Chapter 19Adrenoceptor agonists1. , receptor agonists2. receptor agonists3. receptor agonists

dopaminenorepinephrineepinephrine

Catechol

Structure-activity relationship of catecholamines and related compounds

Substitution on the aromatic nucleus COMT, central activity Substitution on the -carbon atom MAO, uptake-1, NE release Substitution on the amino group sensitivity to the subunits of receptors

Metabolism of catecholamines

Overview of catecholamines

Effect patterns of sympathomimetics

Subtypes of adrenoceptors

Effects of catecholaminestherapeutic doses

Effects of catacholamines and non-catecholamines

BP antagonistepinephrineEpinephrine reversaladrenaline reversalepinephrine

1. , receptor agonistsEpinephrine , Adrenaline

1. , receptor agonists1.1 Pharmacological effects

(1) Cardiac effects 1: HR , output , oxygen consumption , inducing arrhythmia

(2) Vascular effects 1vasoconstriction, especially at larger doses 2vasodilatation of skeletal muscles and coronary vessels

(3) Blood pressure SP , DP (at therapeutic doses) (4) Bronchodilatation 2dilatation of bronchial smooth muscles 1reducing congestion and edema of bronchial mucosa

(5) Metabolic effects blood glucose ; free fatty acids 1. , receptor agonists

1.2 Clinical uses

(1) Cardiac arrest

(2) Anaphylactic shock

(3) Acute bronchial asthma

(4) Local uses adjuvant for local anesthetics; control of bleeding1. , receptor agonists

Clinical uses of epinephrineSystmatic uses:Cardiac arrestAnaphylactic shockAcute bronchial asthmaTopical uses:Adjuvant of local anesthesiaBleeding

1.3 Adverse effects

(1) Cardiac arrhythmia: BP , arrhythmia

(2) Excesive rise of BP: cerebral or subarachnoid hemorrhage

(3) Central excitationanxiety

(4) Contraindications: heart diseases, hypertension, coronary arterial disease, arteriosclerosis, hyperthyroidism1. , receptor agonists

Ephedrine EphedrineEpinephrine

1. , receptor agonists

1.1 Pharmacological effects

Promoting release of NE, weak agonist effects on 1212 receptors

Properties chemically stable, orally effective less potent and longer action duration; central stimulating tachyphylaxis.1. , receptor agonists

1.2 Clinical uses

(1) Prevention of hypotension: anesthetics

(2) Nasal decongestion: nasal drop

(3) Bronchial asthma: mild, chronic cases

(4) Relieving allergic disorders: urticaria, angioneurotic edema1. , receptor agonists

1.3 Adverse effects

(1) Central stimulation

(2) CVS effects

(3) Dependence1. , receptor agonists

Dopamine 1. , receptor agonists

1.1 Pharmacological effects

(1) Cardiac effects1 receptor, weak

(2) Vascular effects and blood pressure DA receptordilatation of renal and mesenteric arteries , blood flow (small doses); 1 receptorvasoconstriction of skin, mesenteric vessels (larger doses)

(3) Renal effectsrenal vasodilatation; natriuretic effects1. , receptor agonists

VasodilatationVasoconstrictionEffects of dopamine on CVS

1.2 Clinical uses (1) Shockcardiac and septic shock: low output, urinary volume , fully adequate replacement of intravascular fluid(2) Acute renal failure combined with furosemide

1.3 Adverse effects tachycardia, arrhythmia, renal vasoconstriction1. , receptor agonists

2. receptor agonists 2-1 1, 2 receptor agonistsNorepinephrine , noradrenaline

2. receptor agonists2.1 Pharmacological effects

(1) Vascular effects 1vasoconstriction (skin, renal, brain, hepatic, mesenteric, etc.) vasodilatation of coronary arteries 2inhibiting NE release

(2) Cardiac effects weak direct stimulation (1); inhibition via reflex

(3) Blood pressure SP , DP (especially at larger doses), larger doses: pulse pressure , blood flow 2. receptor agonists

Actions of norepinephrine on post-synaptic (1) and pre-synaptic (2 ) receptors

2.2 Clinical uses

(1) Shock BP , blood flow , tissue damage used in early phase of some types of shock or BP rise too slow after treatment: small doses and shorter duration

2. receptor agonists

(2) Hypotension due to drug poisoning especially for chlorpromazine

(3) Hemorrhage in upper alimentary tract orally given after dilution2. receptor agonists

2.3 Adverse effects

(1) Ischemia and necrosis at the site of iv administration relieved by filtration with procaine or phentolamine(2) Acute renal failure avoiding larger doses and longer duration; monitoring urinary volume(3) Contraindication hypertension, arteriosclerosis, heart diseases, severe urinary volume , microcirculation disorders2. receptor agonists

Acting on receptors directly, promoting NE release indirectly

Weaker effects and longer duration than NE, weak for renal vessels;

Used in early phase of shock, hypotensionMetaraminol , Aramine2. receptor agonists

2-2 1 receptor agonists

used in hypotension, paroxysmal supraventricular tachycardia (by reflex)Mydriasis (phenylephrine): pupillary dilator muscles, no or less effect on intraocular pressure, short-acting (for several hours) Phenylephrine Methoxamien 2. receptor agonists

3. receptor agonists3-1 1, 2 receptor agonistsIsoproterenol , Isoprenaline

3. receptor agonists3.1 Pharmacological effects

(1) Cardiac effects 1 receptor stimulation

(2) Vascular effects and blood pressure 2 receptor: dilatation of skeletal muscles and coronary vessels SP DP or pulse pressure

(3) Bronchodilatation 2 receptorno effect on edema of mucosa

(4) Metabolism Promoting effects as epinephrine3. receptor agonists

Effects of isoproterenol

3.2 Clinical uses

(1) Cardiac arrest

(2) A-V block

(3) Septic shocklow-output

(4) Bronchial asthma usually 2 receptor agonists

3. receptor agonists

3.3 Adverse effects

(1) Heart stimulation, arrtythmia

(2) Contraindications: coronary heart disease, myocarditis, hyperthyroidism3. receptor agonists

3-2 1 receptor agonists

Heart failure

Cardiac stimulationDobutamine 3. receptor agonists

3-3 2 receptor agonists

Bronchial asthma

Salbutemol 3. receptor agonists