Smooth muscle relaxants used for relief GI and UG spasms. Drugs influencing uterus functions. Antihistamines H1-blocker Flashcards
Agents used
papaverine.
drotaverine. butylscopolamine. misoprostol.
oxytocin.
ergotamine.
terbutaline.
atosiban.
Mg++.
ethanol .
solifenacin.
oxybutinine.
tamsulosin.
Histamine
Organic, nitrogen-containing compound; classified as amine autacoid (physiologically active metabolite, released by specific cells and tissues, having short-lasting and local effects)
▪ Cells with histamine synthesis and storage properties
- CNS neurons (role in sleep-arousal regulation)
- Enterochromaffin cells
- Mast cells
- Basophils, eosinophils
H1
H1
Smooth muscle
Endothelium
Brain
Gq
- Capillary dilation (via NO) → BP ↓
- Capillary permeability → tissue edema
- Bronchiolar smooth muscle contraction
(bronchoconstriction) - Activation of peripheral nociceptive
receptors → pain and pruritus - Nasal and bronchial mucous secretion ↑
H2
H2
Gastric mucosa
Cardiac muscle
Mast cells
Brain
Gs
- Gastric acid secretion ↑
- Cardiac stimulant effect: SA nodal rate
and automaticity ↑, positive inotropic - Negative feedback effect – reduce
histamine release from mast cells
H3
H3
Presynaptic receptors in the CNS and periphery
Gi
- Presynaptic modulation of histaminergic neurons in the CNS and the periphery
H4
H4
Eosinophils
Neutrophils
CD4+ T-cells
Gi
- Chemotactic response in leukocyte (especially eosinophils) and mast cells
Antihistamines
H1 receptor antagonists – 1st gen’:
Diphenhydramine
Promethazine
Dimetindene
H1 receptor antagonists – 2nd gen’
Cetirizine
Loratadine
Fexofenadine
H2 receptor antagonists Cimetidine Ranitidine Famotidine Nizatidine
H1 receptor antagonists – 1st gen’
- Competitive inhibitors of central and peripheral H1 receptors
- α-adrenergic receptor inhibition properties
- M-cholinergic receptor inhibition properties
- Serotonin receptor inhibition properties (only a few agents)
Diphenhydramine
Promethazine
Dimetindene
Diphenhydramine
H1 receptor antagonists – 1st gen’
- Competitive inhibitors of central and peripheral H1 receptors
- α-adrenergic receptor inhibition properties
- M-cholinergic receptor inhibition properties
- Serotonin receptor inhibition properties (only a few agents)
- Oral or parenteral
- Duration of action 4-12 h’
- Metabolism by hepatic CYP450
(affected by drugs that induce/inhibit hepatic metabolism) - Lipophilic (easily cross the blood-brain-barrier)
- IgE-mediated allergies (ex. hay fever, urticaria)
- Sedative (ex. preoperative sedation)
- Antiemetic (ex. chemotherapy-induced vomiting)
- Sleep-aid formulations (over the counter drug)
- Anti-motion sickness
- Control of nausea and vomiting of pregnancy
(in combination with pyridoxine - B6 vitamin) - Management of acute extrapyramidal symptoms
(ex. due to antipsychotics) - Side effects: sedation, antimuscarinic effects
(dry mouth, blurred vision, glaucoma exacerbation), α-adrenoreceptor inhibitory effects (orthostatic hypotension) - Interactions: additive sedation with other sedatives (BZD, alcohol)
Promethazine
H1 receptor antagonists – 1st gen’
- Competitive inhibitors of central and peripheral H1 receptors
- α-adrenergic receptor inhibition properties
- M-cholinergic receptor inhibition properties
- Serotonin receptor inhibition properties (only a few agents)
- Oral or parenteral
- Duration of action 4-12 h’
- Metabolism by hepatic CYP450
(affected by drugs that induce/inhibit hepatic metabolism) - Lipophilic (easily cross the blood-brain-barrier)
- Less anti-motion sickness effect
- More sedative and autonomic effects
Dimetindene
H1 receptor antagonists – 1st gen’
- Competitive inhibitors of central and peripheral H1 receptors
