7.1 Dynamic equilibrium & 7.2 The position of equilibrium

7.1.1 Outline the characteristics of chemical and physical systems in a state of equilibrium.
Chemical systems e.g. Dissociation

Characteristics of an equilibrium
1. Dynamic equilibrium: reactions have not stopped, they're still occurring (see right)
2. Closed systems: This prevents exchange of matter with the surroundings
3. Concentrations remain constant: the products and reactants are produced and destroyed at an equal rate
4. No macroscopic properties change (no observable change): colour, density depends on concentration of the equilibrium mixture
5. Eqm can be reached from either direction: the same eqm mixture will be established under the same conditions, regardless of the starting product/reactant mixture.

Usually in an eqm mixture either products/reactants will have a higher concentration

If the eqm lies to the right = more products are being formed

If the eqm lies to the left = more reactants being formed

7.2.1 Deduce the equilibrium constant expression (Kc) from the equation for a homogeneous reaction.

7.2.2 Deduce the extent of a reaction from the magnitude of the equilibrium constant.
The magnitude of Kc determines the EXTENT of the reaction, not how fast it will achieve eqm.

If Kc >> 1, the reaction is almost to completion

If Kc << 1, the reaction hardly proceeds

7.2.3 Apply Le Chatelier’s principle to predict the qualitative effects of changes of temperature, pressure and concentration on the position of equilibrium and on the value of the equilibrium constant.

"A system at equilibrium when subjected to a change will respond in such a way as to minimize the effect of the change." 

- Le Chatelier's Principle on distrupting the equilibrium

CONCENTRATION

Adding reactants: eqm shifts right (in favour of the products), and a new mixture is established

Adding products: eqm shifts left (in favour of the reactants), and a new mixture is established

Removing reactants: eqm shifts left (in favour of the reactants), and a new mixture is established
Removing products: eqm shifts right (in favour of the products), and a new mixture is established


PRESSURE
Increase: favours the side with less gas molecules/moles
Decrease: favours the side with more gas molecules/moles
This changes the equilibrium, but not Kc. Kc stays the same.

TEMPERATURE
Kc is temperature dependent, a change in temperature will cause a change in Kc.

7.2.4 State and explain the effect of a catalyst on an equilibrium reaction.
A catalyst will speed up both forward AND backward reactions, therefore the eqm will not shift.

7.2.5 Apply the concepts of kinetics and equilibrium to industrial processes.

D.7 Antivirals

D.7.1 State how viruses differ from bacteria.
Viruses - HIV virus with lipid envelope
- lipid envelope
- viral proteins incorporated in envelope
- viral RNA
- core protein
- 25 nm

Bacteria - T4 bacteriophage
- DNA
- protein coat
- sheath
- base plate
- tail fibre
- 98nm

Viruses (e.g. measles, meningitis, polio, AIDs, avian flu)
- contain only 2 components: protein & nucleic acid (RNA or DNA)
- no cellular structure
- only produce inside another living cell
- original hijacker: take over functioning of host cell & use to reproduce, host cell used to assemble new viral particles & in the process the host cell usually dies,  therefore thousands of viral particles are released into the body.

Bacteria
- more complex cellular structure
- survives & reproduces independently


D.7.2 Describe the different ways in which antiviral drugs work.
Mutation: small changes in genetic material

Viruses
- live in cells, therefore can't be easily targeted
- lack bacteria cell structure, therefore not attacked by antibiotics
- speedily multiple, therefore often already spread through the body before symptoms appear
- have a tendency to mutate rapidly, therefore change is susceptible to drugs
e.g. different flu vaccines developed each year according to most abundant strain of cirus

Antibodies
Antivirals - alter cell's DNA, therefore virus can't use to multiply
or - block enzyme activity within host cell, therefore prevents virus reproduction then, relief from symptoms & disease progression halted, but not completely eradicated from the body (e.g. flare-up: herpes infection, cold sores)

Amantadine 
- an effective antiviral drug
- changes cell membrane, therefore prevents virus entry into cells.
- best used as prophylactic (preventive) treatment, or before infection spreads widely.
- effectively used to treat influenza


D.7.3 Discuss the difficulties associated with solving the AIDS problem.
HIV
- primarily infects vital white blood cells (CD4+T cells) in immune system
- binds to specific receptor proteins on cell surface then penetrates cell
- is a retrovirus (has RNA instead of DNA); RNA released into cell & enzyme reverse transcriptase controls synthesis of viral DNA from RNA. Viral DNA integrates itself into host cell's DNA, therefore when the cell divides the viral DNA is also replicated.

