ANS II
Drugs acting on the Autonomous Nervous System
Ulrike Steckelings
IMM - Dept. of Cardiovascular & Renal Research
usteckelings@health.sdu.dk
Læringsmål
1. Beskrive lægemiddel-targets (receptorer, enzymer, anatomiske strukturer)
i det sympatiske og parasympatiske nervesystem
2. Anføre de vigtigste indikationer for brug af:
- non-selektive adrenoceptoragonister [(nor)adrenalin)]
 a1-adrenoceptoragonister (fx fenylefrin)
- non-selektive a1/a2-adrenoceptoragonister (Xylometazoline)
- a1-adrenoceptorantagonister (fx prazosin)
- a2-adrenoceptoragonister (fx clonidin)
- b1-adrenoceptoragonister (fx dobutamin)
- b1-adrenoceptorantagonister (fx propranolol)
- b2-adrenoceptoragonister (fx salbutamol)
- acetylkolin-receptoragonister (fx pilocarpin)
- acetylkolin-receptorantagonister (fx ipratropium)
- acetylkolinesterase-hæmmere (fx neostigmin)
3. Redegøre for ovennævnte lægemiddelgruppers virkningsmekanisme
Læringsmål
1. Beskrive lægemiddel-targets (receptorer, enzymer, anatomiske
strukturer) i det sympatiske og parasympatiske nervesystem
2. Anføre de vigtigste indikationer for brug af:
- non-selektive adrenoceptoragonister [(nor)adrenalin)]
 a1-adrenoceptoragonister (fx fenylefrin)
- non-selektive a1/a2-adrenoceptoragonister (Xylometazoline)
- a1-adrenoceptorantagonister (fx prazosin)
- a2-adrenoceptoragonister (fx clonidin)
- b1-adrenoceptoragonister (fx dobutamin)
- b1-adrenoceptorantagonister (fx propranolol)
- b2-adrenoceptoragonister (fx salbutamol)
- acetylkolin-receptoragonister (fx pilocarpin)
- acetylkolin-receptorantagonister (fx ipratropium)
- acetylkolinesterase-hæmmere (fx neostigmin)
3. Redegøre for ovennævnte lægemiddelgruppers virkningsmekanisme
Nervous System
Peripheral Nervous System (PNS)
Nervous system outside the brain and spinal cord
Involuntary control
Voluntary control
Autonomic Nervous System (ANS)
Communicate with internal
organs and glands
Sympathetic division
“Fight or Flight”
Central Nervous System (CNS)
Brain and spinal cord
Parasympathetic division
“Rest and Digest”
Somatic Nervous System (SNS)
Communicate with sense
organs and voluntary muscle
Sensory nervous
system
sensory input
Motor nervous
system
Motor output
4
Autonomic Nervous System (ANS)
Sympathetic
Parasympathetic
“Fight or flight”
“Rest and digest”
Dilate pupil
Inhibits saliva production
Accelerate respiratory
rate at lung
Constrict pupil
Brain
Stimulates saliva
production
Spinal
cord
Cardiac output 
(Heart rate)
Cardiac output 
(Slow heart rate)
Stimulates adrenaline
and noradrenaline
release
Stimulate glucose
release
Digestion 
Decrease respiratory
rate at lung
Inhibit adrenaline and
noradrenaline release
Sympathetic
Chain Ganglia
Store glucose
Digestion 
Stimulates urination
Inhibit Urination
5
Mediators of the Sympathetic NS
Receptors of the Sympathetic NS
- adrenergic receptors -
a1
vascular smooth
muscle cell
constriction
a2
inhibition of
neurotransmitter
release
b1
increased heart
rate and
contractility
b2
smooth muscle
cell relaxation
in bronchi and
blood vessels
Parasympathetic Mediator Acetylcholine
Receptors of the Parasympathetic NS