- α-adrenergic receptor inhibition properties
- M-cholinergic receptor inhibition properties
- Serotonin receptor inhibition properties (only a few agents)
- Oral or parenteral
- Duration of action 4-12 h’
- Metabolism by hepatic CYP450
(affected by drugs that induce/inhibit hepatic metabolism) - Lipophilic (easily cross the blood-brain-barrier)
- Symptomatic treatment of allergic reactions
- Minimally crosses blood-brain-barrier → milder side
effects with efficient control of allergies
H1 receptor antagonists – 2nd gen’
- Competitive inhibitors of peripheral H1 receptors
- No autonomic or anti-motion sickness effect
Cetirizine
Loratadine
Fexofenadine
- IgE-mediated allergies (hay fever, urticaria, angioedema)
- Side effects (generally milder compared to 1st gen’): sedation, arrhythmias in overdose
- Interactions: additive sedation with other sedatives (BZD, alcohol)
- Much less lipophilic (less likely to cross the blood-brain-barrier)
Cetirizine
H1 receptor antagonists – 2nd gen’
- Competitive inhibitors of peripheral H1 receptors
- No autonomic or anti-motion sickness effect
- Oral or parenteral
- Duration of action 12-24 h’
- Metabolism by hepatic CYP450
(affected by drugs that induce/inhibit hepatic metabolism) - Much less lipophilic (less likely to cross the blood-brain-barrier)
- IgE-mediated allergies (hay fever, urticaria, angioedema)
- Side effects (generally milder compared to 1st gen’): sedation, arrhythmias in overdose
- Interactions: additive sedation with other sedatives (BZD, alcohol)
Loratadine
H1 receptor antagonists – 2nd gen’
- Competitive inhibitors of peripheral H1 receptors
- No autonomic or anti-motion sickness effect
- Oral or parenteral
- Duration of action 12-24 h’
- Metabolism by hepatic CYP450
(affected by drugs that induce/inhibit hepatic metabolism) - Much less lipophilic (less likely to cross the blood-brain-barrier)
- IgE-mediated allergies (hay fever, urticaria, angioedema)
- Side effects (generally milder compared to 1st gen’): sedation, arrhythmias in overdose
- Interactions: additive sedation with other sedatives (BZD, alcohol)
Fexofenadine
H1 receptor antagonists – 2nd gen’
- Competitive inhibitors of peripheral H1 receptors
- No autonomic or anti-motion sickness effect
- Oral or parenteral
- Duration of action 12-24 h’
- Metabolism by hepatic CYP450
(affected by drugs that induce/inhibit hepatic metabolism) - Much less lipophilic (less likely to cross the blood-brain-barrier)
- IgE-mediated allergies (hay fever, urticaria, angioedema)
- Side effects (generally milder compared to 1st gen’): sedation, arrhythmias in overdose
- Interactions: additive sedation with other sedatives (BZD, alcohol)
H2 receptor antagonists
- Competitive inhibitors of peripheral H2 receptors
- No H1, autonomic or anti-motion sickness effects
Cimetidine
Ranitidine
Famotidine
Nizatidine
Cimetidine
H2 receptor antagonists
- Competitive inhibitors of peripheral H2 receptors
- No H1, autonomic or anti-motion sickness effects
- Oral or parenteral
- Duration of action 12-24 h’
- Metabolism by hepatic CYP450
(affected by drugs that induce/inhibit hepatic metabolism) - Acid peptic disease (duodenal and gastric)
- Control of Zollinger-Allison syndrome (gastrin-secreting
neuroendocrine tumor) - Gastroesophageal reflux disease (GERD)
- Stress ulcers, mucosal erosion, gastric hemorrhage in
ICU patients (given IV) - Not 1st-line agent in the reduction of gastric acidity! (initial approach is based on treatment with PPI’s)
- Side effects: cimetidine (but not other agents) is a weak antiandrogenic agent and a potent P450 enzyme inhibitor
Ranitidine
H2 receptor antagonists
