasi Asam Laktat dalam Plasma

Asidosis Metabolik

PENTILENTETRAZOL (METRAZOL)

ACTION

HAMBATAN SISTEM GABA ndash ERGIC

EKSITABILITAS SSP MENINGKAT

EXCITATORY

Efeknya Lebih Kecil Dibanding Pikrotoksin

KINETIK

Absorbsi cepat Distribusi merata

Metabolisme di Hepar cepat

Ekskresi 75 di Urin dalam

keadaan Tidak Aktif

METIL FENIDAT

ACTION Efek Penglepasan Norefineprin

Simpatomimetik Berkurang

Termasuk α2 Agonis

Efek Lebih Menonjol pada Aktivitas

Mental Mirip Amfetamin

α2 AGONIS

Efek Penglepasan Norefineprin

Aktivasi Prot G(i)

Adenilsiklase

ATP cAMP 5AMP + PI

Aktivasi Kanal K+ Hiperpolarisasi

pada Neuron Mienterik Kolinergik

Pelepasan Asetilkolin

Relaksasi Otot Polos

Aktivasi Kanal Ca2+

Sekresi Insulin

Rangsangan

Simpatis dari

CNS

KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam

Distribusi di Otak Lebih Besar

Metabolisme 80 Asam Retanilat

Ekskresi Melalui Urine

DOKSAPRAM DAN NIKETAMID

ACTION

Rangsangan pada seluruh serebrospinal

Meningkatkan derajat Perangsangan

Pada dosis kecil IV Aktivitas Kemoreseptor

karotis dan Neuron Pusat Napas Tidal Volume

Perangsangan Pusat Napas

Direct acting stimulants

Increase nueronal excitability by

decreasing neuronal recovery time or by

increasing responsiveness to excitatory

neurotransmitters eg doxapram

(Dopram)

Claimed to be a specific respiratory

stimulant and to be useful in

treatment of drug induced respiratory

depression Supportive treatment is

better Sometimes used in anesthesia

Analeptics ndash Xanthines Derived

bull Pharmacological properties

ndashMechanism of action ndash act as

antagonists at adenosine receptors

Adenosine receptors are located on

presynaptic terminals of noradrenergic

neurons and blocks NE release So

caffeine increases NE release

ndashInhibition of phosphodiesterase occurs

but only at very high doses

bull Pharmacological properties

ndashCNS ndash stimulate cortex first then

medulla and spinal cord at high doses

ndashDiuresis

ndashStimulation of cardiac muscle

ndashSmooth muscle relaxation

ndashSecretion

ndashSkeletal muscle - diaphragm

bull Adverse effects

ndashAt 1 g dose of caffeine (12 cups

coffee)

bullInsomnia excitement mild

delirium sensory disturbances

bullIncreased heart rate

bullIncreased respiration

ndashAt higher doses (10 g)

bullClonic convulsions rarr death

bull Adverse effects

ndashChronic use in pregnant women

may increase rate of spontaneous

abortion

ndashTolerance and physical dependence

can occur Withdrawal symptoms

include lethargy irritability and

headache

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

Anxiolytic and

Sedative-hypnoticsGeneric Name Trade Name

Chlordiazepoxide Librium

Clonazepam Klonopin

Diazepam Valium

Flurazepam Dalmane

Lorazepam Ativan

Oxazepam Serax

Temazepam Restoril

Triazolam Halcion

Non-

Benzodiazepine

anxiolytics

and hypnotics

Buspirone BuSpar

Chloral hydrate Noctec

Zolpidem tartrate Ambien

Medication

Dose (mg)

Onset of

action

(minutes)

Half-life

(hours)

Metabolic

pathway

Duration of

hypnotic

effect

Estazolam 1-2

(elderly )

05-1 mg

15-30 8-24 Oxidation Intermediate

Flurazepam 15-30 60-120 47-100

including

metabolites

Oxidation Long

Quazepam 75-15

(elderly

75 mg)

20-45 25-41

including

metabolites

Oxidation Long

Temazepam 15-30

(elderly

75-15 mg)

45-60 10-20 Conjugation Intermediate

Triazolam 0125-025

(elderly

15-30 16-54 Oxidation Short

PHARMACOKINETICS

bull A short elimination t12 is desirable for hypnotics although this carries the drawback of increased abuse liability and severity of withdrawal after drug discontinuation

bull Most of the BZDs are metabolized in the liver to produce active products (thus long duration of action)

bull After metabolism these are conjugated and are excreted via kidney

KINETIK

Absorpsi Biasanya diberikan secara peroral

absorpsinya cepat tergantung dari lipofilisitas

obat yang berbeda (Triazolam Diazepam

Lebih Cepat)

Distribusi

Lebih mudah larut lemak lebih cepat memasuki

CNS Semua Sedatif-Hipnotik menembus

Plasenta Barrier tidak dianjurkan pada masa

kebuntingan

Kloralhidrat meningkatkan efek antikoagulan

dari Warfarin

Biotransformasi

Hampir semua Benzodiazepin mengalami

oksidasi mikrosomal (Fase I) Metabolit

Aktif yang waktu Paruhnya lebih lama

Reaksi Fase II Konjugasi oleh Glucuronosyl-

Transferase ekskresi urine Glucoronide

Ekskresi

Metabolit larut air diekskresi lewat ginjal

Penurunan fungsi hepar menurunkan proses

klirens

Classification

1 Long acting barbiturates (More than 8hours) ndash Barbitone

Barbital sodium

Phorobarbital Mephobarbital

2 Intermediate acting barbiturates (4 - 8hours) ndash Allo

barbital hexobarbital

pento hexital sodium

3 Short acting barbiturates (less than 4 hours) ndash Seco

barbital hexobarbital

Pento barbital cyclo barbital

4 Ultra short acting barbiturates ( I-V anaesthetics) ndash

Thiopental sodium

Metho hexital sodium

Mechanism of action Barbiturates either have a Gama amino butyric acid

(GABA) like action or enhance the effect of GABA aninhibitory transmitter

The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters

When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation

Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration

EFEK BARBITURAT

Pada CNS

Dicapainya semua semua tingkat depresi

sedasi ansiolitik hipnosis bbrp tingkat

anestesia koma sampai dengan kematian

Efek Hipnotik dicapai 20-60 menit

Efek Anestesi umum Tiobarbital Oksibarbital

Efek Antikonvulsi Fenobarbital Mefobarbital

Menyerupai kerja Benzodiazepin dosis lebih

tinggi Agonis GABA Depresi lebih berat

MODEL STIMULASI

BLOKADE SISTEM PENGHAMBATAN

(STRIKNIN METRAZOL)

PENINGKATAN RANGSANGAN SINAP

(DOKSAPRAM NIKETAMID XANTIN

DERIVED)

Agents which remove inhibition from CNS

neurons increase synaptic excitation

or alter axonal membrane properties

Net result is CNS stimulation

Pharmacological properties

Produces CNS excitation by blocking

glycine-mediated postsynaptic

inhibition

Sequence of strychnine effects

Tightness of neck and jaw muscles

Hyperreflexia

Tonic extensor thrusts

Tetanic symmetrical convulsions

(opisthotonus)

Respiratory arrest

STRIKNIN

ACTION Kompetitif Antagonis Terhadap Inhibitor

Transmiter GLYSIN (Penghambatan

Pasca Sinap)

Konvulsan Spinal Rangsangan pada Medula Spinalis

Rangsangan pada Medula Oblongata Efek pada

Pusat Vasomotor

Peningkatan Tekanan Darah

Peningkatan Tonus Otot

Sifat Kejang

Ekstensi Tonik Seluruh Tubuh dan Ekstremitas

Kontraksi Ekstensor Simetris yang diperkuat

Rangsangan Sensorik

( Pendengaran Penglihatan dan Perabaan)

KINETIK

Absorbsi Mudah di Tempat Injeksi

Masuk Sirkulasi Masuk Jaringan

Segera Ekskresi Lewat Urine (Ekskresi

Lengkap 10 Jam)

GEJALA KLINIS

Kaku Otot Muka dan Leher

Hiperekstensi

Kontraksi Otot Diafragma Depresi Napas

Akumulasi Asam Laktat dalam Plasma

Asidosis Metabolik

PENTILENTETRAZOL (METRAZOL)

ACTION

HAMBATAN SISTEM GABA ndash ERGIC

EKSITABILITAS SSP MENINGKAT

EXCITATORY

Efeknya Lebih Kecil Dibanding Pikrotoksin

KINETIK

Absorbsi cepat Distribusi merata

Metabolisme di Hepar cepat

Ekskresi 75 di Urin dalam

keadaan Tidak Aktif

METIL FENIDAT

ACTION Efek Penglepasan Norefineprin

Simpatomimetik Berkurang

Termasuk α2 Agonis

Efek Lebih Menonjol pada Aktivitas

Mental Mirip Amfetamin

α2 AGONIS

Efek Penglepasan Norefineprin

Aktivasi Prot G(i)

Adenilsiklase

ATP cAMP 5AMP + PI

Aktivasi Kanal K+ Hiperpolarisasi

pada Neuron Mienterik Kolinergik

Pelepasan Asetilkolin

Relaksasi Otot Polos

Aktivasi Kanal Ca2+

Sekresi Insulin

Rangsangan

Simpatis dari

CNS

KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam

Distribusi di Otak Lebih Besar

Metabolisme 80 Asam Retanilat

Ekskresi Melalui Urine

DOKSAPRAM DAN NIKETAMID

ACTION

Rangsangan pada seluruh serebrospinal

Meningkatkan derajat Perangsangan

Pada dosis kecil IV Aktivitas Kemoreseptor

karotis dan Neuron Pusat Napas Tidal Volume

Perangsangan Pusat Napas

Direct acting stimulants

Increase nueronal excitability by

decreasing neuronal recovery time or by

increasing responsiveness to excitatory

neurotransmitters eg doxapram

(Dopram)

Claimed to be a specific respiratory

stimulant and to be useful in

treatment of drug induced respiratory

depression Supportive treatment is

better Sometimes used in anesthesia

Analeptics ndash Xanthines Derived

bull Pharmacological properties

ndashMechanism of action ndash act as

antagonists at adenosine receptors

Adenosine receptors are located on

presynaptic terminals of noradrenergic

neurons and blocks NE release So

caffeine increases NE release

ndashInhibition of phosphodiesterase occurs

but only at very high doses

bull Pharmacological properties

ndashCNS ndash stimulate cortex first then

medulla and spinal cord at high doses

ndashDiuresis

ndashStimulation of cardiac muscle

ndashSmooth muscle relaxation

ndashSecretion

ndashSkeletal muscle - diaphragm

bull Adverse effects

ndashAt 1 g dose of caffeine (12 cups

coffee)

bullInsomnia excitement mild

delirium sensory disturbances

bullIncreased heart rate

bullIncreased respiration

ndashAt higher doses (10 g)

bullClonic convulsions rarr death

bull Adverse effects

ndashChronic use in pregnant women

may increase rate of spontaneous

abortion

ndashTolerance and physical dependence

can occur Withdrawal symptoms

include lethargy irritability and

headache

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

Medication

Dose (mg)

