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Antidepressants

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: MAO Inhibitors MAO L* .


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Phenelzine
Tranylcypromine

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7
M: Pharmacokinetics
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Generic Name Trade Name Generic Trade
Name Name
Imipramine
Imipramine Tofranil Trimipramine Surmontil
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Amitriptyline Desipramine Norpramin Protriptyline Vivactil

Au V A ?
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receptor Pamelor
Nortriptyline Amoxapine Asendin
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receptor
blockad amoxapine Sinequan
Ludiomil maprotiline
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mACh .
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5-HT2 receptor blockade .
Na Channel blockade .

a  Tricyclic Overdose


.: >4Y ( Often suicidal intent
. "MH Extremely hazardous

:+A $ _ A 2
_ + Manifestations
( ) ?delirium,(V
N)Agitation
(G Gz V
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( )(coma ( u7T ) convulsions
(4;7 3P )Respiratory depression

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(- 4Y 3 )circulatory collapse
( Y ) Hyperpyrexia
0[ Cardiac conduction defects and severe arrhythmias
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: Pharmacokinetics -  :
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Generic Name Trade Name

Fluoxetine Prozac

Fluvoxamine Luvox

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Paroxetine Paxil

Sertraline
Zoloft
citalopram

:u BC
(
N MI) decreased appetite, ( )insomnia (jZ)Anxiety,
.(1H )Tremors
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Adverse effects:
. anxiety, insomnia, weight loss

Contraindications:
> Seizure disorder
4Y  head injury
u I 4Y 5 electrolyte imbalance
:] 4O  alcoholism

> `t $]A 4 


Drugs can cause depression

. Alcohol
. Beta blockers
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. Prednisone
. Cocaine & Amphetamine withdrawal. Reserpine

) ( :
:Dopamine hypothesis
:
) Amphetamine
schizophrenia
(.
) L-dopa ( apomorphine bromocriptine
) (dopamine agonist
.schizophrenia
schizophrenia .
pathways
.
) VTA Ventral
(Tegmental Area schizophrenia

neuroleptics
major tranquillizers

   
   :
( ) Dopamine Antagonists :( D2
( :Serotonin Antagonists


"!   
 :
Phenothiazines :
chlorpromazine -
fluphenazine -
Phenothiazine prochlorperazine -
)(chlorpomazine thioridazine -
promazine -

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)Butyrophenones (haloperidol
  
 

:Butyrophenones
haloperidol -

Thioxanthines
thiothixene -


:
.Aliphatic compounds (
(
Piperidi
Group Drug Trade name .nes
Piperazi (
Chlorpromazine (Thorazine, Largactil)
.nes
Aliphatic Promazine :$&
compounds
Triflupromazine Vesprin

Methotrimeprazine Nozinan

Mesoridazine Chlorprom
Piperidines
Thioridazine Mellaril azine

Fluphenazine


Perphenazine
Piperazines
Stemetil
Prochlorperazine

Trifluoperazine Stelazine
.
.

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)'+ 
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.
.
.
.
.
  3 2" 5  0:
Therapeeutic index
:
: .
Chlorpromezine-) antimuscarinic



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) (.
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Dystonia Tremor ( Rigidity
. Dyskinesia
) (.
D2 ) ( Endocrine

.
&:$
)
(.

  6+:


P-450 .

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Haloperidole dicanoate )(
.

Atypical antipsychotics
clozapine

.

Side effects of clozapine


Sedation.
Hypotension .
Tachycardia .
. Dizziness
Weight gain .

 :2+2 9 + 8/ )(


New generation of antipsychotics
)Risperidone (Risperdal

.


? >  : Pathology

substantia nigra compacta
) .
%. .(%

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melanins .

.
AB :Syptoms
TRAP
) Tremor T( : .
) Rigidity R ( .
) Akinesia A ) (
(.
)
: Postural disturbance P .
) bradykinesia
(.

:Treatment 2C

  :
.
:Transplantation substantia
nigra compacta ......
Stem cells .

 :
 L-Dopa

 MAO

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 COMT
) (L-Dopa
) (MAOI,COMTI
). (dopamine agonists
:
.
.

 2C+:
:L-Dopa -
L-Dopa .
BBB .
: % L-Dopa

% L-

Dopa .
striatum L-Dopa .
:
BBB
L-Dopa .

