/

central nervous system

Drugs of Alzheimers
•

cholinergic Hypothesis ↓ cholinergic neuron

ALZHEIMER'S
-
decrease in cholinergic neurons ↓ disease
-

synthesize Ach ↓ Ach

↓
better Ach level : better memory & learning
poor memory / learning
-

•
Amyloid Hypothesis amyloid aggregation
-

misfolded protein →
amyloid plaque ↓
-

amyloid aggregation neurofibrillary tangles

↓
induce neuro inflammation
↓
disruption of neuronal
communication
↓
poor memory / learning

• TAU hypothesis dissociation of TAU in miorotubles

Note : TAU lengthens & support microtubules
↳ transport information
↓
in biochemical processes
to brain disruption
of communication
↓
poor memory / learning
Management :
*
degrades
'
Ach

•
cholinesterase inhibitors
-

prevent Ach degradation

Donepezil
1-
AChE & BUCHE
Rivastigmine -
act on both

Galant amine

Amyloid plaque
• NMDA -
R Antagonists 1.) f) glutamate
Glu

:;÷:/
" run .mn
.
amt Of glutamate ↓
Neman time 2.) it ) glial cells
.

↑ 61h
-
↑
acid release

Glut NMDA
-
R =
neuronal death

↓
cat channel opens

↓
Cat influx
↓
too much cat
↓
neuronal rupture

↓
neuronal death

faithgsb
 • Glutamate Inhibitors

Adenosine
Lobe / Uzole

• Neuronal Nicotinic Receptors INNRS )

iargacept
"

MOA neuro modulation

"
:

key regulators of NS function

binds to an NNR → normalizes chemical

signaling → allows neurons to

communicate properly ( neuro modulation)

results in ↑
signaling when the Ns is
under stimulated & ↓ signaling when

the Ms is overstimulated → Ns
"
Volume K ? "

Parkinson i Disease PARKINSON 'S

-
↓ Dopamine ; ↑ Ach > damage to the basal ganglia disease

Tx : Replace ; Tx : Anti -

cholinergic
agents

Dopamine
cannot be given as medication
exaggeration Ach
-

tremors .
OF
-
it enter BBB ( Blood Brain Barrier)
-

give L-DOPA
BLOOD :
1.) Trine ✗ µ phenidyt
1.) decarboxylase ( 90% gets destroyed ) 2.) Benz tropine -
DOC

2.) WMT
g.) piperidine
BBB a.) prooyclidme
1- DOPA enters brain

}
capbidopq Diphenhydramine
g.)
-

L-Dopa + decarboxylase f) ↓ decarboxylase

BEQ : -

only for elderly

Dopamine
receptors
Enta Capone , tolcapone MOA : block muscarinic
in the striatum
-
cont f)

GNS
BEQ )
tolcapone (
-

WMT t )

selegiline & Rasagiline

-
MAO f)

Bnmooriptine Pergolide , pramipexole , Ropinirole

,

-
stimulate D receptor

- For maximizing Dopa

Amantadine
-

↑ release of DOPA
BEQ : -

SE : lived reticular is

which one is good

levodopa + carbidopa ✓

levodopa + MAOIs ×

levodopa + Vit .
136 ✗
-
induces decarboxylase
→ more L-DOPA
destroyed
levodopa -1 Antipsychotics ✗
-

antagonistic action

faithgsb
 OTHER
diseases

",!÷"""!¥÷
Huntington 's

Wilson 's
disease

disease
v

↑
GABA

Dopamine
Haloperidol

( chelating agents)

Haloperidol
Tourette syndrome
Molindon

Restless leg syndrome Ropirinot

faithgsb
?⃝
Anxiolytic / sedatives / Hypnotics
Anxiety
-

becomes abnormal when accompanied by

ANXIETY
signs & symptoms

disorder
GABA -
A Receptor

bin opening of Cl
% DCI influx
-

GABA GAR p
Channel
1
inside becomes
, act here
Anxiolytic

[
negative >

I
" "" "

hYPerP%ari µ, ,
,, , ,

calming effect
, , ,, , , ,, , , , , , , , , a- channel opening ( FREQUENCY)
g.
,
, , ↑

