CNS - disorders , symptoms and treatment

1. Central Nervous System
Somaya Nasser
Aysha Abu Hussein
Wafa Atta
Aseel Nasser
Aya Injas

2. Antidepressant

3. What is depression ??
Depression is a mood disorder that causes a persistent feeling of
sadness and loss of interest. Also called major depressive disorder
or clinical depression, it affects how you feel, think and behave and
can lead to a variety of emotional and physical problems.

4. Theories of Depression
• Researchers do not know exactly how or why the process of
neurotransmission is altered in depression, but decades of
research have implicated two key monoamine
neurotransmitters, noradrenaline and serotonin.
• The Biogenic Amine Hypothesis states that depression is
caused by a deficiency of monoamines, particularly
noradrenaline and serotonin
• According to this hypothesis, depression can be alleviated by
drugs that increase the availability of noradrenaline and
serotonin.
• There are other theories like The Serotonin-only Hypothesis,
The Permissive Hypothesis , The Electrolyte Membrane
Hypothesis and The Neuroendocrine Hypothesis.

5. Symptoms of depression
• Intense feelings of sadness
• hopelessness and despair
• Inability to experience pleasure in pleasurable
activities
• Change in sleep patterns
• Suicidal thoughts
‫نفسيا‬ ‫تعبان‬

6. Diagnoses and tests
• Depression symptoms present in most day for month .
• Depression may be secondary to Organic problems like
hypothyroidism, dementia, anemia ,Psychiatric problems like
schizophrenia, drug abuse, anxiety disorders , Use of
depressants drugs such as alcohol .
• Tests help in rule out the problems that lead to depression
Physical exam , Lab tests (test thyroid ) , Psychological
evaluation , DSM-5 (Diagnostic and Statistical Manual of
Mental Disorders ).

7. Treatment
• Psychotherapy talk therapy,”
where you meet with a psychiatrist,
psychologist, social worker, ‫نفسيا‬ ‫تعبانة‬
or other trained mental health
professional. You will learn new
ways to handle challenges and change ways of
thinking that depression affects.
• Drugs (Antidepressants)

8. Antidepressant
• First-generation
-Tricyclics antidepressants (TCAs)
-Monoamine oxidase inhibitors (MAOIs)
• Second-generation
-Selective serotonin reuptake inhibitors (SSRIs)
-Serotonin-norepinephrine reuptake inhibitors (SNRIs)
• Atypical antidepressants

9. ◦ Selective serotonin reuptake inhibitors
(SSRIs)
• MOA : Antidepressant drugs
that specifically inhibit serotonin
reuptake so it block the
reuptake of serotonin,
increasing its concentrations
in the synaptic cleft and its
postsynaptic neuronal activity .
• Have largely replaced TCAs and
MAOIs as the drugs of choice in
treating depression

10. SSRI
• Fluoxetine (Prozac® (lilly),
Fluoxicare®(pharmacare), Flutine®(teva),
Prizma®(unipharm),)
• Citalopram (cipramil®(H.lundbeck),
sitram®‫جاال‬ ‫)بيت‬
• Escitalopram (cipralex® (H.lundbeck))
• Fluvoxamine (favoxil®(perrigo))
• Paroxetine (seroxat ®(gsk),
paxxet®(unipharm))
• Sertraline ( Lustral®(pfizer))

11. SSRI
• Therapeutic uses
• Depression
• Obsessive Compulsive Disorder (OCD)
• Panic disorder
• Generalized Anxiety Disorder (GAD)
• Post Traumatic Stress Disorder (PTSD)
• Social anxiety disorder
• Premenstrual dysphoric disorder
• Bulimia nervosa (only fluoxetine is approved)

12. Adverse Effects
• Headache
• Sweating
• Anxiety and agitation
• GI effects (nausea, vomiting, diarrhea)
• Weakness and fatigue
• Sexual dysfunction
• Changes in weight
• Sleep disturbances (insomnia or somnolence)
Paroxetine and fluvoxamine are more sedating
Fluoxetine or sertraline are more activating
SSRIs

13. Discontinuation syndrome:
• All SSRIs have potential to cause
discontinuation syndrome after abrupt
withdrawal ,Fluoxetine has the lowest risk of
causing SSRI discontinuation
• Signs and symptoms of SSRI discontinuation
syndrome , Headache, malaise, flu-like
symptoms, agitation and irritability,
nervousness, and changes in sleep pattern
• Discontinuation syndrome can be prevented
by taking medication as directed, and when
discontinuing, doing so gradually.