AB 2" : L-Dopa
L-Dopa
:
)( ) (.
) ( .
) (. freezing episode
fluctuation L-Dopa ) L-
Dopa ( L-Dopa
.L-Dopa

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A :dyskinesia E L-Dopa
) dystonia ( ) chorea (
dyskinesia .

 chorea


L-Dopa
L-Dopa

 
dystonia

dyskinesia L-Dopa
.

:
L-Dopa
L-Dopa AADC
BBB
. AADC .caribdopa, benserazide

+& +  :Drug interaction of L-Dopa


:(Pyridoxine) Vitamin B6 .
Vitamin B6 L-Dopa L-Dopa
. L-Dopa
:MAOI . .

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G - 
"& +Dopamine receptor 9
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bromocriptine : :pergolide D1 ) D2
( L-Dopa
L-
Dopa .
) ( )
(.
ropinerole pramipexole
) ( .
% .

H"I - :MAOB
MAO
)
( L-
Dopa L-Dopa .
deprenyl .L-Dopa

MAOI
.
:
MAO .MAOB
MAO .MAOA

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H"I - :COMT
COMT (catechol-O-methyl
) transferase 3-methoxy tyramine
)) (3-MT ( . L-Dopa )
( L-Dopa . 3-O-methyl-dopa
entacarpone, tolcarpone

-B  .0 :9


:Trihexyphenydil )
(.

  8 :Mechanism

cerebral cortex. hippocampus
:
) (depolarization cortex
cerebral hippocampus :
. ) Glutamic acid
(.
. ) GABA (.
. K Na , Ca .
+ + 2+

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ANTICONVULSANTS ( 
 ) 
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Na+ Felbamate
(Benzodiazepines)
(Benzodiazepines)
Phenytoin diazepam Topiramate
Clonazepam
Carbamazepine
Lamotrigine (Barbiturates)
Topiramate Phenobarbital
Valproic acid Valproic acid
Ca+ Gabapentin

Ethosuximide Vigabatrin
Valproic acid Topiramate

Felbamate

Tiagabine

:GABA 819 %" <


;
Na , Ca : Valproic acid 
+ 2+

.GABA
GABA :(GBP)Gabapentin 
.
. GABA :(TPM) Topiramate 
. Carbamazepine 
.GABA

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 .
:
:
.
.
.

B  0A :C CO.0P:


:
.
) Aminotransferase
(.
 Topiramate ) Glu .(AMPA
 Felbamate glycine . NMDA

819 ?1
>=:%
GBP )..... (.
VGB ....(GABA aminotransferase) GABA-T
) SSA (.... VGB
.
TGB .
TPM .

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Side effects
Fatigue
.
Dizziness.
Sedation.
  3
Q 9+,O:

:
:
interneurones

.enkephalin
SP Glu
SP
Glu
.

:
interneuronsdynorphin
kappa ) (Gi
.
& :$ Glu
) ( .
) ( .
:
decsending pathway :
opioid recertors GABA
GABA locus ceruleus
GABA Raphe nucleus

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) ( SP Glu
pain signal .

:
.

neuroaugmentation

) (
)
( .
. acupunture
.
.

  3 / S..B .0,O:


- :Cognition and emotions
euphoria drowsiness Relaxation
. mental confusion
- :Nausea and vomiting

(.
- : cardiovascular effects
.
- :dermatologic effects
.
- :Gastrointestinal tract
. :
.esophegeal reflux.

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. :
.
. :
.
- :Urinary Tract
.
- :Respiratory Tract
)
CO2
( .
- : Cough
.
- :miosis

)( .
.
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) (.
- :
:
. . .cold body
. : )FSH (Follicle stimulating Hormone
b- ACTH (Adrinocortic Trophic Hormone) LH Hormone)(Luteine
.(beta-Endorphin) END
. ) ( :
anorexia
.

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:Stress -

stress:
-Endorphin
ACTH

Pro-
)(opiomelanocortin



ACTH -
.Endorphin
ACTH -Endorphin
stress .sedative
- :Emotions limbic System
Amygdala
.Hypothalamus



.

exogenous
opoids :
. :agonist
.
)codeine
.(propoxyphene

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. - ) ( : :pentazocine
kappa mu .delta
) kappa naloxone . :antagonists mu
naltrexone(.

&$:

Bayer
.
)

(

.

.


 .OB  A 2T /
:Acute intoxication and overdose
.
.
) meperidine (.
) (.
.

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.
)(.

