A systematic review for evidence of efficacy of anticholinergic drugs to treat drooling

Jongerius, Peter H.

doi:10.1136/adc.88.10.911

Cited by 81 publications

(57 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This anticholinergic action in the salivary glands underlies the clinical use of systemically administered glycopyrronium as an antisialorrheaic and preoperative antisecretory agent (Jongerius et al, 2003). Although the therapeutic window of an antimuscarinic bronchodilator improves significantly by topical delivery to the lung, by inhalation, compared with oral dosing (Lu et al, 2006), the decreased systemic exposure at therapeutically relevant doses may not be sufficient to prevent drug activity in extrapulmonary tissues (Ryberg et al, 2008).…”

Section: Pharmacology Of Lung-selective Muscarinic Antagonist Td-4208mentioning

confidence: 99%

In Vivo Pharmacological Characterization of TD-4208, a Novel Lung-Selective Inhaled Muscarinic Antagonist with Sustained Bronchoprotective Effect in Experimental Animal Models

Pulido‐Rios¹,

McNamara²,

Obedencio³

et al. 2013

The Journal of Pharmacology and Experimental Therapeutics

View full text Add to dashboard Cite

Tiotropium is currently the only once-daily, long-acting muscarinic antagonist (LAMA) approved in the United States and other countries for the treatment of chronic obstructive pulmonary disease (COPD). Glycopyrronium has shown promise as a LAMA and was recently approved for once-daily maintenance treatment of COPD in the European Union. Here, we describe the in vivo preclinical efficacy and lung selectivity of a novel inhaled muscarinic antagonist, TD-4208 (biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester) and compare its profile to tiotropium and glycopyrronium. In anesthetized dogs, TD-4208, along with tiotropium and glycopyrronium, produced sustained inhibition of acetylcholine-induced bronchoconstriction for up to 24 hours. In anesthetized rats, inhaled TD-4208 exhibited dosedependent 24-hour bronchoprotection against methacholineinduced bronchoconstriction. The estimated 24-hour potency (expressed as concentration of dosing solution) was 45.0 mg/ml. The bronchoprotective potencies of TD-4208 and tiotropium were maintained after 7 days of once-daily dosing, whereas glycopyrronium showed a 6-fold loss in potency after repeat dosing. To assess systemic functional activity using a clinically relevant readout, the antisialagogue effect of compounds was also evaluated. The calculated lung selectivity index (i.e., ratio of antisialagogue and bronchoprotective potency) of TD-4208 was superior to glycopyrronium after both single and repeat dosing regimens and was superior to tiotropium after repeat dosing. In conclusion, the in vivo preclinical profile suggests that TD-4208 has the potential to be a long-acting bronchodilator for once-daily treatment of respiratory diseases. Its greater functional selectivity for the lung in preclinical models may translate to an improved tolerability profile compared with marketed muscarinic receptor antagonists.

show abstract

Section: Pharmacology Of Lung-selective Muscarinic Antagonist Td-4208mentioning

confidence: 99%

In Vivo Pharmacological Characterization of TD-4208, a Novel Lung-Selective Inhaled Muscarinic Antagonist with Sustained Bronchoprotective Effect in Experimental Animal Models

Pulido‐Rios¹,

McNamara²,

Obedencio³

et al. 2013

The Journal of Pharmacology and Experimental Therapeutics

View full text Add to dashboard Cite

show abstract

“…Present treatments for drooling in children include: behavioural modification programmes to improve body positioning, oromotor manipulation, desensitization techniques, and the use of intra-oral appliances; 5,6 pharmacological treatments such as oral or topical anticholinergic medications; 7 and in severe cases, surgical options such as salivary gland excision, trans-tympanic neurectomy of the chorda tympani, duct ligation or re-routing, and, more recently, laser photocoagulation of the parotids. 8 Botulinum toxin A (BTX-A) has been shown to exert an effect at the neuroglandular junction in animal studies by causing a fully reversible reduction in acetylcholine release from presynaptic nerve terminals.…”

mentioning

confidence: 99%

Parotid and submandibular botulinum toxin A injections for sialorrhoea in children with cerebral palsy

