Contents

PERPHENAZINE 2 MG.

9


13
23

29
35

39
45

49
55

57

58

59

ALPRAZOLAM 1 MG.

AMITRIPTYLINE 25 MG.

LITHUM.CARBONATE 300 MG.

(Antipsychotic drugs)

(Antianxiety drugs)

(Antidepressant drugs)

(Mood Stabilizers)



Drug-Drug, Drug-Food Interaction

1.
2.
3.
4.

(Antipsychotic Drugs)
(Antianxiety Drugs)
(Antidepressant Drugs)
(Mood Stabilizers)

receptor

(+ = , - = )

Adrenergic Receptors (Ad.)

alpha1 -adrenergic receptors

(-) , , reflex tachycardia

alpha2 -adrenergic receptors

(+)
(-) priapism ( )
(-) Clonidine

hydrochloride, guanabenz acetate, methyldopa

Cholinergic Receptors
muscarinic M1 receptors

(+) extrapyramidal side effects

(-) peripheral antimuscarinic effects : ,

(narrow angle glaucoma), ,

,
(-) central antimuscarinic effects :

(cognition)

Dopaminergic Receptors (D)

dopamine D2 receptors
10

(+) (positive psychotic symptoms)

, , ( mesolimbic pathway)
(-) extrapyramidal side effects : dystonia, parkinsonism,

akathisia tardive dyskinesia ( nigrostriatal

pathway)
(-) : prolactin

, ,

( tuburoinfundibular pathway)

Histaminergic Receptors
histaminergic H1 Receptors

(+) (sedation)
(-) ,

(central nervous system depressants)

histaminergic H2 Receptors
(+)

Serotonergic Receptors (HT)

serotonin 5-HT2A receptors

(+) (negative psychotic symptoms)

(blunted affect),
(+) extrapyramidal side effects
(-) (asthenia)

serotonin 5-HT1A receptors

(+)
(+) (obsession) (compulsion)
(+) (panic) (social phobia)
(+) (bulimia)

serotonin 5-HT1D receptors

(+) (antimigraine actions)

serotonin 5-HT2 receptors

(-) (agitation),

(akathisia), , (panic attacks),

serotonin 5-HT3 receptors

(-) , (gastrointestinal distress),

11

(Antipsychotic
drugs)

13

D2 receptor
(D2 receptor antagonism) dopamine
pathway
Mesolimbic pathway
(positive symptoms)
Mesocortical pathway
(negative symptoms) cognitive
Nigrostriatal pathway
extrapyramidal (extrapyramidal side effects : EPS)
Tuberoinfundibular pathway prolactin
galactorrhea gynecomastia
14

dopamine pathways
D2 receptor
60 - 80

mesolimbic
mesocortical nigrostriatal
tuberoinfundibular extrapyramidal
5HT2A receptor
dopamine nigrostriatal EPS

D2 receptor
receptor
dopamine receptor EPS
dopamine

receptor muscarinic receptor

(M1), histamine receptor (H1) alpha-1 adrenergic receptor

(first-pass metabolism)
2-4
15-20 30-60

volume
of distribution
cytochrome P450 2D6
18-40 5-10

1. Typical Antipsychotic Drugs ( 1)

2. Atypical Antipsychotic Drugs
( 2)

15

(Typical Antipsychotic Drugs)

(mg.)

Chlorpromazine
(mg.)

Dopamine (D2)

Histamine (H1)

Muscarinic (M1)

Adrenergic (A1)

200 - 800
200 - 600
8 - 64
6 - 30
1 - 20

100 -
100 -
10 -
5 -
2 -

+
+
++
++
+++

+++
+++
++
++
+

+++
+++
++
++
+

+++
+++
++
++
+

Thioxanthenes
Thiothixene

6 - 30

5 -

+++

Butyrophenones
Haloperidol

6 - 20

2 -

+++

Dibenzoxapines
Loxapine

60 - 100

15 -

++

++

++

++

Dihydroindolones
Molindone

50 - 100

10 -

++

++

++

16

receptor

Phenothiazines
Chlorpromazine
Thioridazine
Perphenazine
Triffuoperazine
Fluphenazine

Typical

Clozapine

Risperidone

Olanzapino

Quetiapine

(typical
antipsychotics Drugs) (Atypical
Antipsychotic Drugs)

+ to ++

++

(Agranulocytosis)

+++

Anticholinergic effects

+ to +++

+++

++

Liver enzyme elevation

Extrapyramidal side effect

(EPS)

+ to +++

(Orthostatic hypotention)

+ to +++

+++

++

++

(Elevation of prolactin)

+ to +++

++

(Sedation)

+ to +++

+++

++

+++

Tardive dyskinesia (TD)

+++

+/0

(Weight gain)

