central nervous system drugs ii

7/23/2019 Central Nervous System Drugs II

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Psychopharmacology:

Central Nervous System Drugs II

AP Dr Ahmad Rohi Ghazali


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Central Nervous System Drugs

CNS Depressants CNS Stimulants

Opioids

Anxiolytics Neuroleptics

PSYCHODYSLEPTICS

PSYCHOSTIMULANTS

ANALEPTICS

OUTLINE


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CNS DEPRESSANTS :

OPIOIDS


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BACKGROUND:

Opioid:

substances with morphine- l ikeeffects.

antagonism with naloxone.

enkephalin, endorphin+ dynorphin+Synthetic analogues).

Opiate:

morphine derivative drugs.

similar chemical structure to morphine.

NOT including endogenous neuropeptides.

OPIUM:

poppy juice extractsPapaver somniferum.medical (diarrhea & pain) + social uses.

about 20 & more active alkaloids.
http://opioids.com/refs/index.html


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Morphine:

OPIUM:

1% Papaverine, 6% Narcotine,

10% Morphine+ 0.5% Codein.

The structure of morphine + all

opium derivatives are

characterized by the piperidinering.

Pharmacological effects:

Analgesic(antinociceptive)

antidiarrheaphysical dependence

respiratory depression

Hydrophiliccompared to heroin
http://opioids.com/heroin.html


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Mechanism of Action, MOA of Opioid:


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Pharmacological Responses of Opioid Sub Receptors :

Receptor Type

/

Analgesia

Supraspinal

Spinal

Peripheral

++/ -

++/ ++

++/ -

-

+

++

-

Respiratory

Depression

++ + -

Pupil (eye) Constriction - Dilatation

GIT Motility

- -

Smooth MuscleSpasm

++ - -

Behaviour / Emotion Euphoria ++

Sedation ++

Dysphoria +

Sedation +

Dysphoria ++

Psychotomimetic

Physical Dependence ++ + -


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Compounds Receptor Type

Opioid Peptides:

Beta-endorphin

Leu-enkaphalin

Dynorphin

+++

+++

+++

++++

+++

-+++

-

--

True Agonist:

Morphine

Codein

Pethidine

Etorphine

Fentanyl

+++

+

+++++

+++

+

+

++++

+

++

+

++++

-

-

-

--

-

Partial Agonist :

PentazocineNalorphine

Buprenorphine

(+)

(++)

+++

+

++

-

++

++

(++)

+

+

-

Antagonist:

Naloxone

Naltrexone

(+++)

(+++)

(++)

(++)

(++)

(++)

-

-


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Opioids Adverse Reactions:

Major side effects are:

constipation + respiratory depression.

Sedation, GIT motility, nausea and vomiting.

Histamine release.

Tolerance also physical and psychological dependence.

Withdrawal:flu-like syndrome, yawn, runny nose,hypertension, diarrhea, muscle spasm, fever and anxiety.(Heroin:3-7 days, Methadone: 10-21 days).

OD Treatment:

Naloxone (Narcan) IV and Naltrexone (long acting).

Contraindication:respiratory depression, chronic lungdisease, liver or kidney disease, prostatic hypertrophy.


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Other Opioids:

Diamorphine:

Heroin,Diacetylmorphine

vinegar smell & v lipophilic (BBB)

Codein:

3-methylmorphine+ antitussive (analgesic)

only 20% analgesia (NO euphoria)

Pethidine (DEMEROL):

NO sedation and antitussive effects.

antimuscarinic & analgesia (giving birth)

Fentanyl (China White) and Sufentanyl:Short acting anaesthesia + ABUSE

(OD:rapid respiratory paralysis)

Etorphine:

Potency 1000X and tranquilizer


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Pentazocine:

partial agonist: agonist / antagonist

arteriole BP

dependence + acute toxicity

very dysphoric + hallucination, nightmares

Buprenorphine:

structurally similar to Etorphine

BUT pharmacological responses are similar to Pentazocine.

Naloxone:

a pure opiate antagonist and prevents or reverses the

effects of opioids including respiratory depression, sedation

and hypotension.
http://opioids.com/images/opioid-receptors.html


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Methadone:

effects similar to morphine, long acting

(t 1/2= 15 -20 h)ie. highly bound + slowly

excreted.

sedative effects and physical

abst inence syndrom e

heroin addiction alternative treatment +morphine (oral)

(+ morphine / heroin injections, at low

doses, NO euphoria)

Mitragyna Speciosa, Ketom, Biak-biak:

Alternative treatment for heroin / opium

(replacement)?.

No naloxone activity


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HAVE A BREAK!


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CNS

DEPRESSANTS :

ANTIPSYCHOTIC

DRUGS

Fertility goddess of harvest and corn, sister of

Zeus, Demeter in agricultural societies.


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Antipsychotic drugsare also known as neurolepticdrugs, antiSchizhopreniaor major tranquilizers.

