Biomed /certified fixed orthodontic courses by Indian dental academy

BIOMED

INDIAN DENTAL ACADEMY
Leader in continuing dental education
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Pain medication
 Paracetamol
 NSAIDs
 Opioids
 Steroids,

radiation, TENS, acupuncture

Physiology
 Afferent,

peripheral nerves C and A δ

0,5-1,5 µm, <1 m/s,
unmyelinated

 C-fibres

 Aδ-fibrer

1-5 µm, 5-35 m/s, myelinated

(larger Aβ touch, vibration, proprioception)

Pain pathways

 Tissue

damage releases bradykinin, serotonin,
histamin, lactate, ATP, ADP, potassium (among
others)

 Glutamate

(excitatory) transmittor in dorsal horn

synapse
 GABA

(inhibitory) transmittor interneuron

Pain, pathways
 Nociceptive

neurons in dorsal root ganglion
 Relays via tractus spinothalamicus,
spinomesencephalicus and spinoreticularis
 Reaches thalamus and pons
 Connects to cortex
 Inhibitory neurons
 Inhibitory mechanoreceptors

Pain, pathways
 Brain

- upwards probably glutamat main
transmittor

 Downwards

neurons GABA, ACh,
monoamines (serotonin, NA, DA).


Endogenous opioids
 Endorphin,

enkephalin, dynorphin

 Spinal

tract dynorphin interneuron,
enkephalin downward inhibitory neurons.

 In

brain around ”pain centre” but also in
areas not involved in nociception and nonneuronal tissues

Opioid receptor

 Receptors

in brain and spinal cord
 4 subtypes: µ(my), δ, κ and NOP (ORL-1)

Opioid receptor

 G-protein
 Intra/extracellular,

intramembranous
 Pre- and postsynaptic membranes

NMDA-receptor
 N-metyl-D-Aspartate
 Learning
 Activation

makes spinal neurons more
sensitive to pain stimulus
 Long-term C-fiberstimulation activates
NMDA  central sensitisation
 NMDA-antagonists


Glutamat
 Presynaptic

ion channel calcium influx 
glutamat release

 Crosses

synapse and binds to NMDAreceptors postsynapticly  depolarisation
 hyperexcitability in nociceptive neurons


Pre- and postsynaptic binding
 G-protein
 Lower

inhibits adenylate cyclase

content intracellular cAMP

 Opens

K+, inhibits Ca2+

 Inhibits

pre-synaptic release of glutamat

The opioid receptor


The opioid receptor
 µ, δ , κ
 identical around 70%
 G-protein binds to 3rd receptor loop


The opioid receptor µ (mu)
 Mainly

analgesic effects
 Respiratory depression
 Nausea / vomiting
 Constipation
 Cough reflex
 Euphoria
 Addiction
 Sedation
 Most analgesic opioids are µ-agonists

The opioid receptor δ (delta)
 Probably
 Some

effects outside the CNS

analgetic effekts

 Seizures?
 Least

knowledge

The opioid receptor κ (kappa)
 Analgesia
 Nausea

on mainly spinal cord level

and dysphoria

 Psychotomimetic

effects – limits abuse

potential


Side effects - mechanisms
 Respiratory

depression
Respiratory centre (medulla oblongata)
Less CO2 stimulation
Decreased respiratory rate
 Nausea / vomiting
Area postrema (medulla oblongata)
(triggerzone vomiting reflex)
Stimulation of DA-receptors
Stimulation mechano/chemoreceptors GI
tract

Side effects - mechanisms
 Constipation

peripheral and central affection
less GI movement and increased tonus
No tolerans
Laxatives necessary
Peroral naloxone possible

 Itching

Histamine release or centrally
mediated

Side effects - Mechanisms
 Sedation

Overdose
Wrong strategy
Sleep dept


Drugs
(µ-receptors)
morphine, metadon, fentanyl, heroin

 Agonists

 Partial agonists

buprenorfin, kodein, tramadol
 Antagonist

naloxone

What is an opioid?
 Alkaloid

(plant) or synthetic

 Morphine

like effekts, inhibited by naloxon


Opium

 Narcotic resin from opium poppies:

morphine 10%, noskapin 6%, papaverin 1%, kodein
0,5%


History
 3400

BC
Opium puppies grown in Mesopotamia

 460

BC
Hippocrates medicine (psychiatric disease
and epidemies)


History
 330

BC
Alexander the Great introduces opium to Persia
and India

 400

AD
Opium with traders to China

 Parcelsus

(1490-1541) opium as medicine

 Laudanum

(opium, sherry, cinnamon, clove bud
oil, saffron) 17th century

History
 Morphin

1806
 Kodein 1832
 Heroin 1832


Morphin

 C17H19NO3
 Greek.

