Analgesics drugs_pdf

Central Nervous System Drugs
(CNS Drugs)
Hypnosedative drugs
Istanbul Atlas University

Faculty of Medicine
Department of Pharmacology
Dr. Sema Ketenci
Nervous system is divided into
• central (central) and
• peripheral nervous system.
The basis of the nervous system

creates;
- nerve cell called neuron,
- extensions of neurons (axons,
dendrites),
- junction points between
neurons, synapses
- neurotransmitter substances.
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• The central nervous system
consists of the brain and
spinal cord.
• Drugs acting on the central
nervous system affect the
transmission between
neurons and the cellular
functions of neurons.
• It is used in various fields
such as anesthesia,
psychiatry and neurology to
detect the etiology of
diseases and to treat them.
• Drugs that show their effects on different parts of
the brain and spinal cord are called central
nervous system drugs.
• Drugs that affect the central nervous system
affect various stages of neurotransmission.
• Some of them show presynaptic effect by
changing the synthesis, storage and termination
phases of neurotransmitter substances.
• Others block or activate postsynaptic receptors.

Mechanisms of Action of Central Nervous
System Drugs
• Increases or decreases the biosynthesis of

neurotransmitters.
• It increases or decreases the metabolic
breakdown of the neurotransmitter.
• At the presynaptic terminals, it alters
neurotransmitter retrieval and reuse.

• WITH THIS LESSON!; You will be able to
distinguish drugs that
• affect the central nervous system,
• their indications,
• side effects and
• contraindications.

You will be able to distinguish
1. sedative and hypnotic drugs.
2. drugs with anticonvulsant effect.
3. the drugs used in the treatment of Parkinson's.
4. the drugs used in the treatment of psychiatric
diseases.
5. drugs with narcotic analgesic effect.
6. drugs with anesthetic effect.
7. neuromuscular blocking drugs.

1- Sedative and hypnotic drugs
• in low doses, improve psychological affects such as
anxiety, anxiety, fear, excitement, restlessness and
tension (anxiety).
• It has a sedative effect by calming down and providing
relaxation (sedation).
• In high doses, it gives sleep and creates a hypnotic
effect. For this reason, they are called sedative-
hypnotic or hypnosedative drugs.
• Sedative and hypnotic drugs are addictive drugs and
are used by green prescription.
• Depresses the central nervous system without being
selective. It causes coma and death in overdoses.

• There is no sharp boundary between the sedative and
hypnotic effects of sedative (sedative) and hypnotic
(sleeping) compounds known as central nervous system
general depressants.
• The same compound can exert both effects, as well as
sedating at low doses, producing hypnotic effects at higher
doses.
• Sedative and hypnotic compounds can be distinguished
from each other in terms of the degree of sedation and
hypnotic effect they exert.
• The compounds may exert sedative, hypnotic and
anesthetic effects, depending on the dose administered to
the patient.

Sedatives and Analgesics

Sedation and Analgesia

Effects of hypno-sedative drugs

Behavioral pain scales
facial pain, valid and reliable, in severely ill patients

Pain scales

Dose dependent effects of sedative and
hypnotic drugs

WHAT ARE SEDATIVE AND HYPNOTIC DRUGS?
• 1. Benzodiazepines
• 2. Barbiturates
• 3. Non-Barbiturate Structures
• 4. Other Sedatives and Hypnotics

1- Benzodiazepines
• They were first marketed in
1960.
• hypnosedative drugs with the
highest therapeutic index.
• do not induce liver
microsomal enzymestheir
addictive potential is lower
than barbiturates.
• they are written on the green
prescription
Benzodiazepine drug action times

Benzodiazepines
• Benzodiazepines are drugs commonly used in treatment.
• It has anti-anxiety, sedative, hypnotic, anticonvulsant and muscle
relaxant effects.
• Indications of benzodiazepines
• Anxiety Disorders: Benzodiazepines are used in anxiety, depression
and anxiety accompanying schizophrenia. They are not used for a
long time in the treatment of severe anxiety due to their addiction.
• Muscle Spasms: Some benzodiazepines are used in the treatment
of increased muscle tone caused by degenerative diseases such as
muscle spasm, multiple sclerosis, and cerebral palsy.
• Convulsions: Clonazepam is used in the treatment of epilepsy, and
Diazepam is used in epileptic seizures.
• Sleep Disorders: Flurazepam, Temazepam, Triazolam from
benzodiazepines are used in the treatment of sleep disorders.