Onset of

action

(minutes)

Half-life

(hours)

Metabolic

pathway

Duration of

hypnotic

effect

Estazolam 1-2

(elderly )

05-1 mg

15-30 8-24 Oxidation Intermediate

Flurazepam 15-30 60-120 47-100

including

metabolites

Oxidation Long

Quazepam 75-15

(elderly

75 mg)

20-45 25-41

including

metabolites

Oxidation Long

Temazepam 15-30

(elderly

75-15 mg)

45-60 10-20 Conjugation Intermediate

Triazolam 0125-025

(elderly

15-30 16-54 Oxidation Short

PHARMACOKINETICS

bull A short elimination t12 is desirable for hypnotics although this carries the drawback of increased abuse liability and severity of withdrawal after drug discontinuation

bull Most of the BZDs are metabolized in the liver to produce active products (thus long duration of action)

bull After metabolism these are conjugated and are excreted via kidney

KINETIK

Absorpsi Biasanya diberikan secara peroral

absorpsinya cepat tergantung dari lipofilisitas

obat yang berbeda (Triazolam Diazepam

Lebih Cepat)

Distribusi

Lebih mudah larut lemak lebih cepat memasuki

CNS Semua Sedatif-Hipnotik menembus

Plasenta Barrier tidak dianjurkan pada masa

kebuntingan

Kloralhidrat meningkatkan efek antikoagulan

dari Warfarin

Biotransformasi

Hampir semua Benzodiazepin mengalami

oksidasi mikrosomal (Fase I) Metabolit

Aktif yang waktu Paruhnya lebih lama

Reaksi Fase II Konjugasi oleh Glucuronosyl-

Transferase ekskresi urine Glucoronide

Ekskresi

Metabolit larut air diekskresi lewat ginjal

Penurunan fungsi hepar menurunkan proses

klirens

Classification

1 Long acting barbiturates (More than 8hours) ndash Barbitone

Barbital sodium

Phorobarbital Mephobarbital

2 Intermediate acting barbiturates (4 - 8hours) ndash Allo

barbital hexobarbital

pento hexital sodium

3 Short acting barbiturates (less than 4 hours) ndash Seco

barbital hexobarbital

Pento barbital cyclo barbital

4 Ultra short acting barbiturates ( I-V anaesthetics) ndash

Thiopental sodium

Metho hexital sodium

Mechanism of action Barbiturates either have a Gama amino butyric acid

(GABA) like action or enhance the effect of GABA aninhibitory transmitter

The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters

When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation

Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration

EFEK BARBITURAT

Pada CNS

Dicapainya semua semua tingkat depresi

sedasi ansiolitik hipnosis bbrp tingkat

anestesia koma sampai dengan kematian

Efek Hipnotik dicapai 20-60 menit

Efek Anestesi umum Tiobarbital Oksibarbital

Efek Antikonvulsi Fenobarbital Mefobarbital

Menyerupai kerja Benzodiazepin dosis lebih

tinggi Agonis GABA Depresi lebih berat

MODEL STIMULASI

BLOKADE SISTEM PENGHAMBATAN

(STRIKNIN METRAZOL)

PENINGKATAN RANGSANGAN SINAP

(DOKSAPRAM NIKETAMID XANTIN

DERIVED)

Agents which remove inhibition from CNS

neurons increase synaptic excitation

or alter axonal membrane properties

Net result is CNS stimulation

Pharmacological properties

Produces CNS excitation by blocking

glycine-mediated postsynaptic

inhibition

Sequence of strychnine effects

Tightness of neck and jaw muscles

Hyperreflexia

Tonic extensor thrusts

Tetanic symmetrical convulsions

(opisthotonus)

Respiratory arrest

STRIKNIN

ACTION Kompetitif Antagonis Terhadap Inhibitor

Transmiter GLYSIN (Penghambatan

Pasca Sinap)

Konvulsan Spinal Rangsangan pada Medula Spinalis

Rangsangan pada Medula Oblongata Efek pada

Pusat Vasomotor

Peningkatan Tekanan Darah

Peningkatan Tonus Otot

Sifat Kejang

Ekstensi Tonik Seluruh Tubuh dan Ekstremitas

Kontraksi Ekstensor Simetris yang diperkuat

Rangsangan Sensorik

( Pendengaran Penglihatan dan Perabaan)

KINETIK

Absorbsi Mudah di Tempat Injeksi

Masuk Sirkulasi Masuk Jaringan

Segera Ekskresi Lewat Urine (Ekskresi

Lengkap 10 Jam)

GEJALA KLINIS

Kaku Otot Muka dan Leher

Hiperekstensi

Kontraksi Otot Diafragma Depresi Napas

Akumulasi Asam Laktat dalam Plasma

Asidosis Metabolik

PENTILENTETRAZOL (METRAZOL)

ACTION

HAMBATAN SISTEM GABA ndash ERGIC

EKSITABILITAS SSP MENINGKAT

EXCITATORY

Efeknya Lebih Kecil Dibanding Pikrotoksin

KINETIK

Absorbsi cepat Distribusi merata

Metabolisme di Hepar cepat

Ekskresi 75 di Urin dalam

keadaan Tidak Aktif

METIL FENIDAT

ACTION Efek Penglepasan Norefineprin

Simpatomimetik Berkurang

Termasuk α2 Agonis

Efek Lebih Menonjol pada Aktivitas

Mental Mirip Amfetamin

α2 AGONIS

Efek Penglepasan Norefineprin

Aktivasi Prot G(i)

Adenilsiklase

ATP cAMP 5AMP + PI

Aktivasi Kanal K+ Hiperpolarisasi

pada Neuron Mienterik Kolinergik

Pelepasan Asetilkolin

Relaksasi Otot Polos

Aktivasi Kanal Ca2+

Sekresi Insulin

Rangsangan

Simpatis dari

CNS

KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam

Distribusi di Otak Lebih Besar

Metabolisme 80 Asam Retanilat

Ekskresi Melalui Urine

DOKSAPRAM DAN NIKETAMID

ACTION

Rangsangan pada seluruh serebrospinal

Meningkatkan derajat Perangsangan

Pada dosis kecil IV Aktivitas Kemoreseptor

karotis dan Neuron Pusat Napas Tidal Volume

Perangsangan Pusat Napas

Direct acting stimulants

Increase nueronal excitability by

decreasing neuronal recovery time or by

increasing responsiveness to excitatory

neurotransmitters eg doxapram

(Dopram)

Claimed to be a specific respiratory

stimulant and to be useful in

treatment of drug induced respiratory

depression Supportive treatment is

better Sometimes used in anesthesia

Analeptics ndash Xanthines Derived

bull Pharmacological properties

ndashMechanism of action ndash act as

antagonists at adenosine receptors

Adenosine receptors are located on

presynaptic terminals of noradrenergic

neurons and blocks NE release So

caffeine increases NE release

ndashInhibition of phosphodiesterase occurs

but only at very high doses

bull Pharmacological properties

ndashCNS ndash stimulate cortex first then

medulla and spinal cord at high doses

ndashDiuresis

ndashStimulation of cardiac muscle

ndashSmooth muscle relaxation

ndashSecretion

ndashSkeletal muscle - diaphragm

bull Adverse effects

ndashAt 1 g dose of caffeine (12 cups

coffee)

bullInsomnia excitement mild

delirium sensory disturbances

bullIncreased heart rate

bullIncreased respiration

ndashAt higher doses (10 g)

bullClonic convulsions rarr death

bull Adverse effects

ndashChronic use in pregnant women

may increase rate of spontaneous

abortion

ndashTolerance and physical dependence

can occur Withdrawal symptoms

include lethargy irritability and

headache

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

PHARMACOKINETICS

bull A short elimination t12 is desirable for hypnotics although this carries the drawback of increased abuse liability and severity of withdrawal after drug discontinuation

bull Most of the BZDs are metabolized in the liver to produce active products (thus long duration of action)

bull After metabolism these are conjugated and are excreted via kidney

KINETIK

Absorpsi Biasanya diberikan secara peroral

absorpsinya cepat tergantung dari lipofilisitas

obat yang berbeda (Triazolam Diazepam

Lebih Cepat)

Distribusi

Lebih mudah larut lemak lebih cepat memasuki

CNS Semua Sedatif-Hipnotik menembus

Plasenta Barrier tidak dianjurkan pada masa

kebuntingan

Kloralhidrat meningkatkan efek antikoagulan

dari Warfarin

Biotransformasi

Hampir semua Benzodiazepin mengalami

oksidasi mikrosomal (Fase I) Metabolit

Aktif yang waktu Paruhnya lebih lama

Reaksi Fase II Konjugasi oleh Glucuronosyl-

Transferase ekskresi urine Glucoronide

Ekskresi

Metabolit larut air diekskresi lewat ginjal

Penurunan fungsi hepar menurunkan proses

klirens

Classification

1 Long acting barbiturates (More than 8hours) ndash Barbitone

Barbital sodium

Phorobarbital Mephobarbital

2 Intermediate acting barbiturates (4 - 8hours) ndash Allo

barbital hexobarbital

pento hexital sodium

3 Short acting barbiturates (less than 4 hours) ndash Seco

barbital hexobarbital

Pento barbital cyclo barbital

4 Ultra short acting barbiturates ( I-V anaesthetics) ndash

Thiopental sodium

Metho hexital sodium

Mechanism of action Barbiturates either have a Gama amino butyric acid

(GABA) like action or enhance the effect of GABA aninhibitory transmitter

The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters

When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation

Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration

EFEK BARBITURAT

Pada CNS

Dicapainya semua semua tingkat depresi

sedasi ansiolitik hipnosis bbrp tingkat

anestesia koma sampai dengan kematian

Efek Hipnotik dicapai 20-60 menit

Efek Anestesi umum Tiobarbital Oksibarbital

Efek Antikonvulsi Fenobarbital Mefobarbital

Menyerupai kerja Benzodiazepin dosis lebih

tinggi Agonis GABA Depresi lebih berat

MODEL STIMULASI

BLOKADE SISTEM PENGHAMBATAN

(STRIKNIN METRAZOL)

PENINGKATAN RANGSANGAN SINAP

(DOKSAPRAM NIKETAMID XANTIN

DERIVED)

Agents which remove inhibition from CNS

neurons increase synaptic excitation

or alter axonal membrane properties

Net result is CNS stimulation

Pharmacological properties

Produces CNS excitation by blocking

glycine-mediated postsynaptic

inhibition

Sequence of strychnine effects

Tightness of neck and jaw muscles

Hyperreflexia

Tonic extensor thrusts

Tetanic symmetrical convulsions

(opisthotonus)