\ NB ↑ a- channel opening ( DURATION)

Barbiturates
-

Panic disorder in closed plac.io d I hypnotic effect )

anxiety Non pz
-
-
• -
,
☐

Zolpidem
social phobia Fear of speaking in front
•

• -

. iaiepion
Of a lot Of people •

Eszopidone
•
Generalized Anxiety -

fear of almost everything × ,

-
hypnotic effect
Disorder a. µ, -
anxiolytic effect
-
e. g. OCD

•
situational Anxiety Disorder ☐ Melatonin -

agonists -
Rame Heon

☐ 511--11 A agonists Henton in agonists) -

pure anxiolytic
-

non
-

sedative
•
Bus pirone
•

Ipsa Pirone
Gepirone
•

Benzodiazepines Barbiturates

•
most widely used anxiolytic 1.) ↑ GABA

1.) ↑ GABA 2.) ↑ duration of a- channel opening

2.) ↑
Frequency of a- channel opening 3.) have GABA mimetic activity at

GABA mimetic high doses

•
have no activity
BZ receptors do not act through BZ receptors
•
act through .

NOTE : much safer than Barbiturates

4) ↓ GM
1.) there is an antidote ( Flumazenil)
2.) increase in
"
dosage will just
"
NOIE :
when dose is too high ,

reach aplateau phase can cause coma

☒ can lead to anesthesia only

USES OF BENZODIAZEPINES

Drug Indications

Alprazolam Anxiety panic phobia , ,

Diazepam Anxiety preop sedation , muscle relaxation ,

,

withdrawal states

lorazepam Anxiety preop sedation

,
,
status epilepticus IN)
"

Midazolam Preop sedation anesthesia IV ,

temazepam sleep disorders

OXAZEPAM sleep disorders , anxiety

faithgsb
 BENZODIAZEPINES

""°
short -

Acting Intermediate -

Acting
Duration : 2- 8 hours
Duration I -3
Duration : 10-20 hours .
:
days
Drugs :
Chaplain Died From
Drugs : Charlie
Drugs :
1.) Lorazepam
1.) Clozapine a- fever

2.) Oxapen 2.) Alprazolam

1) lhlorazepate
3) Midazolam 3.) Temazepam
2.) Chlordiazepozide
4) triazolam 4.) Estozolam
3.) Diazepam
4.) Fluraiepam
5.) Quaiepam

special uses :

•
Diazepam > D% for status epilepticus most common side effect : depressant ; sedation

lvalium)
Antidote : Flumazenil
•
ohlordiazepoxide } DOG for alcohol withdrawal
CI : another depressant
( Librium)
e. g. 132-1 alcohol
•
Alprazolam > DOC for panic attack ( non drug)-

( Xanax )

BARBITURATES
short Acting Ultra short-Acting Intermediate Acting long Acting
- -
-
-

30 minutes Duration : 76hr5

Duration : 2 hours Duration :
Duration : 3. b- hrs

1) thio 1.) Buta 1.) pneno

1.) sew barbital
2) thia 2) A 2.) Mepho
2.) Hexobarbital " V
3.) memo
3.) Pentobarbital

faithgsb
 SCHIZOPHRENIA
DA Hypothesis : ↑ dopamine
or
↑ serotonin
PSYCHOSIS
4 major parts of the brain affected by dopamine :

Mesolimbic
Antipsychotics
Mesowrtical Nigrostriatal
SE :
movement
HIS / SX f) SISX 1.) Eps
IE : EPs
typical atypical 2.) Hypcrprolactinimia

positive & Negative symptoms of schizophrenia

}
Hallucinations Affective flattening
Delusions / wtrkf.ie#n%1Alogia
"' ""' " "" "" " " P ""
"
-

"" & 1- " =

" " " " " ""

Disorganized speech Amotivation

Bizarre behaviour Anhedonia

Insomnia Asocial behaviour

combativeness inattentiveness 130min)

TYPICAL ATYPICAL

Haloperidol , chlorpromazine Risperidone .

