Autacoid Drugs Major autacoids

Autacoid Drugs
• Autacoids (自体活性物质) are biological factors
made in the body that act like “local hormones”,
have a brief duration, act near the site of
synthesis (paracrine), and are not blood borne.
• Autacoids are regulating molecules metabolized
locally.
• These factors can have many different
biological actions.
Major autacoids
• Arachidonic acid metabolites (花生四烯酸)
including：prostaglandins (前列腺素),
thromboxanes (血栓素), leukotrienes (白三烯)
• 5-hydroxytryptamine, 5-HT (五羟色胺）,also
named serotonin (血清素)
• Bradykinin (缓激肽)
• Endothelin (内皮素)
• Substance P (P 物质)
Synthesis of Eicosanoids (二十烷类)
贝前列素 Beraprost
Beraprost is a synthetic analogue of prostacyclin, under clinical trials for the
treatment of pulmonary hypertension. It is also being studied for use in avoiding
reperfusion injury.
As an analogue of prostacyclin PGI2, beraprost effects vasodilation, which in turn
lowers the blood pressure. Beraprost also inhibits platelet aggregation, though the
role this phenomenon may play in relation to pulmonary hypertension has yet to be
determined.
前列地尔 Alprostadil
Prostaglandin E1 (PGE1), known pharmaceutically as alprostadil, is a
prostaglandin. It is a drug used in the treatment of erectile dysfunction[2] and has
vasodilatory properties.
依前列醇 Epoprostenol
Prostacyclin (or PGI2), as a drug, is known as
"epoprostenol". The terms are sometimes used
interchangeably.
Prostacyclin (PGI2) chiefly prevents formation of
the platelet plug involved in primary hemostasis
(a part of blood clot formation). It does this by
inhibiting platelet activation. It is also an
effective vasodilator. Prostacyclin's interactions
in contrast to thromboxane (TXA2), another
eicosanoid, strongly suggest a mechanism of
cardiovascular homeostasis between the two
hormones in relation to vascular damage.
米索前列醇 Misoprostol
Pharmacologically, misoprostol is a synthetic prostaglandin E1 (PGE1) analogue.
Misoprostol is a drug that is used for the prevention of non steroidal anti
inflammatory drug (NSAID) induced gastric ulcers, for early abortion, to treat
missed miscarriage, and to induce labor. The latter use is controversial in the
United States. Misoprostol was invented and marketed by G.D. Searle & Company
(now Pfizer) under the trade name Cytotec.
地诺前列酮 Dinoprostone, PGE2
The naturally occurring prostaglandin E2 (PGE2) is known in medicine as
dinoprostone. It has important effects in labor (softens cervix and causes
uterine contraction) and also stimulates osteoblasts to release factors that
stimulate bone resorption by osteoclasts. PGE2 is also the prostaglandin that
ultimately induces fever.
卡前列素 Carboprost, PGF2α
Carboprost is a synthetic prostaglandin analogue of PGF2α (specifically, it is 15methyl-PGF2α) with oxytocic properties.
Carboprost induces contractions and can trigger abortion in early pregnancy. It
also reduces postpartum bleeding.
Synthesis and inhibition of leukotrienes
Inhibition at the 5-LOX level and at the receptor level.
扎鲁司特 Zafirlukast
孟鲁司特 Montelukast
(Singulair)
Montelukast is a CysLT1 antagonist; that it blocks the action of leukotriene D4
(and secondary ligands LTC4 and LTE4) on the cysteinyl leukotriene receptor
CysLT1 in the lungs and bronchial tubes by binding to it. This reduces the
bronchoconstriction otherwise caused by the leukotriene and results in less
inflammation.
齐留通 Zileuton
5-lipoxygenase inhibitor
Zileuton (introduced in 1996 by Abbott Laboratories) is an active oral
inhibitor of the enzyme 5-lipoxygenase, which forms leukotrienes from
arachidonic acid. Zileuton is indicated for the prophylaxis and chronic
treatment of asthma in adults and children 12 years of age and older.
Zileuton is not indicated for use in the reversal of bronchospasm in acute
asthma attacks. Therapy with zileuton can be continued during acute
exacerbations of asthma.
5-羟色胺 5-hydroxytryptamine, 5-HT
Serotonin (血清素)
5-HT) is a monoamine neurotransmitter. Biochemically derived from
tryptophan, serotonin is primarily found in the gastrointestinal (GI) tract,
platelets, and in the central nervous system (CNS) of animals including
humans. It is a well-known contributor to feelings of well-being; it is also
known to contribute to happiness.