:


 vasoconstiction
 dysphoria
 insomnia
 tachycardia
.
:Treatment 2C
. : methadone
: peak -
. .
:Clonidine . 2 )
( .

&'()*+# Hormones
-
-
-
-
-

:
1- (GHRH) Growth hormone- releasing hormone
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2- Growth hormone- inhibiting hormone or somatostatin


3- (TRH) Thyrotrophin-releasing hormone .
4- (CRH) Corticotropin-releasing hormone .
5- (GnRH) Gonadotropin-releasing hormone .
6- (dopamine) Prolactin-inhibiting hormone .
7- (PRH) Prolactine-releasing hormone .

:
1- (GH) Growth hormone .
2- (TSH) Thyrotropin .
3- (FSH) Follicle-stimulating hormone
4- (LH) Luteinizing hormone .
5- (PRL) Prolactine .
6- (AcTH) Aderncortictropin .
7- (-LpH) - Lipotropin .

.1*)('& ()5&6(78+# 12#/)&)0


?@A# anterior pituitary:8)&<=#
: Somatostatin (Growth hormone-inhibiting hormone) -1
14
.
GH .

.
28 Prosomatostatin
.

:
1-3 min
.


Octreotide
8
45
1.7 hour
1-3 min

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80 . -
: mg 5-200 8
acromegaly
achlorhydria syndrome
diabetic diarrhea, . carcinoid syndrome,
gastrinoma .Glucagonoma

: . Octreotide
: .
: bradycardia
B12 .

: (GH) Somatotropin Growth hormone -


191

Anterior Pituitary
) (
(IGF-I) Insulin-like growth
. factor I

:
 
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anti-insulin  x$
activity  2
Y: Q
^  4Y 0- $ V
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>  ^  4Y7

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0:A  2
Q:  t^  4Y]. -

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GH E.coli
.
20-25 : .
GH
(IGF-I) Somatomedins ) (IGF-II
Somatomedins
.
0.25 mg/Kg 0.45 mg/Kg
.
0.2mg .
: gynecomastia
myalagias . arthralgias

FSH -7 : LH
: :

: FSH .
:LH
:FSH
androgen-binding
.globulin


.
: LH .

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-1 (hMG human Menopausal Gonadotropin) or meotropin


FSH
5-12 hMG
-2 ) - hCG (human chorionic Gonadotropin
- LH 5000 IU
4-6
hCG .
:
.

-8D
Prolactin:



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: >  $ ?I) Pergolide V (D2 Q  3? c A  A
- D2 $ A!- 4Y^- .7

- :oxcytocin

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Ile - Tyr - Cys


Glu - Asn - Cys - Pro - Leu - Gly - NH



.
.
( )
) 2-3min (
.
:
) ( .
:

OT receptor binding

phospholipase C

IP3, Ca2+

contraction of uterine smooth muscle and mammary
myoepithelial cells

-2 ) vasopressin : ( ADH
Phe - Tyr Cys
Glu - Asn - Cys - Pro - Arg - Gly - NH2
) ( :
V2
.
:
osmolality .
.
) (.
- . The renin-angiotensin II system II
.
V1 .
:

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Thyroid Hormones

: T4 T3 
 Z1
.A] 4Y ; 5 m -7
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T3 $ 15  5]T  7  T4 3
. BC T4 $ 5 P Y T3
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Eltroxin 100 mg(tab) L- :


.(triiodothyronine 5.25g (tab))Roxin

:
+ 70 2
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.
:Adult hypothyroidism $^N -N7
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2-3 50g .
.(100-200g/day)
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5 

N A c? 3 :Antithyroid drugs


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. (methimazole) Tabazole

: u | : A
. Carbinazole Methinazole (Tabazole)Propylthiouracil (PTU)

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7
M :
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-7? AY ATA;  J.t :

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.(5-15mg) Carbinazole

(2*L )
#+ ( : Ionic inhibitor
3P  ] @Y N  -N 2N^-N - N6 VN 5NBA NuNT JN
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127I ) 131I s 8 A   P  A
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(5 :
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`L M0 M:


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#i Z -A Mii NN] -N6 : Hypothyroidism


- B.
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-3 x:  .
-5. I -4 ! ! -
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 6 -
 MU GI : a
-1 P -:) 40 T3 .( T4

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- P 4 7 - P -2


:
Levothyroxine(T4).
Liothyroxine(T3).
Liotrix (combination of T3, T4 ).