Respiratory arrest

STRIKNIN

ACTION Kompetitif Antagonis Terhadap Inhibitor

Transmiter GLYSIN (Penghambatan

Pasca Sinap)

Konvulsan Spinal Rangsangan pada Medula Spinalis

Rangsangan pada Medula Oblongata Efek pada

Pusat Vasomotor

Peningkatan Tekanan Darah

Peningkatan Tonus Otot

Sifat Kejang

Ekstensi Tonik Seluruh Tubuh dan Ekstremitas

Kontraksi Ekstensor Simetris yang diperkuat

Rangsangan Sensorik

( Pendengaran Penglihatan dan Perabaan)

KINETIK

Absorbsi Mudah di Tempat Injeksi

Masuk Sirkulasi Masuk Jaringan

Segera Ekskresi Lewat Urine (Ekskresi

Lengkap 10 Jam)

GEJALA KLINIS

Kaku Otot Muka dan Leher

Hiperekstensi

Kontraksi Otot Diafragma Depresi Napas

Akumulasi Asam Laktat dalam Plasma

Asidosis Metabolik

PENTILENTETRAZOL (METRAZOL)

ACTION

HAMBATAN SISTEM GABA ndash ERGIC

EKSITABILITAS SSP MENINGKAT

EXCITATORY

Efeknya Lebih Kecil Dibanding Pikrotoksin

KINETIK

Absorbsi cepat Distribusi merata

Metabolisme di Hepar cepat

Ekskresi 75 di Urin dalam

keadaan Tidak Aktif

METIL FENIDAT

ACTION Efek Penglepasan Norefineprin

Simpatomimetik Berkurang

Termasuk α2 Agonis

Efek Lebih Menonjol pada Aktivitas

Mental Mirip Amfetamin

α2 AGONIS

Efek Penglepasan Norefineprin

Aktivasi Prot G(i)

Adenilsiklase

ATP cAMP 5AMP + PI

Aktivasi Kanal K+ Hiperpolarisasi

pada Neuron Mienterik Kolinergik

Pelepasan Asetilkolin

Relaksasi Otot Polos

Aktivasi Kanal Ca2+

Sekresi Insulin

Rangsangan

Simpatis dari

CNS

KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam

Distribusi di Otak Lebih Besar

Metabolisme 80 Asam Retanilat

Ekskresi Melalui Urine

DOKSAPRAM DAN NIKETAMID

ACTION

Rangsangan pada seluruh serebrospinal

Meningkatkan derajat Perangsangan

Pada dosis kecil IV Aktivitas Kemoreseptor

karotis dan Neuron Pusat Napas Tidal Volume

Perangsangan Pusat Napas

Direct acting stimulants

Increase nueronal excitability by

decreasing neuronal recovery time or by

increasing responsiveness to excitatory

neurotransmitters eg doxapram

(Dopram)

Claimed to be a specific respiratory

stimulant and to be useful in

treatment of drug induced respiratory

depression Supportive treatment is

better Sometimes used in anesthesia

Analeptics ndash Xanthines Derived

bull Pharmacological properties

ndashMechanism of action ndash act as

antagonists at adenosine receptors

Adenosine receptors are located on

presynaptic terminals of noradrenergic

neurons and blocks NE release So

caffeine increases NE release

ndashInhibition of phosphodiesterase occurs

but only at very high doses

bull Pharmacological properties

ndashCNS ndash stimulate cortex first then

medulla and spinal cord at high doses

ndashDiuresis

ndashStimulation of cardiac muscle

ndashSmooth muscle relaxation

ndashSecretion

ndashSkeletal muscle - diaphragm

bull Adverse effects

ndashAt 1 g dose of caffeine (12 cups

coffee)

bullInsomnia excitement mild

delirium sensory disturbances

bullIncreased heart rate

bullIncreased respiration

ndashAt higher doses (10 g)

bullClonic convulsions rarr death

bull Adverse effects

ndashChronic use in pregnant women

may increase rate of spontaneous

abortion

ndashTolerance and physical dependence

can occur Withdrawal symptoms

include lethargy irritability and

headache

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

KINETIK

Absorpsi Biasanya diberikan secara peroral

absorpsinya cepat tergantung dari lipofilisitas

obat yang berbeda (Triazolam Diazepam

Lebih Cepat)

Distribusi

Lebih mudah larut lemak lebih cepat memasuki

CNS Semua Sedatif-Hipnotik menembus

Plasenta Barrier tidak dianjurkan pada masa

kebuntingan

Kloralhidrat meningkatkan efek antikoagulan

dari Warfarin

Biotransformasi

Hampir semua Benzodiazepin mengalami

oksidasi mikrosomal (Fase I) Metabolit

Aktif yang waktu Paruhnya lebih lama

Reaksi Fase II Konjugasi oleh Glucuronosyl-

Transferase ekskresi urine Glucoronide

Ekskresi

Metabolit larut air diekskresi lewat ginjal

Penurunan fungsi hepar menurunkan proses

klirens

Classification

1 Long acting barbiturates (More than 8hours) ndash Barbitone

Barbital sodium

Phorobarbital Mephobarbital

2 Intermediate acting barbiturates (4 - 8hours) ndash Allo

barbital hexobarbital

pento hexital sodium

3 Short acting barbiturates (less than 4 hours) ndash Seco

barbital hexobarbital

Pento barbital cyclo barbital

4 Ultra short acting barbiturates ( I-V anaesthetics) ndash

Thiopental sodium

Metho hexital sodium

Mechanism of action Barbiturates either have a Gama amino butyric acid

(GABA) like action or enhance the effect of GABA aninhibitory transmitter

The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters

When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation

Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration

EFEK BARBITURAT

Pada CNS

Dicapainya semua semua tingkat depresi

sedasi ansiolitik hipnosis bbrp tingkat

anestesia koma sampai dengan kematian

Efek Hipnotik dicapai 20-60 menit

Efek Anestesi umum Tiobarbital Oksibarbital

Efek Antikonvulsi Fenobarbital Mefobarbital

Menyerupai kerja Benzodiazepin dosis lebih

tinggi Agonis GABA Depresi lebih berat

MODEL STIMULASI

BLOKADE SISTEM PENGHAMBATAN

(STRIKNIN METRAZOL)

PENINGKATAN RANGSANGAN SINAP

(DOKSAPRAM NIKETAMID XANTIN

DERIVED)

Agents which remove inhibition from CNS

neurons increase synaptic excitation

or alter axonal membrane properties

Net result is CNS stimulation

Pharmacological properties

Produces CNS excitation by blocking

glycine-mediated postsynaptic

inhibition

Sequence of strychnine effects

Tightness of neck and jaw muscles

Hyperreflexia

Tonic extensor thrusts

Tetanic symmetrical convulsions

(opisthotonus)

Respiratory arrest

STRIKNIN

ACTION Kompetitif Antagonis Terhadap Inhibitor

Transmiter GLYSIN (Penghambatan

Pasca Sinap)

Konvulsan Spinal Rangsangan pada Medula Spinalis

Rangsangan pada Medula Oblongata Efek pada

Pusat Vasomotor

Peningkatan Tekanan Darah

Peningkatan Tonus Otot

Sifat Kejang

Ekstensi Tonik Seluruh Tubuh dan Ekstremitas

Kontraksi Ekstensor Simetris yang diperkuat

Rangsangan Sensorik

( Pendengaran Penglihatan dan Perabaan)

KINETIK

Absorbsi Mudah di Tempat Injeksi

Masuk Sirkulasi Masuk Jaringan

Segera Ekskresi Lewat Urine (Ekskresi

Lengkap 10 Jam)

GEJALA KLINIS

Kaku Otot Muka dan Leher

Hiperekstensi

Kontraksi Otot Diafragma Depresi Napas

Akumulasi Asam Laktat dalam Plasma

Asidosis Metabolik

PENTILENTETRAZOL (METRAZOL)

ACTION

HAMBATAN SISTEM GABA ndash ERGIC

EKSITABILITAS SSP MENINGKAT

EXCITATORY

Efeknya Lebih Kecil Dibanding Pikrotoksin

KINETIK

Absorbsi cepat Distribusi merata

Metabolisme di Hepar cepat

Ekskresi 75 di Urin dalam

keadaan Tidak Aktif

METIL FENIDAT

ACTION Efek Penglepasan Norefineprin

Simpatomimetik Berkurang

Termasuk α2 Agonis

Efek Lebih Menonjol pada Aktivitas

Mental Mirip Amfetamin

α2 AGONIS

Efek Penglepasan Norefineprin

Aktivasi Prot G(i)

Adenilsiklase

ATP cAMP 5AMP + PI

Aktivasi Kanal K+ Hiperpolarisasi

pada Neuron Mienterik Kolinergik

Pelepasan Asetilkolin

Relaksasi Otot Polos

Aktivasi Kanal Ca2+

Sekresi Insulin

Rangsangan

Simpatis dari

CNS

KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam

Distribusi di Otak Lebih Besar

Metabolisme 80 Asam Retanilat

Ekskresi Melalui Urine

DOKSAPRAM DAN NIKETAMID

ACTION

Rangsangan pada seluruh serebrospinal

Meningkatkan derajat Perangsangan

Pada dosis kecil IV Aktivitas Kemoreseptor

karotis dan Neuron Pusat Napas Tidal Volume

Perangsangan Pusat Napas

Direct acting stimulants

Increase nueronal excitability by

decreasing neuronal recovery time or by

increasing responsiveness to excitatory

neurotransmitters eg doxapram

(Dopram)

Claimed to be a specific respiratory

stimulant and to be useful in

treatment of drug induced respiratory

depression Supportive treatment is

better Sometimes used in anesthesia

Analeptics ndash Xanthines Derived

bull Pharmacological properties

ndashMechanism of action ndash act as

antagonists at adenosine receptors

Adenosine receptors are located on

presynaptic terminals of noradrenergic

neurons and blocks NE release So

caffeine increases NE release

ndashInhibition of phosphodiesterase occurs

but only at very high doses

bull Pharmacological properties

ndashCNS ndash stimulate cortex first then

medulla and spinal cord at high doses

ndashDiuresis

ndashStimulation of cardiac muscle

ndashSmooth muscle relaxation

ndashSecretion

ndashSkeletal muscle - diaphragm

bull Adverse effects

ndashAt 1 g dose of caffeine (12 cups

coffee)

bullInsomnia excitement mild

delirium sensory disturbances

bullIncreased heart rate

bullIncreased respiration

ndashAt higher doses (10 g)

bullClonic convulsions rarr death

bull Adverse effects

ndashChronic use in pregnant women

may increase rate of spontaneous

abortion

ndashTolerance and physical dependence

can occur Withdrawal symptoms

include lethargy irritability and

headache

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

Biotransformasi

Hampir semua Benzodiazepin mengalami

oksidasi mikrosomal (Fase I) Metabolit

Aktif yang waktu Paruhnya lebih lama

Reaksi Fase II Konjugasi oleh Glucuronosyl-

Transferase ekskresi urine Glucoronide

Ekskresi

Metabolit larut air diekskresi lewat ginjal

Penurunan fungsi hepar menurunkan proses

klirens

Classification

1 Long acting barbiturates (More than 8hours) ndash Barbitone

Barbital sodium

Phorobarbital Mephobarbital

2 Intermediate acting barbiturates (4 - 8hours) ndash Allo

barbital hexobarbital

pento hexital sodium

3 Short acting barbiturates (less than 4 hours) ndash Seco

barbital hexobarbital

Pento barbital cyclo barbital

4 Ultra short acting barbiturates ( I-V anaesthetics) ndash

Thiopental sodium

Metho hexital sodium

Mechanism of action Barbiturates either have a Gama amino butyric acid

(GABA) like action or enhance the effect of GABA aninhibitory transmitter

The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters

When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation

Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration

EFEK BARBITURAT

Pada CNS

Dicapainya semua semua tingkat depresi

sedasi ansiolitik hipnosis bbrp tingkat

anestesia koma sampai dengan kematian

Efek Hipnotik dicapai 20-60 menit

Efek Anestesi umum Tiobarbital Oksibarbital

Efek Antikonvulsi Fenobarbital Mefobarbital

Menyerupai kerja Benzodiazepin dosis lebih

tinggi Agonis GABA Depresi lebih berat

MODEL STIMULASI

BLOKADE SISTEM PENGHAMBATAN

(STRIKNIN METRAZOL)