- Competitive inhibitors of peripheral H2 receptors
- No H1, autonomic or anti-motion sickness effects
- Oral or parenteral
- Duration of action 12-24 h’
- Metabolism by hepatic CYP450
(affected by drugs that induce/inhibit hepatic metabolism) - Acid peptic disease (duodenal and gastric)
- Control of Zollinger-Allison syndrome (gastrin-secreting
neuroendocrine tumor) - Gastroesophageal reflux disease (GERD)
- Stress ulcers, mucosal erosion, gastric hemorrhage in
ICU patients (given IV) - Not 1st-line agent in the reduction of gastric acidity! (initial approach is based on treatment with PPI’s)
- Side effects: cimetidine (but not other agents) is a weak antiandrogenic agent and a potent P450 enzyme inhibitor
Famotidine
H2 receptor antagonists
- Competitive inhibitors of peripheral H2 receptors
- No H1, autonomic or anti-motion sickness effects
- Oral or parenteral
- Duration of action 12-24 h’
- Metabolism by hepatic CYP450
(affected by drugs that induce/inhibit hepatic metabolism) - Acid peptic disease (duodenal and gastric)
- Control of Zollinger-Allison syndrome (gastrin-secreting
neuroendocrine tumor) - Gastroesophageal reflux disease (GERD)
- Stress ulcers, mucosal erosion, gastric hemorrhage in
ICU patients (given IV) - Not 1st-line agent in the reduction of gastric acidity! (initial approach is based on treatment with PPI’s)
- Side effects: cimetidine (but not other agents) is a weak antiandrogenic agent and a potent P450 enzyme inhibitor
Nizatidine
H2 receptor antagonists
- Competitive inhibitors of peripheral H2 receptors
- No H1, autonomic or anti-motion sickness effects
- Oral or parenteral
- Duration of action 12-24 h’
- Metabolism by hepatic CYP450
(affected by drugs that induce/inhibit hepatic metabolism) - Acid peptic disease (duodenal and gastric)
- Control of Zollinger-Allison syndrome (gastrin-secreting
neuroendocrine tumor) - Gastroesophageal reflux disease (GERD)
- Stress ulcers, mucosal erosion, gastric hemorrhage in
ICU patients (given IV) - Not 1st-line agent in the reduction of gastric acidity! (initial approach is based on treatment with PPI’s)
- Side effects: cimetidine (but not other agents) is a weak antiandrogenic agent and a potent P450 enzyme inhibitor
Eicosanoid agonists
Misoprostol Alprostadil Dinoprostone Carboprost Latanoprost Epoprostenol
Misoprostol
Eicosanoid agonists
PGE1 analogue
- Oral
- Abortifacient, in combination with mifepristone (progesterone antagonist)
- effective up to 60 days into uterine pregnancy (extrauterine abortion is induced with methotrexate)
- GI cytoprotective role → prophylaxis and treatment of NSAID’s-induced ulcers and erosions
Alprostadil
Eicosanoid agonists
PGE1 analogue
- Parenteral
- Male impotence (injection into corpus cavernosum)
- Maintain patency of the ductus arteriosus in infants with transposition of the great vessels (until surgical
correction can be undertaken)
Dinoprostone
Eicosanoid agonists
PGE2 analogue
- Vaginal gel
- Abortifacient (2nd trimester)
- Cervical ripening → soften the cervix at term before
induction of labor with oxytocin
Carboprost
Eicosanoid agonists
PGF2α analogue
- Parenteral
- Control of postpartum uterine bleeding
- Abortifacient (2nd trimester)
Latanoprost
Eicosanoid agonists
PGF2α analogue
- Topical
- Glaucoma (intraocular pressure ↓)
Epoprostenol
Eicosanoid agonists
PGI2 analogue
- Parenteral
- Pulmonary hypertension
- Antiplatelet agent in extracorporeal dialysis
Eicosanoid antagonists
Corticosteroids:
PLA2 inhibitors, COX inhibitors (non-selective)
NSAID's: COX inhibitors (non-selective)
Celecoxib:
COX-2 selective inhibitor
Zileuton:
LOX selective inhibitor
Zafirlukast, Montelukast:
LTD4 receptor antagonists
