Andreas Adiwinata

406191046

1. Fentanyl : opioid analgesik poten

A. Farmakokinetik:
i. Absorpsi: konsentrasi serum mencapai plateu dalam 14-24 jam dari pemakaian
ii. Distribusi: sangat lipofilik, didistribusi dengan cepat dari darah ke paru-paru dan otot,
kemudian ke lemak. Volume distribusi intravena fentanyl adalah 4-6 L/kg. Plasma
protein binding kurang lebih 80%
iii. Fentanyl melewati plasenta dan air susu.
iv. Dalam 72 jam  75% dosis fentanyl di ekskresikan pada urin dan 9% diekskresikan
melalui feses
v. Waktu paruh: 2-4 jam (IV)
vi. Metabolisme: hepar oleh CYP3A4
vii. Ekskresi: via urin (75% sebagai metabolit; <7-10% sebagai obat yang tidak diubah); feses
(sekitar 9%)
B. Farmakodinamik:
Fentanyl meningkatkan ambang nyeri dan mengganggu reseptor nyeri dan menghambat jalur
nyeri dengan mengikat reseptor stereospesific pada CNS
2. Midazolam :
A. Farmakokinetik:
i. Midazolam diserap cepat dari saluran cerna dan dengan cepat melalui sawar
darah otak.
ii. Hanya 50% dari obat yang diserap yang akan masuk ke sirkulasi sistemik karena
metabolisme porta hepatik yang tinggi.
iii. Sebagian besar midazolam yang masuk plasma akan berikatan dengan protein.
iv. Waktu durasi yang pendek dikarenakan kelarutan lemak yang tinggi
mempercepat distribusi dari otak ke jaringan yang tidak begitu aktif juga dengan
klirens hepar yang cepat
v. Waktu paruh midazolam adalah antara 1-4 jam, lebih pendek daripada waktu
paruh diazepam. Waktu paruh meningkat pada pasien tua dan gangguan fungsi
hati.
vi. Pada pasien dengan obesitas, klirens midazolam akan lebih lambat karena obat
banyak berikatan dengan sel lemak. Akibat eliminasi yang cepat dari midazolam,
maka efek pada CNS akan lebih pendek dibanding diazepam.

Awitan aksi :

 IV 30 detik-1 menit
 IM 15 menit
 Intranasal < 5 menit

Efek Puncak

 IV 3-5 menit
 IM 15-30 menit
 PO 30 menit
  Intranasal 10 menit
 Rektal 20-30 menit

Lama aksi

 IV/IM 15-80 menit

 PO/rectal 2-6 jam

Interaksi/toksisitas

Efek depresi SSP dan sirkulasi dipotensiasi oleh alkohol, narkotik, sedatif, anestesik
volatil, menurunkan MAC untuk anestesik volatil; efeknya diantagonis oleh
flumazenil.

vii. Biotransformasi dimediasi oleh cytochrome P-450 3A4. Sitokrom ini terdapat di
hepar dan traktus gastrointestinal.
viii. Metabolit utama yaitu 1-hidroksimidazolam mencakup 60-70% manakala 4-
hidroksimidazolam hanya sebanyak 5% atau kurang.Metabolit ini dengan cepat
dikonjugasi dengan asam glukoronat menjadi 1-hidroksimidazolam glukoronat
yang dieskresikan melalui ginjal.
ix. Metabolisme midazolam akan diperlambat oleh obat-obatan penghambat enzim
sitokrom P-450 3A4 seperti simetidin, eritromisin, calsium channel blocker, obat
anti jamur.
x. Pada pasien paediatrik, obesitas, gagal jantung kongestif, insuffisiensi hepar dan
gagal ginjal didapatkan waktu paruh midazolam lebih lama, klirens plasma
berkurang manakala volume distribusi meningkat berbanding kelompok orang
biasa
B. Farmakodinamik:
i. Short-acting benzodiazepine yang bersifat depresan SSP.
ii. Onset waktu efek sedative setelah pemberian IM pada orang dewasa adalah 15
menit, dengan puncak sedasi terjadi 30 sampai 60 menit setelah injeksi.
iii. Onset waktu efek sedative pada populasi anak dimulai dalam waktu 5 menit dan
mencapai puncak pada 15 sampai 30 menit tergantung pada dosis yang
diberikan.
iv. Pemulihan yang terjadi setelah pasien sadar biasanya terjadi dalam waktu 2
jam, tetapi pemulihan bisa memakan waktu hingga 6 jam dalam beberapa kasus