PENINGKATAN RANGSANGAN SINAP

(DOKSAPRAM NIKETAMID XANTIN

DERIVED)

Agents which remove inhibition from CNS

neurons increase synaptic excitation

or alter axonal membrane properties

Net result is CNS stimulation

Pharmacological properties

Produces CNS excitation by blocking

glycine-mediated postsynaptic

inhibition

Sequence of strychnine effects

Tightness of neck and jaw muscles

Hyperreflexia

Tonic extensor thrusts

Tetanic symmetrical convulsions

(opisthotonus)

Respiratory arrest

STRIKNIN

ACTION Kompetitif Antagonis Terhadap Inhibitor

Transmiter GLYSIN (Penghambatan

Pasca Sinap)

Konvulsan Spinal Rangsangan pada Medula Spinalis

Rangsangan pada Medula Oblongata Efek pada

Pusat Vasomotor

Peningkatan Tekanan Darah

Peningkatan Tonus Otot

Sifat Kejang

Ekstensi Tonik Seluruh Tubuh dan Ekstremitas

Kontraksi Ekstensor Simetris yang diperkuat

Rangsangan Sensorik

( Pendengaran Penglihatan dan Perabaan)

KINETIK

Absorbsi Mudah di Tempat Injeksi

Masuk Sirkulasi Masuk Jaringan

Segera Ekskresi Lewat Urine (Ekskresi

Lengkap 10 Jam)

GEJALA KLINIS

Kaku Otot Muka dan Leher

Hiperekstensi

Kontraksi Otot Diafragma Depresi Napas

Akumulasi Asam Laktat dalam Plasma

Asidosis Metabolik

PENTILENTETRAZOL (METRAZOL)

ACTION

HAMBATAN SISTEM GABA ndash ERGIC

EKSITABILITAS SSP MENINGKAT

EXCITATORY

Efeknya Lebih Kecil Dibanding Pikrotoksin

KINETIK

Absorbsi cepat Distribusi merata

Metabolisme di Hepar cepat

Ekskresi 75 di Urin dalam

keadaan Tidak Aktif

METIL FENIDAT

ACTION Efek Penglepasan Norefineprin

Simpatomimetik Berkurang

Termasuk α2 Agonis

Efek Lebih Menonjol pada Aktivitas

Mental Mirip Amfetamin

α2 AGONIS

Efek Penglepasan Norefineprin

Aktivasi Prot G(i)

Adenilsiklase

ATP cAMP 5AMP + PI

Aktivasi Kanal K+ Hiperpolarisasi

pada Neuron Mienterik Kolinergik

Pelepasan Asetilkolin

Relaksasi Otot Polos

Aktivasi Kanal Ca2+

Sekresi Insulin

Rangsangan

Simpatis dari

CNS

KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam

Distribusi di Otak Lebih Besar

Metabolisme 80 Asam Retanilat

Ekskresi Melalui Urine

DOKSAPRAM DAN NIKETAMID

ACTION

Rangsangan pada seluruh serebrospinal

Meningkatkan derajat Perangsangan

Pada dosis kecil IV Aktivitas Kemoreseptor

karotis dan Neuron Pusat Napas Tidal Volume

Perangsangan Pusat Napas

Direct acting stimulants

Increase nueronal excitability by

decreasing neuronal recovery time or by

increasing responsiveness to excitatory

neurotransmitters eg doxapram

(Dopram)

Claimed to be a specific respiratory

stimulant and to be useful in

treatment of drug induced respiratory

depression Supportive treatment is

better Sometimes used in anesthesia

Analeptics ndash Xanthines Derived

bull Pharmacological properties

ndashMechanism of action ndash act as

antagonists at adenosine receptors

Adenosine receptors are located on

presynaptic terminals of noradrenergic

neurons and blocks NE release So

caffeine increases NE release

ndashInhibition of phosphodiesterase occurs

but only at very high doses

bull Pharmacological properties

ndashCNS ndash stimulate cortex first then

medulla and spinal cord at high doses

ndashDiuresis

ndashStimulation of cardiac muscle

ndashSmooth muscle relaxation

ndashSecretion

ndashSkeletal muscle - diaphragm

bull Adverse effects

ndashAt 1 g dose of caffeine (12 cups

coffee)

bullInsomnia excitement mild

delirium sensory disturbances

bullIncreased heart rate

bullIncreased respiration

ndashAt higher doses (10 g)

bullClonic convulsions rarr death

bull Adverse effects

ndashChronic use in pregnant women

may increase rate of spontaneous

abortion

ndashTolerance and physical dependence

can occur Withdrawal symptoms

include lethargy irritability and

headache

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

Classification

1 Long acting barbiturates (More than 8hours) ndash Barbitone

Barbital sodium

Phorobarbital Mephobarbital

2 Intermediate acting barbiturates (4 - 8hours) ndash Allo

barbital hexobarbital

pento hexital sodium

3 Short acting barbiturates (less than 4 hours) ndash Seco

barbital hexobarbital

Pento barbital cyclo barbital

4 Ultra short acting barbiturates ( I-V anaesthetics) ndash

Thiopental sodium

Metho hexital sodium

Mechanism of action Barbiturates either have a Gama amino butyric acid

(GABA) like action or enhance the effect of GABA aninhibitory transmitter

The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters

When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation

Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration

EFEK BARBITURAT

Pada CNS

Dicapainya semua semua tingkat depresi

sedasi ansiolitik hipnosis bbrp tingkat

anestesia koma sampai dengan kematian

Efek Hipnotik dicapai 20-60 menit

Efek Anestesi umum Tiobarbital Oksibarbital

Efek Antikonvulsi Fenobarbital Mefobarbital

Menyerupai kerja Benzodiazepin dosis lebih

tinggi Agonis GABA Depresi lebih berat

MODEL STIMULASI

BLOKADE SISTEM PENGHAMBATAN

(STRIKNIN METRAZOL)

PENINGKATAN RANGSANGAN SINAP

(DOKSAPRAM NIKETAMID XANTIN

DERIVED)

Agents which remove inhibition from CNS

neurons increase synaptic excitation

or alter axonal membrane properties

Net result is CNS stimulation

Pharmacological properties

Produces CNS excitation by blocking

glycine-mediated postsynaptic

inhibition

Sequence of strychnine effects

Tightness of neck and jaw muscles

Hyperreflexia

Tonic extensor thrusts

Tetanic symmetrical convulsions

(opisthotonus)

Respiratory arrest

STRIKNIN

ACTION Kompetitif Antagonis Terhadap Inhibitor

Transmiter GLYSIN (Penghambatan

Pasca Sinap)

Konvulsan Spinal Rangsangan pada Medula Spinalis

Rangsangan pada Medula Oblongata Efek pada

Pusat Vasomotor

Peningkatan Tekanan Darah

Peningkatan Tonus Otot

Sifat Kejang

Ekstensi Tonik Seluruh Tubuh dan Ekstremitas

Kontraksi Ekstensor Simetris yang diperkuat

Rangsangan Sensorik

( Pendengaran Penglihatan dan Perabaan)

KINETIK

Absorbsi Mudah di Tempat Injeksi

Masuk Sirkulasi Masuk Jaringan

Segera Ekskresi Lewat Urine (Ekskresi

Lengkap 10 Jam)

GEJALA KLINIS

Kaku Otot Muka dan Leher

Hiperekstensi

Kontraksi Otot Diafragma Depresi Napas

Akumulasi Asam Laktat dalam Plasma

Asidosis Metabolik

PENTILENTETRAZOL (METRAZOL)

ACTION

HAMBATAN SISTEM GABA ndash ERGIC

EKSITABILITAS SSP MENINGKAT

EXCITATORY

Efeknya Lebih Kecil Dibanding Pikrotoksin

KINETIK

Absorbsi cepat Distribusi merata

Metabolisme di Hepar cepat

Ekskresi 75 di Urin dalam

keadaan Tidak Aktif

METIL FENIDAT

ACTION Efek Penglepasan Norefineprin

Simpatomimetik Berkurang

Termasuk α2 Agonis

Efek Lebih Menonjol pada Aktivitas

Mental Mirip Amfetamin

α2 AGONIS

Efek Penglepasan Norefineprin

Aktivasi Prot G(i)

Adenilsiklase

ATP cAMP 5AMP + PI

Aktivasi Kanal K+ Hiperpolarisasi

pada Neuron Mienterik Kolinergik

Pelepasan Asetilkolin

Relaksasi Otot Polos

Aktivasi Kanal Ca2+

Sekresi Insulin

Rangsangan

Simpatis dari

CNS

KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam

Distribusi di Otak Lebih Besar

Metabolisme 80 Asam Retanilat

Ekskresi Melalui Urine

DOKSAPRAM DAN NIKETAMID

ACTION

Rangsangan pada seluruh serebrospinal

Meningkatkan derajat Perangsangan

Pada dosis kecil IV Aktivitas Kemoreseptor

karotis dan Neuron Pusat Napas Tidal Volume

Perangsangan Pusat Napas

Direct acting stimulants

Increase nueronal excitability by

decreasing neuronal recovery time or by

increasing responsiveness to excitatory

neurotransmitters eg doxapram

(Dopram)