long, medium and short acting benzodiazepines

• Status epilepticus and withdrawal symptoms are seen in patients
who quit alcohol. In addition to diazepam, benzodiazepines such
as Chlordiazepoxide and Lorezepam are also used in the
treatment of alcohol withdrawal symptoms. There are
pharmaceutical forms of diazepam that are administered orally,
parenterally, and rectally.
• Side effects of diazepam

Side effects such as drowsiness, hypotension, nausea,
confusion, respiratory depression and collapse may occur.
• Contraindications: It is contraindicated in hypersensitivity,

glaucoma, coma, shock and head trauma.Flurazepam
(Dalmadorm): It is a long-acting benzodiazepine. It is used in
sleep disorder.
• Triazolam (Halcion) and Temazepam (Remestan): Other
benzodiazepines used in the treatment of insomnia.

Flumazeline
• It is a benzodiazepine antagonist.
• Antogenizes both benzodiazepines and inverse
agonists.
• It is used to relieve symptoms due to overdose of
benzodiazepines.
• It causes extreme withdrawal syndrome when
given to benzodiazepine addicts.
Each ampoule contains 1 mg of flumazenil in 10 ml of
solution.Each box contains 5 ampoules of 1 mg/10 ml.MAZENIL
reverses the effects of benzodiazepines, a group of drugs used as
strong sleep initiators.It is given slowly into a vein by a single or
continuous injection.

2- Barbiturates
• They exert their effects on the synaptic transmission of the
reticular activator system.
• These drugs raise the threshold of consciousness and
prolong the refractory period of the postsynaptic cell.
Barbituric acid derivatives can be used in combination with
analgesic preparations due to their sedative effects, as well
as hypnotic to ensure sleep and continuity of sleep.
• There are also derivatives used as injection anesthetics in
minor surgeries. Accordingly, the depth of action is
sedative > hypnotic > narcotic.
• Pharmacological properties of barbiturates:
• • Rate of showing sedative > hypnotic > narcotic effects
• • The duration of these effects they show.
• • They are defined according to their impact forces.

Barbiturates
• Barbiturates; It affects the transport of sodium
and potassium in the cell membrane and impairs
the stimulus transmission. Barbiturates have a
narrow safety margin and have many side effects.
Therefore, benzodiazepines have replaced
barbuturates today. However, barbiturates such
as Thiopental are used in anesthesia.

DOSES OF BARBURATES
Barbiturates are classified according to their duration of
action.

Indications for barbiturates
• Very short acting barbiturates such as Thiopental in
anesthesia iv. for the induction of anesthesia;
• Phenobarbital as an anticonvulsant in status epilepticus,

tonic-clonic contractions (Phenobarbital may impair
cognitive functions in children, so it should be used with
caution.)
• In anesthetic doses, it reduces the oxygen use of the
brain, thus reducing cerebral edema caused by trauma or
surgery,
• In the treatment of kernicterus and hyperbilirubinemia
in the newborn (especially phenobarbital)
• It is used as a sedative in anxiety, insomnia and tension.

Effects of barbiturates
• Central nervous system depression: Barbiturates

are sedative at low doses and hypnotic at high
doses. Anesthesia, coma, and death may then
develop.
• Respiratory depression: Barbiturates depress
respiration by reducing sensitivity to carbon
dioxide. Death may occur as a result of
respiratory depression.
• Affecting liver enzymes: Barbiturates affect
enzymes in the liver and the effects of drugs
metabolized in the liver are reduced after long-
term use of barbiturates.
Side effects of barbiturates

The following operations are performed in the
poisoning table:
• The patient is evaluated.

• Respiration and circulation are supported.
• If the drug is taken orally and newly taken, the stomach
contents are emptied.
• Urine is alkalized. (Medicines are given to alkalize the
urine.)
• Excretion of the drug is accelerated by diuresis.
• In high doses, if it is taken in excess, hemodialysis
should be applied.
• Contraindications: Barbiturates are not used during
pregnancy and with alcoholic beverages.