- cholinergic receptors -
muscarinic
M1
M2
inhibition of
neurotransmitter
release
inhibition of
heart rate
nicotinic
M3
smooth muscle
cell constriction
in bronchi,
intestine, etc
N
ganglionic
transmission
neuromuscular
junction
Drugs affecting
noradrenergic
(sympathetic) transmission
- Agonists -
10
Læringsmål
1. Beskrive lægemiddel-targets (receptorer, enzymer, anatomiske strukturer)
i det sympatiske og parasympatiske nervesystem
2. Anføre de vigtigste indikationer for brug af:
- non-selektive adrenoceptoragonister [(nor)adrenalin)]
 a1-adrenoceptoragonister (fx fenylefrin)
- non-selektive a1/a2-adrenoceptoragonister (Xylometazoline)
- a1-adrenoceptorantagonister (fx prazosin)
- a2-adrenoceptoragonister (fx clonidin)
- b1-adrenoceptoragonister (fx dobutamin)
- b1-adrenoceptorantagonister (fx propranolol)
- b2-adrenoceptoragonister (fx salbutamol)
- acetylkolin-receptoragonister (fx pilocarpin)
- acetylkolin-receptorantagonister (fx ipratropium)
- acetylkolinesterase-hæmmere (fx neostigmin)
3. Redegøre for ovennævnte lægemiddelgruppers virkningsmekanisme
Adrenergic Receptors
a1
vascular smooth
muscle cell
constriction
a2
inhibition of
neurotransmitter
release
b1
increased heart
rate and
contractility
b2
smooth muscle
cell relaxation
in bronchi and
blood vessels
Adrenergic agonists
direct acting
selective
non-selective
Phenylephrine
a1
Clonidine
a2
Dobutamine
b1
Salbutamol
b2
Xylometazoline
a1, a2
Isoproterenol
b1, b2
Adrenaline
a1, a2, b1, b2
Noradrenaline
a1, a2, b1
mixed acting
Ephedrine
a1, a2, b1, b2
and releasing agent
indirect acting
Amphetamine
releasing agent
Cocaine
uptake inhibitor
Selegiline
MAO inhibitor
Entacapone
COMT inhibitor
Adrenergic agonists
direct acting
selective
non-selective
Phenylephrine
a1
Clonidine
a2
Dobutamine
b1
Salbutamol
b2
Xylometazoline
a1, a2
Isoproterenol
b1, b2
Adrenaline
a1, a2, b1, b2
Noradrenaline
a1, a2, b1
mixed acting
Ephedrine
a1, a2, b1, b2
and releasing agent
indirect acting
Amphetamine
releasing agent
Cocaine
uptake inhibitor
Selegiline
MAO inhibitor
Entacapone
COMT inhibitor
Drugs affecting
noradrenergic
(sympathetic) transmission
- Agonists -
15
Læringsmål
1. Beskrive lægemiddel-targets (receptorer, enzymer, anatomiske strukturer)
i det sympatiske og parasympatiske nervesystem
2. Anføre de vigtigste indikationer for brug af:
- non-selektive adrenoceptoragonister [(nor)adrenalin)]
 a1-adrenoceptoragonister (fx fenylefrin)
- non-selektive a1/a2-adrenoceptoragonister (Xylometazoline)
- a1-adrenoceptorantagonister (fx prazosin)
- a2-adrenoceptoragonister (fx clonidin)
- b1-adrenoceptoragonister (fx dobutamin)
- b1-adrenoceptorantagonister (fx propranolol)
- b2-adrenoceptoragonister (fx salbutamol)
- acetylkolin-receptoragonister (fx pilocarpin)
- acetylkolin-receptorantagonister (fx ipratropium)
- acetylkolinesterase-hæmmere (fx neostigmin)
3. Redegøre for ovennævnte lægemiddelgruppers virkningsmekanisme
Adrenergic agonists
direct acting
selective
non-selective
Phenylephrine
a1
Clonidine
a2
Dobutamine
b1
Salbutamol
b2
Xylometazoline
a1, a2
Isoproterenol
b1, b2
Adrenaline
a1, a2, b1, b2
Noradrenaline
