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DRUG TREATMENT
PARKINSONS DISEASE
Dr. H. Syahril Aziz, DAFK, Sp.FK, M.Kes.Departement of Pharmacology
Medical Faculty
Sriwijaya University
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Definition
1. Tremor is regular occilative movement andregulararound joint and has special character accordingtoits related activities
2. Chorea is muscle attraction which cannot bedetermined, and irregular that can occur atvariouspart of the body that can disturb general musclemovement.
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3. Athetosis is abnormal movement, slow, and
writhe and it sometimes can remain.4. Ticss is abnormal movement that is regular, andin sudden, tend to return mainly around face and
head and it mostly occur to children.5. Parkinsons is a condition marked by combinationbetween stiff, bradykinesia, tremor, and
instability of postural that can happen in variouscauses, generally it is idiophatic.
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5. Dopamine is derivat catechol aminproduced by gland of adreno medula.Originated from derivat phenylala-nine --- > tyrosine --- > DOPA and Dopaminethrough the process of reaction ofhydroxy lasi and decarboxylasi.katabolisme through the process ofoxidasi ( mono amine oxidase : MAO) orthrough process metilasi ( cathechol-O-methyl transferase COMT ).
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PATOFISIOLOGI
Parkinson happened because of the loweramount of Dopamine in nerve of dopaminergicat Nigra substantia where this dopamin works bypursuing excretion of cells of GABAERGIC instriatum corpus
Drugs can produce Parkinson syndrome is drugwith the character of dopamin receptor
antagonis such as drug of antipsikotik or theoccurance of nerve of nigrostriatal dopaminergiksuch as MPTP ( tetra phenyl methyl hidro-pyridine
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ANTI PARKINSONS DRUGS
1. LEVO DOPA
2. AGONIS DOPAMIN
3. BROMOCRIPTIN
4. PERGOLID
5. MONO AMIN OKSIDASE INHIBITOR
6. KATEKOL-O-METIL- TRANSFERASE INHIBITOR
7. AMANTADIN
8. DRUGS RESISTOR OF ACETYL CHOLINE
9. DIHIDROKSI PHENYL SERINE ( DOPS )
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1. LEVO DOPA
PHARMACOKINETIC
It is easy absorbed through small intestine
especially in empty stomach.
The peak amount is reached 1-2 hour after the
giving.
Duration is 1-3 hours.
Excretion is through urine
1-3 % in the form of intact can enter into the brain
while the rest is metabolized out of brain so that
the giving must be in high dose except when it is
combined with resistor of dekarboksilase dopa
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Clinical Usage It is generally given in the form of combination with
Carbidopa. Levodopa can improve all clinical form
of of Parkinson especially eliminating bradikinesia
In the initial medication 1 / 3 showed good result, 2 /
3 did not show good result and the rest did not show
response at all
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Side Effects
Gastro Intestinal : anorexia, nausea, vomitus.
Cardiovascular : heart disrithmia, tachycardia,
extra systole, ventricular fibrilasi, hypotensi.
Diskinesia.
Behaviour : depression, anxietas, agitation,
insomnia, somnolent, confuse, hallucination,nightmare, euphoria, change of personality
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5. Others : mydriasis, glaucoma, trouble of smell,
urine spit and brown vagina liquid
If there are heavy side effects, DRUGHOLIDAY (the stopping of drug temporarily
until the signs of side effects disappear) must
be done.
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Interaction of Drugs
1. Pyridoxin improve extra metabolism of
levodopa cerebral so that it can reduce its
therapy effect
2. It can not be given together with resistor of
MAO in 2 weeks after drug is discontinued
because it can cause hypertension crisis.
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Contra Indication
1. Don't give it to patient of Psychotic
because can stimulate mental disorder
2. The closed angle Glaukoma.
3. Ulcus Pepticum can occur melena
4. Melanoma
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2. AGONIST DOPAMIN
Some dopamin agonist that have the effect of
anti parkinson such as apomorfin, pyribedil,
lergotril have not been used anymore because
of its heavy side effects
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3. BROMOCRYPTINE
Some generation of ergot is dopaminpartial agonist.
It can be used to depress milk production.
`It is absorbed through GI Tract., the peakamount is 1-2 hour after oral giving,
excretion is through bile dilution and
faeces.
It is the first choice in therapy of parkinsons
disease.
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In everyday practice, medication of
dopaminergik to Parkinson always startedwith combination of carbidova with
levodopa, then followed by the combination
of bromocriptine. Bromocriptine is not generally interacted
with other drugs
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CLINICAL USAGE
1. The giving is always started with small dose
and can be increased little by little. It Is
generally started with dose 7,530 mg /
day2. Can cause hypotensi
3. Medication must be discontinued if there is
trouble of psychiatric, heart dysrithmia,ergotisme or side effects that are difficult to
tolerate
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SIDE EFFECTS
Gastrointestinal : anorexia, nausea, vomiting,constipation, dyspepsia, refluks esophagitis,hematemesis.
Cardiovaskular : hypotensi, finger vasospasme,
dysrithmia. Dyskinesia : abnormal movement trouble
If its happen, drug dose has to be decreased
Mental disorder : confusion, delusion,
hallucination.