:Hyperthyroidism M I -B
.t   [  -2 + 
!;-1 : 
.   -4 . : T -3
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N N; -N 4NY N:( T4) N ; :
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NN 4NNY : 4NNu 5]NNT 4NNY NNA


NNY NN( N NNI NNA N
NNA NNY Iodine inadequate
4NNNNNNNN ;_ 7 NNNNNNNN T3 T4
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iiiiiiiiiiiii-3
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2NNNNNN   NNNNNN $NNNNNN)
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+T  ->(  rY  . --I 4 


s
-4N M :Thyroiditis
  2 u  4
7 A!+A+u 4
7A ^- - 6  N 4 N+  mN70N
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GH ?# *CD#
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-3 *.
-4 .Hyperglycemic emergencies
-5 )
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: DNA ) ( Recombinant DNA
bovine ** porcine
.

hexamer
dimer monomer .SC

parenterally
.
) ( .
.

elimination half-life .
% .
fluctuation

peak timing ) .(pharmacokinetics

* A |Y ] ; -7
A t 5A:| > $ $ ]7 .$7u
**  +I Py $ T  U7
s _A: 47.-

www.syrianclinic.com
  
 

- : /
:(Lispro) Ultrafast/ultra short-acting analogue
* hexamer
.
infusion . )
( Peak
.

-2 " :"R :(Regular) Short-acting Insulin )


(
. 2-4 10.


  >
9.
Ultra fast/ultra lispro
short-acting
regular
Short-acting
[Plasma [Insulin

Intermediate- NPH
acting
lente

Long-acting ultralente

glargine
Ultra long-acting

-3 NPH) Intermediate-acting insulin :(Lent


:

* ) 28 (29

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" isophane insulin "N )(Neutral protamine Hagedorn


NPH
*
.
":Lent "L
:
semilente insulin 30% )
(
ultralente insulin 70%

-4 ":ultralente insulin "U



( .

-5 : :(Insulin glargine)Ultra long-acting insulin


**
microprecipitate pH
.
45 24
.bed time

* .
** 21 B 30

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$ &C >
9.

intermediate-acting
. intensified regimen

.pump .

  3 Q adverse effects 


C
9.

 : Hypoglycemia Type I

) ( ) (.
 : Allergy and resistance to insulin
.
 / ) ( : Lipohytertrophy

*.

&C +0 >


9.

. >
9. 0
.H/ +P "& ^C
.H/

regular

lente


am pm am

&C  > `I
9.

* .

www.syrianclinic.com
  
 

.H  +&A O I + 

. Inhalable insulin
: amphiphilic
.
:gene therapy
. -
O
C NH ( )
HN O
S
O .
O

N N
N H
CH 3

*CD# &IJ&<K GL#


Oral antihyperglycemic:M(N2#
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C NH
HN
S
O drugs
O
O
C 2H 5 )
N N
C 2H 5 H (
O
CH3
- .
O
C NH
HN O
S
O
O
www.syrianclinic.com
C2H5
N N
C2H5 H
O
  
 

zIU  %< TypeII: #1 %


:

 :secretagogue
 . Nateglinide RepaglinideSulfonylureas
 :Insulin sensitizers
 .Thiazolidinedione Biguanides
 :
 .Miglitol Acarbose

secretagogue O >
9.

.Sulfonylureas: A
:
K+ ATP
B
.
tolbutamide .
) potency ( :
: Glipizide 2-4 )(
extended-release
. preparation
) :Glyburide (Glibenclamide 6 24
)( .


0:Glimepiride M s 5 A
   t] -   2 ( Y$]A

0  c -  t  4Y  | .$

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:
: .
) (.
Erythema .
.

:
surgery Severe stress or trauma
.

Eqv. Dose Duration Active
)(mg )(h metabolites

Tolbutamide 1000-1500 12-24 Yes (p-OH
)derivative
Chlorpropamide 250-375 24-60 Yes (2-OH and
)3OH groups
Tolazamide 250-375 12-24 No (4-COOH
)derivative

*
JA! 4Y>:   - y 4Y $A.u

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Glipizide 10 10-24 No (cleavage of


)pyrazine ring
Glyburide 5 16-24 Some (trans + cis 4-
)(glibenclamide )OH groups

Third generation
Glimepiride 1-2 24 Yes (-OH on CH3 of
)R group

Repaglinide .B :Nateglinide
UI 7 M$
Q]A 7 A 0 Y 5 4Y^  .- $
$ r T +Y M$0
*
57Y -D>g . 5 BCT A + BC ; 5Y   +; 4 - BC  J
-  6 BC ? V J 20! J7A; ] -  -! .postprandial

Insulin sensitizers:B  b +


 '& Q
9.

