Hydromorphone Essays

Hydromorphone Essays Hydromorphone Essay Hydromorphone Essay The name of the drug is called Hydromorphone. The systematic name ( IUPAC ) is 4,5-epoxy-3-hydroxy-17-methylmor-phinan-6-one. Hydromorphone hydrochloride has a chemical expression of C17H19NO3. There are four functional groups in Hydromorphone hydrochloride: An Ether group A Ketone group An Amine group ( third ) A Phenol group Stereochemistry and conformation: Hydromorphone hydrochloride has 4 chiral Centres ( Four different groups attached to a sp3 hybridised C one chiral Centre ) . Therefore it has 24 = 16 stereoisomers. Carbon figure 1 has R-configuration Carbon figure 2 has R-configuration Carbon figure 3 has S-configuration Carbon figure 4 has R-configuration Hydromorphone hydrochloride is a semi-rigid molecule because it is composed of a five-member ring system: the phenolic ring ( A ) , the cyclohexane ring ( B ) , the cyclohexanone ring ( C ) , the N-methyl piperidine ring ( D ) , and the tetrahydrofuran ring ( E ) . The molecule has a T form. Ring A, B and E form a perpendicular plane where the C and D form the horizontal plane. Ringing C exists in a chair conformation due to impregnation of C-C two-base hit between C7 and 8. Ringing D besides exists in chair conformation. Synthesis: Commercially, Hydromorphone is made from morphine via either direct rearrangement ( reflux alky or acidic aqueous solution of morphia with Pt or Pd accelerator ) or decrease of morphia via catalytic hydrogenation, this two reactions both produce Dihydromorphine. The Dihydromorphine so undergo Oppenauer oxidization, where it is oxidised with benzophenone in the presence of K tert butoxide or aluminum tert butoxide to organize Hydromorphone. Drug stableness: The half life of Hydromorphone is 2.6hours through unwritten path, where it takes 18.6 hours for sustained release Palladone. Hydromorphone hydrochloride is affected by visible radiation, although Dilaudid hydrochloride injection may develop a little xanthous stain, this alteration does non bespeak loss of authority. Hydromorphone hydrochloride injection should be protected from visible radiation and stored at a controlled room temperature of 25 grades C, but can be exposed to temperatures runing from 15 to30 grades C ; freeze of the injection should be avoided. Hydromorphone hydrochloride tablets should be stored in tight, light-resistant containers, normally at 15 to30 grades C ; nevertheless, the maker recommends that the 8-mg tablets be stored at 15 to 25 grades C. Hydromorphone hydrochloride unwritten solution should be stored in light-resistant containers at 15 to 25 grades C, and suppositories of the drug should be stored at 2 to 8 grades C. Hydromorphone hydrochloride injection reportedly is physically and chemically stable for at least 24 hours in most common IV extract solutions when protected from visible radiation at 25 grades C. Hydromorphone is somewhat soluble in H2O, freely soluble in intoxicant and really soluble in trichloromethane. Formulation and packaging: In the U.K. Hydromorphone is merely available in signifier of unwritten capsules and modified release capsules, which means it is released easy to widen the length of the drug s consequence. Available strengths for Dilaudid hydrochloride ( Palladone A ; reg ; ) : 1.3mg ( orange/clear ) , net monetary value 56-capsules battalion = A ; lb ; 8.82 ; 2.6mg ( red/clear ) , 56- capsules pack = A ; lb ; 17.64. Where for the modified ( let go of Palladone A ; reg ; SR ) : m/r, Dilaudid hydrochloride 2mg ( yellow/clear ) , net monetary value 56- capsules pack = A ; lb ; 20.98 ; 4mg ( pale blue/clear ) , 56- capsules pack = A ; lb ; 28.75 ; 8mg ( pink/clear ) , 56- capsules pack = A ; lb ; 56.08 ; 16mg ( brown/clear ) , 56- capsules pack = A ; lb ; 106.53 ; 24mg ( dark blue/clear ) , 56-cap battalion = A ; lb ; 159.82. [ BNF 56 page 235-236 ] . Lipinski s Rules: The molecular weight of Hydromorphone is 285 g/mol. ( below 500 ) The Log P of Hydromorphone is +1.69. ( lower than +5 ) There is merely one H bond donating group, which is the hydroxyl group in Phenol. ( less than 5 groups ) here are merely three H bond accepting groups. ( less than 10 groups ) The functional groups are by and large stable to metabolism, i.e. hydrolysis and oxidizations. Harmonizing to the Lipinski s regulations of five , Hydromorphone is an orally active drug. LogP and treatment of hydrophobic/hydrophilic belongingss: It is possible to foretell the Log P of a molecule by utilizing the Hydrophilic-Lipophilic Values ( p Values ) for organic fragments. This gives ( +0.5 x 11 ) + ( +2 x 1 ) + ( -1 X 3 ) + ( -1 X1 ) = +3.5. Therefore, the Predicted LogP = +3.5. Since 3.5 is greater than 0.5, Dilaudid is indissoluble in H2O. ( Soluble in H2O if smaller than 0.5 ) Harmonizing to the predicted LogP, Hydromorphone is a really hydrophobic ( lipotropic ) drug and it can go through through the membrane beds in cell and enter the blood stream ( high soaking up ) . Hydromorphone hydrochloride is indissoluble in H2O because of its non-polar groups. They are: The long aliphatic and aromatic hydrocarbons, i.e. cyclohexanes and the phenyl group. These non-polar groups will non interact with polar H2O molecules as they can non organize H bonds together and hence indissoluble. pKa and ionization province: Hydromorphone hydrochloride has a pKa of 8.2 at 20 grades C [ Medicine Complete ] , it is decrepit acidic. To cipher the per centum of ionisation of Hydromorphone ( weak acid ) at different pH, Equation 1 can be used: Equation 1 % ionisation= 1001+antilog ( pKa-pH ) At pH 2: % ionisation = 1001+antilog ( 8.2-2 ) = 6.31 ten 10-5 % At pH 7.4: % ionisation = 1001+antilog ( 8.2-7.4 ) = 13.7 % At pH 10: % ionisation = 1001+antilog ( 8.2-10 ) = 98.4 % From the computations on the old page, I can reason that merely 6.31 ten 10-5 % of Dilaudid is ionized at pH 2, i.e. in the tummy. Therefore, there are 100 % 6.31 ten 10-5 % = 99.9999 % of nonionized Hydromorphone which can go through through the membrane barrier and enter the blood stream. Hydromorphone is extremely absorbed by the organic structure in tummy. Mode of action: Hydromorphone is an opioid anodyne ; it reacts with the opioid mu-receptors. The mu-receptors are discretely distributed in the human encephalon with high denseness in the posterior amygdaloid nucleus, hypothalamus, thalamus, nucleus caudatus, putamen, and certain cortical countries. These receptors are besides found in the spinal cord and GI piece of land. It binds onto the mu-receptors and exerts its principle pharmacological consequence on the Central Nervous System and GI piece of land to bring forth analgesia and sedation. Hydromorphone is extremely absorbed by the human organic structure and it shows the analgesia consequence really rapidly one time enter the organic structure. It is 8 to 10 times stronger than morphia due to its hydrophobicity ( really lipophilic ) . Bibliography: Samuel, B. , Stanley, G. , Robert, R. ( 2004 ) , Process for the Synthesis of Hydromorphone, hypertext transfer protocol: //www.wipo.int/pctdb/en/wo.jsp? WO=2006005112 A ; IA=AU2005001002 A ; DISPLAY=DESC, Date accessed 23/04/10. Author unknown. ( Date unknown ) , One-pot Isomerization of Morphine to Dihydromorphinone ( Hydromorphone ) , hypertext transfer protocol: //www.erowid.org/archive/rhodium/chemistry/dihydromorphinones.html, Date accessed 23/04/10. Author unknown. ( 2006 ) , Hydromorphone, hypertext transfer protocol: //www.patient.co.uk/medicine/Hydromorphone.htm, Date accessed 23/04/10. Hildebrand, K. , Elsberry, D. , Anderson, V. ( 2001 ) , Stability and Compatibility of Hydromorphone Hydrochloride in an Implantable Infusion System , Journal of Pain and Symptom Management, 22 ( 6 ) , Page 1042-1047. Author unknown. ( 2010 ) , Hydromorphone Suppository, hypertext transfer protocol: //www.drugs.com/cdi/hydromorphone-suppository.html, Date accessed 24/04/10 Lipinski, C. ( 2004 ) , Lipinski s rule-of-five, hypertext transfer protocol: //www.bioscreening.com/reference/lipinski_rule.htm, Date accessed 24/04/10. Author unknown. ( 2009 ) , Showing drug card for Hydromorphone ( DB00327 ) , hypertext transfer protocol: //www.drugbank.ca/drugs/DB00327, Date accessed 24/04/10. Clarkes. ( 2006 ) , Clarke s Analysis of Drugs and Poisons Hydromorphone hydrochloride, hypertext transfer protocol: //www.medicinescomplete.com/mc/clarke/2009/CLK0851.htm, Date accessed 24/04/10. Author unknown. ( 2008 ) , Monograph Hydromorphone Hydrochloride, hypertext transfer protocol: //www.medscape.com/druginfo/monograph? cid=med A ; drugid=11338 A ; drugname=Hydromorphone+Rect A ; monotype=monograph A ; print=1, Date accessed 24/04/10. BMJ Group, . ( 2008 ) . British National Formulary 56, London, RPS Publishing. Bruice, P, . ( 2004 ) . Organic Chemistry, Fourth Edition, Prentice Hall, Pearson. Lo, K, . ( 1998 ) Synthesis of N- Phenethylnorhydromorphone, hypertext transfer protocol: //circle.ubc.ca/bitstream/handle/2429/11862/ubc_2001-0456.pdf ; jsessionid=8D12F28D380E801AE9A422C0F9CD3435? sequence=1, Date accessed 26/04/10