thioridazine Clozapine
thiothixene Olanzapine
flu phenazine Quetiapine
Ziprasidone
Prochloroperazine
Aripiprazote

BEQ : Blocks D2 & 5- It -121 Risperidone)

Blocks D2 receptors

BEQ : Blocks Dil 5- It -12C Clozapine )

treats positive symptoms only treats both positive & negative

symptoms

causes movement disorders little to no movement disorders

( will not cause EPs)

•
an
typical are high potency
typical vs Atypical
except chlorpromazine &

thioridanñe

>
high potency :
Typical Atypical
/✗ / Hi
potency M High :D
:
slow , ,
Receptor blockade low : M.a.lt
✗ '
H

Manifestations :
✓
positive symptoms ✓
7.) JH -12C : weight gain
hyperiipidimia Negative symptoms ✗ ✓
hyperglycemia
f) 2 ,
: ↓ BP EPs ✓ ✗
C.) H, : sedation
tardive dyskinesia ✓ ✓

faithgsb
 Motor Disturbances
Antipsychotic -

induced

•
Acute Dystonia
-

sustained muscle anywhere in the body

spasm
-
Tx : Diphenhydramine , benztropine trihexypnenidyl , ,

amantadine ITBADJ

• Parkinsonism ↓ dopamine
-

resting tremor
-

Tx : benz tropine , anticholinergic

• tardive dyskinesia
-

involuntary movement of lips head limbs

, , ,

and trunk
tongue ,

sets in
typically irreversible
-
once

• Akathisia
-

restlessness getting up &, sitting down

-
Tx : lower medication dose BB 132 ,
,
,

anticholinergic
•
Neuroleptic Malignant syndrome
-

life-threatening muscle rigidity fever ,

-
Tx : Dantrolene , bromooriptine ,
amantadine

cool patient , hydrate w/ IV fluids _ -

{
Chemical Classes

Important Uses :
• Phenothiazines
chlorpromazine
}
>
Aliphatic
-

Drug Uses SIE jaundice

piperazine flu phenazine
:
,
-

piperidine tnioridazine
Anti emetic
-
>

Proohlorperazine
-

"

" " " "" " " " " "" " "
Anti
chlorpromazine hiccups
-

• Butyrophenones -

haloperidol
Dinydroindolines Molin done
-

Promethaiine Anti -

histamine
•
-

•
Diphenyl butyl piperidine pimozide _

Clozapine
alternative drug when
every
thing tailed
other toxicity
Aripiprazole & Olanzapine Bipolar Disorder
.
•
clozapine
blood
agranulocytosis
'

Tourette
-

>
Molin done Disease
• thioridazine
>
eyes =
pigmentary retinopathy
other uses of antipsychotics
1 cardiotoxic
•
Antiemetic -
blocks D receptors _
prochlorperazine

chlorpromazine ziprasidone & Quetiapine

hiccups
•
• Intractable -

prometnazine 11in met , Napthine ) > Q & -1 intervals

prolong
Pruritus ( Antihistamine)
-

• -

L U L L

faithgsb
 ANTICONVULSANTS
Anticonvulsants
Glu & inhibitory GABA
-
imbalance between excitatory
inside
Glu binds to gamma receptor →
effect : Na Rca channel opening Na & Ca influx • more + • depolarization ☒ seizure formation

GABA binds to gamma Ct channels open • a influx • more

-

inside •
hyperpolarization • prevent seizure
receptor •

Therefore ,

Inhibit Glu , increase GABA

MOA of Drugs that treat seizure :

