pharmacology of analgesics a1.ppt...
TRANSCRIPT
Pharmacology of AnalgesicsPharmacology of AnalgesicsPharmacology of Analgesics
Datten Bangun Datten Bangun
M.IchwanM.Ichwan
Bagian Farmakologi & Terapeutik Bagian Farmakologi & Terapeutik
Fakultas KedokteranFakultas Kedokteran
USUUSU
• Everyone has experienced mild pain in response to an
intense or noxious stimuli ⇒ This pain helps us to avoid
potential damage by acting as an early warning signal
• In this respect, pain can be an early diagnostic symptom for the onset of many
illnesses
• Everyone has experienced pain in response to an intense or
noxious stimuli ⇒ This pain helps us to avoid potential
damage by acting as an early warning signal
• In this respect, pain can be an early diagnostic symptom for
the onset of many illnesses
• Pain can also be severe and incapacitating, as after an
injury, during recovery from surgery, or in association with
medical conditions such as rheumatoid arthritis
• Under this circumstances, noxious stimuli can elicit severe
pain because of increases in the excitability of the
somatosensory system, and stimuli that would not normally
cause pain can become painful
Pain is the most common symptom for
which patients see a doctor.
The complaint doesn’t mean that an
analgesic is needed.
To manage the pain,the doctor needs to
know what is happening to the patient in
mind and body.
“an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage” *IASP, 1986
• Noxious Stimulus (Nociception)(Nociception)
• Central Modulation
• Perception & Interpretation
• Emotional State (Suffering)
• Reaction or pain behavior
•• AcuteAcute•• NeuropathicNeuropathic•• ChronicChronic
PATOFISIOLOGI NYERI
Impuls Nyeri dari perifer
Substantia Gelatinosa
Rolandi
Tractus Spinothalamicus lateral
Nuclaeus Posterolateral
Ventral Thalamus
Pusat “relay”
di Batang Otak
Gyrus Post
Centralis
Thalamus
• Select the appropriate analgesic drug
• Prescribe the appropriate dose
• Administered through the appropriate route
• Schedule the appropriate dosing interval
• Prevent persistent pain and eliminate breakthrough painpain
• Anticipate, prevent and manage side effects
• Consider sequential and alternative drug trials
• Use appropriate adjuvant
Analgesic drugAnalgesic drug
• A drug that relieves pain due to multiple causes= e.g. paracetamol, morphine
• Drugs that relieve pain due to a single cause or spesificsyndrome only, e.g. ergotamine (migraine), carbamazepine
(neuralgias), glyceryl trinitrate (angina pectoris), are not
classed as analgesics; nor are adrenocortical steroids
that supppress pain of inflammation of any cause.
• are classed as;• NARCOTIC (which act in the CNS and cause drowsiness, i.e. • =opioid• NON-NARCOTIC (which act chiefly peripherally, e.g. diclofenac)
Adjuvant drugsAdjuvant drugs
• are those used alongside analgesics in the management
of pain
• They are not themselves analgesics, though they may
modify the perception or the concomitants of pain thatmodify the perception or the concomitants of pain that
make it worse (anxiety, fear, depression),
e.g. psychotropic drugs,
or they modify underlying causes, e.g. spasm of smooth
or of voluntary muscle
• Acetaminophen & Aspirin
• NSAID’s
• Opioids (Narcotic analgesics)
• Anticonvulsants
• Psychotropics
• Adrenergic agents
Pain is the most common symptom for which patients see a doctor. The
complaint doesn’t mean that an analgesic is needed. To manage the pain,the
doctor needs to know what is happening to the patient in mind and body.
• Opioids (Narcotic analgesics)
• Tricyclic and heterocyclic antidepressants
• SSRI’s
• Serotonin (5-HT) receptor agents
• Adrenergic agents
• Topical agents
• Injection therapy
• Intravenous agents
NSAID ±adjuvant analgesic
± weak opioid
Strong opioid
± NSAID ±adjuvant analgesic
WHO ANALGESIC LADDER
Choosing pain killer and its combinations
± weak opioid(codeine)
paracetamolor NSAID ±
adjuvant analgesic
0 1 2 3 4 5 6 7 8 9 10
Pain tolerancePain threshold
mildmild moderatemoderate severesevere
Pain thresholdPain thresholdPain thresholdPain thresholdPain threshold
Narcotic analgetics (Opioid analgetics)
= opioid----���� similar or produce effects like opium
= opiate---���� a product of Opium= opiate---���� a product of Opium
Concepts=Receptors for endogenous opioid peptides
(enkephalins and endorphines),i.e;µ,ĸ and δ
are targets for opioid analgesics
= Most opioids are nonselective receptors = Most opioids are nonselective receptors
activators,classified as strong,partial or weak
agonist,based on its analgesic efficacy
= Mixed agonist-antagonist (nalbuphine or pen-
tozocine) activate ĸ, but block µ receptor
RESEPTOR OPIOID DI DALAM TUBUH
Ada 4 jenis yang telah diketahui :
� Reseptor µ : µ1 dan µ2
� Reseptor κ : κ1,κ2 dan κ3
� Reseptor δ : δ1 dan δ2
� Reseptor σ : σ1 dan σ2
Reseptor Efek Agonis
µ (mu)
κ (kappa)
δ (delta)
σ (sigma)
Analgesia supraspinal, euforia, myosis,
depresi pernapasan, sedasi, konstipasi
Analgesia spinal, disforia, depresi pernapasan,
sedasi, myosis
Belum diketahui pada manusia, tetapi
analgesia pada hewan
Disforia, halusinasi, efek psikomimetik,
midriasis
ANALGETIKA OPIOID DI DALAM KLINIK
Agonis Kuat Agonis Kerja
Agonis Opioid
Agonis Lemah-Sedang Agonis Kuat
• Morfin
• Pethidine
• Fentanyl
• Methadone
• Levorphanol
Agonis Kerja Campuran
• Nalbuphine
• Buprenorphine
• Butorphanol
• Pentazocine
• Dezocine
Agonis Lemah-Sedang
• Propoxyphene
• Hydrocodone
• Oxycodone
• CodeineCodeine
Subclasses:
= Strong agonist --����strong analgesics
- morphine,meperidine,methadone
= Moderate agonist-���� moderate analget.