3. Propofol :
o Farmakokinetik:
 Distribusi: sekitar 2-8 menit. Dapat melalui plasenta dan air susu
 Metabolisme: hepar
 Eksresi: melalui urin dan feses.
 Waktu paruh 40 menit (inisial) dan 4-7 jam (terminal)
 o Farmakodinamik:
 Kardiivaskuler : menurunkan tekanan darah arterial, preload, & kontraktilitas
jantung
 Respirasi : mendepresi pernafasan  apnea
 SSP : menurunkan cerebral blood flow, cerebral blood volume, dan TIK

4. Atrakurium :
Physical Structure

Like all muscle relaxants, atracurium has a quaternary group; however, a benzylisoquinoline structure is
responsible for its unique method of degradation. The drug is a mixture of ten stereoisomers.

Metabolism & Excretion

Atracurium is so extensively metabolized that its pharmacokinetics are independent of renal and hepatic
function, and less than 10% is excreted unchanged by renal and biliary routes. Two separate processes
are responsible for metabolism.

A. Ester Hydrolysis

This action is catalyzed by nonspecific esterases, not by acetylcholinesterase or pseudocholinesterase.

B. Hofmann Elimination

A spontaneous nonenzymatic chemical breakdown occurs at physiological pH and temperature.

Dosage

A dose of 0.5 mg/kg is administered intravenously for intubation. After succinylcholine, intraoperative
relaxation is achieved with 0.25 mg/kg initially, then in incremental doses of 0.1 mg/kg every 10 to 20
min. An infusion of 5 to 10 mcg/kg/min can effectively replace intermittent boluses.

Although dosage requirements do not significantly vary with age, atracurium may be shorter acting in
children and infants than in adults.

Atracurium is available as a solution of 10 mg/mL. It must be stored at 2°C to 8°C, as it loses 5% to 10%
of its potency for each month it is exposed to room temperature. At room temperature, it should be
used within 14 days to preserve potency. Side Effects & Clinical Considerations

Atracurium triggers dose-dependent histamine release that becomes significant at doses above 0.5
mg/kg.

A. Hypotension and Tachycardia

Cardiovascular side effects are unusual unless doses in excess of 0.5 mg/kg are administered.
Atracurium may also cause a transient drop in systemic vascular resistance and an increase in cardiac
index independent of any histamine release. A slow rate of injection minimizes these effects.
B. Bronchospasm

Atracurium should be avoided in asthmatic patients. Severe bronchospasm is occasionally seen in

patients without a history of asthma.

C. Laudanosine Toxicity

Laudanosine, a tertiary amine, is a breakdown product of atracurium’s Hofmann elimination and has
been associated with central nervous system excitation, resulting in elevation of the minimum alveolar
concentration and even precipitation of seizures. Concerns about laudanosine are probably irrelevant
unless a patient has received an extremely large total dose or has hepatic failure. Laudanosine is
metabolized by the liver and excreted in urine and bile.

D. Temperature and pH Sensitivity

Because of its unique metabolism, atracurium’s duration of action can be markedly prolonged by
hypothermia and to a lesser extent by acidosis.

E. Chemical Incompatibility

Atracurium will precipitate as a free acid if it is introduced into an intravenous line containing an alkaline
solution such as thiopental.

F. Allergic Reactions

Rare anaphylactoid reactions to atracurium have been described. Proposed mechanisms include direct
immunogenicity and acrylate-mediated immune activation. Immunoglobulin E-mediated antibody
reactions directed against substituted ammonium compounds, including muscle relaxants, have been
described. Reactions to acrylate, a metabolite of atracurium and a structural component of some
dialysis membranes, have also been reported in patients undergoing hemodialysis.

