ANALGESIK, ANTIINFLAMASI DAN ANTIPIRETIKvlm.ub.ac.id/pluginfile.php/45437/mod_resource...LABORATORIUM FARMAKOLOGI VETERINER FAKULTAS KEDOKTERAN HEWAN UNIVERSITAS BRAWIJAYA 2020 DEFINISI

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ANALGESIK, ANTIINFLAMASI

DAN ANTIPIRETIK

LABORATORIUM FARMAKOLOGI VETERINER

FAKULTAS KEDOKTERAN HEWAN

UNIVERSITAS BRAWIJAYA

2020

DEFINISI

ANALGESIK

Obat yang mengurangi atau menghilangkan rasa sakit

ANTIINFLAMASI

Obat yang berkhasiat mengurangi inflamasi

ANTIPIRETIK

Obat yang berkhasiat menurunkan demam

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Pain mechanism

and pathwaysSensasi nyeri bisa dimodifikasi dengan cara :

1. Menghilangkan penyebab nyeri

2. Menurunkan sensitivitas nociceptors (analgesic antipiretik, anastesi local)

3. Mengganggu konduksi nociceptive dalamsensory nerve (anastesi local)

4. Mensupresi transmisi impuls nociceptive di spinal medulla (opioids)

5. Menghambat persepsi nyeri (opioids, anastesiumum)

6. Mengubah respon emosional terhadap rasa nyeri (antidepressant sebagai co-analgesics)

BIOSINTESIS PROSTAGLANDIN

DAN MEKANISME KERJA OAINS/NSAIDs

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Mediator-

mediator

Inflamasi

Inflamasi

Gejala : rubor, kalor, dolor, tumor dan function laesa

Selama inflamasi mediator yang dilepaskan : histamin, bradykinin,

leukotriene dan PG

Secara in vitro, prostaglandin E2 (PGE2) dan prostasiklin (PGI2)

menimbulkan eritema, vasodilatasi dan aliran darah lokal

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Nyeri dan Demam PG hanya berperan pda nyeri yang berkaitan dengan kerusakan

jaringan atau inflamasi

PG menimbulkan keadaan hyperalgesia, kemudian mediator

kimiawi seperti bradykinin dan histamin merangsangnya dan

menimbulkan nyeri yang nyata

Suhu badan diatur oleh keseimbangan antara produksi dan

hilangnya panas

Alat pengatur suhu ada di hipotalamus

Secara kimiawi diawali pelepasan pyrogen endogen atau sitokin

yang memacu pelepasan PG yang berlebihan

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Efek samping

Paling sering : tukak lambung, kadang disertai anemia akibat

pendarahan saluran cerna

Berat ringan tergantung jenis obat dan toleransi pasien

Gangguan fungsi trombosit akobat hambatan biosintesis

tromboksan A2 (TXA2) → dimanfaatkan u/ terapi profilaksis trombo-

emboli

Gangguan homeostatic ginjal akibat hambatan biosintesis PG

Reaksi hipersensitivitas : rhinitis, udema, urtikaria, asma bronkial

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Antipiretik Analgesik

Parasetamol (Asetaminofen)

Efektif untuk sakit gigi dan sakit kepala

Efek antiinflamasi minimal, tdk untuk visceral pain

Dimetabolisme lewat konjugasi sulfat atau

glukoronat

Metabolit reaktif (N-asetil-p-benzoquinonimine)

didetoksifikasi oleh glutation

ESO : liver damage

Antidotum : N-asetilsistein

Tidak boleh digunakan pada kucing

Acetylsalicylic Acid (ASA)

Punya efek analgesic, antipiretik, antiinflamasi

Dimetabolisme lewat hidrolisis ester, efekpenghambatan enzim siklooksigenasebersifat irreversible, sehingga durasi kerjanyatergantung dari re-sintesis enzyme

ESO : iritasi mukosa lambung (direct dan inhibisi sitesis PG); bronkokonstriksi (call “aspirin asthma” krna hambatan sintesis PGE2 dan overproduksi leukotriene)

Jangan digunakan pada pasien dengangangguan pembekuan darah; late pregnancy (prolong labor, bleeding tendency on mother and infant, premature closure of ductus arteriosus)

Dipyrone

Efek antipiretik dan

analgesiknya paling tinggi

Efektif untuk visceral pain

Larut dalam air sehingga

tersedia sediaan injeksi

Hati2 ESO agranulosytosis;

cardiovascular collapse untuk

individu yang sensitif

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THERMOREGULASI

Temperatur normal manusia 37ºC ± 1ºC

In resting state, metabolic activity of

vital organ contributes 60% (liver 25%;

brain 20%; heart 8%; kidney 7%)total

heat production.

On exercise muscle can generate up to

90% heat production

Set point temperature is programmed in

the hypothalamic thermoregulatory

center

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Gangguan Termoregulasi

High dose ethanol and barbiturate depress the termoregulatory center

Pyrogen elevate the set poin of the hypothalamic temperature controller ( through mediation PG or IL1)

The body responds by restricting heat loss (cutaneous vasoconstriction → chills) and by elevating heat production (shivering), in order to adjust to the new set point (fever).

OPIOID Mode of action of opioids.

Most neurons react to opioids with

hyperpolarization, reflecting an

increase in K+ conductance. Ca2+

influx into nerve terminals during

excitation is decreased, leading to a

decreased release of excitatory

transmitters and decreased synaptic

activity (A). Depending on the cell

population affected, this synaptic

inhibition translates into a depressant

or excitant effect (B).

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Effects of opioids (B).

The analgesic effect results from actions at the level of the spinal cord (inhibition of nociceptive impulse transmission) and the brain (attenuation of impulse spread, inhibition of pain perception). Attention and ability to concentrate are impaired.

There is a mood change, the direction of which depends on the initial condition.

Aside from the relief associated with the abatement of strong pain, there is a feeling of detachment (floating sensation) and sense of well-being (euphoria), particularly after intravenous injection and, hence, rapid build up of drug levels in the brain.

Uses :

The endogenous opioids (metenkephalin, leuenkephalin, β-endorphin) cannot be used therapeutically because, due to their peptide nature, they are either rapidly degraded or excluded from passage through the bloodbrainbarrier, thus preventing access to their sites of action even after parenteral administration (A).

Morphine can be given orally or parenterally, as well as epidurally or intrathecally in the spinal cord. The opioids heroin and fentanyl are highly lipophilic, allowing rapid entry into the CNS. Because of its high potency, fentanyl is suitable for transdermal delivery (A).

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In opiate abuse,

The user may also resort to other more

unusual routes: opium can be smoked, and

heroin can be taken as snuff (B).

Metabolism (C).

Like other opioids bearing a hydroxyl

group, morphine is conjugated to

glucuronic acid and eliminated renally.

At any rate, the activity of this polar

metabolite needs to be taken into

account in renal insufficiency (lower

dosage or longer dosing interval).

Buprenorphine and Pentazocine are classified as “low-ceiling” opioids (B), because neither is

capable of eliciting the maximal analgesic effect obtained with morphine or meperidine.

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Ketoprofen

Piroxicam

Meloxicam

Fenilbutazone

Aspirin

Morfin

Fentanyl

Tolfen