> Na channel blocker

> Ca channel blocker

> Enhance GABA

partial seizures
-

involve a single hemisphere of the brain

-

simple partial
•
motor ( Jacksonian March)
•
sensory 1 tingling ,
paresthesia)
•
no loss of consciousness ( LOC)

complex partial
-

•
LOC
•
during Loc : hallucinations ,
chewing rubbing
,

Generalized seizures

affect both hemispheres

-

tonic -

clonic / Grand mat

most dramatic
•
* status epilepticus -

prolonged seizure / Grand mat

•
LOC
when brain loses 02 coma
•
tonic ( IOS ) stiffening ⇒
-

•
clonic 11-2 mins ) -
muscle contractions alternating
with relaxation

or Absence / Petit Mal

-

children
* Febrile seizure
-
alternations of consciousness lasting 10-30s
-

seizure then fever

blank stare blinking Loc
-

, ,

☒
Myoclonic
-

involuntary jerking of the facial , limb , or

trunk muscles

-
no LOC

D- sudden loss of postural tone

. faithgsb
 Main problem :

ca channel opens
•
pre ganglionic neuron -

open Na channels →
High voltage-gated
slow type ca channel opens
postganglionic neuron -

Glu Glu in synaptic cleft increases •

positive inside triggers release of

GM binds to NMDA & AMPA receptors in postsynaptic cleft AMPA : Na goes inside cell µ

NMDR : Ca goes " "

Depolarization seizure

Must give GABA :

GABA opens 01 Channels Cl goes in

prevent reuptake :

1- ) GABA T

Na channel blockers

ca channel blockers

NMDA receptor blockers

AMPA blockers

Increase sV2A
> NIA stimulants
•
levetiracetam
Felbamate
•

AMPA Inhibitor
•
topiramate

GABA transporter Inhibitor

•

tiagabine
GABA transporter Inhibitor
•
vigabatrin

Valproic Acid

Ethoiuxsimide

lamotrigine
Topiramate

Both Nalla channel blockers

• Zonisamide DRUG OF CHOICE
•
llalproio acid
•
topiramate Type Of Seizure Drug Of Choice

Na channel blocker simple Partial

carbamazepine
carbamazepine complex Partial
•

lamotrigine
tonic clonic ilalproio Acid
-

SIE :
Absence Etnosuxsimide
1.) Phenytoin
-

Gingival Hyperplasia
Myoclonic llatproic Acid
.

2.) phenytoin valproic ,

acid -

teratogenic
Atonic Halprin Acid

Phenobarbital
Febrile
Diazepam

New : Lorazepam ,
Old :
Diazepam
Status Epilepticus Phenobarbital
Phenytoin llardiotoxio due to
propylene glycol)

Note : All can be used interchangeably EXCEPT Ethosuxsimide lspecific for Absence seizure)

faithgsb
Antidepressants

Depressant =
↓ NE ↓ serotonin
} Bipolar ANTIDEPRESSANTS
Mania =
↑ NE ↑ serotonin -
neurotransmitter
imbalance

Biogenic amine Hypothesis

criteria

major (1)

}
1. Anhedonia
2. Depressed mood 12 weeks )
"" "" "" "" "
' Mai " ← " = " " ""
t
appetite
-

1. ↑/↓
depression
2. wt .

gain / wt loss .

3. insomnia / hypersonic
4. easy fatigu ability
5. loss of concentration
6- suicidal thoughts
7. suicidal attempts

Reuptake Inhibitors

•
selective serotonin Reuptake Inhibitors

first line of Choice

" "

Advantage :
✓ lesser lethality with overdoses

/ !!! !
" "'m :

1.) sertraline -

if you change → change

2.) Fluoxetine
-

longest acting now, to MAOIs

-

give 1 Week
3.) Fluovaxine
4.) Paroxetine TCAs
and line :

5.) citalopram 3rd line : MAOIs

6) Escitalopram
inhibition of b- HT reuptake
NOA : Allosteric

Rts
•
serotonin Norepinephrine
☐ venlafaxine
☐
Desvenlafaxine
☐ Duloxetine

MOA : f) reuptake of NE / serotonin

•
Monoamine oxidase Inhibitors

>
Non-selective

}
also carboxazid
/ & NE
☐ Pnenylezine
"
tranylcypromine
☐
blorgyline
'
MAO -
A I

> MAO BI -

☐
selegiline
☐
Rasagiline
inhibit MAO which metabolizes
MOA : the
eniyme
ME ,
5- HT & dopamine

faithgsb
 •
serotonin Receptor Antagonists
☐ Nefa 20 done
☐ 1- random

MOA : block the 511-1-2 A receptor

Remember ! ! !
1A :
Anxiolytic
26 :
Antipsychotic

tricyclic Antidepressants ( TCAs )