舒马普坦 Sumatriptan
5-HT1B and 5-HT1D agonist
Sumatriptan is a triptan sulfa drug containing a sulfonamide group. It is used for
the treatment of migraine headaches. Sumatriptan is produced and marketed
by various drug manufacturers with many different trade names such as
Sumatriptan, Imitrex, Imigran, Imigran recovery. Sumatriptan is structurally
similar to serotonin (5HT), and is a 5-HT (types 5-HT1D and 5-HT1B) agonist.
The specific receptor subtypes it activates are present on the cranial arteries
and veins. Acting as an agonist at these receptors, Sumatriptan reduces the
vascular inflammation associated with migraine.
丁螺环酮 Buspirone
依沙匹隆 Ipsapirone
Buspirone (trade name Buspar) is an anxiolytic psychoactive drug of the
azapirone chemical class, and is primarily used to treat generalized
anxiety disorder (GAD).
Ipsapirone is a selective 5-HT1A receptor partial agonist of the piperazine
and azapirone chemical classes. It has antidepressant and anxiolytic
effects
芬氟拉明 Fenfluramine
Fenfluramine (3-trifluoromethyl-N-ethylamphetamine, trade names
Pondimin, Ponderax and Adifax) is a drug that was part of the Fen-Phen
anti-obesity medication (the other drug being phentermine). Fenfluramine
was introduced on the U.S. market in 1973. It is the racemic mixture of
two enantiomers, dextrofenfluramine and levofenfluramine. It increases
the level of the neurotransmitter serotonin, a chemical that regulates
mood, appetite and other functions. Fenfluramine causes the release of
serotonin by disrupting vesicular storage of the neurotransmitter, and
reversing serotonin transporter function. The end result is a feeling of
fullness and loss of appetite.
赛庚啶 Cyproheptadine
Selective 5-HT2 blocker
Cyproheptadine (trade name Periactin) is an antihistaminic/anticholinergic
and antiserotonergic agent. It also acts as a 5-HT2 receptor antagonist as
well as blocking calcium channels. Cyproheptadine has shown
effectiveness in the treatment of nightmares including nightmares related
to post traumatic stress disorder
Polypeptide drugs
缓激肽 Bradykinin
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
Bradykinin is a physiologically and pharmacologically active peptide of the
kinin group of proteins, consisting of nine amino acids. Bradykinin is a
peptide that causes blood vessels to dilate (enlarge), and therefore causes
blood pressure to lower. A class of drugs called ACE inhibitors, which are
used to lower blood pressure, increase bradykinin (by inhibiting its
degradation) further lowering blood pressure. Bradykinin works on blood
vessels through the release of prostacyclin, nitric oxide, and endotheliumderived hyperpolarizing factor.
Polypeptide drugs
抑肽酶 Aprotinin
Aprotinin is a monomeric (single-chain) globular polypeptide derived from bovine
lung tissue. It has a molecular weight of 6512 and consists of 16 different amino
acid types arranged in a chain 58 residues long that folds into a stable, compact
tertiary structure of the 'small SS-rich" type. The amino acid sequence for bovine
BPTI is RPDFC LEPPY TGPCK ARIIR YFYNA KAGLC QTFVY GGCRA KRNNF KSAED CMRTC
GGA. There are 10 positively-charged lysine (K) and arginine (R) side chains and
only 4 negative aspartate (D) and glutamates (E), making the protein strongly
basic, which accounts for the basic in its name.
Endothelins (内皮素) and receptors
Endothelin-1 (ET-1) receptor
antagonists. ET-1 is a 21-amino acid
peptide present in high concentrations
in the lung. At normal (low)
concentrations, ET-1 facilitates the
relaxation of arterial smooth muscle
through its stimulation of
prostaglandins and nitric oxide. At high
concentrations, such as in the case of
pulmonary arterial hypertension, ET-1
activates the two receptors (ETA and
ETB) on arterial smooth muscle cells,
resulting in vasoconstriction, SMC
proliferation and reduction in diameter
of arteries.
Endothelins (内皮素) and receptors
Bosentan （波生坦）is a dual receptor antagonist which blocks both ETA
and ETB. Bosentan is orally effective. In a trial of 12 weeks, pulmonary
hemodynamic measurements revealed decreases in pulmonary arterial
pressure and pulmonary vascular resistance and increase in cardiac
output in patients given bosentan, compared with worsening of pulmonary
hemodynamics in patients receiving placebo. Side effects include liver
toxicity (increase in transaminase) and fetal toxicity.