.A : Biguanides
French lilac guanidine
N H

H 2 N N H 2 : Phenformin
) ( Lactic acidosis
.
: metformin
.

:
gluconeogenesis Glucose-6-
phosphorylase .


. LDL
) HDL ( . Type II .
: .

*
www.syrianclinic.com
  
 

: polycystic ovary syndrome


hyperandrogenism
* .

. ( TZD) Thiazolidinediones : B

.

:
: rosiglitazone 99% .
CH 3 3-499% .
N N S O

O
4-8mg.
NH
ROSIGLITAZONE O : pioglitazone
)(BRL-49653

3-7 16-24
> 99%
S O
O
N 15-45mg/day
NH
PIOGLITAZONE O

.

(H"I- glucosidase) Acarbose, Miglitol: b

-
glucosidase


.

)
(.

Acarbose ) 1%
( . .
www.syrianclinic.com
  
 

. :

&T*D# :M
.Alkylating agents ]@A 5 -1
.Alkaloids - -2
.Antimetabolites | > -3
.Antibiotics :| A -4
.Enzymes A -5
.Hormones + -6
.Platinum compounds $   -7
.New anti cancerP-: O  -8
Alkylating agents %T # 
.Nitrogen mustards
.Nitrosoureas
.Methane sulfonic acid esters
.Triazines
.Ethyleneamines

N N+ A N Nitrogen mustards    T  c? $


-N ! 4AN| 4N
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www.syrianclinic.com
  
 

(UN 7 4NY N ] N! N| $N)  I $


4 ! `  2 
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:  D
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: Vinca alkaloids ]7; - 6
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ii
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5A 
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.


:  D
: Vincristine $  ]7;

5 ^? A 7  57  A    4Y 40 >:A 4Y 4 5]T -!^ | A* 


. 

www.syrianclinic.com
  
 

childhood N: 4N;0 -N N| N


4NY TA uA 4Y 5A  -1
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I 7 acute leukemias
.Non-Hodgkins lymphoma $]!
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c-Nu N]7; -N 6 JN NA 4N r NT N| (  Paclitxel) Taxol :
. A  4Y 4^ A  J 3

Antimetabolites <D z
bone marrow N 4NN 5NNP 
N ANN7A N NNA 3NNP N+7]A NN c?N
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B@NN QNN NN7 NNA: 70NN NN A
4NNY * NN >NN| 5-NN
.$-  $ 70
.Antifolates >Y 4 ( a : BP
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:(Methotrexate) Antifolates D#I G( a
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 4Y -
acute lymphocytic leukemia in ;O -7
:; A -
 | -
. ]-7
- | u 4Y -: c BC $] children

.u | >  A +7] 7 A: 70 0P 4 / A *

www.syrianclinic.com
  
 

:purine analogues #


 7( b
: $ 7 +T 4
.(6-MP, Purinethol) mercaptopurine-6 $   -6
.(6- TG) thioguanine -6 $(B -6
./: U ]T DNA 70 J7A -] 7 70 3P
:  D
. ]$ ;  O u  -
 | 4Y -
 lymphocytic leukemia :; A -
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acute nonlymphocytic :; A -  | -  UY 6- TG
. leukemia

: pyrimidine analogues M



 
7( c
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.cytosine arabinoside -7 $  
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:  D

www.syrianclinic.com
  
 

Metastatic carcinomas of the breast NNT 7A -NNP O NN NN


4NNY -
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7 z
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 N   N 4N 5]NT $N7 5A N
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N+ -)
N+ QN O N N_ N $N  +N -N? N N $N] .U7 + : @ -
.$! $
[ >4Y  Cu $]A $!! :
acute lymphocytic NN: NN;A -NN NN| 2NN
NN 6 NN c?NN A NN
.leukemia
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ribonucleotide  N  NN 4NN-+ 3NNP :Hydroxyurea NN 4NN-+ -2


NN]A 5]NNT JNN7A $uNN NN7A -NN] 7 5]NNT JNN7A 4NN reductase
.DNA 
.chronic granulocytic leukemia $ A 4: - | u 4Y 5A 

