PHAR1812 Summary Notes for Semester (2021) PDF

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Table of ContentsLecture 23: Drugs in Solution 2 ......................................................... Error! Bookmark not defined. Lecture 24: Drugs in Solution 3 ......................................................... Error! Bookmark not defined.Week 9 ..........................................

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Semester 1

2020

Table of Contents Week 1 .............................................................................................................................. 3 Lecture 1: Introductory Lecture .................................................................................................. 3 Lecture 2: Mathematics 1........................................................................................................... 5 Lecture 3: Mathematics 2........................................................................................................... 7

Week 2 .............................................................................................................................. 8 Lecture 4: Molecular Properties 1 .............................................................................................. 8 Lecture 5: Mathematics 3......................................................................................................... 17 Lecture 6: Mathematics 4......................................................................................................... 18

Week 3 ............................................................................................................................ 18 Lecture 7: Molecular Properties 2 ............................................................................................ 18 Lecture 8: Mathematics 5......................................................................................................... 28 Lecture 9: Mathematics 6......................................................................................................... 28

Week 4 ............................................................................................................................ 29 Lecture 10: Molecular Properties 3 .......................................................................................... 29 Lecture 11: Mathematics 7 ....................................................................................................... 40 Lecture 12: Mathematics 8 ....................................................................................................... 40

Week 5 ............................................................................................................................ 40 Lecture 13: Molecular Properties 4 .......................................................................................... 40 Lecture 14: Mathematics 9 ....................................................................................................... 40 Lecture 15: Mathematics 10 ..................................................................................................... 41 Workshop 7: Molecular Properties ................................................... Error! Bookmark not defined.

Week 6 ............................................................................................................................ 42 Lecture 16: Molecular Properties 5 .......................................................................................... 42

Week 7 ............................................................................................................................ 58 Lecture 19: Thermodynamics 1 ................................................................................................ 58 Lecture 20: Thermodynamics 2 ................................................................................................ 63 Lecture 21: Thermodynamics 3 ........................................................Error! Bookmark not defined.

Week 8 ............................................................................................................................ 67 Lecture 22: Drugs in Solution 1................................................................................................. 67 Lecture 23: Drugs in Solution 2.........................................................Error! Bookmark not defined. Lecture 24: Drugs in Solution 3.........................................................Error! Bookmark not defined.

Week 9 ................................................................................... Error! Bookmark not defined. Lecture 25: Drugs in Solution 4.........................................................Error! Bookmark not defined. Lecture 26: Sources of Drugs 1 – Bush Medicines ..................................................................... 86

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Lecture 27: Phytonutrients....................................................................................................... 92

Week 10 .......................................................................................................................... 98 Lecture 28: Sources of Drugs 2 ................................................................................................. 98 Lecture 29: Sources of Drugs 3 ................................................................................................105 Lecture 30: Drug Targets .........................................................................................................112

Week 11 ........................................................................................................................ 134 Lecture 33: Dosage Forms 1 ....................................................................................................134

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Week 1 Lecture 1: Introductory Lecture LO2 LO6 1. Identify different functional groups and classes of compounds Functional Groups A group of atoms/bonds that has a predictable chemical behaviour -

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Alkyl Groups o Alkanes: simplest form of hydrocarbon, saturated (max hydrogens bonded) § Methane CH4 § Ethane C2H6 à CH3CH3 § Propane C3H8 à CH3CH2CH3 § Butane § Pentane § Hexane o Alkenes: unsaturated, double bond (not max hydrogens bonded) § Ethene § Propene § 2-Butene § 1-Pentene § 3-Hexene § Cyclopropene § Cyclobutene § Cyclopentene § Cyclohexene o Alkynes: unsaturated, triple bonds § Ethyne § Propyne § 2-Butyne § 1-Pentyne § 3-Hexyne Aryl Groups o Aromatic rings (delocalised electrons) § Benzene = 6 membered ring with alternating single-double carbon bonds, delocalised structure represented by the circle inside the hexagon Alcohols (-OH hydroxyl group) o Methanol o Ethanol o Propanol o Butanol o 2-Pentanol o 3-Hexanol o Cyclopropanol 3