+ to +++

+++

+++

Advers effect
(Agitation)

(Seizures)

17

18

(Antipsychotic drugs)

1. dopamine blocker pathway

-
- Extrapyramidal side effects (EPS)
i. Acute dystonia

(oculogyric crisis) (torticollis)

ii. Akathisia

iii. Parkinsonism

2 - 3
iv. Tardive dyskinesia

3 5
v. Neuroleptic malignant syndrome

autonomic

nervous system

0.1

10 20
- amenorrhea,

galactorrhea, impotence
2. alpha-1 adrenergic blocker

norepinephrine epinephrine
beta-adrenergic receptor
3. anticholinergic agent (muscarinic type)

( )

4.
- Cardiotoxicity QT prolong

chlorpromazine thioridazine t-wave

19

20

- Hematological effects 3

5 10,000
- Ophthalmological effects : thioridazine 800 ./

chlorpromazine
- Dermatological effects

- Weight gain
- Jaundice 1 1,000
-

chlorpromazine clozapine
- retrograde ejaculation, Eretile

dysfunction
-

extrapyramidal side effects

Anticholinergic drugs EPS

akathisia propranolol benzodiazepine

anticholinergic

EPS EPS

acute dystonia benztropine (Cogentin)
1-2 . IM IV diphenhydramine (Benadryl) 50 . IV
diazepam 5-10 . IV 15
Parkinsonism
4-8
2
anticholinergic
delirium
dementia

Antichlinergic

Bentropine mesylate

Cogentin

1 - 4 . 1 - 3

1 - 2 .

Biperidine

Akineton

2 . 1 - 3

2 .

Trihexyphenidyl
hydrochloride

Artane,
Benzhexol

2 - 5 . 1 - 3

21



(Antipsychotic drugs)

CHLORPROMAZINE
50 MG.

CHLORPROMAZINE
100 MG.
24

CHLORPROMAZINE
200 MG.

CLOZAPINE
25 MG.

CLOZAPINE
100 MG.

HALOPERIDOL
0.5 MG.
25

HALOPERIDOL
2 MG.

HALOPERIDOL
5 MG.

HALOPERIDOL
10 MG.

PERPHENAZINE
2 MG.
26

PERPHENAZINE
4 MG.

PERPHENAZINE
8 MG.

PERPHENAZINE
16 MG.

THIORIDAZINE
10 MG.
27

THIORIDAZINE
25 MG.

THIORIDAZINE
50 MG.

THIORIDAZINE
100 MG.

TRIFLUOPERAZINE
5 MG.
28

TRIFLUOPERAZINE
10 MG.

(Antianxiety Drugs)

30

Benzodiazepine GABA A receptor

GABA-benzodiazepine receptor complex

chloride ion channel chloride

hyperpolarization benzodiazepine

benzodiazepine
receptor cerebellum
ataxia reticular formation
hippocampus
spinal cord muscle relaxation
GABA receptor
benzodiazepine barbiturate ethanol
cross-tolerance
benzodiazepine

Benzodiazepine
30 6-8
(lipid solubility) benzodiazepine
oxidation (phase I metabolism)
conjugation (phase II metabolism)
lorazepam, temazepam oxazepam ()
conjugation 3


Benzodiazepine
benzodiazepine clorazepate 0.5 ,
diazepam 1 , triazolam 1.3 , alprazolam
lorazepam 2

( distribution half-life )

diazepam, alprazolam, chlordiazepoxide lorazepam

31

32

benzodiazepine

myasthenia gravis

conjugation

1.
nystagmus dysarthria serum globulin

2



2. anterograde amnesia
benzodiazepine triazolam

3. Disinbibition

4. Paradoxical excitement

(organic brain syndrome)

benzodiazepine

(half-life) (metabolism) (equivalent
does,mg) (mg. )

Triazolo
Triazolam
Alprazolam

Oxidation
Oxidation

3-hydroxy
Lorazepam
Oxazepam
Temazepam

Conjugation
Conjugation
Conjugation

1
15
5

1-6
30 - 120
7.5 - 30

0.25 - 0.5 0.125 - 0.25

0.25
0.5 - 4

2-keto
Chlordiazepoxide
Clonazepam

Chlorazepate

Diazepam

Flurazepam

Halazepam

Oxidation
Oxidation
Oxidation
Oxidation
Oxidation
Oxidation

10
0.5
7.5
5
5
20

10 - 150
1-6
15 - 30
2 - 40
15 - 30
60 - 160

Prazepam

Oxidation

10

20 - 60

33

Benzodiazepine

34

1.
diazepam
(panic symptom)

(terminal insomnia)
2.
2 - keto
3 - hydroxy triazolo
2 - 3
3.