Hormones #N
GLUCOCORTICOIDS
ESTROGENS
ANTIESTROGENS
Androgen antagonists
N;A  N BN] 3NP :GLUCOCORTICOIDS ] - ]]-1
.;A -  | 5A 
JN7A N+ QN  N  O 4Y 5A  : ESTROGENS7! > -2
-NP O N NuA N - N .4  J!   $!- 5]T
.C $ -
N 4Y7  $; : ANTIESTROGENS$! | > -3
.-P O 4Y -P  B] 3P 
47!-NNN NNN Flutamide : Androgen antagonists$!-NNN NNN -4
.  O 4Y - 
.  O  -   ! -
.(c- 20 >) A7  + 3P +Y $  UT :Octerotide -

Platinum compounds 
 <
N
  N 2N
N A c?N+ 5N BC sT
U! O  A   JA! 6 + Q
.
 P ] -
:Cisplatin $ x; 0 c?    $
QNNN NNN ]@A 5NNN BCNNN NNN UNNNT c BCNNN NNNg
. Y ] 7 U 7 4Y ] 4I - 
NNN  3NNN UNNN 5]NNNT DNANNN 3 NNN NNN+Y
.U 50 Cross-links
- NN ?NN NN NN6 NNu $NN xNN NNBg
$NN NN  - NN NN NN JNN NNTA
.Carboplatin $ ]5P  BC s 

:  D
:    $   5A 
.$ 7; $  J TA : testicular cancer$   O
. bladder cancerPA O
.5 ; $  TA : 6  O

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cyclophosphamide -;NNNNNNNY ] JNNNNNN NNNNNNTA :  NNNNNN O NNNNNN


. doxorubicin
*
. etoposide J TA : O
 !" $"% ")(&
Obstacles in chemotherapy
BN] 4  A  Au  $ -- O   Y[y O   5 
N( N !B  @A . T  u  4 0  : 5P 

. (
tNN $N]A QN 7O NN 5N
N| NN] -N6 DNAN 2NN
B@NA O N N
.( | t ^4Y)  O -:; @ O
:


N; Anemia N;@ N :Bone Marrow Suppression N 4N 3NP -1
.( u ` 4Y 5TA) @ - :; - ; _ ]  -
N -N6) N6 P( Diarrhea + Stomatitis ; + :A|  0[ -2
.(4; +> : $ 98% $] 4A| t
. Alopecia T -Y -3
. !-7
 -4
xNN NN0: $NN
 NN7 NN_ NNA  :Hyperuricemia -NN 4NNY NN_ NNA NNY -5
.7
NN
 N0 NNIT tN :Extravasation uN NN - N
$NN -N N -6
.A - 4
. 5]
!  7 -7

*
.- A ; U0P  Y[y DNA 70 3P - ?

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!
   <U B: Resistance Mechanisms
-6]N A N- N-N
tN Y N-N 2N0A ]  N QNN  NNu
g A - :5P
-  5- .
-NNN ; NNNNNN` u Y-+ NNNA :NNN 7-NNN  NNN $NNN 3-NNN: JNNN6A $NNN
DNA   ;O - J7A - ?+ .J6A
-g 3NNNT7NNN  NNN NNN -A[ NNN ANNN 3NNNP 4NNN +
70NNN BCNNNNNN
) -Y V - !.($
 A : A -6 DNA / C0 U

/ . G + B '. ^0 O


Dyslipidimia and Hypolipidemic
agents
:
Dyslipidimia
.
) (200mg/dl
.Combined Dyslipidimia
panceatitis atherosclerosis
.
\
) .(mg/dL 220-150

 
. P :Dietary Cholesterol
) ( C27H45OH


.
1gr
.
400mg 200mg
) 1gr 800mg
.(de novo synthesis

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.
 ."0, :lipoproteins

Complexes

. lipoprotein

)
(exogenous
)
.(endogenous
)
)
apolipoprotein - apoproteins(.
.  ."0,:

apoprotein )
.(ultracentrifugation
:

== A1@
:chylomicrons
100-1000nm
Apoprotein
) (A,C,E
Apoprotein B48
.
Very Low-Density
$AF1 E
= B C
")  0 )(VLDL
:Lipoprotein
) ( TG 30-80nm
.B100

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VLDL ILD . LDL


$AF1 G0 ) E
=:Low Density Lipoprotein (LDL) B C
bad choleserol 20-30nm
.AII LDL
.

