The Adrenergic System Flashcards
neurotransmitters of the adrenergic system are
catecholamines -
adrenaline and noradrenaline.
catecholamines -
adrenaline and noradrenaline.
( physiology - mechanism )
+ look the steps from pic of atlas
1) - They are synthesized in the cytoplasm of cells adrenergic neurons from tyrosine which converts in dopa (by tyrosine hydroxilase ) , an amino acid which then transforms into dopamine. ( tyrosine -> DOPA -> DOPAMINE )
2) Dopamine -> NE (noradrenaline) which
is converted into -> epinephrine (adrenaline).
3) Catecholamines are released from the deposit granules by exocytosis.
4) From the synaptic cleft it diffuses and stimulate specific receptors - adrenergic receptors.
5) Termination of the effect of catecholamines is done by passive diffusion,
reuptake and metabolism by 2 enzymes - monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT)
Sympathomimetics
Agents that activate adrenergic receptors
Sympatholytics
Agents that blocks the activation of adrenergic receptors
Adrenergic receptors
G protein coupled receptors and are of two
types - α and β.
α-adrenergic receptors:
- postsynaptic α1 receptors
- presynaptic, postsynaptic and extrasinaptic α2 receptors.
adrenergic receptors G coupled + production of 2nd messenger
α1 receptors are coupled with Gq proteins. -> ACTIVATES : phospholipase C , producing IP3 & DAG
α2 receptors are coupled with Gi proteins -> INHIBIT : adenyl cyclase , decreasing cAMP formation
β-adrenergic receptors are coupled with Gs proteins -> STIMULATE : Adenyl cyclase with an increase in intracellular cAMP
β-adrenergic receptors -
β1, β2, β3
Effects of adrenergic receptor stimulation
α1 receptors: (6)
VASCULAR LEVEL : o vasoconstriction, (thus ↑BP); o decreased bronchial secretion , o mydriasis, GI LEVEL : o spleen capsule contraction, o piloerection, o decreased insulin secretion.
presynaptic α2 receptors:
decreases the release of norepinephrine into the synaptic cleft -
feedback mechanism. ( negative feedback)
- inhibition of neurotransmitter release ( noradrenaline + acetylcholine )
α2 postsynaptic receptors:
Vasoconstriction
extrasynaptic α2 receptors:
o stimulates platelet aggregation
+ contraction of vascular smooth muscles
+ inhibition of insulin release
β1 receptors:
increases the activity of the heart (increases contractility, A-V conduction, excitability)
o stimulates renin secretion
- CNS = anxiety
β2 receptors:
o vasodilation, ( in skeletal muscle ) o bronchodilation, o relaxes uterine muscles, o tremor, o agitation, o nervousness, o increases gluconeogenesis and glycogenolysis, o increases insulin secretion
β3 receptors:
o lipolysis and glycogenolysis.
Direct sympathomimetics
are substances that have affinity for
adrenergic receptors and intrinsic activity
Adrenaline
- stimulates all adrenergic receptors.
Effects: - anxiety, insomnia, nervosity, vasoconstriction in the
subcutaneous, splanchnic and renal territories and - vasodilation in the muscular,
cardiac and cerebral territories, stimulation of the heart. - Systolic blood pressure
rises, - diastolic blood pressure does not change. - Bronchodilation.
Indications.
- anaphylactic shock. - type I hypersensitivity reactions
- acute asthma attack.
- cardiac arrest
- antihemorrhagic in association with local anesthetics.
Side effects: increased blood pressure with strokes, severe heart arrhythmias, ventricular fibrillation, worsening of ischemic heart disease,
myocardial infarction, tremor of the extremities, anxiety, psychomotor agitation
Noradrenaline ( Norepeinephrine )
- stimulates α adrenergic receptors;
- no β adrenergic effects.
- Effects:
1) vasoconstriction in all territories,
2) contraction of the spleen capsule.
3) Increases blood pressure, both systolic and diastolic.
Indications :
hypovolemic shock with collapse
- administration by intravenous infusion
Dopamine
- stimulates adrenergic and dopaminergic receptors
- Effects:
1) vasodilation in the splanchnic and renal territory.
2) In high doses the drug can stimulate : - β1 adrenergic receptors by increasing heart activity
- α adrenergic receptors by increasing blood pressure.
Indications: selected cases of shock in intravenous infusion.
Isoprenaline
Dilation
- selective β1 and β2 receptors agonist.
- Effects:
o bronchodilation,
o heart stimulation,
o vasodilation,
o decreases diastolic blood pressure and increases systolic blood pressure.
