FARMAKOTERAPI I

 CINV: chemotherapy-induced nausea and vomiting

 CTZ: chemoreceptor trigger zone
 NK1: neurokinin1
 NVP: nausea and vomiting of pregnancy
 PONV: postoperative nausea and vomiting
 RINV: radiation-induced nausea and vomiting
 SSRI: selective serotonin reuptake inhibitor
DEFINISI
 Mual dan muntah adalah keluhan yang terjadi karena
gangguan pencernaan
 Penyebabnya sangat variabel, sehingga
penanganannya tergantung penyebabnya
 Mual didefinisikan sebagai kecenderungan untuk
muntah atau sebagai perasaan dalam tenggorokan atau
epigastric yang mengingatkan seorang akan terjadi
muntah .
 Muntah didefinisikan sebagai ejeksi atau pengusiran
dari isi lambung melalui mulut .
 Mual dan muntah merupakan kondisi yang
berhubungan dan menjadi salah satu atau kondisi
kompleks dari presentasi klinis.
Penyebab
 Penyakit yang menyertai mual muntah misalnya
penyakit kardiovaskular, neurologi dan penyakit
metabolik.

 Mual dan muntah dapat terjadi pada kehamilan, pada

prosedur operasi , penggunaan obat-obatan.
Patofisiologi
 Emesis di koordinasi oleh pusat muntah dalam medula .

 Sumber stimulasi yang penting dari pusat muntah

adalah chemoreseptor trigger zone ( CTZ) yang terdapat
pada daerah postema.

 CTZ bisa distimulasi oleh toksin atau obat dalam

sirkulasi darah karena CTZ tidak dilindungi oleh sawar
darah-otak.

 CTZ adalah bagian dari sistem sirkumventrikular.

 CTZ memiliki banyak reseptor dopamin ( hal ini
menjelaskan mengapa obat dopaminergik pada terapi
parkinson dapat menyebabkan mual muntah )

 Dopamin adalah suatu neurotransmitter yang terbentuk di

otak dan organ tubuh lain. Neurotransmiter adalah
senyawa yang menghantarkan sinyal atau rangsangan
antar sel saraf atau antara sel saraf dengan sel lainnya.

 Dopamin merupakan suatu hormon yang dihasilkan

oleh hipotalamus.

 CTZ juga memiliki reseptor 5HT3 ( serotonin)

 Pusat muntah berada pada farmasio retikularis lateral
medula pada tingkat nukleus olivarius.

 Pusat muntah menerima serabut aferen dari daerah

berikut;
1. Korteks limbik yang betanggung jawab pada kejadian
mual karena bau, penglihatan.
2. Medula spinalis ( serabut sponoretikular) yang
terlibat dalam keadaan trauma fisik
3. Sistem vestribular , berhubungan dengan penyakit
vestibular ( contoh vertigo) dan motion sickness
 CTZ selain banyak terdapat reseptor dopamin dan
serotonin juga terdapat sinaps kolinergik dan
histaminergik yang terlibat dalam transmisi dari aparatus
vestibular ke pusat muntah.

 Pusat muntah berjalan ke syaraf vagus dan ke neuron

motorik spinalis yang mempersarafi otot abdomen.

 Pusat muntah berperan terhadap koordinasi kejadian

kompleks yang mendasari emesis.

 Peristaltik terbalik memindahkan isi usus halus bagian atas

ke dalam lambung , kemudian glotis menutup, nafas di
tahan, sfingter esofagus dan sfingter gaster relaksasi dan
akhirnya otot abdomen berkonstraksi mengeluarkansisi
lambung.
Terapi
Pengobatan mual dan muntah sangat bervariasi,
tergantung pada kondisi yang berkaitan
a. dugaan etiologi dan gejala;
b. frekuensi , durasi , dan tingkat keparahan
c. pemilihan cara pakai
d. penggunaan antiemetik sebelumnya
ANTACIDS

 Patients who are experiencing simple nausea and vomiting may use
various antacids.

 In this setting, single or combination nonprescription antacid products, especially

those containing magnesium hydroxide, aluminum hydroxide, and/or calcium
carbonate, may provide sufficient relief, primarily through gastric acid neutralization.

 Common antacid regimens for the relief of acute or intermittent nausea and
vomiting include one or more 15 to 30 mL doses of single- or multiple-agent
products. Potential adverse effects from antacids are usually related to the
presence of magnesium, aluminum,or calcium salts.

 Specifically, osmotic diarrhea from magnesium and constipation from aluminum or

calcium salts may be of concern to patients, particularly those self-medicating with
high or frequently administered antacid doses. Generally, however, when used
occasionally for acute episodic relief of nausea and vomiting, antacids do not produce
serious toxicities.
H2-RECEPTOR ANTAGONISTS
 Patients may use histamine2-receptor antagonists in low
doses to manage simple nausea and vomiting associated
with heartburn or gastroesophageal reflux.

 Individual dosages of cimetidine 200 mg, famotidine 10

mg, nizatidine 75 mg, or ranitidine 75 mg may be used
for brief periods. Except for potential drug interactions
with cimetidine, these agents cause few side effects when
used for episodic relief.
ANTIHISTAMINE–ANTICHOLINERGIC DRUGS
 Antiemetic drugs from the antihistaminic–anticholinergic
category appear to interrupt various visceral afferent pathways
that stimulate nausea and vomiting and may be appropriate in
the treatment of simple nausea and vomiting.

