analgesik, antiinflamasi dan antipiretikvlm.ub.ac.id/pluginfile.php/45436/mod_resource... ·...
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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