Drugs acting on the gastrointestinal and genitourinary tracts
Smooth muscle contraction:
- Bethanechol
- Neostigmine
Smooth muscle relaxation:
- Butyl- scopolamine
- Solifenacin
- Oxybutynin
- Tolterodine
- Papaverine
- Drotaverine
Bethanechol
SM contraction
Muscarinic agonist (selective) (direct-acting sympathomimetic)
- Oral
- Duration of action 30 min’ - 2 h’
- Poor lipid solubility (no CNS effects)
- Non-obstructive ileus (postoperative)
- Urinary retention
Neostigmine
SM contraction
Acetylcholine-esterase inhibitor (indirect-acting sympathomimetic)
- Oral
- Duration of action 2-4 h’
- Quaternary amine – does not enter CNS
- Non-obstructive ileus (postoperative)
- Urinary retention
Butyl- scopolamine
Smooth muscle relaxation
Cholinergic receptor blocker (non-selective)
- Oral
- No CNS effects
- GI spasm
- Management of abdominal pain and discomfort caused
by GI cramps, menstrual cramps, biliary colic, renal colic
Solifenacin
Tolterodine
Smooth muscle relaxation
Cholinergic receptor blockers (modest selectivity for M3)
- Oral, transdermal patch
- No CNS effects
- Bladder spasm (post-operative, neurogenic)
- overactive bladder
- Urinary incontinence
Oxybutynin
Smooth muscle relaxation
Cholinergic receptor blockers (modest selectivity for M3)
- Oral, transdermal patch
- No CNS effects
- Bladder spasm (post-operative, neurogenic)
- Urinary incontinence
Papaverine
Smooth muscle relaxation
Ca2+-channel blocker PDE inhibitor (non-selective)
- Opioid alkaloid derivative
- Oral, parenteral
- Gastrointestinal and genitourinary spasm
Side effects:
- Cardiac → negative ionotropic, arrhythmia, hypotension
- Hepatotoxicity
- GI irritation
- Priapism
Drotaverine
Smooth muscle relaxation
Ca2+-channel blocker PDE inhibitor (non-selective)
- Opioid alkaloid derivative
- Oral, parenteral
- Used to enhance cervical dilation during childbirth
Drugs acting on the female reproductive system
Tocolytic drugs – Agents relaxing the pregnant uterus
- Atosiban
- Terbutaline
- Mg2+-sulphate
- Ethanol
Agents relaxing the non-pregnant uterus
- NSAID’s
- Ibuprofen
- Naproxen
Agents contracting the pregnant uterus
- Oxytocin (Pitocin)
- Ergotamine
- Ergonovine
- Misoprostol
- Dinoprostone
- Carboprost
Atosiban
Tocolytic drugs – Agents relaxing the pregnant uterus
Oxytocin receptor antagonist
- IV
- Not approved in all countries
- Tocolytic agent (suppress preterm labor) *effective from gestational week 24
Side effects:
- Increased rates of infant death
Terbutaline
Tocolytic drugs – Agents relaxing the pregnant uterus
β2-selective agonist (SABA)
- Aerosol inhalation, parenteral, oral
- Rapid onset of action
- Tocolytic agent
- effective from gestational week 16
Side effects:
- Cardiac stimulant effect with arrhythmias
(may affect both mother and fetus)
Mg2+-sulphate
Tocolytic drugs – Agents relaxing the pregnant uterus
IV
- Tocolytic agent
- Seizure prevention in preeclampsia/eclampsia
- Protective role on fetal brain
Side effects:
- Maternal → flushing, lethargy, headache, weakness,
pulmonary edema, cardiac arrest
- Neonatal → hypotension, respiratory depression
Ethanol
Tocolytic drugs – Agents relaxing the pregnant uterus
IV
- Tocolytic agent
NSAID’s
- Ibuprofen
- Naproxen
Agents relaxing the non-pregnant uterus
COX inhibition → reduced PGF2α → uterine contraction ↓
- Oral
- Dysmenorrhea (menstrual cramps)
- Contraindicated during pregnancy
(PGE2 maintains patent ductus arteriosus)
Oxytocin (Pitocin)
▪ Agents contracting the pregnant uterus
Oxytocin receptor agonist (induces uterine contraction)
Oxytocin Receptor (OTR): G-protein coupled receptor family, Gq. - Induces uterine contractions (frequency and intensity).