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o Cyclobutanol o Cyclopentanol o Cyclohexanol o Phenol Ethers (R-O-R): carbon-oxygen-carbon linkage is an ether o Dimethyl ether o Diethyl ether o Methoxybenzene (anisole) o Dibenzyl ether Carbonyl Compounds (something attached to C=O) o Aldehydes (Alkanal) (END) § Methanal § Ethanal § Propanal § Butanal o Ketones (MIDDLE) § Propanone § Butanone § Cyclopropanone § Cyclobutanone § Cyclopentanone § Cyclohexanone o Carboxylic Acids (Alkanoic): Carbonyl + hydroxyl group § Ethanoic acid (acetic acid) § Propanoic acid § Butanoic acid § Cyclopropanoic acid § Cyclobutanoic acid § Cyclopentanoic acid § Cyclohexanoic acid § Benzoic acid o Esters (O-R=O) § Methyl ethanoate (methyl acetate) § Ethyl ethanoate (ethyl acetate) § Methyl propanoate § Ethyl butanoate § Butyl benzoate § Dihydrofuranone o Amines (-NH2) § Primary Amines • Methylamine • Ethylamine § Secondary Amines • Dimethylamine • Diethylamine § Tertiary Amines • Trimethylamine

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• N-diethyl-N-methylamine § Cyclo amines • Cyclopentylamine • Pyrrolidine § Aryl amines • Aniline § Aromatic amine • Pyridine o Amides (O=R-NH2) ß ONE SIDE § Primary Amides • Ethylamide • Acetamide § Secondary Amides • N-Methylacetamide • N-Ethylacetamide § Tertiary Amides • N,N-Dimethylacetamide § Pyrrolidin-2-one o Imides (O=C-NH-C=O) ß BOTH SIDES SURROUNDED WITH C=O group) § N-acteylacetamide 2. Recognise that most drugs are low molecular weight chemicals

Lecture 2: Mathematics 1 LO17 LO18 LO19 LO20 LO21 1. Carry out simple numerical manipulations in the context of common pharmaceutical calculation problems 2. Carry out simple algebraic manipulations 3. Demonstrate numerical reasoning and recognise when answers to problems are not numerically possible 4. Apply appropriate numeracy skills to the solution of pharmacy problems 5. Demonstrate the ability to deal with the concept of uncertainty by devising alternatives which take account of qualifying, affording, and constraining variables, and appreciate that not all problems have a single correct solution. In general: ! = #$ ± #& $ is a real number and & is really small, therefore, error is small. Number of decimal places suggests bound on possible error: n decimal places implies accuracy to within 0.5 x 10!" Definitions 1) & (epsilon) is called absolute error # 2) | is called the relative error or the percentage error |%

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|$| = # *

$#+#$ ≥ 0 ###⌈$⌉ ≥ 0 −$#+#$ < 0#

Examples: 1. m = 10.0 ß this is an abbreviation for m = 10.0 ± 0.05 in this case $ = 10 and & = 0.05 9.95# ≤ !# ≤ 10.05 & = 0.05 is the absolute error # &.&( ) ) = # )& = 0.005 = # *&& = # * % is the percentage error |%| 2. m = 12.0 a. absolute error: & = 0.05 = 0.5# ×# 10!) # &.&( ) ) ) b. percentage error: |%| = # )* = *+& ≈ # *(& = 4 )&&& = 0.4% 3. m = 12.00 a. absolute error: & = 0.005 = 0.5# ×# 10!* # &.&&( &.&( b. percentage error: | | = # = = 0.4% %

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Facts 1) Addition or subtraction causes absolute errors to accumulate addictively. 2) Multiplication or division causes the percentage errors to accumulate addictively. a. The percentage error of m1m2 is equal to the sum of the percentage errors of m1 and m2 Problem 95.0 grams of compound A are added to 0.32 litres of solvent S. Only some of it dissolves. The precipitate P weighs 52 grams. Calculate the concentration of the solution using the following formula. A?=@?AB1AC>?9>D 9EBFG 9C?9@AH@B =>?=@?AB1AC>?9C? 9?=@?AB1AC>?9>D 9EBFG 9C?9=HJ>B>D>BK =>?=@?AB1AC>?9C? 9 Ae = 10 – 0.0537 = 9.94623… Therefore, percentage extracted = 99.46% Problem 5: A basic drug with pKa 8.2 is to be extracted from water into ethylacetate at pH 9.5. The ethylacetate/water partition coefficient of the unionised form of this drug is 60. What percentage of the drug will remain in the aqueous phase after extraction if equal volumes of water and ethylacetate are used? *internal check: make sure Papp < Ptrue *don’t necessarily need volumes or amounts to figure out partition extraction Answer