a1, a2, b1
mixed acting
Ephedrine
a1, a2, b1, b2
and releasing agent
indirect acting
Amphetamine
releasing agent
Cocaine
uptake inhibitor
Selegiline
MAO inhibitor
Entacapone
COMT inhibitor
Adrenergic Receptors
a1
vascular smooth
muscle cell
constriction
a2
inhibition of
neurotransmitter
release
b1
increased heart
rate and
contractility
b2
smooth muscle
cell relaxation
in bronchi and
blood vessels
a1-Adrenergic Receptor Signalling
a1
Vascular Smooth Muscle Cell
a1-Receptor Agonist Phenylephrine
Adrenergic agonists
direct acting
selective
non-selective
Phenylephrine
a1
Clonidine
a2
Dobutamine
b1
Salbutamol
b2
Xylometazoline
a1, a2
Isoproterenol
b1, b2
Adrenaline
a1, a2, b1, b2
Noradrenaline
a1, a2, b1
mixed acting
Ephedrine
a1, a2, b1, b2
and releasing agent
indirect acting
Amphetamine
releasing agent
Cocaine
uptake inhibitor
Selegiline
MAO inhibitor
Entacapone
COMT inhibitor
Adrenergic Receptors
a1
vascular smooth
muscle cell
constriction
a2
inhibition of
neurotransmitter
release
b1
increased heart
rate and
contractility
b2
smooth muscle
cell relaxation
in bronchi and
blood vessels
a1/a2-Receptor Agonists
Xylometazoline
=> a1-/a2-agonist
a1- and a1/a2-Receptor Agonists
Phenylephrine, Xylometazoline
Indication: nasal congestion
Side effects: irritation of nasal mucosa
addiction
necrosis of nasal mucosa
dry mouth
hypertension (high dose)
a1/a2-Receptor Agonists
Rang & Dale:
Methoxamine
Indication:
Side effects:
hypotension
hypertension
Adrenergic agonists
direct acting
selective
non-selective
Phenylephrine
a1
Clonidine
a2
Dobutamine
b1
Salbutamol
b2
Xylometazoline
a1, a2
Isoproterenol
b1, b2
Adrenaline
a1, a2, b1, b2
Noradrenaline
a1, a2, b1
mixed acting
Ephedrine
a1, a2, b1, b2
and releasing agent
indirect acting
Amphetamine
releasing agent
Cocaine
uptake inhibitor
Selegiline
MAO inhibitor
Entacapone
COMT inhibitor
Adrenergic Receptors
a1
vascular smooth
muscle cell
constriction
a2
inhibition of
neurotransmitter
release
b1
increased heart
rate and
contractility
b2
smooth muscle
cell relaxation
in bronchi and
blood vessels
a2-Adrenergic Receptor Agonist
Clonidine
Indication:
hypertension
(rarely used)
Side effects: hypotension
dry mouth
dizziness
Adrenergic agonists
direct acting
selective
non-selective
Phenylephrine
a1
Clonidine
a2
Dobutamine
b1
Salbutamol
b2
Xylometazoline
a1, a2
Isoproterenol
b1, b2
Adrenaline
a1, a2, b1, b2
Noradrenaline
a1, a2, b1
mixed acting
Ephedrine
a1, a2, b1, b2
and releasing agent
indirect acting
Amphetamine
releasing agent
Cocaine
uptake inhibitor
Selegiline
MAO inhibitor
Entacapone
COMT inhibitor
Adrenergic Receptors
a1
vascular smooth
muscle cell
constriction
a2
inhibition of
neurotransmitter
release
b1
increased heart
rate and
contractility
b2
smooth muscle
cell relaxation
in bronchi and
blood vessels
Sympathetic Innervation of the Heart
b1
b1
Control of heart rate
and contractility
b1-Adrenergic Receptor Agonist
Shock is a medical emergency characterised by inadequate perfusion of vital
organs, usually because of a very low arterial blood pressure
Cardiogenic Shock
Sudden inability of the
heart to pump
properly.