Banerjee

Glasson

O'Flaherty

2006

Develop Med Child Neuro

View full text Add to dashboard Cite

The aim of this study was to determine whether botulinum toxin A (BTX‐A) injected into the parotid and submandibular salivary glands of children aged 6 to 16 years with cerebral palsy (CP) and relative sialorrhoea significantly decreases their drooling and improves their quality of life. Twenty children (10 males, 10 females; mean age 10y 1mo [SD 3y 8mo]; range 6y 1mo‐16y 7mo) with CP, identified as having significant daily drooling (scoring at least 6 on drooling frequency/severity scales) were recruited. BTX‐A (2U/kg; maximum 70U) was injected under sedation, using ultrasound guidance (1.4U/kg and 0.6U/kg divided between parotid and submandibular glands respectively). Nineteen children completed the study: 15 with spastic quadriplegia (Gross Motor Function Classification System [GMFCS] Level V); one with dystonia (GMFCS Level V); one with hemiplegia (GMFCS Level II); and two with a mixed pattern of CP (GMFCS Levels III and V). Drooling was assessed by five methods at baseline, and 4 and 12 weeks after injection. Qualitative assessment of drooling frequency and severity scores showed statistically significant reductions at 4 weeks (p≤0.001) and 12 weeks (p=0.006). Qualitative assessment of quality of life scores (rated by parents and teachers separately) also significantly improved (p≤0.001 and P=0.023 respectively). Quantitative assessments showed that the number of bibs/scarves changed per day was significantly reduced at 4 weeks (p≤0.001). There was no side effect from the injections themselves; 89% of parents and children wished for further intrasalivary BTX‐A injections in the future. We conclude that percutaneous intrasalivary BTX‐A injections into the parotid and submandibular salivary glands can reduce drooling in children with CP and relative sialorrhoea, leading to an improvement in their quality of life.

show abstract

“…Pharmacological agents such as anticholinergic drugs are preferentially considered to be treatment option for hypersalivation 16. However, the use of anticholinergic drugs is limited due to adverse reactions in some patients 17. In particular, their unwanted effects can aggravate autonomic dysfunction related to anti‐NMDAR encephalitis, which may be seriously dangerous.…”

Section: Discussionmentioning

confidence: 99%

Botulinum toxin treatment for hypersalivation in anti‐NMDA receptor encephalitis

Jun

Seo

Lee

et al. 2017

Ann Clin Transl Neurol

View full text Add to dashboard Cite

Hypersalivation is one of the intractable symptoms of anti‐N‐methyl‐d‐aspartate receptor (NMDAR) encephalitis. While anticholinergic medications partially improve the hypersalivation, they can aggravate the autonomic dysfunctions associated with anti‐NMDAR encephalitis. Thus, we investigated the efficacy and safety of botulinum toxin type A injection on hypersalivation refractory to anticholinergics in six patients with anti‐NMDAR encephalitis. Hypersalivation was well‐controlled without remarkable adverse reaction over 16 weeks after botulinum toxin type A, although two patients were reinjected at 12 weeks due to reaggravation of hypersalivation. Our findings suggest that botulinum toxin type A might be a better choice than anticholinergics for management of hypersalivation in patients with anti‐NMDAR encephalitis.

show abstract

A systematic review for evidence of efficacy of anticholinergic drugs to treat drooling

Cited by 81 publications

References 11 publications

In Vivo Pharmacological Characterization of TD-4208, a Novel Lung-Selective Inhaled Muscarinic Antagonist with Sustained Bronchoprotective Effect in Experimental Animal Models

In Vivo Pharmacological Characterization of TD-4208, a Novel Lung-Selective Inhaled Muscarinic Antagonist with Sustained Bronchoprotective Effect in Experimental Animal Models

Parotid and submandibular botulinum toxin A injections for sialorrhoea in children with cerebral palsy

Botulinum toxin treatment for hypersalivation in anti‐NMDA receptor encephalitis

Contact Info

Product

Resources

About