Side effects
- worsening of ischemic heart disease,
- acute myocardial infarction,
- ventricular fibrillation, tachycardia, palpitations,
- extremity tremor,
- psychomotor agitation, anxiety
Selective α1 sympathomimetics
phenylephrine, ethylephrine -
produce vasoconstriction; used in the treatment of particular types of shock or
as a decongestant of the nasal or conjunctival mucosa (local applications)
Selective α2 sympathomimetics
clonidine - lowers blood pressure -
is used to treat high blood pressure.
Selective β1 sympathomimetics
dobutamine - increases the
contraction force of the myocardium, increases the cardiac output; used in cardiogenic shock
Selective β2 sympathomimetics
1) salbutamol,
2) phenoterol,
3) orciprenaline,
4) terbutaline,
5) salmeterol
produce bronchodilation, vasodilation
and relaxation of the uterine smooth muscles. Indications: treatment of asthma,
treatment of painful uterine contractions in pregnant women.
* Inhalatory , oral , injectable ( terbutaline )
EFFECTS :
- Low-intensity cardiac side effects, * ( angina , tachycardia ,arrythmia - β1 rec activation )
- tremor of the extremities,
- increased excitability of the central nervous system,
- anxiety.
Indirect sympathomimetics
- amphetamine
- Ephedrine
- Cocaine
- Nafazolin
- Tricyclic antidepressants
- IMAO antidepressants
1) increase the availability of catecholamines
in the synaptic cleft, by increasing the release (ephedrine, amphetamine),
2) preventing the reuptake of catecholamines from the synaptic cleft (cocaine, tricyclic antidepressants) or
3 ) inhibiting their metabolism (antidepressants
IMAO)
Ephedrine
- indirect sympathomimetic
- increases the release of catecholamines into the synaptic cleft.
- It is effective in oral administration and crosses the blood-brain barrier.
Nafazolin
mechanism of action identical to that of ephedrine, used as a decongestant of the nasal mucosa.
Amphetamine
is another indirect sympathomimetic that has
virtually all the effects of ephedrine but the effects on the central nervous system are much more intense
Cocaine
- indirect sympathomimetic
- is a local anesthetic that prevents the reuptake of
catecholamines from the synaptic cleft. - It produces adrenergic side effects, and
on the central nervous system it produces phenomena similar to those produced by amphetamine.
Tricyclic antidepressants
- indirect sympathomimetics
- increase the availability of catecholamines
in the synaptic cleft by preventing their reuptake from the synaptic cleft
IMAO antidepressants
block catecholamine metabolization by blocking MAO enzymes.
Sympatholytics
are substances that prevent the effects of sympathoadrenergic stimulation
Direct sympatholytics
have affinity for adrenergic receptors without
intrinsic activity.
Tolazoline, phentolamine
1 ) non-selectively block both α1 and α2 receptors,
2) producing vasodilation with decreased blood pressure and
3 ) reflex tachycardia.
4 ) Are used in the diagnosis and treatment of pheochromocytoma
Selective blockers of α1 adrenergic receptors
- prazosin,
- doxazosin,
- tamsulosin
1) produce vasodilation without reflex tachycardia. Are used in the treatment of hypertension and benign prostatic hypertrophy
β Adrenergic receptor blockers
1) Decrease the heart activity by :
- blocking the β1 adrenergic receptors and
- aggravate asthma by blocking the β2 adrenergic receptors.
Indications:
1 ) treatment of hypertension,
2) angina pectoris and
3) cardiac arrhythmias,
4) prevention of migraine attacks (propranolol),
5) tremor of the extremities in conditions of anxiety
( propranolol), treatment of glaucoma (timolol) in local administration.
Side effects:
- excessive hypotension,
- bradycardia ,
- atrioventricular block,
- worsening of asthma or peripheral vascular-spastic diseases.
β non-selective blockers
propranolol
* ( + Alprenolol + Oxprenolol )
β1 selective blockers
- atenolol, metoprolol, acebutolol.
( Nevibolol , cervedilol ) - They have the same indications and the same efficacy as non-selective blockers but can also
be used in patients with asthma or peripheral ischemia syndromes. - they are antiarrythmic , anti- aginal + anti- hypertensive drugs
- side effects : bronchoconstriction , bradycardia , cardiac failure , cold extremities , insomnia , depression
Indirect sympatholytics
- neurosympatholytics, or blockers of sympathetic endings, prevent the accumulation of catecholamines in the synaptic cleft.
- It works by decreasing the release of the neurotransmitter in the synaptic cleft
- guanethidine or by depleting catecholamine deposits
- reserpine