Process:
1. HIV destroys T-helper cells (cells that defend the body against the virus)
2. HIV mutates very rapidly even within a patient (estimated there are more variations of HIV in a single patient than influenza world wide in a year)
Variation: virus 'escapes' immune response, because patient has to develop a new response to the newly mutated virus.
3. HIV often lies dormant in host cells, therefore immune system has nothing to respond to.


AIDs - caused by HIV
- the failure of the immune system, therefore the body falls prey to pneumonia/cancers (~40 million are HIV positive, they have a likelyhood of developing AIDs)


Antiretroviral drugs
- helps fight against HIV at different stages of HIV lifecycle
- targets to inhibit enzyme reverse transcriptase, b/c its specific to virus & doesn't affect host cell.

Zidovudine (AZT)
- effectively delays disease progression
- used to prevent mother-to-child transmission of HIV during pregnancy

Other antiretrovirals 
- blocks HIV binding to cell membranes
- or inhibits assembly of new viral particles in cells

*****

Unpleasant to serious side effects, but successful in helping prolong length & quality of life of HIV infected.

Vaccine for HIV/AIDs failed so far, because variable virus nature & immune response acts too slowly in the case of HIV infection.

*****

D.6 Antibacterials

D.6.1 Outline the historical development of penicillins.
Discovered by Alexander Fleming, developed by Florey and Chain

Alexander Fleming (1928)
- mould contaminated some of his cultures, around it was a clear region where no bacterial colonies grew
- mould produced something that inhibited bacterial growth

Howard Florey & Ernest Chain (1940s)
- isolated penicillin as antibacterial agent
- used for the first time in WWII
- 1941: large scale production used deep fermentation tanks containing corn steep liquor & sterile air was forced in.

Dorothy Hopkins (1945)
- x-ray crystallography determine penicillin G structure


D.6.2 Explain how penicillins work and discuss the effects of modifying the side-chain.
Penicillin
- chemical used to kill pathogens (methylene blue in malaria treatment)
- 'magic bullet' - chemical designed to target a specific disease but not host cells (treated syphilis with arsenic bug)
- Prontosil: sulfonamide drug to cure septicaemia

*****Penicillin G can be broken down by stomach acid, therefore needs to be directly injected into the blood.
'R' = modified side chain - different forms of penicillin, therefore some enable drug to retain activity when ingested as a pill.*****

Bacterial resistance
- penicillin ineffective against some bacteria
- bacteria produced enzyme 'penicillinase' which can open the beta-lactam ring rendering it ineffective.

Antibiotic resistance
- bacteria genetic mutation
- no. of resistant organisms increase with increase exposure to antibiotics

Superbugs: bacteria which carry several resistant genes


D.6.3 Discuss and explain the importance of patient compliance and the effect of penicillin overprescription.
Response to antibiotic resistances:
- developing different forms of penicillin (modified side chains able to withstand penicillinase)
- controlling and restricting antibiotic use to make them prescription-only, encourage doctors not to prescribe them
- education and encouragement of patients in the importance of completing full treatment with an antibiotic - 'patient compliance', essential to prevent resistant bacteria prolonging

The use of penicillin in animal feed-stock when they are not ill also contributes to the resistance problem.

D.5 Stimulants

D.5.1 List the physiological effects of stimulants.
Stimulants:
- increase activity in the brain & mental alertness; prevents drowsiness, allowing greater concentration
- affects CNS, functions oppositely to depressants

Physiological effects:
- help facilitate breathing (relaxes air passage ways) & treats respiratory infections (e.g. severe bronchitis)
- may reduce appetite
- may cause palpitation/tremors
- in excess: extreme reslessness, sleeplessness, fits, delusions & hallucincations

D.5.2 Compare amphetamines and epinephrine (adrenaline).
Amphetamines
- stimulants that mimic adrenaline
- acts to enhance effects of adrenaline and noradrenaline
- similar structure to adrenaline and noradrenaline
- also called sympathomimetic drugs - stimulates sympathetic nervous system
- increases mental alertness & physical energy
- side effects: dilation of pupils, decrease appetite, possible blurred vision & dizziness
- regular use: rapid development of tolerance & dependence; long-term effects: severe depression & reduced infection resistance.