Claimed to be a specific respiratory

stimulant and to be useful in

treatment of drug induced respiratory

depression Supportive treatment is

better Sometimes used in anesthesia

Analeptics ndash Xanthines Derived

bull Pharmacological properties

ndashMechanism of action ndash act as

antagonists at adenosine receptors

Adenosine receptors are located on

presynaptic terminals of noradrenergic

neurons and blocks NE release So

caffeine increases NE release

ndashInhibition of phosphodiesterase occurs

but only at very high doses

bull Pharmacological properties

ndashCNS ndash stimulate cortex first then

medulla and spinal cord at high doses

ndashDiuresis

ndashStimulation of cardiac muscle

ndashSmooth muscle relaxation

ndashSecretion

ndashSkeletal muscle - diaphragm

bull Adverse effects

ndashAt 1 g dose of caffeine (12 cups

coffee)

bullInsomnia excitement mild

delirium sensory disturbances

bullIncreased heart rate

bullIncreased respiration

ndashAt higher doses (10 g)

bullClonic convulsions rarr death

bull Adverse effects

ndashChronic use in pregnant women

may increase rate of spontaneous

abortion

ndashTolerance and physical dependence

can occur Withdrawal symptoms

include lethargy irritability and

headache

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

Mechanism of action Barbiturates either have a Gama amino butyric acid

(GABA) like action or enhance the effect of GABA aninhibitory transmitter

The effects of barbiturates on synaptic transmissionare caused by an alteration of post synaptic sensitivityof the neurons to excitatory and inhibitorytransmitters

When GABA receptors are activated chloridechannels are open and chloride enters the cell hyperpolarizes it and produces decreased excitation

Barbiturates bind to picrotoxin site of GABAreceptor and decrease chloride ion flux and producean increased chloride ion concentration

EFEK BARBITURAT

Pada CNS

Dicapainya semua semua tingkat depresi

sedasi ansiolitik hipnosis bbrp tingkat

anestesia koma sampai dengan kematian

Efek Hipnotik dicapai 20-60 menit

Efek Anestesi umum Tiobarbital Oksibarbital

Efek Antikonvulsi Fenobarbital Mefobarbital

Menyerupai kerja Benzodiazepin dosis lebih

tinggi Agonis GABA Depresi lebih berat

MODEL STIMULASI

BLOKADE SISTEM PENGHAMBATAN

(STRIKNIN METRAZOL)

PENINGKATAN RANGSANGAN SINAP

(DOKSAPRAM NIKETAMID XANTIN

DERIVED)

Agents which remove inhibition from CNS

neurons increase synaptic excitation

or alter axonal membrane properties

Net result is CNS stimulation

Pharmacological properties

Produces CNS excitation by blocking

glycine-mediated postsynaptic

inhibition

Sequence of strychnine effects

Tightness of neck and jaw muscles

Hyperreflexia

Tonic extensor thrusts

Tetanic symmetrical convulsions

(opisthotonus)

Respiratory arrest

STRIKNIN

ACTION Kompetitif Antagonis Terhadap Inhibitor

Transmiter GLYSIN (Penghambatan

Pasca Sinap)

Konvulsan Spinal Rangsangan pada Medula Spinalis

Rangsangan pada Medula Oblongata Efek pada

Pusat Vasomotor

Peningkatan Tekanan Darah

Peningkatan Tonus Otot

Sifat Kejang

Ekstensi Tonik Seluruh Tubuh dan Ekstremitas

Kontraksi Ekstensor Simetris yang diperkuat

Rangsangan Sensorik

( Pendengaran Penglihatan dan Perabaan)

KINETIK

Absorbsi Mudah di Tempat Injeksi

Masuk Sirkulasi Masuk Jaringan

Segera Ekskresi Lewat Urine (Ekskresi

Lengkap 10 Jam)

GEJALA KLINIS

Kaku Otot Muka dan Leher

Hiperekstensi

Kontraksi Otot Diafragma Depresi Napas

Akumulasi Asam Laktat dalam Plasma

Asidosis Metabolik

PENTILENTETRAZOL (METRAZOL)

ACTION

HAMBATAN SISTEM GABA ndash ERGIC

EKSITABILITAS SSP MENINGKAT

EXCITATORY

Efeknya Lebih Kecil Dibanding Pikrotoksin

KINETIK

Absorbsi cepat Distribusi merata

Metabolisme di Hepar cepat

Ekskresi 75 di Urin dalam

keadaan Tidak Aktif

METIL FENIDAT

ACTION Efek Penglepasan Norefineprin

Simpatomimetik Berkurang

Termasuk α2 Agonis

Efek Lebih Menonjol pada Aktivitas

Mental Mirip Amfetamin

α2 AGONIS

Efek Penglepasan Norefineprin

Aktivasi Prot G(i)

Adenilsiklase

ATP cAMP 5AMP + PI

Aktivasi Kanal K+ Hiperpolarisasi

pada Neuron Mienterik Kolinergik

Pelepasan Asetilkolin

Relaksasi Otot Polos

Aktivasi Kanal Ca2+

Sekresi Insulin

Rangsangan

Simpatis dari

CNS

KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam

Distribusi di Otak Lebih Besar

Metabolisme 80 Asam Retanilat

Ekskresi Melalui Urine

DOKSAPRAM DAN NIKETAMID

ACTION

Rangsangan pada seluruh serebrospinal

Meningkatkan derajat Perangsangan

Pada dosis kecil IV Aktivitas Kemoreseptor

karotis dan Neuron Pusat Napas Tidal Volume

Perangsangan Pusat Napas

Direct acting stimulants

Increase nueronal excitability by

decreasing neuronal recovery time or by

increasing responsiveness to excitatory

neurotransmitters eg doxapram

(Dopram)

Claimed to be a specific respiratory

stimulant and to be useful in

treatment of drug induced respiratory

depression Supportive treatment is

better Sometimes used in anesthesia

Analeptics ndash Xanthines Derived

bull Pharmacological properties

ndashMechanism of action ndash act as

antagonists at adenosine receptors

Adenosine receptors are located on

presynaptic terminals of noradrenergic

neurons and blocks NE release So

caffeine increases NE release

ndashInhibition of phosphodiesterase occurs

but only at very high doses

bull Pharmacological properties

ndashCNS ndash stimulate cortex first then

medulla and spinal cord at high doses

ndashDiuresis

ndashStimulation of cardiac muscle

ndashSmooth muscle relaxation

ndashSecretion

ndashSkeletal muscle - diaphragm

bull Adverse effects

ndashAt 1 g dose of caffeine (12 cups

coffee)

bullInsomnia excitement mild

delirium sensory disturbances

bullIncreased heart rate

bullIncreased respiration

ndashAt higher doses (10 g)

bullClonic convulsions rarr death

bull Adverse effects

ndashChronic use in pregnant women

may increase rate of spontaneous

abortion

ndashTolerance and physical dependence

can occur Withdrawal symptoms

include lethargy irritability and

headache

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

EFEK BARBITURAT

Pada CNS

Dicapainya semua semua tingkat depresi

sedasi ansiolitik hipnosis bbrp tingkat

anestesia koma sampai dengan kematian

Efek Hipnotik dicapai 20-60 menit

Efek Anestesi umum Tiobarbital Oksibarbital

Efek Antikonvulsi Fenobarbital Mefobarbital

Menyerupai kerja Benzodiazepin dosis lebih

tinggi Agonis GABA Depresi lebih berat

MODEL STIMULASI

BLOKADE SISTEM PENGHAMBATAN

(STRIKNIN METRAZOL)

PENINGKATAN RANGSANGAN SINAP

(DOKSAPRAM NIKETAMID XANTIN

DERIVED)

Agents which remove inhibition from CNS

neurons increase synaptic excitation

or alter axonal membrane properties

Net result is CNS stimulation

Pharmacological properties

Produces CNS excitation by blocking

glycine-mediated postsynaptic

inhibition

Sequence of strychnine effects

Tightness of neck and jaw muscles

Hyperreflexia

Tonic extensor thrusts

Tetanic symmetrical convulsions

(opisthotonus)

Respiratory arrest

STRIKNIN

ACTION Kompetitif Antagonis Terhadap Inhibitor

Transmiter GLYSIN (Penghambatan

Pasca Sinap)

Konvulsan Spinal Rangsangan pada Medula Spinalis

Rangsangan pada Medula Oblongata Efek pada

Pusat Vasomotor

Peningkatan Tekanan Darah

Peningkatan Tonus Otot

Sifat Kejang

Ekstensi Tonik Seluruh Tubuh dan Ekstremitas

Kontraksi Ekstensor Simetris yang diperkuat

Rangsangan Sensorik

( Pendengaran Penglihatan dan Perabaan)

KINETIK

Absorbsi Mudah di Tempat Injeksi

Masuk Sirkulasi Masuk Jaringan

Segera Ekskresi Lewat Urine (Ekskresi

Lengkap 10 Jam)

GEJALA KLINIS

Kaku Otot Muka dan Leher

Hiperekstensi

Kontraksi Otot Diafragma Depresi Napas

Akumulasi Asam Laktat dalam Plasma

Asidosis Metabolik

PENTILENTETRAZOL (METRAZOL)

ACTION

HAMBATAN SISTEM GABA ndash ERGIC

EKSITABILITAS SSP MENINGKAT

EXCITATORY

Efeknya Lebih Kecil Dibanding Pikrotoksin

KINETIK

Absorbsi cepat Distribusi merata

Metabolisme di Hepar cepat

Ekskresi 75 di Urin dalam

keadaan Tidak Aktif

METIL FENIDAT

ACTION Efek Penglepasan Norefineprin

Simpatomimetik Berkurang

Termasuk α2 Agonis

Efek Lebih Menonjol pada Aktivitas

Mental Mirip Amfetamin

α2 AGONIS

Efek Penglepasan Norefineprin

Aktivasi Prot G(i)

Adenilsiklase

ATP cAMP 5AMP + PI

Aktivasi Kanal K+ Hiperpolarisasi

pada Neuron Mienterik Kolinergik

Pelepasan Asetilkolin

Relaksasi Otot Polos

Aktivasi Kanal Ca2+

Sekresi Insulin

Rangsangan

Simpatis dari

CNS

KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam

Distribusi di Otak Lebih Besar

Metabolisme 80 Asam Retanilat

Ekskresi Melalui Urine

DOKSAPRAM DAN NIKETAMID

ACTION

Rangsangan pada seluruh serebrospinal

Meningkatkan derajat Perangsangan

Pada dosis kecil IV Aktivitas Kemoreseptor

karotis dan Neuron Pusat Napas Tidal Volume

Perangsangan Pusat Napas

Direct acting stimulants

Increase nueronal excitability by

decreasing neuronal recovery time or by

increasing responsiveness to excitatory

neurotransmitters eg doxapram

(Dopram)