14. Counseling
• Patient must know that it take a few weeks before he feel the
positive effects of the medication (cause he may stop taking it
if he feel that it dose not do anything …… Maximum benefit
may require ≥12 weeks ) .
• do not stop the medication without counseling the doctor ( to
prevent the Discontinuation syndrome) .
• Teenagers and children behavior must be watched (~ 2%
children report suicidal ideation with SSRI) .
• The patient must know the side effects and he must
communicate with the doctor if other side effects appeared
(may be dangerous )
• The patient must asked if he take another medications to
prevent any drugs interactions

15. Serotonin-norepinephrine reuptake
inhibitors (SNRIs)
• MOA : Inhibit the reuptake of both 5-HT and NE ,
Venlafaxine and desvenlavfaxine are potent
inhibitor of 5-HT reuptake and, at medium to higher
doses, is an inhibitor of NE reuptake
Duloxetine inhibit serotonin and norepinephrine
reuptake at all doses.
Uses
• treating depression in patients where SSRIs are
ineffective
• Effective against chronic painful symptoms, such as
backache and muscle aches (This pain is modulated
by 5-HT and NE pathways in the CNS)

16. Serotonin-norepinephrine reuptake
inhibitors (SNRIs)
• Duloxetine (Cymbalta®lilly)
• Venlafaxine (viepax® dexcel, Effexor®
newpharm)
• Desvenlafaxine
• Levomilnacipran

17. Adverse effects
• Side effects of venlafaxine and
desvenlafaxine , Nausea, headache,
sedation, dizziness, insomnia Sexual
dysfunction , Constipation
• Adverse effects of Duloxetine Nausea , Dry
mouth , Constipation , Insomnia , Sexual
dysfunction , Risk for an increase in either
blood pressure or heart rate

18. Atypical antidepressants
Bupropion:
Mechanism of action: weak dopamine nor-
epinephrine reuptake inhibitor.
Therapeutic use: smoking cessation, cocaine
withdrawal and antidepressant.
Side effects: dry mouth, nervousness, tremors
and seizures at high doses

19. Atypical antidepressants
Mirtazapine:
Mechanism of action: blocks α2 presynaptic
receptors and serotonin receptors.
Therapeutic use: antidepressant.
Side effects: sedation, increased appetite and
weight gain.

20. Atypical antidepressants
Nefazodone & Trazodone:
Mechanism of action: weak inhibitors of serotonin
reuptake and serotonin receptor blockers.
Therapeutic use: antidepressants.
Side effects: sedation (H1 blockers), orthostatic
hypotension, dizziness.
Nefazodone is hepatotoxic.

21. Tricyclic Antidepressants (TCAs)
• Imipramine
• Clomipramine
• Desipramine
• Trimipramine
• Amitriptyline
• Maprotiline
• Nortriptyline
• Protriptyline
• Amoxapine
• Doxepin

22. Mechanism of action
• Inhibition of neurotransmitter reuptake : TCAs are
potent inhibitors of the neuronal reuptake of
norepinephrine and serotonin.
** Maprotiline and desipramine are relatively selective
inhibitors of norepinephrine reuptake
• Blocking of receptors : TCAs also block α-adrenergic,
histaminic, and muscarinic receptors causing many
adverse effects

23. Actions
• Elevate mood.
• Improve mental alertness.
• Increase physical activity, and reduce morbid
preoccupation in 50-70% of individuals with major
depression .
>> Slow withdrawal to minimize discontinuation
syndromes and cholinergic rebound effects

24. Therapeutic uses
• TCAs are effective in treating moderate to severe
depression .
• TCAs particularly amitriptyline have been used to
help prevent migraine headache and treat chronic
pain disorders .
• Low doses of TCAs (especially doxepin) can be used
to treat insomnia
• Imipramine has been used to control bed-wetting in
children (> 6 years) by causing contraction of the
internal sphincter of the bladder

25. Adverse effects
• Blockade of muscarinic receptors causes blurred
vision, xerostomia, urinary retention, sinus
tachycardia, constipation.
• Block α-adrenergic receptors, causing orthostatic
hypotension, dizziness, and reflex tachycardia .
• Blockade of H1 receptors leads to sedation.
• Affect cardiac conduction which may precipitate life-
threatening arrhythmias in overdose
• Weight gain
• Sexual dysfunction

26. Monoamine Oxidase Inhibitors (MAOIs)
• Isocarboxazid
• Phenelzine
• Tranylcypromine
• Selegiline

27. Mechanism of action
• MAOIs form stable complexes with MAO causing
irreversible inactivation .
• This causes increased stores of norepinephrine,
serotonin, and dopamine within the neuron and
diffusion of excess neurotransmitter into the synaptic
space .
• These drugs inhibit MAO not only in the brain but also in
the liver and gut that catalyze oxidative deamination of
drugs and potentially toxic substances .
** Selegiline and tranylcypromine have an amphetamine-
like stimulant effect that may produce agitation or
insomnia

28. Therapeutic uses
• Indicated for depressed patients who are
unresponsive or allergic to TCAs or who
experience strong anxiety.
• Treatment of a special subcategory of
depression called atypical depression .