Frequent cause:
Myocardial infarction
Dobutamine
β1 > β2 > α1
Indication: Cardiogenic shock
(acute heart failure)
Side effects: Dysrhythmias
But less severe
tachycardia than with
other
b1-agonists
Adrenergic agonists
direct acting
selective
non-selective
Phenylephrine
a1
Clonidine
a2
Dobutamine
b1
Salbutamol
b2
Xylometazoline
a1, a2
Isoproterenol
b1, b2
Adrenaline
a1, a2, b1, b2
Noradrenaline
a1, a2, b1, b2
mixed acting
Ephedrine
a1, a2, b1, b2
and releasing agent
indirect acting
Amphetamine
releasing agent
Cocaine
uptake inhibitor
Selegiline
MAO inhibitor
Entacapone
COMT inhibitor
Unselective a/b-agonists
Adrenaline
Noradrenaline
β1 = β2 > α1 = α2
β1 = α 1 > β2 = α 2
Indication (adrenaline):
Anaphylactic shock: shock (life-threatening drop
in blood pressure) due to a severe allergic
reaction.
It may also include swelling of throat and mouth,
general rush, asthma attack, etc.
Why not dobutamine as first line treatment?
Epi-pen
Adrenergic Receptors
a1
vascular smooth
muscle cell
constriction
a2
inhibition of
neurotransmitter
release
b1
increased heart
rate and
contractility
b2
smooth muscle
cell relaxation
in bronchi and
blood vessels
b1/2-Adrenergic Receptors
Heart
b1 >> b2
cardiomyocyte
Increase in contractility
and heart rate
Blood Vessel
only b2
smooth muscle cell
vasorelaxation
b1/2-Adrenergic Receptors
Heart
b1 >> b2
Bronchi
only b2
Note!
Stimulation of b1- and b1-receptors leads to an
increase in cAMP.
But in cardiomyoctes, this results in constriction,
while in smooth muscel cells of blood vessels
and bronchi, it results in relaxation
cardiomyocyte
Increase in contractility
and heart rate
smooth muscle cell
Bronchorelaxation
Læringsmål
1. Beskrive lægemiddel-targets (receptorer, enzymer, anatomiske strukturer)
i det sympatiske og parasympatiske nervesystem
2. Anføre de vigtigste indikationer for brug af:
- non-selektive adrenoceptoragonister [(nor)adrenalin)]
 a1-adrenoceptoragonister (fx fenylefrin)
- non-selektive a1/a2-adrenoceptoragonister (Xylometazoline)
- a1-adrenoceptorantagonister (fx prazosin)
- a2-adrenoceptoragonister (fx clonidin)
b2-agonists for the
- b1-adrenoceptoragonister (fx dobutamin)
treatment of asthma
- b1-adrenoceptorantagonister (fx propranolol)
are a focus of the
- b2-adrenoceptoragonister (fx salbutamol)
lecture
- acetylkolin-receptoragonister (fx pilocarpin)
- acetylkolin-receptorantagonister (fx ipratropium)
- acetylkolinesterase-hæmmere (fx neostigmin)
3. Redegøre for ovennævnte lægemiddelgruppers virkningsmekanisme
Adrenergic agonists
direct acting
selective
non-selective
Phenylephrine
a1
Clonidine
a2
Dobutamine
b1
Salbutamol
b2
Xylometazoline
a1, a2
Isoproterenol
b1, b2
Adrenaline
a1, a2, b1, b2
Noradrenaline
a1, a2, b1
mixed acting
Ephedrine
a1, a2, b1, b2
and releasing agent
indirect acting
Amphetamine
releasing agent
Cocaine
uptake inhibitor
Selegiline
MAO inhibitor
Entacapone
COMT inhibitor
Adrenergic Receptors
a1
vascular smooth
muscle cell
constriction
a2
inhibition of
neurotransmitter
release
b1
increased heart
rate and
contractility
b2
smooth muscle
cell relaxation
in bronchi and
blood vessels
Bronchial Asthma
bronchoconstriction
Inflammation; mucus production; swelling
Treatment of Bronchial Asthma
Bronchodilatation
b2-agonists
Salbutamol etc
bronchus