3- Non-Barbiturate Structures
Chloral hydrate, Paraldehyde
They are aldehyde group drugs.
It is used in sleep disorder. Paraldehyde can be used in epilepsy due
to its anticonvulsive effect. Taste and smell are bad. It is excreted
from the lungs through respiration. It is not used in lung patients,
peptic ulcer patients.
Ethanol
Ethanol (ethyl alcohol) is anxiolytic and sedative. It is a central
nervous system depressant. The sedative effect turns into a
hypnotic effect as the dose increases. When taken together with
alcohol, antihistamines and barbiturates, it depresses the central
nervous system.
Antihistamines
Diphenhydramine, Doxylamine are used in cases of mild insomnia.
It is not effective in the treatment of severe insomnia. It has many
side effects.

4- Other Sedatives and Hypnotics
• Zolpidem: It has a sedative and hypnotic

effect. It is mostly used for its sedative effect.
It has no anticonvulsant or muscle relaxant
effect.
• Buspirone: It is a sedative drug.
• Hydroxyzine: It is antiemetic. It also has a
sedative effect.

Other Sedatives and Hypnotics
• Zolpidem has a different binding site on benzodiazepine
receptors and exerts a sedative effect by increasing GABA-
mediated inhibition.
• Does not cause withdrawal symptoms.
• Rebound insomnia is rare.It has no anticonvulsant and
muscle relaxant effects.
• It has side effects such as nightmares, agitation, dizziness,
daytime sleepiness.effect can be eliminated with
flumazellin.
• alpidem, zaleplon, zopiclone
• they are like zolpidem.
• They bind to the same site as zolpidem.
• Dose adjustment is required in the elderly and those with
hepatic impairment.

• Buzpyron is a potent but non-selective 5-HT1a agonist.
• Its anxiolytic effect occurs after days or weeks.
• Used in chronic anxiety. side effects are milder.
• Causes dizziness, drowsiness, headache,
nausea.sedation, psychomotor cognitive impairment
are rare. addiction does not occur.
• rifampicin induces the P450 system and reduces the
half-life of buzpyron.
• Analogs such as insapirone, gepiron and andospirone
have been developed.
• Chloralhydrate: Initiates sleep in 30 minutes. It takes
6 hours. causes epigastric pain.

• Glutethamide and meprobamate are formerly used

sedative hypnotics. cause worsening of porphyria.
cause peripheral neuropathy and osteomalacia (only
glutethitis).
• antihistamines:diphenhydramine, doxylamine,
hydroxyzine are used for anxiolytic purposes. addiction
rarely develops.
• beta-blockers (propranolol): they relieve the physical
symptoms of anxiety (tachycardia, tremor, sweating).
They suppress the peripheral sympathetic response
rather than the central effect.

Questions
• 1. Indication of benzodiazepines, which of
the following?
• A) Anxiety disorders
• B) Muscle spasms
• C) Convulsion
• D) sleep disorders
• E) all

Questions
• 1. Indication of benzodiazepines, which of
the following?
• A) Anxiety disorders
• B) Muscle spasms
• C) Convulsion
• D) sleep disorders
• E) all

• 2. Which of the following is the drug used in
overdose with benzodiazepines?
• A) Flumazenil
• B) Fliazolam
• C) Flurazepam
• D) Triazolam
• E) Alprazolam

• 2. Which of the following is the drug used in
overdose with benzodiazepines?
• A) Flumazenil
• B) Fliazolam
• C) Flurazepam
• D) Triazolam
• E) Alprazolam

• 3. Which of the following is the
benzodiazepine group drug used in epilepsy
attack?
• A) Alprazolam
• B) Chlordiazepoxide
• C) Diazepam
• D) Triazolam
• E) Fluazolam
• 3. Which of the following is the
benzodiazepine group drug used in epilepsy
attack?
• A) Alprazolam
• B) Chlordiazepoxide
• C) Diazepam
• D) Triazolam
• E) Fluazolam
• 4. Which of the following is a short-acting
barbiturate used in anesthesia?
• A) Phenobarbital
• B) Thiopental
• C) secobarbital
• D) Pentobarbital
• E) Amobarbital

