Léčiva ovlivňující motorický systém Antiparkinsonika

Transkript

Antiemetics
&
Prokinetics
Jan Strojil
Ústav farmakologie LF UP
October 17, 2006
Jan Strojil
Antiemetics & Prokinetics
Intro
Antidopaminergic
Antihistaminic
Anti 5‐HT3
Antimuscarinic
Outline
n Introduction ‐ physiology
o Antidopaminergic
p Antihistaminic
q Anti 5‐HT3
r Antimuscarinic
s Other, Prokinetics & Emetics
Jan Strojil
Other
Intro
Antidopaminergic
Antihistaminic
Anti 5‐HT3
Antimuscarinic
Other
Physiology
Úvod
Vomiting: forceful expulsion of the contents of oneʹs stomach
through the mouth (wikipedia.org)
• good poison ingestion
gastric irritation
• bad
kinetosis
gravidity
chemotherapy (or other drugs)
intracranial processes (↑ pressure)
vestibular disorders
Jan Strojil
Intro
Antidopaminergic
Antihistaminic
Anti 5‐HT3
Antimuscarinic
Physiology
Úvod
Consequences of repeated vomiting
• hypochloremic metabolic alkalosis
• secondary hypokalemia (kidneys)
• teeth damage
• aspiration
Jan Strojil
Other
Intro
Antidopaminergic
Antihistaminic
Anti 5‐HT3
Antimuscarinic
Other
Physiology
Úvod
Stimulus
Pain, repulsive
sights and smells,
emotions
Input
Sensory afferents
and CNS pathways
H1 and M
blockers
Motion sickness
Integration
Output
Higher centers
Dopamine
antagonists,
5-HT3 blockers
Labyrinth
Vestibular nuclei
(H1 and mACh R)
CTZ
(D2 and
5-HT3 R)
Vomiting
centre
(mACh R)
Nerves to
visceral
and somatic
receptors
Blood
Endogenous
toxins, drugs
Release of emetogenic
agents (5-HT,
prostanoids, free radicals)
Stimuli from
pharynx
and stomach
M blockers
Nucleus tractus
solitarii
(mACh and H1 R)
Visceral afferents
(5-HT3 R?)
H1 blockers
5-HT3
blockers
Rang, Ritter, Dale & Moore, Pharmacology, 2003
Jan Strojil
Intro
Antidopaminergic
Antihistaminic
Anti 5‐HT3
Antimuscarinic
Antidopaminergic
o Antidopaminergic
p Antihistaminic
q Anti 5‐HT3
r Antimuscarinic
Jan Strojil
Other
Intro
Antidopaminergic
Antihistaminic
Anti 5‐HT3
Antimuscarinic
Other
Physiology
Úvod
Stimulus
Pain, repulsive
sights and smells,
emotions
Input
Sensory afferents
and CNS pathways
H1 and M
blockers
Motion sickness
Integration
Output
Higher centers
Dopamine
antagonists,
5-HT3 blockers
Labyrinth
Vestibular nuclei
(H1 and mACh R)
CTZ
(D2 and
5-HT3 R)
Vomiting
centre
(mACh R)
Nerves to
visceral
and somatic
receptors
Blood
Endogenous
toxins, drugs
agents (5-HT,
Stimuli from
pharynx
and stomach
M blockers
Nucleus tractus
solitarii
(mACh and H1 R)
Visceral afferents
(5-HT3 R?)
H1 blockers
5-HT3
blockers
Jan Strojil
Intro
Antidopaminergic
Antihistaminic
Anti 5‐HT3
Antimuscarinic
Antidopaminergic
‐ D2 receptor blockers
Úvod
• mechanisms of action
– block transmission in CTZ
– cancel dopamine inhibition of the stomach
– in high doses also 5‐HT3
• indications
– PONV
– drug induced N/V
– migraine
– gastric paresis in DM
– before GI radiology (prokinetic)
Jan Strojil
Other
Intro
Antidopaminergic
Antihistaminic
Anti 5‐HT3
Antimuscarinic
Antidopaminergic
‐ side effects