#@ABC = " #DEE (1 + 10FGH!FI ) 60" = " #DEE (1 + 10?.*!,.( )""""" #DEE = 57.1 L 57.1 = " L# D

=D

#

Ae = 57.1 Aw Ae + Aw = 100% Solving simultaneously Aw = 1.72% Ae = 98.28%

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Problem 6: An acidic drug with a pKa of 8.4 is to be extracted from a buffer at pH 7.4 into chloroform. The partition coefficient at pH 1 is 75. If the volume of water is 20 mL and the volume of chloroform is 40 mL, what percentage of the drug will be extracted into the chloroform? pH is 7.4 units lower than its pKa à therefore, fully unionised and therefore, also Ptrue (not Papp) Step 1: Calculate the apparent partition coefficient IMPORTANT: note that at pH 1, an acidic drug with pKa 8.4 will be 100% unionised. Therefore, the partition coefficient at this pH is the TRUE partition coefficient. To calculate the apparent partition coefficient at pH 8.4, use the equation: GL)(M = % G!&& (1 + 10N4 .NO1 ) 75 = % G!&& (1 + 10P.Q.R.Q ) = 1.1. Papp Therefore, Papp = 68.2 Step 2: Calculate the % extracted Papp = 68.1 = =

D $%# D #%$

=

L$ L#

*&MD$ +&MD#

Ao = 136.4 Aw Ao + Aw = 100% Solve simultaneously, 137.4 Aw = 100 Aw = 0.728% Ao = 100 – 0.728% = 99.272% Effect of pH on Partition – SUMMARY 1) Acidic and basic drugs can ionise in the aqueous phase only (intermolecular forces aren’t in non-polar solvents) 2) Only the unionised form of the drug can partition between phases – the partition coefficient of the ionised form is 0 3) The result is that the partition coefficient APPEARS to vary according to pH 4) The effect of pH can be calculated using the Henderson Hasselbalch equation 5) The true and apparent partition coefficients can be related to each other through two equations – one for acidic drugs and one for basic drugs 6) The apparent partition coefficient for an acidic or basic drug ranges from 0 to the true partition coefficient 7) Changes in apparent partition coefficient occur within 2 pH units either side of the drug’s pKa

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Lecture 26: Sources of Drugs 1 – Bush Medicines Learning objectives 1. Describe some of the changes that have occurred to the health of the Aboriginal people since colonisation 2. Describe some of the projects and roles involving pharmacists in providing health services to Aboriginal peoples 3. Broadly describe the ways in which Aboriginal people use Bush Medicines 4. Explain how specific bush medicines could be sources of drugs

Relevance of Bush Medicine in Pharmacy When? • When is it of value for a pharmacist to know about bush medicines? o Research for sourcing ‘new’ drugs o Rural community pharmacy practice o Hospital pharmacy practice o Inter-professional and patient communications Why? • Why does a pharmacist need to know about Bush Medicines? o Because you are living and working in Australia o Bush Medicines are part of a traditional health practice for members of the Australian community and these may be used concurrently or as an alternative to conventional care The impact of colonisation • The impact of colonisation and the subsequent displacement and disconnection of people both from their traditional lands and later from their traditional families has been significant in its subsequent effect in the use of traditional practices including traditional medicine What was Aboriginal peoples health like before colonisation? • Before colonisation: o Good health o Likely better than white settlers • The main conditions suffered were: o Joint and muscle pain o Headaches o Skin infections/itchy skin o “women’s” problems Diet •

Before colonisation: o Bush foods o Full use of food in region o Variety, especially in fertile areas o Wide variety of fruits, vegetables and animal meat o Diet balance and healthy (sufficient vitamins, fats and protein) o Healthy lifestyle (5-6 hour exercise per day)

