A17. Smooth muscle relaxants used for relief GI and UG spasms. Drugs influencing uterus functions.

Question 1

Relaxers:

Answer 1

Relaxers: o Atosiban - oxytocin antagonist; given by injection; used in 2nd half pregnancy. Also inhibits vasopressin. o β-2 stimulants: these drugs are not only for asthma/COPD • Terbutaline - injection • Sometimes see salbutamol or fenoterol used • Has systemic side effects (tachycardia, hypotension, hyperglycemia) and tolerance • Used from week 16 to delay preterm labor (“tocolytic”) up to 48 hours. • Can be used to delay a situation where uterus may rupture, e.g. right before birth the position of baby is crooked and the uterine contractions make it worse. Helps delay potential uterine rupture until emergency c-section can take place. o COX inhibitors: NSAIDs can be effective in dysmenorrhea, especially prophylactically • Indomethacin ▪ Indications:menstrualcramps ▪ Contraindications: ↓ PG levels can close the ductus arteriosus, so most NSAIDs not given in pregnancy; for high fevers in pregnancy, paracetamol + cold baths are recommended o Calcium Channel Blockers • Nifedipine - a DHP Ca channel blocker → vasodilation + heart effects ▪ Indications: delaying preterm labor o Magnesium sulfate - as an injection. Magnesium relaxes the uterus probably via calcium antagonism. Commonly used during pregnancy with vitamin B6. • Indications: ▪ Delaying preterm labor - up to 48 hours; usually when other tocolytics fail / cause side effects ▪ Pre-eclampsia-↓risktoprogresstoeclampsia;↓seizuresineclampsia o Ethanol: small amount can stop uterus constrictions. Riba says may even work for dysmenorrhea o Progesterone – only during 1st trimester, can use if at risk for a miscarriage. Intravaginal or oral form.

Question 2

prostaglandins

Answer 2

Prostaglandins: • Misoprostol –probably the most important synthetic prostaglandin to know because it pops up in other topics. Synthetic PGE1; induces labor. Also used sometimes with gastric ulcer (protects mucosa) • Dinoprostone - PGE2; given as vaginal gel or tablet • Sulprostone - synthetic PGE2; termination of pregnancy during 2nd/3rd trimester ▪ partial bile elimination • Dinoprost - PGF2α; termination of pregnancy during 2nd trimester ▪ causes bronchoconstriction • Kinetics: completely metabolized; eliminated via urine (except sulprostone) • Side Effects: ▪ abdominal pain, fever, hypotension ▪ bronchoconstriction - dinoprost only

Question 3

contractors:

Answer 3

• Contractors: o Oxytocin - given by injection; speeds up labor with rhythmic contractions, reduces postpartum bleeding • mostly sensitive during 2nd half of pregnancy • can be given intranasally for lactation o Ergotamine - given as drops. • Kinetics: liver metabolism, bile elimination • Not used during labor because it causes a tonic contraction rather than rhythmic; can be given post- partum to reduce hemorrhage • Side Effects ▪ Ergotism - central/peripheral vasospasm ▪ ↑BP ▪ GI ischemia

Question 4

Drugs Influencing Uterine Function:

Answer 4

contractors: prostaglandins: relaxers:

Question 5

other

Answer 5

Other: o Mebeverine - musculotropic antispasmodic, not anticholinergic • unknown MOA; direct SM effects; possibly anesthetic and Ca+ channel effects • for spasms related to IBS o (Bencyclane - spasmolytic also for peripheral vascular disease as vasodilator / platelet aggregation inhibitor)

Question 6

parasympatholytics

Answer 6

Parasympatholytics: o Atropine - oral/parenteral; see antimuscarinics topic A-8 o Homatropine methylbromide - quaternary → no BBB entry • for GI spasms / abdominal cramps • CI in untreated glaucoma, severe HF, thyrotoxicosis and myasthenia gravis o Butylscopolamine - semisynthetic; oral/parenteral • for abdominal pain, esophageal spasm, renal colic + bladder spasms o Antimuscarinics for urinary incotinence: • Non-selective: Oxybutinin, Tolterodine • M3 selective: Solifenacin, Darifenacin

Question 7

calcium channel inhibitors

Answer 7

• Calcium Channel Inhibitors: o Pinaverin • for spasms related to IBS and biliary disorders

Question 8

cPDE inhibitors/L-type ca channel inhibitors:

Answer 8

• cPDE inhibitors / L-type Ca channel inhibitors: papaverine (natural) and drotaverine (synthetic) o Kinetics: oral or injection o Indications: • Spasms - GI, bile ducts, ureters • Vasodilation - cerebral/coronary for SAH/bypass surgery; combo with angioplasty o Side Effects: • Hypotonia • Sedative - if given IV • Coronary steal

Question 9

Smooth muscle relaxants for gastrointestinal / urogenital spasms:

Answer 9

cPDE inhibitors/L type ca channel inhibitors: calcium channel inhibitors: parasympatholytics: other: