Adrenoceptor activating

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Adrenoceptor activating Other Sympathomimetic
drugs
Pawitra Pulbutr M.Sc. In Pharm (Pharmacology)
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Objectives

• ?????????????????????? Adrenoceptor ??? Molecular
  mechanism ????????????? adrenoceptor
• ???????????????????????????????? ???????????????
  ?????????????? ???????????????????????
  ?????????????????? ???????????????????????????????
  ?????????????????????????? ???????? direct acting
  ??? indirect acting agents

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Sympathetic nervous system

• Essential control of CVS Response to stress
• Neurotransmitters Norepinephrine (NE)
• Adrenal medulla release NE Epinephrine (Epi)
  Hormone
• Act on RC called Adrenoceptor
• Drugs causing sympathetic NS like action .
  Sympathomimetic drugs (agents)
• Mimic Like

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The mode spectrum of action of sympathomimetic
drugs

• Direct acting sympathomimetic drugs
• Binding to adrenoceptor gtgtgt Adrenoceptor agonist
• Indirect acting sympathomimetic drugs
• Increase NE at synaptic cleft
• Replacement of NE at vesicle
• Uptake via uptake 1 into nerve terminal
• Increase NE release from vesicle
• Amphetamine, Tyramine, Ephedrine
• Inhibit NE reuptake
• Inhibit uptake 1 action
• Also inhibit action of the above group
• Cocaine, Tricyclic antidepressants (TCA)

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Basic Pharmacology

• Adrenoceptor
• Beta (?)-adrenoceptor
• ?1, ?2, ?3 adrenoceptor
• ?1 Affinity NE Epi
• ?2 Affinity Epi gtgt NE
• Alpha (?)-adrenoceptor
• ?1, ?2 adrenoceptor
• ?-1A, ?-1B, ?-1D
• ?-2A, ?-2B, ?-2C
• ?1 antagonist Prazosin
• ?2 antagonist Yohimbine
• ?1 ?2 antagonist (non-selective)
  Dihydroergotamine

• Difference of adrenoceptor
• Affinity of selected agents
• Molecular Genes

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• Dopamine receptor
• Dopamine (DA) Catecholamine
• Bind to Dopamine receptor Adrenoceptor
• Important in CNS function disease
• Psychosis over DA
• Parkinsons disease lack of DA
• Some effects on splanchnic renal vascular
• D1-like receptor
• D1-, D5-receptor
• D2-like receptor
• D2-, D3-, D4-receptor

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Receptor selectivity
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(No Transcript)
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Gi
Gs
cAMP-dep. Protein kinase
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Distribution of adrenoceptor subtypes
Type Tissue Actions
Alpha1 Most vascular smooth muscle (innervated) Contraction
Pupillary dilator muscle Contraction (dilates pupil)
Pilomotor smooth muscle Erects hair
Prostate Contraction
Heart Increases force of contraction
Alpha2 Postsynaptic CNS adrenoceptors Probably multiple
Platelets Aggregation
Adrenergic and cholinergic nerve terminals Inhibition of transmitter release
Some vascular smooth muscle Contraction
Fat cells Inhibition of lipolysis
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Beta1 Heart Increases force and rate of contraction
Beta2 Respiratory, uterine, and vascular smooth muscle Promotes smooth muscle relaxation
Skeletal muscle Promotes potassium uptake
Human liver Activates glycogenolysis
Beta3 Fat cells Activates lipolysis
D1 Smooth muscle Dilates renal blood vessels
D2 Nerve endings Modulates transmitter release
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Central Nervous System (CNS)

• Catecholamine can not penetrate into CNS
• Non-catecholamine can penetrate into CNS
  Amphetamine, Cocaine
• Alertness, Nervousness, Increased concentration
  of work, Insomnia, Euphoria, Anorexia, Paranoid
• Dopamine-mediated increase pleasure Drug
  addiction Drug abuse

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Clinical Pharmacology

• Factors considered before sympathomimetic use
• Intrinsic activity
• Receptor selectivity
• Duration of action
• Route of administration
• Bioavailability
• ADRs (esp. CVS)

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Clinical uses

• Hypotension
• Shock
• Decreased local blood flow
• Decongestion
• Asthma
• Anaphylaxis
• Glaucoma
• Delay of labour
• CNS disordergtgtgt attention deficit, narcolepsy
• Others Drug craving, hot flush

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Toxicity of sympathomimetics

• CVS
• Hypertension (hypertensive crisis) cerebral
  hemorrhage, pulmonary edema, increase heart work
  load angina, myocardial infarction (MI)
• Sinus tachycardia, Serious ventricular arrhythmia
• Use with caution in elderly, hypertensive
  patients, coronary artery disease patients
• Antagonised by Specific adrenoceptor antagonist
• CNS esp Amphetamine
• Restlessness, tremor, insomnia, anxiety, paranoid
• Cocaine may worsen convulsion or cerebral
  hemorrhage

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Example of sympathomimetic drugs
Dobutamine HCl (Dobutrex) Vial 250 mg/ 20
ml Dopamine HCl (Dopaminex) Amp 50 mg/ 5ml, 200
mg/ 10 ml, 250 mg/ 10 ml Isoproterenol
(Isuprel) Amp 0.2 mg/ ml Adrenaline
(Epinephrine) Amp 1 mg/ ml Brimonidine
(Alphagan) Ophth soln 0.2 Metaraminol
bitartrate (Aramine) Vial 10 mg/
ml Methylphenidate (Rubifen) Tab 10 mg children
w/ attention def Midodrine (Gutron) Tab 2.5
mg Naphazoline (Albalon) Ophth soln
0.1 Oxymetazoline (Iliadin) Nasal drop 0.025,
nasal spray 0.05 Phenylephrine
combined Phenylpropanolamine combined Pseudoep
hedrine combined Norepinephrine
combined Xylometazoline (Otrivin) Metered
dose nasal spray 0.1