Claimed to be a specific respiratory

stimulant and to be useful in

treatment of drug induced respiratory

depression Supportive treatment is

better Sometimes used in anesthesia

Analeptics ndash Xanthines Derived

bull Pharmacological properties

ndashMechanism of action ndash act as

antagonists at adenosine receptors

Adenosine receptors are located on

presynaptic terminals of noradrenergic

neurons and blocks NE release So

caffeine increases NE release

ndashInhibition of phosphodiesterase occurs

but only at very high doses

bull Pharmacological properties

ndashCNS ndash stimulate cortex first then

medulla and spinal cord at high doses

ndashDiuresis

ndashStimulation of cardiac muscle

ndashSmooth muscle relaxation

ndashSecretion

ndashSkeletal muscle - diaphragm

bull Adverse effects

ndashAt 1 g dose of caffeine (12 cups

coffee)

bullInsomnia excitement mild

delirium sensory disturbances

bullIncreased heart rate

bullIncreased respiration

ndashAt higher doses (10 g)

bullClonic convulsions rarr death

bull Adverse effects

ndashChronic use in pregnant women

may increase rate of spontaneous

abortion

ndashTolerance and physical dependence

can occur Withdrawal symptoms

include lethargy irritability and

headache

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

MODEL STIMULASI

BLOKADE SISTEM PENGHAMBATAN

(STRIKNIN METRAZOL)

PENINGKATAN RANGSANGAN SINAP

(DOKSAPRAM NIKETAMID XANTIN

DERIVED)

Agents which remove inhibition from CNS

neurons increase synaptic excitation

or alter axonal membrane properties

Net result is CNS stimulation

Pharmacological properties

Produces CNS excitation by blocking

glycine-mediated postsynaptic

inhibition

Sequence of strychnine effects

Tightness of neck and jaw muscles

Hyperreflexia

Tonic extensor thrusts

Tetanic symmetrical convulsions

(opisthotonus)

Respiratory arrest

STRIKNIN

ACTION Kompetitif Antagonis Terhadap Inhibitor

Transmiter GLYSIN (Penghambatan

Pasca Sinap)

Konvulsan Spinal Rangsangan pada Medula Spinalis

Rangsangan pada Medula Oblongata Efek pada

Pusat Vasomotor

Peningkatan Tekanan Darah

Peningkatan Tonus Otot

Sifat Kejang

Ekstensi Tonik Seluruh Tubuh dan Ekstremitas

Kontraksi Ekstensor Simetris yang diperkuat

Rangsangan Sensorik

( Pendengaran Penglihatan dan Perabaan)

KINETIK

Absorbsi Mudah di Tempat Injeksi

Masuk Sirkulasi Masuk Jaringan

Segera Ekskresi Lewat Urine (Ekskresi

Lengkap 10 Jam)

GEJALA KLINIS

Kaku Otot Muka dan Leher

Hiperekstensi

Kontraksi Otot Diafragma Depresi Napas

Akumulasi Asam Laktat dalam Plasma

Asidosis Metabolik

PENTILENTETRAZOL (METRAZOL)

ACTION

HAMBATAN SISTEM GABA ndash ERGIC

EKSITABILITAS SSP MENINGKAT

EXCITATORY

Efeknya Lebih Kecil Dibanding Pikrotoksin

KINETIK

Absorbsi cepat Distribusi merata

Metabolisme di Hepar cepat

Ekskresi 75 di Urin dalam

keadaan Tidak Aktif

METIL FENIDAT

ACTION Efek Penglepasan Norefineprin

Simpatomimetik Berkurang

Termasuk α2 Agonis

Efek Lebih Menonjol pada Aktivitas

Mental Mirip Amfetamin

α2 AGONIS

Efek Penglepasan Norefineprin

Aktivasi Prot G(i)

Adenilsiklase

ATP cAMP 5AMP + PI

Aktivasi Kanal K+ Hiperpolarisasi

pada Neuron Mienterik Kolinergik

Pelepasan Asetilkolin

Relaksasi Otot Polos

Aktivasi Kanal Ca2+

Sekresi Insulin

Rangsangan

Simpatis dari

CNS

KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam

Distribusi di Otak Lebih Besar

Metabolisme 80 Asam Retanilat

Ekskresi Melalui Urine

DOKSAPRAM DAN NIKETAMID

ACTION

Rangsangan pada seluruh serebrospinal

Meningkatkan derajat Perangsangan

Pada dosis kecil IV Aktivitas Kemoreseptor

karotis dan Neuron Pusat Napas Tidal Volume

Perangsangan Pusat Napas

Direct acting stimulants

Increase nueronal excitability by

decreasing neuronal recovery time or by

increasing responsiveness to excitatory

neurotransmitters eg doxapram

(Dopram)

Claimed to be a specific respiratory

stimulant and to be useful in

treatment of drug induced respiratory

depression Supportive treatment is

better Sometimes used in anesthesia

Analeptics ndash Xanthines Derived

bull Pharmacological properties

ndashMechanism of action ndash act as

antagonists at adenosine receptors

Adenosine receptors are located on

presynaptic terminals of noradrenergic

neurons and blocks NE release So

caffeine increases NE release

ndashInhibition of phosphodiesterase occurs

but only at very high doses

bull Pharmacological properties

ndashCNS ndash stimulate cortex first then

medulla and spinal cord at high doses

ndashDiuresis

ndashStimulation of cardiac muscle

ndashSmooth muscle relaxation

ndashSecretion

ndashSkeletal muscle - diaphragm

bull Adverse effects

ndashAt 1 g dose of caffeine (12 cups

coffee)

bullInsomnia excitement mild

delirium sensory disturbances

bullIncreased heart rate

bullIncreased respiration

ndashAt higher doses (10 g)

bullClonic convulsions rarr death

bull Adverse effects

ndashChronic use in pregnant women

may increase rate of spontaneous

abortion

ndashTolerance and physical dependence

can occur Withdrawal symptoms

include lethargy irritability and

headache

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

Pharmacological properties

Produces CNS excitation by blocking

glycine-mediated postsynaptic

inhibition

Sequence of strychnine effects

Tightness of neck and jaw muscles

Hyperreflexia

Tonic extensor thrusts

Tetanic symmetrical convulsions

(opisthotonus)

Respiratory arrest

STRIKNIN

ACTION Kompetitif Antagonis Terhadap Inhibitor

Transmiter GLYSIN (Penghambatan

Pasca Sinap)

Konvulsan Spinal Rangsangan pada Medula Spinalis

Rangsangan pada Medula Oblongata Efek pada

Pusat Vasomotor

Peningkatan Tekanan Darah

Peningkatan Tonus Otot

Sifat Kejang

Ekstensi Tonik Seluruh Tubuh dan Ekstremitas

Kontraksi Ekstensor Simetris yang diperkuat

Rangsangan Sensorik

( Pendengaran Penglihatan dan Perabaan)

KINETIK

Absorbsi Mudah di Tempat Injeksi

Masuk Sirkulasi Masuk Jaringan

Segera Ekskresi Lewat Urine (Ekskresi

Lengkap 10 Jam)

GEJALA KLINIS

Kaku Otot Muka dan Leher

Hiperekstensi

Kontraksi Otot Diafragma Depresi Napas

Akumulasi Asam Laktat dalam Plasma

Asidosis Metabolik

PENTILENTETRAZOL (METRAZOL)

ACTION

HAMBATAN SISTEM GABA ndash ERGIC

EKSITABILITAS SSP MENINGKAT

EXCITATORY

Efeknya Lebih Kecil Dibanding Pikrotoksin

KINETIK

Absorbsi cepat Distribusi merata

Metabolisme di Hepar cepat

Ekskresi 75 di Urin dalam

keadaan Tidak Aktif

METIL FENIDAT

ACTION Efek Penglepasan Norefineprin

Simpatomimetik Berkurang

Termasuk α2 Agonis

Efek Lebih Menonjol pada Aktivitas

Mental Mirip Amfetamin

α2 AGONIS

Efek Penglepasan Norefineprin

Aktivasi Prot G(i)

Adenilsiklase

ATP cAMP 5AMP + PI

Aktivasi Kanal K+ Hiperpolarisasi

pada Neuron Mienterik Kolinergik

Pelepasan Asetilkolin

Relaksasi Otot Polos

Aktivasi Kanal Ca2+

Sekresi Insulin

Rangsangan

Simpatis dari

CNS

KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam

Distribusi di Otak Lebih Besar

Metabolisme 80 Asam Retanilat

Ekskresi Melalui Urine

DOKSAPRAM DAN NIKETAMID

ACTION

Rangsangan pada seluruh serebrospinal

Meningkatkan derajat Perangsangan

Pada dosis kecil IV Aktivitas Kemoreseptor

karotis dan Neuron Pusat Napas Tidal Volume

Perangsangan Pusat Napas

Direct acting stimulants

Increase nueronal excitability by

decreasing neuronal recovery time or by

increasing responsiveness to excitatory

neurotransmitters eg doxapram

(Dopram)

Claimed to be a specific respiratory

stimulant and to be useful in

treatment of drug induced respiratory

depression Supportive treatment is

better Sometimes used in anesthesia

Analeptics ndash Xanthines Derived

bull Pharmacological properties

ndashMechanism of action ndash act as

antagonists at adenosine receptors

Adenosine receptors are located on

presynaptic terminals of noradrenergic

neurons and blocks NE release So

caffeine increases NE release

ndashInhibition of phosphodiesterase occurs

but only at very high doses

bull Pharmacological properties

ndashCNS ndash stimulate cortex first then

medulla and spinal cord at high doses

ndashDiuresis

ndashStimulation of cardiac muscle

ndashSmooth muscle relaxation

ndashSecretion

ndashSkeletal muscle - diaphragm

bull Adverse effects

ndashAt 1 g dose of caffeine (12 cups

coffee)

bullInsomnia excitement mild

delirium sensory disturbances

bullIncreased heart rate

bullIncreased respiration

ndashAt higher doses (10 g)

bullClonic convulsions rarr death

bull Adverse effects

ndashChronic use in pregnant women

may increase rate of spontaneous

abortion

ndashTolerance and physical dependence

can occur Withdrawal symptoms

include lethargy irritability and

headache

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

STRIKNIN

ACTION Kompetitif Antagonis Terhadap Inhibitor

Transmiter GLYSIN (Penghambatan

Pasca Sinap)

Konvulsan Spinal Rangsangan pada Medula Spinalis

Rangsangan pada Medula Oblongata Efek pada

Pusat Vasomotor

Peningkatan Tekanan Darah

Peningkatan Tonus Otot

Sifat Kejang

Ekstensi Tonik Seluruh Tubuh dan Ekstremitas

Kontraksi Ekstensor Simetris yang diperkuat

Rangsangan Sensorik

( Pendengaran Penglihatan dan Perabaan)

KINETIK

Absorbsi Mudah di Tempat Injeksi

Masuk Sirkulasi Masuk Jaringan

Segera Ekskresi Lewat Urine (Ekskresi

Lengkap 10 Jam)

GEJALA KLINIS

Kaku Otot Muka dan Leher

Hiperekstensi

Kontraksi Otot Diafragma Depresi Napas

Akumulasi Asam Laktat dalam Plasma

Asidosis Metabolik

PENTILENTETRAZOL (METRAZOL)