☐ Ami / nor / pntryptiline
☐ Homi / desi / imipramine
☐
Doxepin
a
Amoxapine

Atypical Antidepressants
☐ Bupropion
f) Dopamine reuptake
1- 1 DAT

☐ Mirta rapine

f) ✗ 2

Vila 20 done
}
☐ 1-1 SERT

☐ Vortioxetine f) 51512A receptor

faithgsb
 BIPOLAR
108770000 disorder
↑ NE ,
↑ Serotonin

Bipolar Affective Disorder

treatment
☐ lithium carbonate is the universally preferred
esp . in manic phase .

achieving remission
-
80% overall success rate for

MOA :

☐
f) synthesis
lanabolism )

↑
reuptake
f)
↓ Release

↑ ME ↑ destroy
↑ serotonin 1 catabolism)

I/ Receptor sensitivity
-

lithium carbonate Clithase)

bipolar disorders
-

first
-

line agent for the tx & prevention of

Moa :

& NE release

↓
↑ NE metabolism

↓
↑ NE reuptake
↓
b- NE 851ft
-

receptor
sensitivity
-
lithium vs Na
X
-

Pregnant :

☒ii*awmm
Baseline labs Adverse effects

Function Hypothyroidism
thyroid
IT 3,1-4

BUN / Crea Renal Insufficiency

Electrolytes Decreased Na
lesp sodium)
.
( check Nat

CBO leukooytosis
( ↑ WBC)

if no lithium ,
alternative : chlorpromazine
Mannitol
DOC for lithium toxicity :

osmotic diuretic
no Na
-

effect on

faithgsb
 ⑧ PD⑧0④8iᵈ⑧ fFB8
"
narcotics
"
-

a.k.a
-

alkaloid :
juice of opium poppy seed
delta receptors in CNS
-
my ,
Kappa ,

Receptors
like loperamide
•
M receptor
*
-

supra spinal & spinal analgesia ; euphoria ; sedation ;

respiratory depression ; decreased GI motility
:
*
Usual cause of death
tolerance & physical dependence
•
K
-

supra spinal & spinal analgesia : sedation ;

↓ GI motility
•
0 lsigma )
opiates mimic symptoms
psycho mimetic effects ; hallucinations ; dysphoria •
indite
-

of psychotic
.

•
0 : unknown 1 delta)

• Morphine
choice for all types of pain
-

analgesic of

except pain of pancreas & biliary tract

classification Bone CA
•
Meperidine
Full agonist ( FHM 3) most Painful
-

•
-

for pain of pancreas & biliary tract

CA px
•
pancreatic CA
☐
Fentanyl
-

more potent ; for

☐ Morphine -

t week only , px dies • Methadone

☐ Meperidine -

opiate withdrawal
☐ Methadone liver CA
•
Heroin
☐ Heroin very thin ( metabolite)
-

diacetylmorphine
partial Agonist can enter BBB & become
-

morphine
t antitussive

☐ Oxycodone
-4 Hydrocodone
☐
Oxy morphine
☐ Hydro morphine
☐ codeine
other ways to classify

a.) Natural
mixed Agonist / Antagonist
☐ Morphine
•

☐ Pentazocine ☐ codeine
Nalbuphine BEQ naloxone
☐
☐ Thebaine -

precursor substrate for the synthesis of

☐ Butorphan 01

• Full Antagonist b.) semi synthetic

-

diacetylmorphine i did morphine

Heroin
acting
-

☐ Naloxone -
snorter -
☐

Apomorphine -
emetic
Naltrexone longer acting
-
☐
☐ -

☐ Hydrocodone -
antitussive
☐
Oxycodone
a Hydro morphine
☐
Oxy morphine

c.) Purely synthetic

☐ Methadone
a loper amide , diphenoxylate
☐ Meperidine BEQ
☐ Fentanyl
☐ tramadol

☐ Pentazocine
faithgsb
?⃝
Trust in the Lord with
all your heart
Proverbs 3:5-6