ANTISPASMODICS, SPASMOLYTICS
Doc. PharmDr. Jan Juřica, Ph.D.
ANTISPASMODICS
̶ a group of drugs with a relaxing effect on smooth muscles
̶ therapy of functional diseases of the GIT, GU system
̶ symptomatic therapy, aimed at suppressing subjective difficulties caused by incr. tone of
smooth muscles (cramps), dyskinesia and smooth muscle hyperkinesia (hypermotility of GIT)
̶ Indications: therapeutic and diagnostic examinations - endoscopy, e.g. ERCP
̶ reduction of motility, suppression of pain, diarrhea, convulsions, nausea, vomiting, COPD / AB
hyperactive bladder, supportive treatment in Parkinson's disease
̶ enteric nervous system (plexus myentericus Auerbachi), ANS, other agents (NO, ATP, VIP)
ANTISPASMODICS
Contraindication:
̶ Paralytic ileus
̶ Maystenia gravis
̶ Pyloric stenosis)
̶ BPH
̶ Pregnancy + lactation
AE:
̶ Constipation
̶ Dry mouth
̶ (+ other anticholinergic AE)
̶ Flatulence
̶ Pyrosis
Classification of ANTISPASMODICS
1. Neurotropic
- parasympatolytics (atropine - not currently used as antispasmodic,
oxybutynine, solifenacine, darifenacine, otilonium, fenpiverine, Nbutylscopolamine,
trospium, tolterodine)
2. Myotropic
(drotaverin, alverin, mebeverin, pitofenon)
+ carminative, spasmoanalgesics, deflatulent agents
(dimethicone, simeticone)
+ others (NSAIDs, opioids, nitrates, antidepressants with
anticholinergic action etc.)
1. NEUROTROPIC ANTISPASMODICS
- VNS receptors, only splanchnic smooth muscle
a) Anticholinergics / parasympatholytics
with tertiary N, lipophilic substances, via HEB (CNS AE)
̶ atropine – spasmolytic eff. on the GIT, obsolete
̶ oxybutinin – selectively for the urinary systém, I: pollakiuria, incontinence,
hyperactive urine. Bladder
̶ darifenacin, solifenacin – urinary bladder hyperactivity, incontinence, pollakiuria
b) Parasympatholytics
- Quaternary N, does not pass through HEB
otilonium – spasms of the GIT, biliary system, G-U system
fenpiverine – combination with metamizole and pitofenone, spasmoanalgesic
system, GIT, GU, dysmenorrhea
N-butylscopolamine – spasms of the GIT, biliary system, G-U system, endoscopy
fesoterodine, tolterodine, trospium– functional disorders of the GIT and GU
system
ipratropium, tiotropium – bronchodilators, often in combination with beta 2
agonists
1. NEUROTROPIC ANTISPASMODICS
2. MYOTROPIC ANTISPASMODICS
• direct effect on smooth muscles, smooth muscles in the vessels
• Various MoA - blockade of calcium channels, activation of potassium
channels, stimulation of NO production, increase of cAMP / cGMP, ...
papaverine
originating from opium - phosphodiesterase inhibitor, visceral spasms,
colic (biliary, renal), vasospasm
drotaverine – phosphodiesterase inhibitor, gynecological indications
(dysmenorrhea, adnexitis), smooth muscle spasms (irritable bowel
syndrome, billiary colic, bladder tenesmas, ...), headache of vascular
etiology
̶ alverine – phosphodiesterase inhibition, combination with simethicone,
functional GIT difficulties - flatulence, flatulence, IBS
̶ mebeverine – more MoA including local anesthetic effect, irritable bowel
syndrome, GIT spasms
̶ pitofenone – phosphodiesterase inhibition, combination with
metamizole and fenpiverine - spasmoanalgesia, IBS
2. MYOTROPIC ANTISPASMODICS
3. OTHER ANTISPASMODICS
̶ beta 3 agonist – mirabegron – I: hyperactive bladder
̶ Alpha 1 antagonist – alfuzosine, tamsulosine, I: BPH
̶ glucagon - premedication for endoscopy
̶ TCA - amitriptyline (anticholinergic action)
̶ Ca2+ channel blockers nifedipin, Nitrates - esophageal motility disorders,
esophageal achalasia
̶ opioids – pethidin- acute painful spasms, biliary system spasm (rather obsolete)
SPASMOANALGESICS
̶ combination of antispasmodics with analgesics (metamizole, paracetamol,
opioids - codeine, tramadol, pethidine)
̶ i.v. admin - accelerating onset of the effect
̶ I: dysmenorrhea, smooth muscle spasms with pain, obstetrics surgery,
instrumental procedures
Antiflatulents (or deflatulents), Carminative drugs
̶ Herbal volatile oils – antispasmodic action
̶ DDF – aromatic waters, herbal teas
̶ weak spasmolytic effect
̶ cumin, fennel, chamomile, anise
̶ simetikon – surfactants – decr. surface tension, decay of gas bubbles in the
intestine - gas absorption throught the GIT mucosa, or evacuated via peristalsis,
I: flatulence, X-ray / USG examination of the splanchnic, antidote for detergent
pisoning