ACTION

HAMBATAN SISTEM GABA ndash ERGIC

EKSITABILITAS SSP MENINGKAT

EXCITATORY

Efeknya Lebih Kecil Dibanding Pikrotoksin

KINETIK

Absorbsi cepat Distribusi merata

Metabolisme di Hepar cepat

Ekskresi 75 di Urin dalam

keadaan Tidak Aktif

METIL FENIDAT

ACTION Efek Penglepasan Norefineprin

Simpatomimetik Berkurang

Termasuk α2 Agonis

Efek Lebih Menonjol pada Aktivitas

Mental Mirip Amfetamin

α2 AGONIS

Efek Penglepasan Norefineprin

Aktivasi Prot G(i)

Adenilsiklase

ATP cAMP 5AMP + PI

Aktivasi Kanal K+ Hiperpolarisasi

pada Neuron Mienterik Kolinergik

Pelepasan Asetilkolin

Relaksasi Otot Polos

Aktivasi Kanal Ca2+

Sekresi Insulin

Rangsangan

Simpatis dari

CNS

KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam

Distribusi di Otak Lebih Besar

Metabolisme 80 Asam Retanilat

Ekskresi Melalui Urine

DOKSAPRAM DAN NIKETAMID

ACTION

Rangsangan pada seluruh serebrospinal

Meningkatkan derajat Perangsangan

Pada dosis kecil IV Aktivitas Kemoreseptor

karotis dan Neuron Pusat Napas Tidal Volume

Perangsangan Pusat Napas

Direct acting stimulants

Increase nueronal excitability by

decreasing neuronal recovery time or by

increasing responsiveness to excitatory

neurotransmitters eg doxapram

(Dopram)

Claimed to be a specific respiratory

stimulant and to be useful in

treatment of drug induced respiratory

depression Supportive treatment is

better Sometimes used in anesthesia

Analeptics ndash Xanthines Derived

bull Pharmacological properties

ndashMechanism of action ndash act as

antagonists at adenosine receptors

Adenosine receptors are located on

presynaptic terminals of noradrenergic

neurons and blocks NE release So

caffeine increases NE release

ndashInhibition of phosphodiesterase occurs

but only at very high doses

bull Pharmacological properties

ndashCNS ndash stimulate cortex first then

medulla and spinal cord at high doses

ndashDiuresis

ndashStimulation of cardiac muscle

ndashSmooth muscle relaxation

ndashSecretion

ndashSkeletal muscle - diaphragm

bull Adverse effects

ndashAt 1 g dose of caffeine (12 cups

coffee)

bullInsomnia excitement mild

delirium sensory disturbances

bullIncreased heart rate

bullIncreased respiration

ndashAt higher doses (10 g)

bullClonic convulsions rarr death

bull Adverse effects

ndashChronic use in pregnant women

may increase rate of spontaneous

abortion

ndashTolerance and physical dependence

can occur Withdrawal symptoms

include lethargy irritability and

headache

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

Sifat Kejang

Ekstensi Tonik Seluruh Tubuh dan Ekstremitas

Kontraksi Ekstensor Simetris yang diperkuat

Rangsangan Sensorik

( Pendengaran Penglihatan dan Perabaan)

KINETIK

Absorbsi Mudah di Tempat Injeksi

Masuk Sirkulasi Masuk Jaringan

Segera Ekskresi Lewat Urine (Ekskresi

Lengkap 10 Jam)

GEJALA KLINIS

Kaku Otot Muka dan Leher

Hiperekstensi

Kontraksi Otot Diafragma Depresi Napas

Akumulasi Asam Laktat dalam Plasma

Asidosis Metabolik

PENTILENTETRAZOL (METRAZOL)

ACTION

HAMBATAN SISTEM GABA ndash ERGIC

EKSITABILITAS SSP MENINGKAT

EXCITATORY

Efeknya Lebih Kecil Dibanding Pikrotoksin

KINETIK

Absorbsi cepat Distribusi merata

Metabolisme di Hepar cepat

Ekskresi 75 di Urin dalam

keadaan Tidak Aktif

METIL FENIDAT

ACTION Efek Penglepasan Norefineprin

Simpatomimetik Berkurang

Termasuk α2 Agonis

Efek Lebih Menonjol pada Aktivitas

Mental Mirip Amfetamin

α2 AGONIS

Efek Penglepasan Norefineprin

Aktivasi Prot G(i)

Adenilsiklase

ATP cAMP 5AMP + PI

Aktivasi Kanal K+ Hiperpolarisasi

pada Neuron Mienterik Kolinergik

Pelepasan Asetilkolin

Relaksasi Otot Polos

Aktivasi Kanal Ca2+

Sekresi Insulin

Rangsangan

Simpatis dari

CNS

KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam

Distribusi di Otak Lebih Besar

Metabolisme 80 Asam Retanilat

Ekskresi Melalui Urine

DOKSAPRAM DAN NIKETAMID

ACTION

Rangsangan pada seluruh serebrospinal

Meningkatkan derajat Perangsangan

Pada dosis kecil IV Aktivitas Kemoreseptor

karotis dan Neuron Pusat Napas Tidal Volume

Perangsangan Pusat Napas

Direct acting stimulants

Increase nueronal excitability by

decreasing neuronal recovery time or by

increasing responsiveness to excitatory

neurotransmitters eg doxapram

(Dopram)

Claimed to be a specific respiratory

stimulant and to be useful in

treatment of drug induced respiratory

depression Supportive treatment is

better Sometimes used in anesthesia

Analeptics ndash Xanthines Derived

bull Pharmacological properties

ndashMechanism of action ndash act as

antagonists at adenosine receptors

Adenosine receptors are located on

presynaptic terminals of noradrenergic

neurons and blocks NE release So

caffeine increases NE release

ndashInhibition of phosphodiesterase occurs

but only at very high doses

bull Pharmacological properties

ndashCNS ndash stimulate cortex first then

medulla and spinal cord at high doses

ndashDiuresis

ndashStimulation of cardiac muscle

ndashSmooth muscle relaxation

ndashSecretion

ndashSkeletal muscle - diaphragm

bull Adverse effects

ndashAt 1 g dose of caffeine (12 cups

coffee)

bullInsomnia excitement mild

delirium sensory disturbances

bullIncreased heart rate

bullIncreased respiration

ndashAt higher doses (10 g)

bullClonic convulsions rarr death

bull Adverse effects

ndashChronic use in pregnant women

may increase rate of spontaneous

abortion

ndashTolerance and physical dependence

can occur Withdrawal symptoms

include lethargy irritability and

headache

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

GEJALA KLINIS

Kaku Otot Muka dan Leher

Hiperekstensi

Kontraksi Otot Diafragma Depresi Napas

Akumulasi Asam Laktat dalam Plasma

Asidosis Metabolik

PENTILENTETRAZOL (METRAZOL)

ACTION

HAMBATAN SISTEM GABA ndash ERGIC

EKSITABILITAS SSP MENINGKAT

EXCITATORY

Efeknya Lebih Kecil Dibanding Pikrotoksin

KINETIK

Absorbsi cepat Distribusi merata

Metabolisme di Hepar cepat

Ekskresi 75 di Urin dalam

keadaan Tidak Aktif

METIL FENIDAT

ACTION Efek Penglepasan Norefineprin

Simpatomimetik Berkurang

Termasuk α2 Agonis

Efek Lebih Menonjol pada Aktivitas

Mental Mirip Amfetamin

α2 AGONIS

Efek Penglepasan Norefineprin

Aktivasi Prot G(i)

Adenilsiklase

ATP cAMP 5AMP + PI

Aktivasi Kanal K+ Hiperpolarisasi

pada Neuron Mienterik Kolinergik

Pelepasan Asetilkolin

Relaksasi Otot Polos

Aktivasi Kanal Ca2+

Sekresi Insulin

Rangsangan

Simpatis dari

CNS

KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam

Distribusi di Otak Lebih Besar

Metabolisme 80 Asam Retanilat

Ekskresi Melalui Urine

DOKSAPRAM DAN NIKETAMID

ACTION

Rangsangan pada seluruh serebrospinal

Meningkatkan derajat Perangsangan

Pada dosis kecil IV Aktivitas Kemoreseptor

karotis dan Neuron Pusat Napas Tidal Volume

Perangsangan Pusat Napas

Direct acting stimulants

Increase nueronal excitability by

decreasing neuronal recovery time or by

increasing responsiveness to excitatory

neurotransmitters eg doxapram

(Dopram)

Claimed to be a specific respiratory

stimulant and to be useful in

treatment of drug induced respiratory

depression Supportive treatment is

better Sometimes used in anesthesia

Analeptics ndash Xanthines Derived

bull Pharmacological properties

ndashMechanism of action ndash act as

antagonists at adenosine receptors

Adenosine receptors are located on

presynaptic terminals of noradrenergic

neurons and blocks NE release So

caffeine increases NE release

ndashInhibition of phosphodiesterase occurs

but only at very high doses

bull Pharmacological properties

ndashCNS ndash stimulate cortex first then

medulla and spinal cord at high doses

ndashDiuresis

ndashStimulation of cardiac muscle

ndashSmooth muscle relaxation

ndashSecretion

ndashSkeletal muscle - diaphragm

bull Adverse effects

ndashAt 1 g dose of caffeine (12 cups

coffee)

bullInsomnia excitement mild

delirium sensory disturbances

bullIncreased heart rate

bullIncreased respiration

ndashAt higher doses (10 g)

bullClonic convulsions rarr death

bull Adverse effects

ndashChronic use in pregnant women

may increase rate of spontaneous

abortion

ndashTolerance and physical dependence

can occur Withdrawal symptoms

include lethargy irritability and

headache

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

KINETIK

Absorbsi cepat Distribusi merata

Metabolisme di Hepar cepat

Ekskresi 75 di Urin dalam

keadaan Tidak Aktif

METIL FENIDAT

ACTION Efek Penglepasan Norefineprin

Simpatomimetik Berkurang

Termasuk α2 Agonis

Efek Lebih Menonjol pada Aktivitas

Mental Mirip Amfetamin

α2 AGONIS

Efek Penglepasan Norefineprin

Aktivasi Prot G(i)

Adenilsiklase

ATP cAMP 5AMP + PI

Aktivasi Kanal K+ Hiperpolarisasi

pada Neuron Mienterik Kolinergik

Pelepasan Asetilkolin

Relaksasi Otot Polos

Aktivasi Kanal Ca2+

Sekresi Insulin

Rangsangan

Simpatis dari

CNS

KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam

Distribusi di Otak Lebih Besar

Metabolisme 80 Asam Retanilat

Ekskresi Melalui Urine

DOKSAPRAM DAN NIKETAMID

ACTION

Rangsangan pada seluruh serebrospinal

Meningkatkan derajat Perangsangan

Pada dosis kecil IV Aktivitas Kemoreseptor

karotis dan Neuron Pusat Napas Tidal Volume

Perangsangan Pusat Napas

Direct acting stimulants

Increase nueronal excitability by

decreasing neuronal recovery time or by

increasing responsiveness to excitatory

neurotransmitters eg doxapram

(Dopram)

