Слайд 5
MAO-A - metabolizes Noradrenaline and Serotonin,
MAO-B –
Dopamine, Phenylethylamine and Tyramine
Tyramine is a product of tyrosine
metabolism and
is found in fermented foods:
Cheese - 130 mg/100 g
Beans - also contain Dopamine
Chicken Liver
Chocolate - also contains Phenylethylamine
Fermented Sausage, Beer,
Smoked or Pickled Fish
MAO inhibitors: Nialamid, Transamine and
MAO-A inhibitors: Moklobemid, Pirazidol – ??BP
Слайд 6
α1 Receptors: on the Postsynaptic Membrane of
the
Effector organs –
on smooth muscle and glands and
are excitatory
α2 Receptors: on the Pre- and Postsynaptic Membrane of
the Effector organs.
The stimulation of the Presynaptic α2-Receptors => Feedback Inhibition of noradrenaline release from
the stimulated Adrenergic neuron –
Negative Feedback
Слайд 7
β1-receptors: HEART and are Excitatory
β2-receptors: on Smooth Muscle
of –
Bronchi
Vasculature of Skeletal Muscle
Miometrium
Glands
and are Inhibitory
β3-receptors:
Adipose (Fat) cell =>
stimulation of lipolysis
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I. Adrenomimetics of Direct Action
1). α-, β- Adrenomimetics:
∙ Adrenaline hydrochloride - α1, α2,
β1, β2 , β3
amp. 0.1%-1ml; vial 0.1%-10 ml
∙ Noradrenaline hydrotartrate - α1, α2, β1
amp. 0.2% -1 ml (IV infusion)
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THE MAIN EFFECTS of ADREANALINE :
►Cardiac
Stimulation
► Relaxation of Bronchial Muscle
►
Dilation of Skeletal Muscle Vasculature
► Significant Hyperglycemia:
⮟ ↑Glycogenolysis in the Liver (β2 effect)
⮟ ↓ Release of Insulin (α2 effect).
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Adrenaline is metabolized by 2 enzymatic pathways:
COMT and
MAO
Clinical uses:
⮟ Bronchospasm
⮟ Anaphylactic shock: is the drug
of choice
⮟ Cardiac arrest and acute ?AP
⮟ Hypoglycemic coma (overdose with Insulin)
⮟ Glaucoma
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Noradrenaline hydrotartrate: α1, α2, β1
the strongest Peripheral Vasoconstrictor
↑↑
Total Peripheral Resistance => ↓ HR
↑ Systolic and
Diastolic AP
∙ ↓Blood Flow to Vital Organs, Skin, and Skeletal Muscle
∙ Constriction of Renal Blood Vessels
∙ ↑Heart Contraction
Clinical Uses: Acute Hypotensive States,
GI Bleeding.
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2). α-Adrenomimetics:
Mesatone (Phenylephrine) (α1)– amp. 1%-1 ml
Naphthyzine (Naphtazoline)
(α2)
Vial 0.05% and 0.1% - 10 ml
Halazoline (Xylometazoline)
(α2)
Vial 0.05% and 0.1%-10 ml
Clofeline (Clonidine) (α2) –
Tab. 0.000075 g and 0.00015 g,
amp. 0.01% - 1 ml
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Clopheline is an α2-agonist used
in Essential Hypertension
to lower BP.
It acts mainly on Central α2-Receptors =>
Inhibition
of Sympathetic Vasomotor centers - Negative Feedback.
↓Peripheral Vascular Resistance =>
=> ↓Cerebral Sympathetic Outflow.
Clopheline may stimulate
Peripheral Postsynaptic α2-Receptors,
producing Transient Vasoconstriction.
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Beta - Adrenomimetics
Isadrin (Isoprenaline) (β1, β2)
Tab. 5 mg,
vial 1%-25.0 ml
Dopamine (β1)– amp 4%-5 ml; 0.5% -
5 ml
Dobutamine (β1)– amp 5%-5 ml; 1.25%-20 ml
Salbutamol (β2)– Tab 2 mg, aeroz
Terbutaline (β2) – Tab 2.5 mg, aeroz.
Salmeterol (β2)- aeroz
Fenoterol (Berotec, Partusisten) (β2)
Formoterol (β2) (turbuhaler 4.5 and 9 mkg/dose)
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Dopamine activates β1-Receptors and
is the metabolic precursor
of Norarenaline
D-receptors are prominent in the periphery
(splanchnic and
renal vasculature),
where they mediate Vasodilation => useful in SHOCK and Acute Heart Failure.
↑Blood Flow to the Kidney =>
↑ the Glomerular Filtration Rate =>
Na+ Diuresis
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Cardiovascular action:
Stimulation of β1-Receptors =>
inotropic and
chronotropic effects
Renal and viscera :
D1-receptors => Dilation of Renal
Arterioles =>
↑ Blood Flow to the Kidneys and other Viscera.