Adrenaline (epinephrine) enables body to cope with pain, fear, cold and shock - it is a part of the 'flight or fight' response, which stimulates pathways that increase:
- heart rate and blood pressure
- blood flow to the brain and muscles
- air flow to the lungs
- mental awareness

Noradrenaline (norepinephrine)
- a neurotransmitter
- similar structure & physiological effects to adrenaline
- responsible for communication in the sympathetic nervous system, and to stimulate pathways.

They are derivatives of the phenylethylamine structure:

Designer drugs
(e.g. speed, crystal meth, ecstasy)
- modified amphetamine structure (inclues methamphetamine)
- powerful & dangerously addictive stimulant
- long-term use: serious brain damage/ small doses for some is also fatal



D.5.3 Discuss the short- and long-term effects of nicotine consumption.
Nicotine

- found in tobacco plants; low concentration in tomato, potato, eggplant & green pepper plants
- stimulant & highly addictive
- lipid soluble, able to cross blood-brain barrier (rapid effects on brain activity) - increases levels of adrenaline & alters concentration of certain neurotransmitters in the brain.
- effects change with increased consumption
- habit forming (dependence/ addiction)
- addiction: suffers withdrawal symptoms of consumption (e.g. nausea, weight gain, drowsiness, inability to concentration, depression & craving)
- most widespread & abused stimulant; often linked to social factors e.g. peer pressure

Nicotine in tobacco - includes tar & carbon monoxide
- long term smoking: correlated with increased risk of chronic lung disease, adverse pregnancy effects, lung, mouth, throat cancer
- high costs of obtaining tobacco
- stains skin & nails
- lingering smell on clothes


D.5.4 Describe the effects of caffeine and compare its structure with that of nicotine.
Caffeine
- in coffee, tea, chocolate & colas
- acts to reduce physical fatigue & restore mental alertness (people work longer hours & cope with body clock changes)
- acts as a respiratory stimulant
- increase rate of energy release within cells
- enhances & prolongs adrenaline effects

Consumption in small amounts
- mental energy, alertness & concentration ability enhancement
- acts as a diuretic, increases urine volume; can cause dehydration.

Consumption in large amounts
- causes anxiety, irritability & insomnia
- causes dependence, withdrawal
- side-effects: headaches, nausea

**helps body absorb some analgesics

D.4 Depressants

D.4.1 Describe the effects of depressants.
- They act on the brain and spinal cord, altering concentration and activity of neurotransmitters. Therefore decreases brain activity and causes a 'depression'.
- Includes tranquilizers, sedatives, hypnotics
- Anti-depressants are used to treat clinical depression

D.4.2 Discuss the social and physiological effects of the use and abuse of ethanol.
- Ethanol is in beer, wine, hand liquor; and is a psychoactive drug
Low doses 
- mild excitement, more talkative, confident, relaxed
- beneficial to circulation and diminish cardiovascular diseases because of mild anti-clotting effect.

Use:
- antiseptic properties
- can be used in skin before injection, to clean a small wound

Abuse:
- CNS depressant, therefore change in behaviour, which becomes more adverse/negative as dosage increases
- effects multiply by duration which it occurs

D.4.3 Describe and explain the techniques used for the detection of ethanol in the breath, the blood and urine.

Detection by breath

- Ethanol establishes equilibrium between being dissolved in the blood & released into the air in exhaled breath

- equilibrium constant Kc is fixed at a particular temperature (see Ch.7) so ethanol measured in the breath can be used to assess blood alcohol concentration.

Breathalyzer test

- crystals of potassium dichromate (VI) oxidizes ethanol to ethanal & ethanoic acid. Potassium dichromate (VI) reduced to Cr 3+ ions.

- colour change seen from orange to green, is measured by a photocell and determines concentration but it is not very accurate.