Treatment of Bronchial Asthma
Treatment algorithm for bronchial
asthma according to WHO
+
+
+
low Dosis
Oral corticoids
long-acting ß2-agonists,
chronic treatment / prevention
inhaled glucocorticoids
medium Dosis
high Dosis
fast-acting b2-agonists – on demand in asthma attack
Step 1
Step 2
Step 3
Step 4
Treatment of Bronchial Asthma
Fast-acting b2-agonists as on-demand medication
Long-acting b2-agonists as chronic medication
Pharmacokinetics:
-
fast-acting b2-agonists act after 20-30 sec, max effect after 30 minutes, and
effect lasts up to 5 hours
long-acting b2-agonists act up to 12/24 hours
fast-acting (<6h)
Fenoterol - Berotec®
Salbutamol - Sultanol®
Terbutaline - Bricanyl®
long-acting (12h)
Salmeterol - Serevent®
Formoterol - Foradil®, Oxis®
Indacaterol
24 h Onbrez®
Treatment of Bronchial Asthma
Side effects:
Main side effect (at high dose):
Tachycardia
 because at high doses, all drugs
incl. b2-agonists start losing
selectivity
 b2-agonists will start acting on
b1-receptors in the heart and
increase heart rate
Adrenergic agonists
direct acting
selective
non-selective
Phenylephrine
a1
Clonidine
a2
Dobutamine
b1
Clenbuterol
b2
Xylometazoline
a1, a2
Isoproterenol
b1, b2
Adrenaline
a1, a2, b1, b2
Noradrenaline
a1, a2, b1
mixed acting
Ephedrine
a1, a2, b1, b2
and releasing agent
indirect acting
Amphetamine
releasing agent
Cocaine
uptake inhibitor
Selegiline
MAO inhibitor
Entacapone
COMT inhibitor
Clenbuterol
Drugs affecting
noradrenergic
(sympathetic) transmission
- Antagonists -
48
Læringsmål
1. Beskrive lægemiddel-targets (receptorer, enzymer, anatomiske strukturer)
i det sympatiske og parasympatiske nervesystem
2. Anføre de vigtigste indikationer for brug af:
- non-selektive adrenoceptoragonister [(nor)adrenalin)]
 a1-adrenoceptoragonister (fx fenylefrin)
- non-selektive a1/a2-adrenoceptoragonister (Xylometazoline)
- a1-adrenoceptorantagonister (fx prazosin)
- a2-adrenoceptoragonister (fx clonidin)
- b1-adrenoceptoragonister (fx dobutamin)
- b1-adrenoceptorantagonister (fx propranolol)
- b2-adrenoceptoragonister (fx salbutamol)
- acetylkolin-receptoragonister (fx pilocarpin)
- acetylkolin-receptorantagonister (fx ipratropium)
- acetylkolinesterase-hæmmere (fx neostigmin)
3. Redegøre for ovennævnte lægemiddelgruppers virkningsmekanisme
Adrenergic antagonists
a-receptor antagonists
a1
Prazosin
a2
Yohimbine
Not in
clinical use
Hypertension
(rarely used)
non-selective
Phentolamine
Phenoxybenzamine
Pheochromocytoma:
a tumour producing
(nor)adrenline
Adrenergic antagonists
a-receptor antagonists
a1
Prazosin
a2
Yohimbine
Not in
clinical use
non-selective
Phentolamine
Phenoxybenzamine
b1-receptor antagonists
b1-receptor antagonists
for the treatment of
hypertension and heart
failure are a focus of the
lecture
Adrenergic Receptors
a1
vascular smooth
muscle cell
constriction
a2
inhibition of
neurotransmitter
release
b1
increased heart
rate and
contractility
b2
smooth muscle
cell relaxation
in bronchi and
blood vessels
Beta-blockers
b-adrenergic receptor antagonists
• Propranolol, Atenolol, Metoprolol
Sir James Black
Beta-blockers
b-adrenergic receptor antagonists
Sir James Black
• Propranolol, Atenolol, Metoprolol
• Reduce the adrenergic stimulation of
the heart: Decrease in heart rate and in
contractility.