(terminal insomnia)
4.

5.

oxidation
conjugation



(Antianxiety drugs)

ALPRAZOLAM
0.25 MG.

ALPRAZOLAM
0.5 MG.
36

ALPRAZOLAM
1 MG.

DIAZEPAM
2 MG.

DIAZEPAM
5 MG.

DIAZEPAM
10 MG.
37

DIPOT.
CHLORAZEPATE
5 MG.

LORAZEPAM
0.5 MG.

LORAZEPAM
1 MG.

MEDAZEPAM
5 MG.
38

MEDAZEPAM
10 MG.

PRAZEPAM
5 MG.

(Antidepressant drugs)

39

40

1. (short-term effect)

. monoamine presynaptic
neuron receptor 3

reuptake presynaptic neuron

catechol-o-netgyl transferase (COMT)
monoamine oxidase (MAO)

reuptake
norepinephrine / serotonin presynaptic neuron
neurotransmitter neuron

. receptor
muscarinic receptor (M1), histaminergic receptor (H1), alpha
receptor, dopaminergic receptor (D2) serotonin receptor (5HT2)
receptor

2. (long-term effect)

density function beta-2-drenergic

receptor serotonin type 2 receptors
down regulation receptor

4
1. tricyclic tricyclic ring
imipramine, amitriptyline, nortriptyline, clomipramine doxepin
2. Monoamine oxidase inhibitor
Reversible Inhibitors of MAO subtype A (RIMA) moclobemide
3. selective serotonin reuptake inbibitors (SSRI)
5 fluoxetine, fluvoxamine, paroxetine,
sertraline citalopram reuptake
serotonin
4. new generation mianserin, trazodone,
tianeptine, bupropion venlafaxine mirtazapine

tricyclic
1-6 30-70
metabolized (first-pass effect) tricyclic lipid
solubility

5-10 volumn of
distribution (10-30 /)

tricyclic 10-90
24
5-7

41

(Antidepressant drugs)

42

1. Sedation tricyclic sedation

amitriptyline doxepin tolerance
mianserin trazodone

SSRI moclibemide
2. anticholinergic
tertiary amine

central anticholinergic syndrome

delirium peripheral
Physostigmine 1-2 . 30-60
bethanechol 25-50 . 3-4 /
bulk - laxative Metamucil

3. Cardiovascular tricyclic (amitriptyline)
EKG QRS
complex PR interval T-wave flattening

postural hypotension
10-20

nortriptyline
4. Fine tremor 10

propranolol 20-30 ./

5. Seizure tricyclic seizure threshold

maprotiline

6. amitriptyline
fluoxetion
7. Sexual effect erectile ejaculatory
dysfunction reversible
bethanechol 20 . 1-2 neostigmine
7.5-15 .
anorgasmia cyproheptadine 4 ./
8. (Akathisia)
serotonin reuptake inhibitor Fluoxetine


2-3
trazodone tricyclic (
amitirptyline) benzodiazepine
2-3

43

(mg.)

Sedation

Anticholinergic
effect

Orthostatic
Hypotension

Weight
gain

75 - 300
75 - 300
50 - 150
100 - 250

+++
++
++
+++

+++
++
++
+++

+++
++
++
+++

+++
++
++
+++

Inhibitor (SSR)
Fluoxetin
Sertraline
Paroxetine

20 - 80
50 - 150
20 - 40

+
+
+

0
0
0/+

0
0
0

NA
NA
+

Phenylethylamine
Venlafaxine

75 - 375

50 - 600

+++

++

++

Heterocyclics
Amitryptyline
Imipramine
Nortryptyline
Clomipramine
44

Serotonin Reuptake

Triazolopyridines
Trazodone

+++ = , ++ = , + = ,
0 = , NA =



(Antidrepressant drugs)

AMITRIPTYLINE
10 MG.

AMITRIPTYLINE
25 MG.
46

FLUOXETINE
20 MG.

IMIPRAMINE
10 MG.

IMIPRAMINE
25 MG.

IMIPRAMINE
50 MG.
47

NORTRIPTYLINE
10 MG.

NORTRIPTYLINE
25 MG.

TRAZODONE
50 MG.

TRAZODONE
100 MG.
48


(Mood Stabilizers)

bipolar disorder mania

1. Lithium
2.

Lithium

50

first messenger
neurotransmitter presynaptic neuron neurotransmitter
receptor G protein G protein
second messenger

second messenger cAMP

calcium ion phosphotidylinositol
bipolar disorder
inositol monophosphate phosphatase (IMP)
(GSK)-3-beta diacylglycerol/
protein kinase C
transcription factors gene expression

300

8 mEq

1.5-2
water soluble
metabolism
95 glomerular
filtration rate (GFR) GFR
thiazide
30 - 50 furosemide

20-24
5 - 7

51

1.
40

antidiuretic hormone (ADH)

hydrochlorothiazide 50 ./

thiazide

peak level

2. 30 - 60
fine tremor
Propranolol 40-120 ./

tolerance propranolol

52

3.