• 4. Which of the following is a short-acting
barbiturate used in anesthesia?
• A) Phenobarbital
• B) Thiopental
• C) secobarbital
• D) Pentobarbital
• E) Amobarbital

• 5. Which of the following is done in
barbiturate poisoning?
• A) Breathing, circulation are supported
• B) If taken orally, stomach contents are
emptied
• C) Diuresis is increased
• D) urine is alkalized
• E) all

• 5. Which of the following is done in
barbiturate poisoning?
• A) Breathing, circulation are supported
• B) If taken orally, stomach contents are
emptied
• C) Diuresis is increased
• D) urine is alkalized
• E) all

2. ANTICONVULSAN DRUGS (ANTIEPILEPTICS)
• Anticonvulsant (antiepileptics) drugs are mostly used in the treatment of

epilepsy. Epilepsy develops due to the spread of abnormal and high-frequency
stimuli in the brain. anticonvulsant drugs; it prevents seizures from occurring
or prevents the spread of abnormal electrical discharges to other parts of the
brain.
• Epilepsy can be hereditary or due to various factors. Initial treatment in
epilepsy is based on the seizure type.
• Phenytosine (epdantoin), Carbamazepine (tegretol) are the drugs of choice in
simple partial seizures. Phenobarbital, Primidone (granmid) are also used.
• Phenytoin, Carbamazepine, Phenobarbital, Primidone, Valproic (valproic
acid) are used.

• Absence seizures (Petit mal); These are brief seizures with sudden
loss of consciousness. It occurs in childhood. Movements such as
looking at a point, blinking are seen. Ethosuximide (petimide),
Clonazepam (rivotril) and Trimetadione (tridone) are the drugs
used.
• Myoclonic seizures are short-term involuntary muscle contractions.
Hypoxia, uremia, drug intoxication, encephalitis etc. may occur due
to permanent neurological damage. Clonazepam and Valproic Acid
are used.
• Febrile seizures occur in young children (3 months-5 years) due to
febrile diseases. They are short-term generalized tonic-clonic
seizures. Rarely, drug therapy is used. Phenobarbital and Primidone
are drugs used.
• Status epilepticus is a type of seizure that follows each other at
short intervals. In treatment, Diazepam (10 mg.) or Clonazepam is
given intravenously. If the intravenous route is not available,
diazepam is administered rectally. Phenytoin, Phenobarbital are
other drugs used.

Some of the drugs used in the treatment of epilepsy;
DRUG SIDE EFFECTS
Phenytoin •Central nervous system depression in the cerebellum

and vestibular system causes ataxia and nystagmus.
Phenytoin is used in the • Nausea, vomiting,
treatment of all partial • Gingival hyperplasia in children,
seizures and status • Megaloblastic anemia by impairing the absorption
epilepticus. of vitamin B 12,
• Hyperglycemia, glycosuria,
It is preferred in the • It inhibits the secretion of antidiuretic hormone,
treatment of adults. • It has teratogenic effects. Cleft palate, lip, heart
disease, as well as regression in growth and mental
It prevents the propagation of development are seen in the babies of patients who
abnormal warnings. use it during pregnancy.
It is not used in petit mal • Affects liver enzymes,
epilepsy. •Hair growth (hirsutism),
• Increases or decreases the mechanism of action of
It is used in chronic some drugs.
treatment, orally, and IV in
status epilepticus..
DRUG SIDE EFFECT
Phenobarbital
• In chronic use, ataxia, nystagmus,
Phenobarbital also has an
anticonvulsant effect independent vertigo, and psychotic attacks are
of its sedative effect. seen.
It is used in simple partial • Nausea, vomiting,
seizures, febrile convulsions,
tonic-clonic seizures unresponsive • Rash,
to diazepam and phenytoin. •Agitation, convulsions,
It prevents the propagation of •When the drug is discontinued,
stimuli in the brain.
It is well absorbed orally. recurrent seizures (rebound seizure)
are seen.

