How do you get rid of ulcers on your legs? occlusive (air- and water-tight) dressings – ulcers heal better when they are covered. These dressings should be changed weekly. compression treatment – boosts internal pressure, using either elasticised bandages or stockings. This is particularly effective if multiple layers are used.

1. CNS pharmacology- part I
Antipsychotics
Doc. dr Dragana Drakul

2. CNS pharmacology
• The mechanisms by which various drugs act in
the CNS have not always been clearly
understood.
• In recent decades, dramatic advances have
been made in the methodology of CNS
pharmacology.

3. CNS pharmacology
• Introduction, neurohumoral transmission in CNS
• Antipsyhotics and Lithium
• Antidepressives
• Anxiolytics, sedatives and hypnotics
• Antiseizure drugs
• General and local anesthetics
• Sceletal muscle relaxants
• Opioid analgesics and antagonists
• Drugs for Parkinsonism and other movements disorders
• Alcohols
• Drugs of abuse

4. Neurohumoral transmission in CNS

5. Neurotransmitters
• Must be present in presynaptic neuron
• Must be released from presinaptic neuron
• Ensimatic mechanisms of sinthesis/degradationin
neuron must be known
• Fluctuation of NT concentration are related to
function
• Blockers of neurotransmiter function must be
known

6. Cellular organization in CNS
• Hierarchical systems
• Diffuse systems
• Non-myelinated neurons
• Branches from the same neuron can
innervate several functionally different
parts of the CNS.
Pathways involved in sensory
perception and motor control
Myelinated neurons (50 m/s)

7. CNS neurotransmitters
• Amins (Ach, NE, dopamin, 5HT, histamin)
• Aminoasids (glutamat, GABA, glycine)
• Peptids (substance p, cholecystokinin)
• GABA i glycin are inhibitory NT
• Glutamat is ekscitatory NT
• Dopamin is inhibitory/ekscitatory NT

9. Glutamate and aspartate
• Precursor - glucose
• Effects- glutamate receptors in CNS
• Ionotropic and metabotropic
• Ionotropic: NMDA, AMPA i kainate
• Metabotropic coupled with G proteins
• Excitatory effects, learning, memory

11. GABA
• Precursor for GABA synthesis is glukose
• There are 200 to 1000 times more GABA in brain then
D, NA, 5HT ili Ach
• The most important inhibitory NT in CNS
• Receptors: α, β, γ subunits
• GABAA receptors are located postsinapticly, activation
opens Cl- channels and induces inhibitory PSP
• GABAB receptors are located presinapticly, activation
decreases releasing of GABA (K+ channel)
• Physical and mental relaxation (anxity, seizures)

12. Dopamin / receptors
5 types of receptors: D1 – D5
D1 and D5 activate the AC
D2-4 inhibit AC
Extrapyramidal system: motor functions
Limbic system: emotions, behavior
Tuberoinfundibular system: prolactin
secretion
Disorders: Psychosis, parkinsonism,
attention, motor functions, prolactin
inhibition

13. Norepinephrine (NE)
Central effects
• Concentration
• Vigilance
• Attention
• Energy
• Mood
• Disorders: ↑vigilance
↓depression
Peripheral effects
• Tachycardia
• Hypertension
• Glukose
• Essential organs

14. Serotonin 5HT
• Neuron bodies in the raphe nucleus,
ascending and descending fibers
• Head (pleasure, social contacts, migraine;
lack: anxiety, impulsive reactions,
decreased libido)
• Red (platelet function)
• Fed (GIT disorders: increased peristalsis,
nausea, vomiting)
• Serotonin syndrome (head, red, dead) –
never 2 drugs that increase 5HT at the
same time

15. Acetylcholin (Ach)
• Autonomic
system
bradycardia
GI motility
salivation
urination
sexual function
• Contraction
Corpus striatum
skeletal muscles
• Hippocampus
learning
memory
vigilance
attention

16. Opioids
• They regulate the perception of pain
• Enkephalins, endorphins
– Analgesia
– Respiratory depression
– Miosis
– Euphoria
– Mental function
– Constipation

17. Ekscitatory and inhibitory PSP

18. Possible drug targets
• AP propagation in the presynaptic fiber
• Biosynthesis of neurohumoral transmitter
• Depositing the transmitter
• Release the transmitter
• Transmitter reuptake
• Biological degradation of transmitters
• Effect of the transmitter on the postsynaptic
receptor
• Changes in ion permeability in the
postsynaptic membrane

19. Antipsyhotics
Neuroleptics
Major
tranquilizers

20. Shizofrenia
• Schizophrenia is a mental
disorder characterized by significant
alterations in perception, thoughts, mood
and behavior:

21. Pathophysiology
• Neurodevelopmental disease:
– significant disorder of brain structure and
function (frontal)
– Hereditary (genetic, epigenetic)
– Goal: improve cognitive functions and quality
of life
:

22. Neurotransmitter teories:
Dopamine – hyperactive dopamine in the mesolimbic pathway
Glutamate – NMDA receptors hypofunction
Serotonin- 5HT2 receptors hypofunction in the cortex
Dopamine theory Additional theories

25. Dopaminergic transmission

26. Antipsychotic drugs
 I generation, typical
 Phenotiazines
 diethylaminopropyls (chlorpromazine, levopromazine,
promazine, triflupromazine)
 piperazines (trifluperazine, perphenazin, fluphenazine,
prochlorperazine)
 piperidines (thioridazine)
 Thioxantenes (chlorprothixene, flupenthixol)
 Butyrophenones (haloperidol, droperidol, penfluridol)
 Others (loxapine, molindone, pimozide)
 II generation, atypical
 Clozapine, olanzapine, risperidone, sulpiride, quetiapine,
ziprasidone, aripiprazole, paliperidone, lurasidone

27. Antypsichotics
I generation, typical II generation, atypical

30. Adverse effects
 Dystonia (involuntary contractions of the muscles of the
limbs, trunk, head, tongue)
 Akathisia (physiological and mental restlessness)
 Extrapyramidal syndrome
 pronounced - requires antiparkinsonian drugs
(anticholinergics)
 Tardive dyskinesia
 abnormal orofacial movements (50% - after1 year)
 upregulation of dopamine receptors
 Other side effects
 somnolence, lethargy, orthostatic hypotension,
constipation, icterus (stoppage of bile flow), neuroleptic
malignant syndrome, thermoregulation disorder,
amenorrhea, galactorrhea, gynecomastia, erectile
dysfunction

31. Adverse effects
Receptor Adverse effect Drug
D2 Extrapyramidal syndrome, prolactin
increase
ALL: haloperidol
fluphenazine
tioxanten
Alpha 1 Postural hypotension chlorpromazine
H1 Sedation, drowsiness, weight gain chlorpromazine
clozapine
M1 Confusion, memory loss, constipation,
urinary retention, blurred vision, dry
mouth
Chlorpromazine,
thioridazine
5-HT
(1B, 2C)
Weight gain Risperidone,
clozapine

32. Adverse Signs Time Mechanism Treatment
effects
Dystonia Muscle spasm 1-5 days Unknown Antiparkinsonics
(tongue, face,
nack, back)
Akathizia Restlessness 5-60 days Unknown dose decreasing
propranolol,BZD
Ext.piramidal Bradykinezia 5-30 days Antagon. Antiparkinsonics
syndrome rigidity, tremor dopamine
Tardive abnormal several M to dopamine Prevention
diskinezia orofacial Y potenciation
movements
Neuroleptic Catatonia, stu- several weeks dopamine discont. therapy
malignant por, fever, antag. dantrolene
syndrome myoglobinemia bromocriptine
Adverse effects treatment