Beta-blockers
b-adrenergic receptor antagonists
• Propranolol, Atenolol, Metoprolol
• Reduce the adrenergic stimulation of the
heart: Decrease in heart rate and in
contractility
• => Protection of the heart from excessive,
„unhealthy“ workload
 Reduction of the adrenergic effect on renin
secretion
Sir James Black
Regulation of Renin Secretion
Direct stimulation of renin
release through
b1-receptors on JG cells
=> blocked by beta-blockers
b1
Inhibition of the RAS by b-blockers
b1
Vasoconstriction
Rise in blood pressure
b-blockers
Beta blockers
• Indications: Hypertension, Heart failure
• Contraindications: bronchial asthma/COPD
• Side effects:
– impaired cardiac peformance
– bronchial asthma
bronchus
bronchus
Beta blockers
• Indications: Hypertension, Heart failure
• Contraindications: bronchial asthma/COPD
• Side effects:
– impaired cardiac peformance
– bronchial asthma
– blood flow in peripheral tissues 
resistance arteries
b2
bronchus
peripheral arteries e.g. in
muscular tissue
Beta blockers
• Indications: Hypertension, Heart failure
• Contraindications: bronchial asthma/COPD
• Side effects:
– impaired cardiac peformance
– bronchial asthma
– blood flow in peripheral tissues 
– bradycardic arrhythmia, blockade of AV-conduction
– pro-diabetic effects (inhibition of insulin release)
bronchus
Islet cell in the pancreas
b1
ç
Inhibition of insulin
release through blockade
of b1-receptors
Beta blockers
• Indications: Hypertension, Heart failure
• Contraindications: bronchial asthma/COPD
• Side effects:
– impaired cardiac peformance
– bronchial asthma
– blood flow in peripheral tissues 
– bradycardic arrhythmia, blockade of AV-conduction
– pro-diabetic effects (inhibition of insulin release)
– impaired libido
– Rebound phenomenon
bronchus
Rebound Phenomenon
b1
Treatment with b1-antagonist
Compensatory increase in
b1-receptors
Abrupt end of treatment
 number of receptors remains
increased
: b1-receptor antagonist / beta-blocker
Risk of hypertensive crisis !
Drugs affecting cholinergic,
parasympathetic
transmission
65
Læringsmål
1. Beskrive lægemiddel-targets (receptorer, enzymer, anatomiske strukturer)
i det sympatiske og parasympatiske nervesystem
2. Anføre de vigtigste indikationer for brug af:
- non-selektive adrenoceptoragonister [(nor)adrenalin)]
 a1-adrenoceptoragonister (fx fenylefrin)
- non-selektive a1/a2-adrenoceptoragonister (Xylometazoline)
- a1-adrenoceptorantagonister (fx prazosin)
- a2-adrenoceptoragonister (fx clonidin)
- b1-adrenoceptoragonister (fx dobutamin)
- b1-adrenoceptorantagonister (fx propranolol)
- b2-adrenoceptoragonister (fx salbutamol)
- acetylkolin-receptoragonister (fx pilocarpin)
- acetylkolin-receptorantagonister (fx ipratropium)
- acetylkolinesterase-hæmmere (fx neostigmin)
3. Redegøre for ovennævnte lægemiddelgruppers virkningsmekanisme
Cholinergic Receptors
muscarinic
M1
M2
inhibition of
neurotransmitter
release
inhibition of
heart rate
nicotinic
M3
smooth muscle
cell constriction
in bronchi,
intestine, etc
N
ganglionic
transmission
neuromuscular
junction
Drugs Affecting Cholinergic Transmission
Muscarinic
AcetylcholineReceptor Antagonists
AcetylcholineReceptor Agonist
Acetylcholine-esterase
Inhibitor
Atropine
Ipratropium bromide
Pilocarpine
Neostigmine
Drugs Affecting Cholinergic Transmission
Muscarinic
AcetylcholineReceptor Antagonists
AcetylcholineReceptor Agonist
Acetylcholine-esterase
Inhibitor
Atropine
Ipratropium bromide
Pilocarpine
Neostigmine
Atropine
muscarinic
M1
M2
M3
Atropa belladonna
Atropine:
inhibition of
neurotransmitter
release
inhibition of
heart rate
smooth muscle
cell constriction
in bronchi,
intestine, etc
non-selective
muscarinic
receptor antagonist
Clinical use (rare):
increase of heart rate;
nerve agent intoxication
Drugs Affecting Cholinergic Transmission
Muscarinic
AcetylcholineReceptor Antagonists
AcetylcholineReceptor Agonist
Acetylcholine-esterase
Inhibitor
Atropine
Ipratropium bromide
Pilocarpine
Neostigmine
M3-acetylcholine
receptor antagonists for
the treatment of chronic
obstructive lung disease
(KOL) are a focus of the
lecture
Ipratropiumbromide
muscarinic
M3
Ipratropiumbromide:
selective muscarinic
M3-receptor antagonist
smooth muscle
cell constriction
in bronchi,
intestine, etc
Treatment of Chronic Obstructive Lung Disease
Muscarinic M3-receptor antagonists
Ipratropimbromide
bronchus
Treatment of Chronic Obstructive Lung Disease
Muscarinic M3-Receptor Antagonists
Muscarinic M3-Receptor Antagonists
Side Effects:
- dry mouth due to inhibition of spittle production
- basically no systemic side effects
Detour: Drug Application by Inhalation
Drug Application by Inhalation
Pressurised metered
dose inhalers
Dry powder inhalor / disk
Spacer
Drug Application by Inhalation
trachea/bronchi
oesophagus
Bronchi
Gastro-intestinal-tract
(swallowed)
Where does the drug go to,
when it is swallowed instead of
being inhaled?