DRUG SıDE EFFECT
Primidone
• Initially sedates. Sedation decreases with
It is used in the treatment of partial, use.
tonic-clonic seizures. It is often used in •Skin rash
combination with carbamazepine and • Acute psychic disorder
phenytoin. • Blood picture changes are among its side
effects.
Valproic acid
Valproic acid inhibits the propagation •nausea, vomiting,
of abnormal electrical impulses. • Sedation, ataxia, tremor,
It increases the level of endogenous • Hepatotoxic effect,
substance GABA (gabaamino butyric •Skin rashes
acid) in the brain. •Hair shedding
It is an effective drug in the treatment • It has side effects such as
of myoclonic seizures. It is also used in thrombocytopenia and inhibition of platelet
the treatment of petit mal and grand aggregation.
mal epilepsy.
Drug Side effect
Carbamazepine •Prolonged use can lead to stupor, coma,

Carbamazepine blocks the respiratory depression, vertigo and
propagation of the abnormal drowsiness.
stimulus in the brain. •Nausea, vomiting,
It is used to prevent all partial • Aplastic anemia
seizures. •Disorders in the blood picture
It is also used in the treatment of (agranulocytosis, thrombocytopenia),
grand mal epilepsy, trigeminus •Liver toxicity
neuralgia (painful lesion of the 5th • It has side effects such as teratogenic effect.
cranial nerve).
Ethosuximide •nausea, vomiting,
It prevents the spread of abnormal •Sleepiness
electrical stimulation in the brain. • Lethargy, dizziness, restlessness, agitation,
It is the drug of first choice in the anxiety,
treatment of petit mal epilepsy. •Skin rashes
• Leukopenia, aplastic anemia,
thrombocytopenia may occur.
Drug Side effect
Benzodiazepines Clonazepam (Rivotril)

•Clonazepam is used in petit mal, grand mal and
Benzodiazepines have status epilepticus. The drug should not be stopped
antiepileptic effects. abruptly, but the dose should be tapered off.
Clonazepam is used in chronic Clonazepam side effects
treatment and diazepam in - Fatigue, drowsiness, sleepiness,
status epilepticus. Among - Slowing in reflexes,
epileptic drugs, benzodiazepines - Respiratory depression is among its side effects.
are drugs that are safe and have
few serious side effects. Diazepam is used in status epilepticus and in cases
with convulsions other than epilepsy.
Other Antiepileptic drugs Gabapentin and lamotrigine are used in the

treatment of partial and generalized seizures.
Gabapeptin and Lamotrigine Its effects on the central nervous system are weak.
A common side effect of lamotrigine is skin rashes.

Questions
• Which of the following is a benzodiazepine

drug used in the treatment of epilepsy?
• A) Phenytoin
• B) Phenobarbital
• C) Ethosuximide
• D) Clonazepam
• E) Valproic acid

• 5. Which of the following is a benzodiazepine
drug used in the treatment of epilepsy?
• A) Phenytoin
• B) Phenobarbital
• C) Ethosuximide
• D) Clonazepam
• E) Valproic acid

3. DRUGS USED IN THE TREATMENT OF
PARKINSON
• Parkinson's;
• It is a progressive neurological disease characterized
by tremor,
• muscle rigidity (muscle stiffness), bradykinesia
(slowness in initiating and maintaining voluntary
movements),
• posture and gait disturbances.
• Parkinson's develops due to the decrease in

dopaminergic activity in the central nervous system
and muscle movements are impaired.

Drugs Used in Parkinson's Disease
• The normal functions of striated muscles depend on the balance
between acetylcholine and dopamine in the central nervous
system.
• In Parkinson's, dopaminergic activity decreases and cholinergic
activity increases.
• In treatment, drugs that increase dopaminergic activity, drugs that
decrease cholinergic activity, or a combination of these are used.
• With treatment, the dopamine-acetylcholine balance is tried to be
achieved.
• Drugs are useful in temporary control of symptoms; but it cannot
reverse and stop the resulting degeneration.
1- Drugs that Increase Dopaminergic Activity