29. Adverse effects
• Drowsiness
• Orthostatic hypotension
• Drug-food and drug-drug interactions :
Individuals receiving a MAOI are unable to degrade
tyraminecausing the release of large amounts of
stored catecholamines from nerve terminals,
resulting in “hypertensive crisis”
• Phentolamine and prazosinare helpful in the
management of tyramine-induced hypertension

31. Psychosis

32. Psychosis
• Psychosis: a mental disorder caused by brain
• dysfunction
• Schizophrenia :
• Type of psychosis characterized by:
• Delusions
• Hallucinations (often in the form of voices)
• Thinking or speech disturbances

33. Diagnosis of psychosis:
At least two of the characteristic symptoms:
Grossly disorganized behavior
Negative symptoms (blunted affect, anhedonia, apathy, social isolation,
poor hygiene, poor memory, impaired attention and poor cognition)
Deterioration in function
Duration at least 6 months

34. Antipsychotic drugs
Affect dopamine by blocking dopamine
receptors.
*First generation antipsychotics
◦low potency
◦high potency
*Second generation antipsychotics

35. Antipsychotic drugs
*Many of these agents also block cholinergic,
adrenergic, and histaminergic receptors
causing adverse effects
1. Antipsychotic actions
2. Extrapyramidal effects
3. Antiemetic effects
4. Anticholinergic effects
5. Other effects

36. First generation antipsychotic:
*Low potency
◦Chlorpromazine: has anticholinargic effect,
antihistamine(sedation)
◦Prochlorperazine: has antiemetic effect
◦Thioridazine: has anticholinergic effect
*High potency
◦Haloperidol: has antiemetic effect
◦Fluphenazine
◦Pimozide
◦Thiothixene
◦Loxapine
◦Trifulperazine

37. First generation antipsychotic:
*Competitive blockers of D2 receptors
*Associated with movement disorders,
especially the ones with stronger binding to
dopamine receptors

38. Second generation antipsychotic:
*Risperidone
*Olanzapine: has anticholinergic,antihistamine effect
*Quetiapine: has anti histamine effect
*Clozapine: has anticholinergic,antihistamine effect
##s.e: Bone marrow suppression,
Seizures,Cardiovascular side effects
*Aripiprazole

39. Second generation antipsychotic:
*block both dopamine and serotonin receptor.
*fewer EPS than first generation
*min. risk of deblitating movement disorder
than first generation
*Associated with a higher risk of metabolic
side
effects like diabetes, hypercholesterolemia and
weight gain

40. Side effect:
1.Extrapyramidal side effects
2.Tardive dyskinesia
3.Antipsychotic malignant syndrome
4.Drowsiness occurs due to CNS depression and
antihistaminic effects
5.Antimuscarinic activity produces dry mouth, urinary retention,
constipation
6.Blocking α-adrenergic receptors results in orthostatic hypotension
7.The antipsychotics depress the hypothalamus, affecting
thermoregulation and causing amenorrhea, galactorrhea,
gynecomastia, infertility, and impotence
8. Weight gain
9. Hyperglycemia and hypercholesterolemia (second generation
atipsychotics)

42. Opioids
Opioids are the drug of choice for sever or
chronic pain.
Mechanism of action:
They work by binding to opioid μ receptors,
thus relieving pain.

43. Opioids are divided into:
Strong agonists.
Moderate/low agonists.
Mixed agonist-antagonists & partial agonists.

44. Strong agonists
-Morphine
-Meperidine
-Methadone
-Fentanyl
-Heroin
-Others.

45. Morphine:
Mechanism of action: Next to acting as μ receptor
agonist, they also act at κ receptors, and decreases
the release of substances P and thus modulating
pain perception.
Therapeutic effects: Analgesic and antitussive.
Side effects: respiratory depression, hypotension,
vomiting, tolerance and physical dependence.

46. Meperidine:
Mechanism of action: strong μ receptor
agonist.
Therapeutic use: analgesic for acute pain.
Adverse effects: respiratory depression,
(anxiety, tremors, muscle twitches upon
repeated administration).

47. Methadone:
Mechanism of action: μ receptor agonist.
Therapeutic use: analgesia, controlling
withdrawal symptoms of morphine and
heroin.
Causes less euphoria and dependence than
morphine.

48. Fentanyl:
Mechanism of action: μ receptor agonist.
Therapeutic uses: anesthesia induction, labor
and post operative analgesic.
Side effects: hypoventilation.
**Has a hundred fold the analgesic potency
of morphine.

49. Heroin:
Synthetic derivative of morphine.
It is three times more potent than
morphine, and causes more euphoria.
*** It has NO medical use.