Claimed to be a specific respiratory

stimulant and to be useful in

treatment of drug induced respiratory

depression Supportive treatment is

better Sometimes used in anesthesia

Analeptics ndash Xanthines Derived

bull Pharmacological properties

ndashMechanism of action ndash act as

antagonists at adenosine receptors

Adenosine receptors are located on

presynaptic terminals of noradrenergic

neurons and blocks NE release So

caffeine increases NE release

ndashInhibition of phosphodiesterase occurs

but only at very high doses

bull Pharmacological properties

ndashCNS ndash stimulate cortex first then

medulla and spinal cord at high doses

ndashDiuresis

ndashStimulation of cardiac muscle

ndashSmooth muscle relaxation

ndashSecretion

ndashSkeletal muscle - diaphragm

bull Adverse effects

ndashAt 1 g dose of caffeine (12 cups

coffee)

bullInsomnia excitement mild

delirium sensory disturbances

bullIncreased heart rate

bullIncreased respiration

ndashAt higher doses (10 g)

bullClonic convulsions rarr death

bull Adverse effects

ndashChronic use in pregnant women

may increase rate of spontaneous

abortion

ndashTolerance and physical dependence

can occur Withdrawal symptoms

include lethargy irritability and

headache

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

α2 AGONIS

Efek Penglepasan Norefineprin

Aktivasi Prot G(i)

Adenilsiklase

ATP cAMP 5AMP + PI

Aktivasi Kanal K+ Hiperpolarisasi

pada Neuron Mienterik Kolinergik

Pelepasan Asetilkolin

Relaksasi Otot Polos

Aktivasi Kanal Ca2+

Sekresi Insulin

Rangsangan

Simpatis dari

CNS

KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam

Distribusi di Otak Lebih Besar

Metabolisme 80 Asam Retanilat

Ekskresi Melalui Urine

DOKSAPRAM DAN NIKETAMID

ACTION

Rangsangan pada seluruh serebrospinal

Meningkatkan derajat Perangsangan

Pada dosis kecil IV Aktivitas Kemoreseptor

karotis dan Neuron Pusat Napas Tidal Volume

Perangsangan Pusat Napas

Direct acting stimulants

Increase nueronal excitability by

decreasing neuronal recovery time or by

increasing responsiveness to excitatory

neurotransmitters eg doxapram

(Dopram)

Claimed to be a specific respiratory

stimulant and to be useful in

treatment of drug induced respiratory

depression Supportive treatment is

better Sometimes used in anesthesia

Analeptics ndash Xanthines Derived

bull Pharmacological properties

ndashMechanism of action ndash act as

antagonists at adenosine receptors

Adenosine receptors are located on

presynaptic terminals of noradrenergic

neurons and blocks NE release So

caffeine increases NE release

ndashInhibition of phosphodiesterase occurs

but only at very high doses

bull Pharmacological properties

ndashCNS ndash stimulate cortex first then

medulla and spinal cord at high doses

ndashDiuresis

ndashStimulation of cardiac muscle

ndashSmooth muscle relaxation

ndashSecretion

ndashSkeletal muscle - diaphragm

bull Adverse effects

ndashAt 1 g dose of caffeine (12 cups

coffee)

bullInsomnia excitement mild

delirium sensory disturbances

bullIncreased heart rate

bullIncreased respiration

ndashAt higher doses (10 g)

bullClonic convulsions rarr death

bull Adverse effects

ndashChronic use in pregnant women

may increase rate of spontaneous

abortion

ndashTolerance and physical dependence

can occur Withdrawal symptoms

include lethargy irritability and

headache

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

KINETIK Absorbsi Sal Cerna Peak Plasma 2 Jam

Distribusi di Otak Lebih Besar

Metabolisme 80 Asam Retanilat

Ekskresi Melalui Urine

DOKSAPRAM DAN NIKETAMID

ACTION

Rangsangan pada seluruh serebrospinal

Meningkatkan derajat Perangsangan

Pada dosis kecil IV Aktivitas Kemoreseptor

karotis dan Neuron Pusat Napas Tidal Volume

Perangsangan Pusat Napas

Direct acting stimulants

Increase nueronal excitability by

decreasing neuronal recovery time or by

increasing responsiveness to excitatory

neurotransmitters eg doxapram

(Dopram)

Claimed to be a specific respiratory

stimulant and to be useful in

treatment of drug induced respiratory

depression Supportive treatment is

better Sometimes used in anesthesia

Analeptics ndash Xanthines Derived

bull Pharmacological properties

ndashMechanism of action ndash act as

antagonists at adenosine receptors

Adenosine receptors are located on

presynaptic terminals of noradrenergic

neurons and blocks NE release So

caffeine increases NE release

ndashInhibition of phosphodiesterase occurs

but only at very high doses

bull Pharmacological properties

ndashCNS ndash stimulate cortex first then

medulla and spinal cord at high doses

ndashDiuresis

ndashStimulation of cardiac muscle

ndashSmooth muscle relaxation

ndashSecretion

ndashSkeletal muscle - diaphragm

bull Adverse effects

ndashAt 1 g dose of caffeine (12 cups

coffee)

bullInsomnia excitement mild

delirium sensory disturbances

bullIncreased heart rate

bullIncreased respiration

ndashAt higher doses (10 g)

bullClonic convulsions rarr death

bull Adverse effects

ndashChronic use in pregnant women

may increase rate of spontaneous

abortion

ndashTolerance and physical dependence

can occur Withdrawal symptoms

include lethargy irritability and

headache

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

Direct acting stimulants

Increase nueronal excitability by

decreasing neuronal recovery time or by

increasing responsiveness to excitatory

neurotransmitters eg doxapram

(Dopram)

Claimed to be a specific respiratory

stimulant and to be useful in

treatment of drug induced respiratory

depression Supportive treatment is

better Sometimes used in anesthesia

Analeptics ndash Xanthines Derived

bull Pharmacological properties

ndashMechanism of action ndash act as

antagonists at adenosine receptors

Adenosine receptors are located on

presynaptic terminals of noradrenergic

neurons and blocks NE release So

caffeine increases NE release

ndashInhibition of phosphodiesterase occurs

but only at very high doses

bull Pharmacological properties

ndashCNS ndash stimulate cortex first then

medulla and spinal cord at high doses

ndashDiuresis

ndashStimulation of cardiac muscle

ndashSmooth muscle relaxation

ndashSecretion

ndashSkeletal muscle - diaphragm

bull Adverse effects

ndashAt 1 g dose of caffeine (12 cups

coffee)

bullInsomnia excitement mild

delirium sensory disturbances

bullIncreased heart rate

bullIncreased respiration

ndashAt higher doses (10 g)

bullClonic convulsions rarr death

bull Adverse effects

ndashChronic use in pregnant women

may increase rate of spontaneous

abortion

ndashTolerance and physical dependence

can occur Withdrawal symptoms

include lethargy irritability and

headache

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

Analeptics ndash Xanthines Derived

bull Pharmacological properties

ndashMechanism of action ndash act as

antagonists at adenosine receptors

Adenosine receptors are located on

presynaptic terminals of noradrenergic

neurons and blocks NE release So

caffeine increases NE release

ndashInhibition of phosphodiesterase occurs

but only at very high doses

bull Pharmacological properties

ndashCNS ndash stimulate cortex first then

medulla and spinal cord at high doses

ndashDiuresis

ndashStimulation of cardiac muscle

ndashSmooth muscle relaxation

ndashSecretion

ndashSkeletal muscle - diaphragm

bull Adverse effects

ndashAt 1 g dose of caffeine (12 cups

coffee)

bullInsomnia excitement mild

delirium sensory disturbances

bullIncreased heart rate

bullIncreased respiration

ndashAt higher doses (10 g)

bullClonic convulsions rarr death

bull Adverse effects

ndashChronic use in pregnant women

may increase rate of spontaneous

abortion

ndashTolerance and physical dependence

can occur Withdrawal symptoms

include lethargy irritability and

headache

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

bull Pharmacological properties

ndashCNS ndash stimulate cortex first then

medulla and spinal cord at high doses

ndashDiuresis

ndashStimulation of cardiac muscle

ndashSmooth muscle relaxation

ndashSecretion

ndashSkeletal muscle - diaphragm

bull Adverse effects

ndashAt 1 g dose of caffeine (12 cups

coffee)

bullInsomnia excitement mild

delirium sensory disturbances

bullIncreased heart rate

bullIncreased respiration

ndashAt higher doses (10 g)

bullClonic convulsions rarr death

bull Adverse effects

ndashChronic use in pregnant women

may increase rate of spontaneous

abortion

ndashTolerance and physical dependence

can occur Withdrawal symptoms

include lethargy irritability and

headache

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

bull Adverse effects

ndashAt 1 g dose of caffeine (12 cups

coffee)

bullInsomnia excitement mild

delirium sensory disturbances

bullIncreased heart rate

bullIncreased respiration

ndashAt higher doses (10 g)

bullClonic convulsions rarr death

bull Adverse effects

ndashChronic use in pregnant women

may increase rate of spontaneous

abortion

ndashTolerance and physical dependence

can occur Withdrawal symptoms

include lethargy irritability and

headache

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

bull Adverse effects

ndashChronic use in pregnant women

may increase rate of spontaneous

abortion

ndashTolerance and physical dependence

can occur Withdrawal symptoms

include lethargy irritability and

headache

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

XANTIN (TEOFILIN gtgt KAFEIN gt TEOBROMIN

ACTION

Efek Perangsangan CNS Kuat Kontraksi Otot Jantung

Efek Diuresis

Relaksasi Otot Polos Bronkus

Menghambat Fosfodiesterase

Mirip Agonis β2 Adrenergik (Salbutamol)

Pada CNS Terutama Teofilin dan Kafein Untuk Depresi

Med Oblongata Merangsang Pusat Napas Kepeka-

an Terhadap CO2

Kardiovaskuler Unt Payah Jantung Krn Tekanan Darah

Perifer

Meningkatkan Frekuensi Jantung

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

Stimulasi Pusat Vasomotor dan Stimulasi Miokard

Tekanan Darah

Stimulasi Pusat Vagus dan Vasodilatasi

Tekanan DarahEfek Resultan

Sedikit Tekanan Darah

Mekanisme Seluler

Translokasi Ion Kalsium Intra seluler

Peningkatan Siklik AMP dan GMP

Blokade Reseptor Adenosin

KINETIK

Absorbsi Cepat Peroral PE Suppositoria

Peak Plasma Teofilin 2 jam Kafein 1 jam

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin

Distribusi

Seluruh Jaringan Trans Plasenta Protein

Binding

Metabolisme Hepar

Ekskresi Urine Dalam Bentuk Asam Metil urat

atau Metilxantin