Úvod
• side effects
– extrapyramidal
– ↑ prolactin
– malign neuroleptic syndrome
– dizziness
• contraindications
– prolactinoma
– Parkinson’s
• interactions
– can improve absorption
Jan Strojil
Other
Intro
Antidopaminergic
Antihistaminic
Anti 5‐HT3
Antimuscarinic
Antidopaminergic
‐ drugs
Úvod
• metoclopramide (Reglan
® [USA], Maxolon® [UK])
– 10‐20 mg p.o., i.m., i.v.
– crosses BBB
• itopride (Ganaton
® [D], Itax® [USA])
– also some i‐ACHE activity
– better prokinetic
• cisapride (Propulsid )
®
– QT prolongation
– discontinued
• alizapride, domperidone (Motilium )
®
– do not cross BBB
Jan Strojil
Other
Intro
Antidopaminergic
Antihistaminic
Anti 5‐HT3
Antimuscarinic
Antidopaminergic
‐ drugs
Úvod
• antipsychotics
– chlorpromazine
– methotrimeprazine
– perphenazine
– prochlorperazine
– trifluoperazine
– triflupromazine
Jan Strojil
Other
Intro
Antidopaminergic
Antihistaminic
Anti 5‐HT3
Antimuscarinic
Antihistamines
o Antidopaminergic
p Antihistaminic
q Anti 5‐HT3
r Antimuscarinic
Jan Strojil
Other
Intro
Antidopaminergic
Antihistaminic
Anti 5‐HT3
Antimuscarinic
Other
Antihistaminic
‐ physiology
Úvod
Stimulus
Pain, repulsive
sights and smells,
emotions
Input
Sensory afferents
and CNS pathways
H1 and M
blockers
Motion sickness
Integration
Output
Higher centers
Dopamine
antagonists,
5-HT3 blockers
Labyrinth
Vestibular nuclei
(H1 and mACh R)
CTZ
(D2 and
5-HT3 R)
Vomiting
centre
(mACh R)
Nerves to
visceral
and somatic
receptors
Blood
Endogenous
toxins, drugs
agents (5-HT,
Stimuli from
pharynx
and stomach
M blockers
Nucleus tractus
solitarii
(mACh and H1 R)
Visceral afferents
(5-HT3 R?)
H1 blockers
5-HT3
blockers
Jan Strojil
Intro
Antidopaminergic
Antihistaminic
Anti 5‐HT3
Antimuscarinic
Antihistaminic
‐ H1 receptor blockers
Úvod
– block vestibular and visceral system
– also sedative action
– many have anti M as well
• indications
– kinetosis (motion or sea sickness)
– gravidity
– Meniér‘s disease
Jan Strojil
Other
Intro
Antidopaminergic
Antihistaminic
Anti 5‐HT3
Antimuscarinic
Antihistaminic
‐ side effects
Úvod
• side effects
– sedation
– can mask symptoms of aminoglycoside damage
– parasympatolytic
– dizziness
– asthma
– ileus
• interactions
– i‐MAOs
Jan Strojil
Other
Intro
Antidopaminergic
Antihistaminic
Anti 5‐HT3
Antimuscarinic
Antihistaminic
‐ drugs
Úvod
• dimenhydrinate (Travel‐Gum )
®
– unsuitable for drivers
• embramine (Medrin)
– vertigo
– Meniér‘s
• meclozine (meclizine) (Antivert , Bonine )
®
®
– same as dimenhydrinate
Jan Strojil
Other
Intro Antidopaminergic Antihistaminic Anti 5‐HT3
Antimuscarinic Other
Anti 5‐HT3
o Antidopaminergic
p Antihistaminic
q Anti 5‐HT3
r Antimuscarinic
Jan Strojil
Anti 5‐HT
Úvod
3 ‐ physiology
Stimulus
Pain, repulsive
sights and smells,
emotions
Input
Sensory afferents
and CNS pathways
H1 and M
blockers
Motion sickness
Integration
Output
Higher centers
Dopamine
antagonists,
5-HT3 blockers
Labyrinth
Vestibular nuclei
(H1 and mACh R)
CTZ