LDL .100mg/dl

$AF1 HIA E
=:Intermediate-Density Lipoprotein (IDL) B C
VLDL .LDL

$AF1 ;
9 E
=:High-Density Lipoprotein (HDL) B C
nm 20 -7

HDL .40mg/dl
LP(a) lipoprotein

 ."0:9

endogenous .exogenous

- H g':Exogenous S
TG


Lipoprotein Lipase uptake .
)
(

Chylomicrons
) remnants
(

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) (30-50nm remnants
hepatocyte Endocytosis
) (.

bile acids
.VLDL

- H g+: Endogenous 0
VLDL

) ( .
IDL
) LDL (
.
LDL Endocytosis LDL
LDL
LDL coated vesicles Endosomes
) PH( LDL
.
LDL ) (
.

.LDL
LDL
.
.HDL

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F+! E$ J LDL
=!
A:
)
(HMG-CoA reductase ) (ACAT
.LDL


SREBP



DNA
RNA
.LDL
:
)
(statins LDL
.

/ . G + :Dyslipidimia
Dyslipidimia primary :seconadry

B B  0 A#L


:
:
-1/ 
. + :Familial Hypercholesterolemia 0C
ischemic heart disease
LDL
) (Homozygot 1000mg/dl Niacin

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atorvastatin resins
.

-2/ . G +  0C " :0' i>" .".B9


: Familial Ligand-Defective Apolipoprotein B
B
) LDL (

LDL LDL
(.

)

:Primary Triglyceridemias -/  
0P+   &IB
VLDL
800mg/dl

fibric acid derivatives .

<@"
A@ C  0 A#L
:
) ( :
:DM .
:hyperthyroidism
.



:Birth Control Pills



) (.

) protease inhibitors
(AIDS .

:
.(Atorvastatin, Pravastatin, Lovastatin) Statins
.(Gemfibrozil and Fenofibrate) Fibric Acid Derivatives

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Bile Acid Binding Resins


) .(Cholestyramine, Colestipol
) Nicotinic acid Niacin .(B3
.Ezetimibe

(HMG-CoA Reductase Inhibitors


,)
, Atorvastatin Fluvastatin ,Simvastatin, Pravastatin Lovastatin
.Rosuvastatin

'
=" :;O
hydroxy-methyl-glutaryl coenzyme A (HMG-
).CoA
HMG-CoA Reductase ) (rate limiting

HMG-CoA . Mevalonic acid
) .(HMG-CoA


LDL LDL



.LDL





. HDL
atorvaststin . HMG-CoA Reductase

 3 
, B :
) expression endothelial :eNOS
(nitric oxide synthase .nitroc oxide

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  6+:
.
) lovastatin and (simvastatin prodrug
.
: ) (% .
- atorvastatin T1/2=14
hrs

  3 2":
HMG-CoA Reductase
:
.
)
(.
.teratogenic

 " I
!:
:
.
.

Fibric Acid Derivatives "/


) Fibric acid( ciprofibrate bezafibrate
fenofibrategemfibrizol .clofibrate

VLDL
10% LDL 10% .HDL
Peroxisome preliferator-
activated Receptor (PPAR)
) (
apo A-I apo A-II .HDL

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) lipoprotein lipase (expression


VLDL
.
VLDL LDL
)
(.
  +:
" % ..

  3 2":
.
. arrhythmias
myopathy
.
hypokalemia .
.cholesterol gallstones

 )"H:
.
.

))C 
:
) (
.VLDL

 b,  ".  i  /8


Bile Acid Binding Resins

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colestyramine colestipol



.









LDL ) (upregulation
LDL LDL .
:
HDL .
: .

  3 2":
systemic toxicity
abdominal bloating
) (.
unappetizing .

+& +:
) (A, D, E, and K
.

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))C 
:
)
(.
.

B 3
OB^ .
.  k. ,:,

\

:
VLDL
LDL
.
HDL . AI, AII
.LPL
LDL-Cholesterol

  3 2":
flushing palpitations .
.hyperuricemia
.peptic ulcer disease
)
(.

  6+:
-.
.
 )"H:
.

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:Ezetimibe
:
.
cholesterol pool
LDL LDL .
)'+ 
:
.
.
 )"H:
.
.hypercholesterolemia

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