Others : headache, nasal congestive, difficult ofsleep, infiltrat lungs, erythromeralgia ( redfoot/feet, painful and swollen joint, artralgia)
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CONTRA INDICATION
History of Psychotic.
Cardiovaskular : myocard infark, Raynauld
and Buerger disease.
Patient with hystory of peptic ulcer.
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4. PERGOLIT
It is agonist dopamin
It is often combined with levodopa
It is generally tolerated very well
Average dose is 3 mg / day
It can be combined with levodopa.
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5. MONO AMIN OKSIDASE INHIBITOR
( MAO INHIBITOR )
There are 2 kinds of MAO
MAO A : metabolism of norepinephrine and of
serotonin. MAO B : metabolism of dopamine.
MAO B selective resistor of MAO which
will slow down resolving of dopamin and alsoimproving and lengthening effect of levo dopa
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This drug is used in the form of
combination with dopa levo to overcome
the decreasing of response of dopa levo
The important point is to pay attention on
side effects of hypertension because of
accumulation and release epinephrine in
blood.
Standard dose is 2 x 5 mg after breakfastand lunch
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6. KATEKOL AMIN O TRANSFERASE
INHIBITOR.
This Drug is rarely used in medication of
Parkinson except as addition in the form of
combination
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7. AMANTADIN
It is anti viral drugs which coincidencely
have effect of anti parkinson.
It is unknown clearly Its function as anti
parkinson and anticipated can improve thefunction of Dopaminergic by influencing
sintesa not only excretion but also removal
of dopamin
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Farmakokinetik
The peak level concentration is 1-4 hours after oral giving
duration is 214 hours
Excretion through urine mostly in intact form
Clinical Usage
Less effective compared to levodopa
however can be used to overcome
bradykinesia, rigiditas and tremor parkinson.
Standard dose : 2 x 100 mg / day
Sid ff
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Side effects
1. Central Nerve System : headache, anxiety,depression, iritability, insomnia, agitation,
excitation, hallucination, confusion. Big dose can
cause acute toxic psychosis and convultion.
2. Skin : peripheral oedem.
3. Cardiovaskular : Decompensatio Cordis, postural
hypotensi.
4. GI Tract : anorexia, nausea, dry mouth.
5. Urine retention
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Contra indication
1. Contraindicated at patient with heart
failure
2. Patient with spastic history and epilepsy
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8. DRUG RESISTOR OF ACETYL
CHOLINE
Drug resistor of acetylcholine : antimuscarinic
can be used as anti parkinson because it isdopaminergik
Clinical UsageIt can be used to cure tremor and rigiditasParkinson but it can cause bradycardiaalthoughit is small
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Side effects
Central Nerve System : sleepy, mental disorder,lack of attention,anxiety, confusion, agitation,
delusion, hallucination, change of way of thinking.
GI Tract. : queasy, vomiting, constipation
Heart : takikardia, palpitasi, dysrithmia.
Respiration : tachypneu.
Eye : the increase of pressure of intra okuler,
mydriasis, blurry eyesight
Side effects is tentative and it will lose after drug
is discontinued
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Contra Indication
Prostate Hypertrophy
Gastrointestinal Obstructif for example
stenosis pyloric and ileus obstrukctive.
Close Angle glaucoma.
Don't give it at the same time with anti
histamin and trisiclic anti depressant.
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9. DIHIDROKSI FENIL SERIN ( DOPS )
Lack of norepinephrine in brain to thepatient with parkinson supports the theory
that the patient lacking of dopamin will also
cause lacking of epinefrin The giving of DOPS as norepinefrin
precursor is reported can improve
phenomenon at some cases. This drug is rarely used
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PARKINSON BECAUSE OF DRUG
Drug that can cause Parkinson
Reserpin and Tetrabenazin.
This Drug will remove mono amin biogenik
out of its placebo so that the amount of
dopamin in blood will be decreased
Phenotiazine and haloperidol.
This drug will pursue dopamin reseptor so
that dopamin doesn't have catch point at
target organ.
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Other drugs which is often used to help to
slow down the growth of parkinson's disease
for example : Vitamin E : however still in debate
Neurotropik Vitamin : to give good response
to nerve cell Pyracetam : to help cell of glia nerve gets
better
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GROUP I : OBAT ANESTETIK GAS
DAN ANESTETIK INTRA-
VENA
GROUP II : OBAT ANESTETIK
VOLATIL.
GROUP III : OBAT ANTI KONVULSI
GENERASI KE DUA.
GROUP IV : OBAT-OBAT PRE ANES-
TESI MEDIKASI.
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GROUP V : FENITOIN, FENOBAR-
BITAL DAN KARBAMAZEPIN.GROUP VI : SUKSINIMID, ASAM
VALPROAT, BENZODIAZEPIN
GROUP :ASAM VALPROAT,ASETIL UREA DAN KARBONIK
ANHIDRASE
GROUP VIII : THE APPLICATION OF THETREATMENT OF OTHERDISTURBANCE OF MOVEMENT .