Dopamine is far Superior to Noradrenline, which
↓the Blood Supply to the Kidney and
may cause Kidney Shutdown.
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Dobutamine (amp. 5%-5 ml)
selective β1 AM -
the
most commonly used
Inotropic Agent after Cardiac Glycosides.
↑cAMP
=> the Activation of Protein Kinase.
Slow Ca2+ channels are one important site of Phosphorylation by Protein Kinase.
When phosphorylated, the Entry of Ca2+
into the Myocardial Cells ↑=>
=> CONTRACTION ↑
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Beta2 agonists Salbutamol, Terbutaline, Fenoterol,
Salmeterol, Formoterol:
⮟ Relax
smooth muscle of the Bronchial tree, Vasculature, Uterus and
Intestines
⮟ Hepatic and Muscle glycogenolysis =>
=> HYPERGLYCEMIA
Beta2 agonists are used as:
⮟ Bronchodilators
⮟ Tocolytics – to Relax the Uterus
and delay delivery in premature labor
All β2-AMs have some degree of β1-activity =>
Some degree of Cardiostimulation may occur
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I. α- Adrenoblockers:
I. Non-Selective Adrenoblockers:
PHENTOLAMINE (α1, α2) –
Tab 25 mg
TROPAPHENE (α1, α2) – Amp 20 mg
II.
Selective Adrenoblockers:
PRAZOSINE (α1) – Tab 1, 3, 5 mg
DOXAZOSINE (α1) – Tab 2 and 4 mg
YOHIMBINE (α2) –Tab 5 mg
Слайд 26
Phentolamine – α1-, α2- AB
The action lasts for
4 hours.
α-Receptors Blockade =>
Prevention Peripheral Blood Vessels Vasoconstriction
by CATECHOLAMINES.
?Peripheral Resistance => Reflex Tachycardia
⮞ Postural Hypotension
Phentolamine had been used in the diagnosis of pheochromocytoma and in other situations associated
with excess release of catecholamines.
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PRAZOSIN
TERAZOSINE
DOXAZOSINE (Cardura)
⮞ Relaxation of Arterial and Venous
Smooth Muscle
⮞ ↓ Peripheral Vascular Resistance
⮞ ↓
AP
⮞ ↓ Tone in the smooth muscle of the Bladder Neck and Prostate
⮞ Improve Urine Flow
Clinical use: Hypertension,
Benign Prostatic Hypertrophy
Слайд 29
β-ADRENOBLOCKERS
1) NON-SELECTIVE:
Propranolol (Anaprilin) (β1, β2)
Nadolol (Corgard) (β1,
β2)
Timolol (β1, β2)
2) SELECTIVE:
Atenolol (β1)
Metoprolol
(β1)
3).β1-, α1- Blockers:
Labetalol
Carvediol
Слайд 30
Propranolol (Anaprilin) – β1- , β2- AB
Tab. 10
and 40 mg;
amp. 0.25%-1 ml
Cardiovascular Effects:
⮞
Negative Inotropic - ? Cardiac Output
⮞ Negative Chronotropic effects - ? HR
⮞ Depresses Sino-Auricular and AV activity
=> ? Cardiac Work and O2 consumption
Слайд 31
CLINICAL uses of Propranolol (Anapriline):
? Hypertension
?
Angina Pectoris, Myocardial Infarction,
? Arrhythmias
? Glaucoma, Migraine
,
? Hyperthyroidism
Adverse effects:
● Bronchoconstriction
● Peripheral Vasoconstriction
● Arrhythmias, Sexual impairment
● Disturbances in Metabolism:
● ↓Glycogenolysis and ↓Glucagon Secretion
Слайд 32
Overdose with Propranolol: ?AP, ?HR,
heart failure, bronchospasm.
Treatment: Gastric
lavage, Activated charcoal,
Symptomatic and Supportive care:
Treat Bradycardia with ATROPINE,
ISADRINE
Treat Cardiac Failure with
Cardiac Glycosides: Strophanthine
and Diuretics: Furosemide
Treat Hypotension with vasopressors:
ADRENALINE is preferred.
Treat Bronchospasm with ISADRINE ,
EUPHYLLINE (AMINOPHYLLINE)
Слайд 33
SYMPATHOLYTICS:
Reserpine –Tab. 0.1 mg and 0.25 mg
Octadin
– Tab. 0.025 g
Ornid – amp, 5% -
1 ml
Reserpine - a Plant Alkaloid from the roots of
an Indian plant Rauwolfia Serpentina.
It blocks Mg2+/ATP–dependent transport of
biogenic amines =>?the ability of
Aminergic Vesicles o take up and store biogenic amines :
Noradrenaline
Dopamine
Serotonine
from the cytoplasm into storage vesicles in
the Adrenergic Nerves of ALL BODY TISSUES.