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Changes in diet since colonisation • Modern diet a function of: o Loss of land o Disruption of traditional lifestyle o Introduced flour and sugar o Occasional meat or offal § Handed out to Aboriginal peoples working as station hands § Nutritionally much poorer • Increased prevalence of chronic disease o Raised blood pressure/cholesterol o Diabetes o Cancer Poor / malnutrition • Aboriginal children are at high risk of malnutrition • The Early Childhood Nutrition and Anaemia Prevention Project looked at six remote communities across the Northern Territory, Western Australia and Queensland, and found almost 90% of children has been anaemic at least once during the ages of six months to 24 months o It also found that 56% of the infants were anaemic at their first haemoglobin check at six to nine months, which was worse than expected o The World Health Organisation classifies these levels as a severe health problem • Primary Health Care for Aboriginal peoples is currently addressed by either government run health services or community run health services and referred to as Aboriginal Community Controlled Health Services (ACCHS) o Offer biomedical health care and employment to trained Aboriginal Health Workers (AHWs). ACCHS are initiated and governed by the local Aboriginal Community to enable delivery of holistic and culturally appropriate healthcare to the respective community/ies § National Aboriginal Community Controlled Health Organisation is the national peak body representing 144 Aboriginal controlled health Services in over 34o clinics and health settings § Over 50% of the workforce is Aboriginal NACHO Projects National Aboriginal Community Controlled Health Organisation • Ear and Hearing Health Project o The project aims to progress the training of health workers for the ear health and hearing screening component of the Improving Eye and Ear Health Services • Foetal Alcohol Spectrum Disorder (FASD) o NACCHO has partnered with Menzies School of Health Research and the Telethon Kids Institute (TKI) to develop and implement a flexible, modular package of Foetal Alcohol Spectrum Disorders (FASD) Prevention and Health Promotion Resources • NACCHOs position paper on Aboriginal male health (2010) o Describes the key policy areas and programmes NACCHO has documented that should be developed in male health

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Current Programmes • Syphilis • Aboriginal Male Health • Healthy Futures • COVID-19 • NACCHO is involved in the oversight and management of several projects and programs related to medicines and pharmacy. NACCHO also provides national Aboriginal and Torres Strait Islander medicines policy leadership.

Current NACHO Projects – QUMAX • Improving the delivery of medicines • Quality Use of Medicines Maximised for Aboriginal and Torres Strait Islander People (QUMAX) o In 2020 QUMAX was funded by the Commonwealth Department of Health under the Seventh Community Pharmacy Agreement (7CPA) QUMAX Seven Support Categories • Dose Administration Aid (DAA) arrangements aims to reduce the financial barriers to accessing comprehensive DAA services provided by community pharmacies to improve medication adherence and management for ACCHO clients • QUM Pharmacy Support: aims to provide additional capacity for community pharmacy involvement and support in areas including Quality Use of Medicines (QUM) planning, policy, and protocol development and QUMAX Work Plan development • Home Medicine Review (HMR) Models of Support aims to reduce the cultural and logistical barriers of access to HMR services by ACCHO clients • QUM Devices: aims to reduce the financial barriers to access to QUM devices to improve overall delivery of medicines and management of chronic disease by ACCHO clients • QUM Education: aims to reduce financial barriers associated with access to QUM educations and health promotion for ACCHO employees and their clients. This category may also help ACCHOs access current medicine resources, promoting suitable, safe and effective medication management for ACCHO clients • Cultural Awareness: aims to improve access and delivery of Cultural Awareness .. training for Community Pharmacy to promote a culturally aware and safe pharmacy environment

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Transport: aims to reduce barriers of access to medicines and community pharmacy providing transport support

Guild Closing the Gap

So what is happening in Australia to integrate traditional health approaches? • It is acknowledged that in remote areas in other countries it is common for traditional medicine to coexist with biomedical healthcare as part of a pluralist medical system • Within government funded established primary health care clinics in Aboriginal Australia roughly one fifth offer traditional healers and one tenth offer bush medicines as part of the healthcare service (details about these services are lacking) • Many people in the local community, as well as visitors from other communities, come to get the bush medicines for a range of ailments o Such as colds and flus, sore muscles, wounds, headaches and skin rashes o Elders are passing on this knowledge to young people, and that bush medicines have always been used o Bush medicines are being widely used, however, qualitative and quantitative data is not investigated to understand the ‘why’, ‘how’, and ‘when’ of trad...