- oxycodone,codeine,nalbuphine,pentzocine
= weak agonist -���� mild analgesic= weak agonist -���� mild analgesic
- propoxyophene,
Mechanism of action
In terms of analgesia, opioids exert both spinal
and supraspinal actions:
1.Spinal analgesia occurs by activation of
presynaptic opioid receptors--���� decreased
calcium influx -----���� decreased release of calcium influx -----���� decreased release of
neurotransmitter involved in nociception
2.Supraspinal analgesia, occurs by activation
of postsynaptic opioid receptors in the medulla
midbrain,---���� inhibition of neurons involved in
pain pathways via increased flux of potassium
ions
Pharmacokinetic:
-most opioid are well absorbed by s.c, i.m, or
oral route, but due to first-pass effect-----����
oral route need higher dose
is very difficult to predict in different patient.
- Codein and oxycodone : less first-pass effect
Pharmacodynamics:1.Analgesia : - efficacy is variable,depending
on the drug
2. Sedation : - strong agonists cause more
sedation (euphoria)
3. Respiratory depression:
Increased PCO2Increased PCO2
causes cerebral vasodilation;
decreased respiratory drive is
the cause of death in overdose
4. Cerebro/Cardiovascular:cerebral vasodilation mayincrease intracranial pressure,morphine causes vasodilationvia histamin release.
5.Gastro-intestinal;- decrease peristalsis-----���� constipation
6.Other smooth muscle:- relaxation of uterine smooth muscle,
- contraction of biliary, bladder and
ureteral smooth muscle ( except ureteral smooth muscle ( except
meperidine)
7. Pupils : opioids (except meperidine)----���� miosis
8. Cough suppression----���� antitussive
9. Emesis------ via CTZ
10. Tolerance:
- chronic use leads to marked tolerance to
most actions except constipation and
miosis
11.Dependence
-psychological and physical dependence
- abuse liability is greatest with strong
agonist
- on abrupt discontinuance-----���� withdrawal
(abstinence) syndrome ---�SAKAW
Clinical Use:
1.Analgesia
2.Cough suppression---�-codein
- dextromethorphan
3.Diarrheal states -----� - loperamide
- diphenoxylate- diphenoxylate
4.Anesthesia------------� - fentanyl
- morphine
5.Withdrawal states---� - methadone
6.Pulmonary edema--���� due to its vasodilating
effect--����reduce preload
Toxicities:
Overdose:
- hypotension
- respiratory depression--���� coma
Chronic use------���� tolerance and dependence
Efek dari heroin (diacetyl morphine
- hilang rasa takut
- hilang rasa sakit
- menenangkan
- timbul rasa enak
Dipergunakan dibidang
medis (dulu)
Disalah gunakan
Efek heroin pada penggunaan khronis:Efek heroin pada penggunaan khronis:- toleransi ���� dosis yang diperlukan makin
besar / tinggi.
- ketergantungan ���� psikis ���� “sugesti”
���� fisik
Sakaw = sakit oleh karena putaw
Gejala sakaw
�Timbul setelah ± 6 jam penggunaan terakhir dengan
gejala sebagai berikut.
� Rasa sakit yang hebat diseluruh badan istimewa di
perut.
� Bulu roma berdiri (goose-flesh reflex)
� Air liur, ingus, air mata bercucuran���� flu-like � Air liur, ingus, air mata bercucuran���� flu-like
syndrome
�Setelah beberapa jam, gejala ini menurun / menghilang,
NAMUN esoknya gejala ini muncul lagi tapi dengan
intensitas berkurang.
TIDAK ADA YANG MATI OLEH KARENA SAKAW.