(peak level)

4.
5. acneiform
eruption, maculopapular eruption,
follicular eruption, hair loss,
exfoliative dermatitis

l
l

preparation

hypothyroidism ()

l

6.
benign effect

hypokalemia

T wave flattening inversion

sick sinus syndrome
sinus node
ST segment

depression QT interval

prolongation

7.
8-10
1-2

8.
renal function

l
l

spironolactone 50 ./

l
l

9.
Simple goiter, euthyroid
L-thyroxin

5-10
50-100 /

serum TSH
Clinical hypothyroid

Goiter



TSH T4

53



(Mood Stabilizers)

LITHIUM
CARBONATE
300 MG.

LITHIUM
CARBONATE
300 MG.
56

Antidepressants
Imipramine
Desipramine
Amitriptyline
Nortriptylin
Doxepine
Fluoxetine
Fluvoxamine
Paroxetine
Sertraline
Mood stabilizers
Lithium salts
Valproate
Carbamazepine
Anitpsychotic medications
Chlorpromazine
Perphenazine
Trifluoperazine
Thioridazine
Haloperidol
Risperidone
Anitianxiety and hypnbotic medicatione
Alprazolam
Diazepam
Flurazepam
Lorazepam
Temazepam
Triazolam
Zolpidem

(mg / day)


25 - 300

10 - 300

25 - 300

10 - 150

10 - 300

5 - 80

25 - 150

5 - 20

50 - 150


75 - 900
250 - 1,000
200 - 1,200


30 - 300

8 - 32

1 - 15

25 - 300

2 - 20

2 - 4

0.25 - 2

2 - 60

15 - 30
0.5 - 6

15 - 30
0.125 - 0.25
2.5 - 5

57

Dose

58

Alprazolam
2-4 mg./day ()
Diazepam
40 - 60 mg./day
Dipot. Chlorazepate 15 - 30 mg./day
Lorazepam
10 mg./day
Chlorpromazine
600 - 800 mg./day
Clozapine
600 - 900 mg./day
Flupentixol (fluanxol) 18 mg.dialy, for inj 20 mg. - 300 mg./month
Fluphenazine (fendec) 20 mg. dialy, for inj 25 mg. - 300 mg./month
Haloperidol
20 - 40 mg. dialy, for inj 50 mg. - 300mg./month
Lithium
900 - 2400 mg./day
Perphenazine
64 mg./day
Thioridazine
600 mg./day
Zuclopentixol (clopixol) in: acetate max dose: 400 mg./dose

decanote max dose: 600 mg./month

Oral: 100 mg./day
Fluoxetine
80 mg./day
Trazodone
600 mg./day

(Drug-Drug, Drug-Food Interaction)

Lithium

1. Risk of Neurotoxicity
Lithium + Phenytoin (Dilantin)

+ Carbamazepine (Tegretal)

+ Fluoxetine (Fulox)

+ Amitriptyline, Nortriptyline

+ Haloperidol

+ Chlorpromazine, Perphenazine

+ Verapamil, Diltiazem

+ Methyldopa
2. Risk of Blood Lithium Toxicity
Lithium + Diuretics

+ NSAIDs ( Aspirin, Sulindac)

+ ACE-I (Enalapril)

+ Tetracycline

+ COX-2 Inhibitor
3.
Lithium + Chlorpromazine
4. Lithium
Lithium + Sodium bicarbonate

+ Sodium Chloride

+ Caffeine

+ Theophylline

59

Carbamazepine

60

1. Risk of Neurotoxicity
Carbamazepine + Lithium
2. Risk of Hepatotoxicity
Carbamazepine + Paracetamol
3.
Carbamazepine + Theophylline
4.
Carbamazepine + Haloperidol

+ Valproic acid

+ TCA

+ Benzodiazepine
5. Carbamazepine
Carbamazepine + Cimetidine

+ Erythromycin

+ Isoniazid

+ Verapamil
6. Carbamazepine
Carbamazepine + Charcoal

Clozapine

1. Risk of Antichlolinergic effect

Clozapine + quinidine

+ Procainamide
2. Risk of Hypotension
Clozapine + Epinephrin
3. Risk of Hyperglycemia
Clozapine + Glucose
4. Risk of Severe Cardiopulmonary reaction
Clozapine + Antipsychotic

+ Benzodiazepines
5. Clozapine
Clozapine + Charcoal

61

1. , . : ,

2547.
2. , .

, 2547.

62