AISYAH AMIRULLAH

150 2011 0300

KELAS 76
TUGAS !
Cari satu obat lengkap dengan reseptornya (sesuai dg huruf awal nama
mahasiswa) !

Jawab:
1. Ikatan asetilkolin dgn asetilkolinesteras
IKATAN ASETILKOLIN DENGAN ASETILKOLINESTERASE

CH3
+
H3C C O CH2 CH2 N+ CH3

O
c

CH3

O
OH
b

a
a

a = Ikatan van der Waals atau ikatan hidrofob

b = Ikatan hidrogen
c = Ikatan dipol-dipol
d = Ikatan ion (elektrostatik)

AISYAH AMIRULLAH
150 2011 0300
KELAS 76
TUGAS !
Apa perbedaan proses metabolisme paracetamol/asetaminofen pada bayi
dan orang dewasa?
Jawab:
Goodman & Gilmans, 2008
Beberapa metabolit obat yang tidak stabil secara kimiawi dan disebut
sebagai intermediat reaktif; mempertimbangkan metabolit asetaminofen
(Gambar 64-1), yang mengikat nukleofil seperti glutation; ketika glutation
sel habis, metabolit tersebut mengikat makromolekul sel, mekanisme oleh
asetaminofen membunuh sel-sel hati. Kedua parathion dan asetaminofen
lebih beracun dalam kondisi di mana CYPs meningkat, seperti berikut
etanol atau paparan fenobarbital, karena CYPs menghasilkan metabolit
beracun.
Pengikatan obat dengan protein plasma lebih sedikit dari dengan NSAID
lainnya. Sekitar 90-100% dari obat dapat ditemukan dalam urin pada hari
pertama pada pemberian dosis terapi, terutama setelah konjugasi hepatik
dengan asam glukuronat (~60%), asam sulfat (~35%), atau sistein (~ 3%);
sejumlah kecil metabolit dihidroksilasi dan deasetilasi juga telah
terdeteksi.

Anak-anak

memiliki

kapasitas

lebih

glukuronidasi obat dibandingkan orang dewasa.

sedikit

untuk

1116

SECTION XV Toxicology

FIGURE 641 Pathways of acetaminophen metabolism.

to produce the active toxin: parathion is biotransformed to paraoxon, a stable metabolite that
binds to and inactivates cholinesterase (see Chapter 8). Some drug metabolites are not chemically
stable and are referred to as reactive intermediates; consider the metabolite of acetaminophen
(Figure 641), which binds to nucleophiles such as glutathione; when cellular glutathione is
depleted, the metabolite binds to cellular macromolecules, the mechanism by which acetaminophen kills liver cells (see Chapters 3 and 26). Both parathion and acetaminophen are more toxic
under conditions in which CYPs are increased, such as following ethanol or phenobarbital exposure, because CYPs produce the toxic metabolites.
Some chemicals can be activated in the skin by ultraviolet (UV) and/or visible radiation. In
photoallergy, radiation absorbed by a drug, such as a sulfonamide, results in its conversion to a
more potent allergen than the parent compound. Phototoxic reactions to drugs, in contrast to photoallergic ones, do not have an immunological component. Drugs that are either absorbed locally
into the skin or have reached the skin through the systemic circulation may be the object of photochemical reactions within the skin; this can lead directly either to chemically induced photosensitivity reactions or to enhancement of the usual effects of sunlight. Tetracyclines,
sulfonamides, chlorpromazine, and nalidixic acid are examples of phototoxic chemicals; generally, they are innocuous to skin if not exposed to light.

SPECTRUM OF UNDESIRED EFFECTS

In therapeutics, a drug typically produces numerous effects, but usually only one is sought as the
primary goal of treatment; most of the other effects are referred to as undesirable effects of that drug
for that therapeutic indication. Side effects of drugs usually are nondeleterious; they include effects
such as dry mouth occurring with tricyclic antidepressant therapy. Some side effects may be