Schizo(split) /phrenia(mind) :

1% world population.

Positive Symptoms (+):ACUTE

delusion, thought disturbances,

speech abnormalities, inner voicesand hallucination.

Negative Symptoms (-):CHRONIC

self-isolation (paranoid), less

emotional response and slowmental and physical reaction (eg.

dementia).

Causes :combination genetic, environment

(anxiety + stress) + neurobiology (excess dopamine)


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Function

D1 D2

D1 D5 D2 D3 D4

Distribution:

Cortex Arousal, mood +++ - ++ - +

Limbic System Emotion,

stereotype

behaviour

+++ + ++ +

Striatum Motor Control +++ + ++ + +

Ventral

Hypothalamus +

Anterior pituitary

Prolactin

modulation

- - ++ + -

Dopamine Receptor Subtypes:


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AntiSchizophrenia Drugs:

Classification of Antipsychotic Drugs:

Typical

Conventional (non-selective)

Block both dopamineand serotoninreceptors

Cause several adverse effects eg. hypotension,

anticholinergic effects, extrapyramidal side effects

(EPS) eg. Chlorpozamine, Haloperidol

Atypical

Selective dopamine receptors

Primarily dopamine receptor blockers

May alleviate some of unpleasant effects

eg. Sulpiride, Clozapine


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MOA of Neuroleptic Drugs:

More antagonisme at the dopamine receptor D2.

Also antagonisme at other monoamine receptors eg.

NAd, histamine, ACh and 5-HT.

neuroleptic side effects are from the actions onother receptors than dopamine.

Onset time is long (days to weeks) and probable increase

of dopamine receptorsmay occur.


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MOA of Neuroleptic Drugs:


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Pharmacological Responses and Side Effects:

Antiemesis:

(+ cancer treatment, renal failure and pregnant mothers).

Endocrine effects:

serum prolactin concentration (gynaecomastia).

growth hormone secretion.

Others: Effects from monoamine receptors inhibition:

M U S C A R I N E

Cardiovascular effects:

Vasodilatation, hypotension.

Idiosyncratic Effects and Hypersensitivity:

Jaundice (Chlorpromazine).

Leukopenia + agranulocytosis.

Skin reaction eg. Urticaria.


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Extrapyramidal Syndrome (EPS):

PseudoParkinsonism (reversible and acute):

Tremor, dystonia, and muscle spasm

Direct inhibition at nigrostriatal receptors.

Tardive dysk inesia:

Involuntarily movement inhibition

Rabbit Syndrome

proliferation of dopamine receptors

at corpus striatum.

Tardive dyskinesiaincidence is less occurring withatypical drugs (Clozapine, Sulpiride).


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A BEAUTIFUL MINDSCHIZOPHRENIA IS FOR LIFE

There is no remission


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B A D A M E R I C A N S :

B-Bradycardia and hypotension

A-Antitussive effect

D-Deep tendon reflexes are Depressed.

A-Analgesic effect

M-Miosis

E-Euphoria

R-Respiratory depression

I-Intracranial pressure is increased.C-Constipation

A-Acute intoxication, Anaphylaxis - respiratory Acidosis,

N-Nausea and vomiting

S-Sedation

SUMMARY: EFFECTS OF OPIOIDS


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Drugs Receptor Affinity Side Effects NotesD1 D2 H1 mACh 5HT EPS Se HiT Lain2

Typical:Chlorpromazine

Haloperidol

Flupenthixol

++

+

++

+++

+++

+++

++

++

++

+

-

+

++

+/-

-

++

+

+++

++

+++

++

++

-

+

++

++

+

Prolactin,

hypothermia,

anticholinergic,hypersensitivity +

JAUNDICE.

SAME (NO jaundice

+ anticholinergic).

Prolactin, anxiety.

Phenothiazine group (same with

Fluphenazine but no jaundice,

hypotension, EPS.

Butyrophenone group. Usual

Neuroleptic. EPS.

Same with Clopenthixol. Depot

preparation.

Atypical:

Sulpiride

Clozapine

Quetiapine

-

++

-

+++

++

+

-

++

+++

-

+

-

-

++

+

-

+++

+

+

-

+

+

++

++

-

+

++

Prolactin.

Risk of

agranulocytosis (1%).

Epilepsy. Sedation.

Saliva.

Anticholinergicity

effects.

Body weight.

Tachyicardia.

Agitation. Dry mouth.

Body weight.

Benzamide group (same with

Pimozide). Selective towards

D2/3. absorption. EPS.

Dibenzodiazepine group (same

with Olanzepine but no risk of

agranulocytosis). Also at D4. NOEPS. Effective for symptoms +/-

Schizophrenia. Suitable for

resistant patients to treatment.

Novel type. At alpha-

adrenoreceptor. Still under study.


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THANK YOU

central nervous system drugs ii

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