Pharmacology
Structure and function
Plecanatide is a 16 amino acid peptide with the amino acid sequence:

H-Asn1-Asp2-Glu3-Cys4-Glu5-Leu6-Cys7-Val8-Asn9-Val10-Ala11-Cys12-Thr13-Gly14-Cys15-Leu16-OH

(one-letter sequence: NDECELCVNVACTGCL). Plecanatide is nearly structurally identical to human uroguanylin, apart from the substitution of Asp3 with Glu3. Disulfide bonds exist between Cys4 and Cys12, as well as Cys7 and Cys15.Plecanatide has two important motifs. The first being the acidic residues Asp2 and Glu3 which modulate the affinity for its receptor in response to environmental pH. Simulations predict the optimal activity of Plecanatide to occur at pH 5,  making it suitable for targeting cells within the proximal intestine, which has a pH of between 5 and 6. The second is the ACTGC motif (residues Ala11 to Cys15) which is the region responsible for its binding to the receptor, guanylate cyclase-C. Mechanism of action
Plecanatide works as a laxative by drawing water in to the gastrointestinal tract thereby softening stool and encouraging its natural passage. Similar to its endogenous counterpart, plecanatide activates guanylate cyclase-C on endothelial cells within the gastrointestinal tract. The activation of guanylate cyclase-C catalyses the production of the second messenger guanosine 3’,5’-cyclic monophosphate (cGMP) which leads to the protein kinase A (PKA) and protein kinase G II (PKGII)-mediated phosphorylation of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR is an anion channel and upon activation it will secrete negatively charged ions, particularly chloride (Cl−) and bicarbonate (HCO3−) in to the GI tract lumen.
Presence of systemic health problemsILI utilization is expected to increase because dental patients prefer fewer soft tissue anesthesia and dentists aim to reduce administration of traditional inferior alveolar nerve block (INAB) for routine restorative procedures.Injection methodology: The periodontal ligament space provides an accessible route to the cancellous alveolar bone, and the anesthetic reaches the pulpal nerve via natural perforation of intraoral bone tissue.Advantages of ILI over INAB: rapid onset (within 30 seconds), small dosage required (0.2-1.0 mL), limited area of numbness, lower intrinsic risks such as neuropathy, hematoma, trismus/jaw sprain and self-inflicted periodontal tissue injury, as well as decreased cardiovascular disturbances. Its usage as a secondary or supplementary anesthesia on the mandible has reported a high success rate of above 90%.Disadvantages: Risk of temporary periodontal tissue damage, likelihood of bacteriemia and endocarditis for at-risk populations, appropriate pressure and correct needle placement are imperative for anesthetic success, short duration of pulpal anesthesia limits the use of ILIs for several restorative procedures that require longer duration, postoperative discomfort, and injury on unerupted teeth such as enamel hypoplasia and defects. Technique description:

All plaque and calculus to be eradicated, optimally before the operative visit to assist gingival tissue healing. Before injection, disinfect gingival sulcus with 0.2% chlorhexidine solution. Administration of soft tissue anesthesia is recommended prior to ILI administration. This helps to enhance patient comfort. Needle gauges of sizes 27-gauge short or 30-gauge ultra-short needle are usually utilized.