- Sensitivity only in the peripartum period.
Indication: labor initiation, pain intensity, postpartum haemorrhage, promote milk release.
- formul.: inj. (i.v., i.m.), nasal spray.
- Short duration (t1/2 few min)
- IV, intranasal
- Induction and augmentation of labor
- Control of postpartum uterine hemorrhage (high doses)
- Induction of lactation (intranasal preparation)
Side effects:
- Fetal distress
- Placental abruption
- Uterine rupture
Ergotamine
Ergonovine
▪ Agents contracting the pregnant uterus
Induces vasoconstriction and uterine contraction
- Ergot alkaloid derivatives
- Parenteral
- Control of postpartum uterine hemorrhage
- must not be given before delivery of the placenta
Misoprostol
▪ Agents contracting the pregnant uterus
PGE1 analogue
- Oral
- Abortifacient, in
combination with mifepristone (progesterone antagonist)
*effective up to 60 days into pregnancy
Dinoprostone
▪ Agents contracting the pregnant uterus
PGE2 analogue
- Vaginal gel
- Abortifacient (2nd trimester)
Carboprost
▪ Agents contracting the pregnant uterus
PGF2α analogue
- Parenteral
- Control of postpartum uterine hemorrhage
- Abortifacient (2nd trimester)
Drugs acting on the male reproductive system
Agents acting on the male reproductive system
Tamsulosin
Sildenafil
Tamsulosin
‘Uroselective’ α-blocker
(inhibits α1A sparing α1B receptors→ no hypotension)
- Oral
- Hypertension
- Benign prostatic hyperplasia (BPH) → relax the muscle
of the prostate and bladder neck, which allows urine to flow more easily
Sildenafil
PDE-5 inhibitor
- Oral
- Erectile dysfunction
- Pulmonary hypertension
Side effects:
- Severe hypotension in combination with nitrates
- Priapism (prolonged erection)
- Blue-tinted vision (via inhibition of PDE-6 in retina)
Treatment of glaucoma
Pilocarpine: Ciliary muscle contraction (up) aqueous humors outflow decrease in intraocular pressure
Ergotamine
Affects several receptors (5HT-, D-, α-adrenergic Receptors).
Potent uterine contrictor narrows the blood vessels running through myometrium reduces bleeding.
Use: post-partum bleeding, promote involution.
Side effects: increased blood pressure, reflex bradycardia.
Migraine therapy
(constriction of the intracranial extracerebral blood vessels)
(ergotamine and dihydroergotamine)
Endogenous smooth muscle relaxants
Ach
Amines:
adrenaline (ß2 arteries and bronchi)
histamine (reduces peripheral vascular resistance)
Nitric oxide (NO): relaxation of the smooth muscle in the corpora cavernous—the initiating factor in penile erection.
ATP and its derivatives
Neuropeptides (VIP, PACAP,
Bradykinin
Anticholinergic agents:
Contraindications and side effects
Contraindications
- Partial or complete GI obstruction.
- Paralytic ileus.
- Urinary retention.
- Narrow angle glaucoma.
- Gastric retention.
- Myasthenia gravis.
- Obstructive uropathy.
Side agents effects:
Dry mouth
Constipation
Blurred vision