50. Others:
Oxycodone.
Oxymorphone.
Hydromorphone.
Hydrocodone.

51. Equivalency between opioids
How would it differ if we used parenteral or
oral dosage forms of the same opioid?

52. Dose equianalgesic to 10 ml parenteral
morphine.
Parenteral dose (ml)Oral dose (ml)Opioid
1030Morphine
75300Meperidine
103-5Methadone***
0.1-0.2N/AFentanyl
1N/AOxymorphone
1.57.5Hydromorphone
N/A30Hydrocodone
N/A20Oxycodone
https://palliative.stanford.edu/opioid-conversion/equivalency-table/

53. Moderate/low agonist
• Codeine
 Good antitussive activity at doses that do not cause analgesia
 Metabolized to morphine in the body by CYP2D6 causing analgesic
effects (30% that of morphine)
 Causes euphoria
 Lower abuse potential than morphine at commonly used doses
• *** BRONCHOLOTE FORTE SYRUP (pseudoephedrine HCl
20mg,diphenydramine 10mg,codeine 5mg ):for cough accomanied py
nasal or auditory congestion.
• *** PULMADRIN (triprolidine HCl 1.25mg, pseudoephedrine HCl 30mg ,
codeine 10mg ): antihistamine decogestant and antitussive
• ***NUROFEN PLUS(ibuprofen 200mg,codeine 10mg) :migraine
,headache,dental paine ,backage and muscular paine,manstrual,
rheumtic paine.

54. Mix agonist –antagonist & and partial agonist
 Drugs that stimulate one receptor but block another .
 The effects of these drugs depend on previous exposure to
opioids :
 In individuals who have not recently received opioids (naïve
patients), mixed agonist-antagonists show agonist activity and
are used to relieve pain
 In patient with opioid dependence, the agonist-antagonist
drugs may show primarily blocking effects and produce
withdrawal symptoms

55. Pentazocine
• Mechanism of action: Acts as an agonist on κ receptors and a weak
antagonist at μ and δ receptors .
• Therapeutic effects : promotes analgesia by activating receptors in
the spinal cord, and it is used to relieve moderate pain
• Side effects: Produces less euphoria than morphine
In angina, pentazocine increases the mean aortic pressure and
pulmonary arterial pressure increasing the work of the heart .
Tolerance and dependence develop on repeated use
• At higher doses :
respiratory depression,increase blood pressure and can cause
hallucinations, nightmares, dysphoria, tachycardia, and dizziness

56.  Burenorphine
• Mechanism of action: Partial μ receptor agonist. has less severe and
shorter duration of withdrawal symptoms compared to methadone
Has a long duration of action because of its tight binding to the μ
receptor
• Therapeutic effects: opiate detoxification
• Side effects:Respiratory depression that cannot easily be reversed by
naloxone ,Nausea ,Dizziness

57. Opioid antagonists

58. opioid antagonists
 Bind with high affinity to opioid receptors but fail to
activate the receptor-mediated response
 Administration of opioid antagonists produces no
profound effects in normal individuals
 In patients dependent on opioids, antagonists rapidly
reverse the effect of agonists, such as morphine or any
full μ-agonist causing symptom of opiate withdrawal

59. Naloxone
 Mechanism of action : . a competitive antagonist at μ, κ, and δ,
receptors rapidly displaces all receptor-bound opioid molecules
reversing their effects.
 Therapeutic effects :Used to reverse the coma and respiratory
depression of opioid overdose
 Within 30 seconds of IV injection of naloxone the respiratory
depression and coma characteristic of high doses of morphine are
reversed causing the patient to be revived and alert
 Short half life (30-80 min)
 Can cause withdrawal symptoms in opioid abusers

60. Naltrexone
 Similar effects to naloxone with a longer duration of action
 A single oral dose can block Heroin effects for up to 48 hours
 Can cause hepatotoxicity

61. Other analgesics
 Tramadol
 Mechanism of action: μ-opioid receptor ,Weakly inhibits reuptake of
norepinephrine and serotonin .
 Therapeutic effects :Centrally acting analgesic Used to manage
moderate to moderately severe pain .
• Adverse effects :
 Less respiratory depression than morphine .
 Anaphylactoid reactions.
 Toxicity through drug-drug interactions with medications, such as
SSRIs and TCAs or in overdose leads to CNS excitation and seizures .
Contrindication :Tramadol should be avoided in patients taking MAOIs .

62. *** Zaldiar (tramadol hydrochloride and paracetamol )
*** Tramal (tramadol hydrochloride )
 Tapentadol
 Mechanism of action :binds the μ-opioid receptor and is also a
norepinephrine reuptake inhibitor
 Therapeutic effects: Centrally acting analgesic that Used to manage
moderate to severe pain