2- Anticholinergic Drugs
3- Antihistamines

1- Drugs that Increase Dopaminergic Activity
DRUG SIDE EFFECT
Levodopa (L-Dopa)
•loss of appetite, nausea,
Levodopa is the precursor involved
in the production of dopamine. vomiting,Tachycardia, hypotension,
In treatment, it increases ventricular extrasystole,
dopamine concentration. •Mydriasis, increased intraocular
Blood crosses the brain barrier.
It is converted to dopamine in the pressure in the patient with
central nervous system and glaucoma,
peripheral. • Visual, auditory hallucinations,
It is used together with Carbidopa
(sinemed) and Benserazid mood changes,those involuntary
(madopar) to increase the amount movementso short-term loss of drug
transferred to the central nervous efficacy several times a day. (on-off
system and decrease the amount in
the periphery. syndrome)
Levodopa significantly reduces
Parkinson's symptoms.
Dopaminerjik EtkinliğiArtıran İlaçlar
(Dopaminerjikler)
Drug Side effect
Digestive system disorder,
Bromocriptine hypotension and hallucination side
Bromocriptine is a herbal medicine. It is used in effects
patients who do not benefit from levodopa.
Used with levodopa in drug-responsive patients.
Amantadine Side effects include orthostatic

Amantadine is an antiviral drug. Increases hypotension, urinary retention, dry
dopamine reuptake in neurons. Causes toxic mouth, peripheral edema, and
psychosis in high doses psychic changes.
Deprenil (Selegiline)
Deprenil increases dopamine levels. It can lead
to a hypertensive crisis. Recent studies have
shown that early use of deprenil delays the onset
of severe symptoms by 50%.

Anticholinergic drugs
• Anticholinergic drugs prevent the increased
parasympathomimetic activity due to the
increase in acetylcholine in Parkinson's disease.
• Trihexyphenidyl (artane), Biperiden (akineton) are
anticholinergic drugs used. Biperiden green is
subject to prescription. It is effective in tremors.
• Side effects of anticholinergic drugsdry
mouth,Blurring of consciousness, confusion,
hallucinations,Urinary retention is one of its side
effects.
• It is contraindicated in patients with glaucoma,
pleural stenosis and prostatic hypertrophy.

Antihistamines
• Among the antihistamines, Diphenhydramine

(benadryl), Chlorfenoxamine is used in
Parkinson's because of its anticholinergic
effects.
• Diphenhydramine is more commonly used.
• Dry mouth, darkening of the mucus,
constipation, sedation are among the side
effects.

Questions
• Which drug is a precursor in the production
of dopamine and used in the treatment of
Parkinson's?
• A) Levodopa
• B) Bromocriptine
• C) Deprenil
• D) Amantadine
• E) Diphenhydramine

• Which drug is a precursor in the production
of dopamine and used in the treatment of
Parkinson's?
• A) Levodopa
• B) Bromocriptine
• C) Deprenil
• D) Amantadine
• E) Diphenhydramine

• Which of the following is the mechanism of action of
anticholinergic drugs in the treatment of Parkinson's?
• A) In Parkinson's disease, it prevents
parasympathomimetic activity due to the increase in
acetylcholine.
• B) Increases acetylcholine level.
• C) It increases the dopamine level and creates a
parasympatholytic effect.
• D) Increases dopamine and acetylcholine levels.
• E) It reduces dopamine levels by creating a

• Which of the following is the mechanism of action of
anticholinergic drugs in the treatment of Parkinson's?
• A) In Parkinson's disease, it prevents
parasympathomimetic activity due to the increase in
acetylcholine.
• B) Increases acetylcholine level.
• C) It increases the dopamine level and creates a
• D) Increases dopamine and acetylcholine levels.
• E) It reduces dopamine levels by creating a

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Central Nervous System Drugs

Istanbul Atlas University

The basis of the nervous system

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• Increases or decreases the biosynthesis of

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• Side effects of diazepam

• Contraindications: It is contraindicated in hypersensitivity,

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• Phenobarbital as an anticonvulsant in status epilepticus,

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• Central nervous system depression: Barbiturates

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• The patient is evaluated.

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• Zolpidem: It has a sedative and hypnotic

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• Glutethamide and meprobamate are formerly used

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• Anticonvulsant (antiepileptics) drugs are mostly used in the treatment of

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Phenytoin •Central nervous system depression in the cerebellum

DRUG SIDE EFFECT

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Carbamazepine •Prolonged use can lead to stupor, coma,

Benzodiazepines Clonazepam (Rivotril)

Other Antiepileptic drugs Gabapentin and lamotrigine are used in the

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• Which of the following is a benzodiazepine