Morpheus (God of dreams)
 1806 from opium
 1956 chemical structure


Morphine

 Half

life 2-4 hours
 Bioavailability 10-50% (30%)
 Distribution volume 3L/kg
 Bioaactive morphine-6-glucuronid (kidneys)
 M6G half life 4-15 hours

Heroin


C21H23NO5 (morphin
C17H19NO3)

 Higher

fat solubility
 Produced 1874
 Bayer 1899
 Drug Sweden until
1964
 Half life 30 minutes
 Morphine

Kodein
 C18H21NO3 (morfin

C17H19NO3)

 Produced

1832
 Low receptor affinity
 10% into morphine  M6G
 7-10% non-responders
 Half life 2-4 hours.
 10 mg morfin  Kodein 60mg

Dextropropoxifen
 Half

time 8-18 (90) hours
 Active metabolite norpropoxyfen
 Metabolite half life 30-45 (100) hours
 Alcohol enhances respiratory inhibition
 10mg morfin  100mg Dextropropoxifen


Tramadol
 Halflife

4-6 hours
 Active metabolite D-desmetyltramadol
 Halflife metabolite 9-12 hours
 5-10% non-responders
 Inhibits reuptake NA / 5-HT


Fentanyl
 ”Complicated

kinetics”
 Halflife 1 min, 8 min, 8 tim
 Active metabolites unknown
 10mg morfin  0,05 mg fentanyl (iv)


Pethidine
 synthetic
 Most

opioid

histamine release. Seizures.

 100mg

 10mg morphine

 Shivering


Ketogan
 Ketobemidon(hydroklorid)
 NMDA

– receptor antagonist?
 Halflife 2-4 hours
 Unknown metabolite activity
 Abuse risk
 ”Less documented morphine alternative”
 ”only” indication  renal failure (+NMDA?)
 10mg morphine  10mg ketobemidon

Oxicodon
 Halflife

2-4 timmar
 Probably inaktiva metaboliter
 10mg morfin  5mg oxikodon


Metadon
 NMDA-receptor

antagonist ?
 Halflife 15-40 hours
 ”Bad reputation”
 Advanced pain treatment


Clinical use
 Cancer

pain
 Postoperative pain
 Long-term pain ?
 Neurogenic pain?
 ”Always” in combination with paracetamol
and NSAID
 Elderly ?
 Try not to mix different opioids

Intoxication
 Mios

(small pupils)
 Lower conscience
 Breathing


Antidote – Naloxone (Narcanti)
 opioid

antagonist
 reverses endogenous and exogenous
substanses and acupuncture
 effect within 2 minutes
 Iterated
 iv + im when abuse overdose


Abstinence
 sweating,

fever (”cold turkey”), shakings,
muscular cramps, itching, diarrhea,
nausea, vomiting (the flu)

 At

pain treatment because of to quick
withdrawal  re-medicate!


Cold Case
 Cancer
 Current

medication:
Tb. Dolcontin (longacting morphine)
60mgx2
Tb. Morphine (shortacting) 20mg as req.
inj. Ketogan 5mgvb
Tb. Tramadol 100mgx2

 Pain.

What to do?

Patientfall
 Patient

insatt på Ketogan tablett 5mgx6
med god effekt. Översatt till Dolcontin
20mgx2. Inkommer efter 1 vecka till
akuten: illamående, kräkning

 Diffdiagnos

(opioidrelaterat) ?
 Ytterligare status etc?
 Vad göra?

Afterlife …..
 Morphina
 Renal
 Treat

is currently Golden Standard

failure

pain!


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Biomed /certified fixed orthodontic courses by Indian dental academy

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