(D2 and
5-HT3 R)
Vomiting
centre
(mACh R)
Nerves to
visceral
and somatic
receptors
Blood
Endogenous
toxins, drugs
agents (5-HT,
Stimuli from
pharynx
and stomach
M blockers
Nucleus tractus
solitarii
(mACh and H1 R)
Visceral afferents
(5-HT3 R?)
H1 blockers
5-HT3
blockers
Jan Strojil
5‐HT
Úvod3 receptor blockers
– serotonine block (mainly in CTZ)
– very effective
• indications
– chemotherapy N/V (cis‐platine)
– postradiotherapy N/V
– PONV
– most other causes
Jan Strojil
5‐HT
Úvod3 receptor blockers ‐ side effects
• side effects
– usually mild
– obstipation • contraindications
– no info on children and pregnant women
• interactions
– none known
Jan Strojil
5‐HT
Úvod3 receptor blockers ‐ drugs
• ondansetron (Zofran , Ondemet )
®
®
– a breaktrough in chemotherapy
– short T½ (3 hours)
• tropisetron, dolasetron
– longer T½
• palosetron, granisetron
– parenteral application
• beneficial combination with dexamethasone
• alosetron used in IBS
Jan Strojil
Antimuscarinic
Antimuscarinic
o Antidopaminergic
p Antihistaminic
q Anti 5‐HT3
r Antimuscarinic
Jan Strojil
Other
Antimuscarinic
Other
Antimuscarinic
‐ physiology
Úvod
Stimulus
Pain, repulsive
sights and smells,
emotions
Input
Sensory afferents
and CNS pathways
H1 and M
blockers
Motion sickness
Integration
Output
Higher centers
Dopamine
antagonists,
5-HT3 blockers
Labyrinth
Vestibular nuclei
(H1 and mACh R)
CTZ
(D2 and
5-HT3 R)
Vomiting
centre
(mACh R)
Nerves to
visceral
and somatic
receptors
Blood
Endogenous
toxins, drugs
agents (5-HT,
Stimuli from
pharynx
and stomach
M blockers
Nucleus tractus
solitarii
(mACh and H1 R)
Visceral afferents
(5-HT3 R?)
H1 blockers
5-HT3
blockers
Jan Strojil
Antimuscarinic
Other
Antimuscarinic
Úvod
– M receptor block
– mainly vestibular
• indications
– kinetosis
Brugmansia x insignis
Jan Strojil
Antimuscarinic
Antimuscarinic
‐ side effects
Úvod
• side effects
– sedation
– parasympatolytic
– glaucoma
• MKULTRA project
Jan Strojil
Other
Antimuscarinic
Antimuscarinic
‐ drugs
Úvod
• skopolamin (hyoscine)
– maily for kinetosis
– several mg per os
– today in the form of TTS (0,5 mg)
Jan Strojil
Other
Antimuscarinic
o Antidopaminergic
p Antihistaminic
q Anti 5‐HT3
r Antimuscarinic
Jan Strojil
Other
Úvod
• NK‐1 receptor blockers
– aprepitant
– central action
– in combination with 5‐HT3 and dexamethasone
• steroids
– dexamethasone
• BDZ
–
• magnesium
Jan Strojil
Prokinetics ‐
summary
Úvod
• D2 blockers
– e.g. metoclopramide, itopride
– GERD, diabetic gastroparesis, radiology
• iACHE
– stigmines
• motilin
– natural substance (erythromycin)
Jan Strojil
Emetics
Úvod
• Tinctura ipecacuanhae
– strong emetic
– deprecated
– only certain indications
– not as effective as lavage
• emetics in small doses
– expectorans
Jan Strojil
Úvod
Family Guy, © Fox Network
Úvod
Thank you for your attention
Jan Strojil

Léčiva ovlivňující motorický systém Antiparkinsonika

Transkript

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