The Fate of a Swallowed Drug
Prevention of Systemic Side Effects
Prevent absorption
from intestine
Rapid metabolism in the liver
Application of drugs by
inhalation as such does not
protect from systemic side
effects
Additional measures need to be taken
to prevent systemic side effects,
e.g. prevention of absorption from the gut
or rapid metabolism in the liver
Muscarinic M3-Receptor Antagonists
Side effects:
Dry oral mucosa

Very low incidence of adverse effects when inhaled, because
Ipratropium/Tiotropium are very poorly resorbed
Prevent absorption
from intenstine
Rapid metabolism in the liver
Drugs Affecting Cholinergic Transmission
Muscarinic
AcetylcholineReceptor Antagonists
AcetylcholineReceptor Agonist
Acetylcholine-esterase
Inhibitor
Atropine
Ipratropium bromide
Pilocarpine
Neostigmine
Parasympathetic Innervation of the Eye
Activation of M3-receptor
causes constriction of iris
sphincter muscle
 Miosis (narrowing of pupil)
M3
Glaucoma
Parasympathetic Innervation of the Eye
M3
Activation of M3-receptors by
pilocarpine causes constriction of
ciliary muscle
 Angle for access to canal of
Schlemm opens
 Aqueous humour can drain
Muscarinic M3-Receptor Agonist Pilocarpine
Glaucoma
Activation of M3-receptor causes
constriction of ciliary muscle
 Angle for access to canal of
Schlemm opens
 Aqueous humour can drain
Drugs Affecting Cholinergic Transmission
Muscarinic
AcetylcholineReceptor Antagonists
AcetylcholineReceptor Agonist
Acetylcholineesterase Inhibitor
Atropine
Ipratropium bromide
Pilocarpine
Neostigmine
Acetylcholinesterase (AChE)
Neostigmin
Myasthenia Gravis
Treatment => Acetylcholinesterase inhibitor
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Læringsmål
1. Beskrive lægemiddel-targets (receptorer, enzymer, anatomiske strukturer)
i det sympatiske og parasympatiske nervesystem
2. Anføre de vigtigste indikationer for brug af:
- non-selektive adrenoceptoragonister [(nor)adrenalin)]
 a1-adrenoceptoragonister (fx fenylefrin)
- non-selektive a1/a2-adrenoceptoragonister (Xylometazoline)
- a1-adrenoceptorantagonister (fx prazosin)
- a2-adrenoceptoragonister (fx clonidin)
- b1-adrenoceptoragonister (fx dobutamin)
- b1-adrenoceptorantagonister (fx propranolol)
- b2-adrenoceptoragonister (fx salbutamol)
- acetylkolin-receptoragonister (fx pilocarpin)
- acetylkolin-receptorantagonister (fx ipratropium)
- acetylkolinesterase-hæmmere (fx neostigmin)
3. Redegøre for ovennævnte lægemiddelgruppers virkningsmekanisme
Thank you