1
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Adrenal galds release adrenalin (epinephrin) and noradrenalin (norepinephrin) into
blood stream. Adrenergic receptor agonists and antagonists affects mainly receptors
for circulating A and NA
3
4
Biosynthesis of neurotransmitters Dopamine, Noradrenaline (Norepinephrine) and
Adrenaline (Epinephrine)
5
3 gene families: alpha1, alpha2 and beta. All families consists of 3 subtypes (similar to
each other)
together 9 different receptors with own genes on various chromozomes
6
Receptors consists of 7 transmembrane loops and are connected with different G
proteins
Gq protein activates PLC (proteinkinase C) - leads to increase of intracelular Ca2+
Gs protein activates AC (adenylylcyclase) – leads to increased cAMP
Gi protein inhibits AC – leads to decrease of c AMP
7
Tissue response. Most of mentioned effects are involved in clinical use of AR agonists
and antagonists
8
Therapeutic use of agonists
9
Direct agonists binds to receptor and activates it. Specifity can be focused to family or
particular subtype.
10
Derivatives or analogues of phenylethylamine. Two carbons between phenyl and
amino moiety is necessary.
The lesser degree of substitution on NH, the greatest selectivity for αlpha; increase
volume of NH substituent adds the selectivity towards beta.
R1 substitution inhibits monoamino oxidase – prolonged action and facilitates
indirect mechanism of action
R3, R4: OH groups necessary for activation of both alpha and beta. No hydroxyl
increases central stimulation effect.
11
low dosis activates only D receptor (indication: cardiovascular shock prevention)
medium dosis activates D + beta1 (i: cardiotonic)
high dosis activates D + beta1 + alpha1 (i: severe hypotension, acute hearth failure)
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local decongescent
higher dosis i.v. severe hypotension, cardiovascular shock
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indication: cardiovascular shock, ventricle fibrilation; allergic shock
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Cardial effect, CNS stimulator, weak vasoconstrictor
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vasoconstriction in mucosa reduces mucus production
20
indication: atonic uterus (womb), uterus bleeding
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Prolonged effect due to higher lipophilicity and tissue accumulation
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Due to partial system effect cardiovascular diseses are contraindicated
34
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optimal lipophilicity to pass blood-brain barrier
indication: arterial hypertension
36
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intravenous application in the case of hypertension crisis
local application in ophthalmology - reduces increased intraocular pressure
38
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administered by continual i.v. infusion
indication: heart insufficiency after transplantation, bradycardia
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indication: hert failure
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indication: bronchial asthma, ChOPN (chronical obstructive pulmonary disease)
48
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p.o. administration is not possible due to partial system effect via beta1 activation
53
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long term p.o. application for prevention of bronchial asthma symptoms
57
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bronchodilation is weak
61
highly selective: only weak cardiovascular side effects, no bronchial side efect
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ADHD – retarded dosage forms once a day
narcolepsia – non-retarded dosage forms 2-3x day
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increases motoric activity and wakefulness
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antidepressive agent, diabetic neuropathy 60mg 1x a day
stress urinary incontinence 40mg 2x a day
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