 Adverse reactions associated with the use of the antihistaminic–

anticholinergic agents primarily include drowsiness, confusion,
blurred vision, dry mouth, and urinary retention, and possibly
tachycardia, particularly in elderly patients.

 Also,as doses are increased or are more frequently administered,

patients with narrow-angle glaucoma, prostatic hyperplasia, or
asthma are at greater risk of complications from the
anticholinergic effects of these drugs.
 Antihistamin adalah zat-zat yang dapat mengurangi
atau menghalangi efek histamin terhadap tubuh
dengan memblok reseptor –histamin

 Antikolinergik sekelompok obat yang menstimulasi

saraf parasimpatik dengan melepaskan neurohormon
yang menghambat asetilkolin
Phenothiazines
 Phenothiazines have been the most widely prescribed antiemetic
agents and appear to block dopamine receptors, most likely in the CTZ.

 Phenothiazines are marketed in an array of dosage forms, none of which

appears to be more efficacious than another. These agents may be most
practical for long-term treatment and are inexpensive in comparison
with newer drugs. Rectal administration is a reasonable alternative in
patients in whom oral or parenteral administration is not feasible.

 Phenothiazines are most useful in adult patients with simple nausea and
vomiting. Intravenous prochlorperazine provides quicker and more
complete relief with less drowsiness than intravenous promethazine in
adult patients treated in an emergency department for nausea and
vomiting associated with uncomplicated gastritis or gastroenteritis.
There are numerous potential side effects with these medications,
including extrapyramidal reactions, hypersensitivity reactions with
possible liver dysfunction, bone marrow aplasia
BUTYROPHENONES
 Two butyrophenone compounds that have antiemetic activity are
haloperidol and its congener droperidol; both block dopaminergic
stimulation of the CTZ.

 Although each agent is effective in relieving nausea and vomiting,

haloperidol is not considered first-line therapy for uncomplicated
nausea and vomiting but has been used in palliative care situations

 The current labeling of droperidol recommends that all patients

should undergo a 12-lead electrocardiogram prior to
administration, followed by cardiac monitoring for 2 to 3 hours
after administration because of the possibility of the development
of potentially fatal QT prolongation and/or torsade depointes.
CANNABINOIDS
Cannabinoids adalah kelas senyawa kimia yang
bertindak pada reseptor sel cannabinoid yang dapat
menekan pengeluaran neurotransmitter di otak
CORTICOSTEROIDS
 Mekanisme kerja
1. penurunan produksi mediator inflamasi yang diketahui bekerja pada area CTZ
2. perbaikan fungsi sawar otak.
3. Penurunan 5- hydroxytryptopan di syaraf
4. menurunkan serotonin
5. meningkatkan sensitifitas reseptor antimual.

 Corticosteroids have demonstrated antiemetic efficacy since the initial recognition that patients who
received prednisone as part of their Hodgkin disease protocol appeared to develop less nausea and vomiting
than did those patients who were treated with protocols that excluded this agent.

 Methylprednisolone has also been used as a component of an antiemetic regimen, but the majority of trials
have included dexamethasone.

 Dexamethasone has been used successfully in the management of chemotherapy-induced and postoperative
nausea and vomiting, either as a single agent or in combination with selective serotonin reuptake inhibitors
(SSRIs).

 For chemotherapy-induced nausea and vomiting (CINV), dexamethasone is effective in the prevention of
both cisplatin- induced acute emesis and when used alone or in combination for the prevention of delayed
nausea and vomiting associated with
Metoklorpamid dan domperidon
 Merupakan antagonis dopamin dan juga mempunyai
efek prokinetik pada usus dan meningkatkan absorpsi

 Memblok reseptor dopamin sentral pada

chemoreseptor trigger zone

 Meningkatkan kontraksi lambung dan memperkuat

tonus sfingter esofagus bawah

 Domperidon tidak menembus sawar otak

SUBSTANCE P/NEUROKININ 1 RECEPTOR ANTAGONISTS

 Substance P is a peptide neurotransmitter in the neurokinin (NK) family whose

preferred receptor is the NK1 receptor.

 The acute phase of CINV is believed to be mediated by both serotonin and

substance P, whereas substance P is believed to be the primary mediator of the
delayed phase.

 Aprepitant is the first substance P/NK1 receptor antagonist in clinical use;

others are in development. The efficacy of aprepitant was demonstrated in
patients receiving highdose cisplatin-based chemotherapy1 and in patients
receiving doxorubicin and cycophosphamide,20 a regimen of moderate emetic
risk.
SELECTIVE SEROTONIN REUPTAKE INHIBITORS

 SSRIs block presynaptic serotonin receptors on sensory

vagal fibers in the gut wall, effectively blocking the
acute phase of CINV.

 These agents do not completely block the acute phase

of The most common side effects associated with these
agents are constipation, headache, and asthenia. Safety
and efficacy in children younger than 2 years old have
not been established.