5. Vekuronium :

Physical Structure
Vecuronium is pancuronium minus a quaternary methyl group (a
monoquaternary relaxant). This minor structural change beneficially alters side effects without
affecting potency.
Metabolism & Excretion
Vecuronium is metabolized to a small extent by the liver. It depends primarily on biliary
excretion and secondarily (25%) on renal excretion. Although it is a satisfactory drug for patients
with kidney failure, its duration of action will be moderately prolonged. Vecuronium’s brief
duration of action is explained by its shorter elimination half-life and more rapid clearance
compared with pancuronium. After long-term administration of vecuronium to patients in
intensive care units prolonged neuromuscular blockade (up to several days) may be present
after drug discontinuation, possibly from accumulation of its active 3-hydroxy metabolite,
changing drug clearance, and in some patients, leading to the development of a
polyneuropathy. Risk factors seem to include female gender, kidney failure, long-term or high-
 dose corticosteroid therapy, and sepsis. Thus, these patients must be closely monitored, and the
dose of vecuronium carefully titrated. Long-term relaxant administration and the subsequent
prolonged lack of ACh binding at the postsynaptic nicotinic ACh receptors may mimic a chronic
denervation state and cause lasting receptor dysfunction and paralysis. Tolerance to
nondepolarizing muscle relaxants can also develop after long-term use. The best approach is to
avoid unnecessary paralysis of patients in critical care units.

6. Analgesic step ladder

By the clock:
To maintain freedom from pain, drugs should be given “by the clock” or “around the clock”
rather than only “on demand” (i.e. PRN). This means they are given on a regularly scheduled
basis. The frequency will depend on whether it is a long- or short-acting preparation.

By the mouth:
The oral route is usually the preferred route for ease of use in a variety of care settings.
However, it may not be possible for all patients (e.g. end-of-life, unconscious, swallowing
issues). When the oral route is not feasible, the least invasive route should be considered (e.g.
sub-lingual or sub-cutaneous before intra-venous.). The intra-muscular route should never be
used.

By the ladder:
If pain occurs there should be prompt administration of drugs in the following order:
• non-opiods (e. g. acetaminophen)
• as necessary, mild opiods (e. g. codeine)
• then strong opiods (e. g. morphine or hydromorphone) until the patient is free of pain.

Drug selection should be appropriate to the severity of the pain. It may be most appropriate
with severe pain to begin at the top of the ladder with a strong opioid; it is not always necessary
to start at step one. When pain is controlled, the patient should be maintained on the dose that
is effective. It is usually not necessary to step down the ladder unless the cause of pain is
believed to have resolved (e.g. post-operatively, in remission from cancer). Along any step in the
ladder, additional drugs – “adjuvants”- may be used. Adjuvants include: antidepressants (e.g.
amitriptyline), anticonvulsants (e.g. gabapentin), corticosteroids (e. g. dexamethasone), and
anxiolytics (e.g. diazepam).

7. Penilaian nyeri menurut Visual Analog Scale (VAS)

VAS adalah suatu instrumen yang digunakan untuk menilai intensitas nyeri dengan
menggunakan sebuah tabel garis 10 cm dengan pembacaan skala 0–100 mm dengan rentangan
makna:
 Cara penilaiannya adalah penderita menandai sendiri dengan pensil pada nilai skala yang sesuai
dengan intensitas nyeri yang dirasakannya setelah diberi penjelasan dari peneliti tentang makna
dari setiap skala tersebut. Penentuan skor VAS dilakukan dengan mengukur jarak antara ujung
garis yang menunjukkan tidak nyeri hingga ke titik yang ditunjukkan pasien.

8. Penilaian nyeri pasca bedah pada pediatrik dan tatalaksana

  Distraksi
 Breathing technique
 Guided imagery
 Progressive muscle relaxant
 Biofeedback
 Hypnosis
 Transcutaneal electrical nervus stimulations (TENS)

Terapi farmako

 NSAID: Ibuprofen, Ketorolac, acetaminophen

 Analgesicc Opioid: Codeine, morfin, fentanil, hidromorfin, hidrokordon, oksikodon.
 Sedasi sadar
 Analgesi epidural