Adenosine receptors and drugs
4 types of adenosine receptors:
• A1: decrease heart rate
• A2a: coronary artery vasodilation
• A2b: bronchospasm
• A3: cardioprotective in cardiac ischemia, inhibition of
neutrophil degranulation
Caffeine is an adenosine receptor blocker. Because
adenosine inhibits dopamine release, caffeine indirectly
enhances dopamine neurotransmission.
Selected adenosine receptor drugs
Selected adenosine receptor drugs
Drugs for Respiratory Tract Disorders
• Anti-inflammatory drugs (抗炎药)
• Anti-asthmatic drugs (平喘药)
• Antitussives (镇咳药)
• Expectorants (祛痰药)
Bronchodilators (支气管扩张药)
沙丁胺醇 Salbutamol
班布他林 Bambuterol
Salbutamol or albuterol is a short-actingβ2-adrenergic receptor agonist used
for the relief of bronchospasm in conditions such as asthma and chronic
obstructive pulmonary disease. Salbutamol was the first selective β2-receptor
agonist to be marketed — in 1968. The drug was an instant success, and has
been used for the treatment of asthma ever since. Salbutamol sulfate is
usually given by the inhaled route for direct effect on bronchial smooth muscle.
This is usually achieved through a metered dose inhaler (MDI), nebulizer or
other proprietary delivery devices (e.g. Rotahaler or Autohaler). In these forms
of delivery, the maximal effect of salbutamol can take place within five to
twenty minutes of dosing, though some relief is immediately seen. It can also
be given orally as an inhalant or intravenously.
氨茶碱 Aminophylline
Aminophylline is a bronchodilator. It is a compound of the bronchodilator
theophylline with ethylenediamine in 2:1 ratio. The ethylenediamine improves
solubility, and the aminophylline is usually found as a dihydrate. Aminophylline
is a competitive nonselective phosphodiesterase inhibitor which raises
intracellular cAMP, activates PKA, inhibits TNF-alpha and leukotriene synthesis,
and reduces inflammation and innate immunity. It is also a nonselective
adenosine receptor antagonist.
Causes bronchodilatation, diuresis, CNS and cardiac stimulation, and gastric
acid secretion by blocking phosphodiesterase which increases tissue
concentrations of cyclic adenine monophosphate (cAMP) which in turn
promotes catecholamine stimulation of lipolysis, glycogenolysis, and
gluconeogenesis and induces release of epinephrine from adrenal medulla cells.
异丙托溴铵 Ipratropium bromide
Anticholinergic (M3 receptor blocker)
Ipratropium bromide is an anticholinergic drug used for the treatment of
chronic obstructive pulmonary disease and acute asthma. It blocks the
muscarinic acetylcholine receptors in the smooth muscles of the bronchi
in the lungs, opening the bronchi.
Anti-asthmatic drugs (平喘药)
色甘酸钠 Cromolyn sodium
Pharmacology. Stabilizes mast cells, which release histamine and other
mediators of allergic reactions.
酮替芬 Ketotifen
Ketotifen is a second-generation H1-antihistamine
and mast cell stabilizer. It is most commonly sold
in as a salt of Fumaric Acid, Ketotifen fumarate,
and is available in two forms. In its ophthalmic
form, it is used to treat allergic conjunctivitis, or the
itchy red eyes caused by allergies. In its oral form,
it is used to prevent asthma attacks. Side effects
include drowsiness, weight gain, dry mouth,
irritability, and increased nosebleeds.
Antitussives (镇咳药)
Codeine
Dextromethorphan, pentoxyverine
Codeine or 3-methylmorphine (a natural isomer of methylated morphine, the
other being the semi-synthetic 6-methylmorphine) is an opiate used for its
analgesic, antitussive, and antidiarrheal properties. Codeine is the second-most
predominant alkaloid in opium, at up to three percent; it is much more prevalent
in the Iranian poppy (Papaver bractreatum), and codeine is extracted from this
species in some places although the below-mentioned morphine methylation
process is still much more common. It is considered the prototype of the weak
to midrange opioids (tramadol, dextropropoxyphene, dihydrocodeine,
hydrocodone, oxycodone).
Benproperine
Dioxopromethazine
Expectorants (祛痰药)
Bromhexine
Bromhexine is a mucolytic agent used in the treatment of respiratory disorders
associated with viscid or excessive mucus. In addition, bromhexine has
antioxidant properties. Bromhexine is a synthetic derivative of the herbal
active ingredient vasicine. It has been shown to increase the proportion of
serous bronchial secretion, making it more easily expectorated. Bromhexine
also enhances mucus transport by reducing mucus viscosity and by activating
the ciliated epithelium. In clinical studies, Bromhexine showed secretolytic and
secretomotoric effects in the bronchial tract area which facilitates
expectoration and eases cough.