A more accurate process: infrared spectroscopy in an intoximeter
- different molecules absorb different wavelengths of an infrared spectrum, because of different bonds and functional groups.
Ethanol has an absorption band at 2950cm^-1 because of its C-H bond, the O-H bond is also present in water vapour, therefore that bond is not used to detect ethanol.
The size of the peak on the graph indicates the ethanol concentration compared to the ambient air.

** people who have diabetes often have propanone vapour in their breath, therefore it can give a positive result in the infrared rest for ethanol even if they did not consume alcohol.

A fuel cell
- a version of the intoximeter where in the presence of a catalyst, ethanol is oxidised in the air into ethanoic acid then to water and carbon dioxide.
- it converts the energy released in oxidation into detectable electrical voltage that cn be used to measure ethanol very accurately.

Detection by blood and urine

Gas-liquid chromatography
- blood/urine vapourised and injected into a stream of inert gas (mobile phase) over the surface of a non-volatile liquid (stationary phase)
- vapour components move at different rates depending on boiling point and relative solubility , therefore each leaves the column after a specific time interval - its retention time
- a peak at the retention time corresponding to ethanol can be used to confirm its presence in the vapour, area under peak = measure of ethanol concentration, then it is compared to a known standard mixture of propan-1-ol, therefore an accurate assessment of ethanol levels.

*****vapourised blood/urine injected into inert gas (e.g. helium) then travels through a heated column, which the tube it's traveled through is coated with a non-volatile liquid, which effectively slows down the movement of the gas. This allows them to emerge from the column at different times. The time between injection and emersion is recorded.*****


D.4.4 Describe the synergistic effects of ethanol with other drugs.
Ethanol -OH group forms a hydrogen bond with water, so it's readily soluble in aq. solution.
Able to dissolve in lipids, therefore enables crossing cell membranes easily.
Ethanol passes from gut into blood, usually through stomach wall then circulates to all the tissue around the body - therefore short time interval between ingestion and effects.
~90% of alcohol is processed through the liver, rest is by lungs and kidneys
Ethanol also passes through the placenta to the fetus when consumed during pregnancy, also passes into breast milk and then to nursing infant.

SYNERGY

- potential to increase activity of other drugs when consumed at the same time.
**careful when taken with medication - could lead to fatal results.

Examples of synergy
- with aspirin: increased stomach lining bleeding & risk of ulcers
- with other depressants (e.g. barbiturates/ sleeping pills): heavy sedation, possibly coma
- with tobacco: increase incidence of cancers, esp. in intestines & liver
- with many other drugs: interfere with their metabolism by the liver - possibly greater & more prolonged drug effects.

D.4.5 Identify other commonly used depressants and describe their structures.
Benzodiazepines
- depresses brain emotional activity, therefore are tranquilizers for anxiety disorders & related insomnia.
- commonly used as sleeping pills & muscle relaxants
- relatively few side effects, can cause dependence, therefore mostly used in short-term treatments.
- Includes Diazepam (Valium) & Nitrazepam (Mogadon)
They are non-polar & high in lipid solubility, therefore able to cross the blood-brain barrier

Fluoxetine hydrochloride (Prozac)
- anti-depressant drug: increases levels of serotonin (a neurotransmitter)
- treats depression & eating & panic disorders
- does not depress CNS activity, therefore NOT a depressant.

D.3 Analgesics

D.3.1 Describe and explain the different ways that analgesics prevent pain.
Mild analgesics e.g. aspirin, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) like ibuprofen
- prevents stimulation of nerve endings at the site of pain
- inhibits prostaglandin release from the site of injury (gives inflammation, fever and pain relief)
- analgesics do not interfere with brain function, therefore are called non-narcotics
** Paracetamol - inhibits prostaglandin release in brain than site of injury

Strong analgesics e.g. morphine related opioids
- binds to opioid receptors in the brain. It blocks pain signals transmitting between brain cells, so it alters perception of pain.
- can cause drowsiness or possible changes in mood/behaviour
called narcotics
- most effective painkillers
** has side effects and potential problems with dependence (usage must be medically supervised)

D.3.2 Describe the use of derivatives of salicylic acid as mild analgesics, and compare the advantages and disadvantages of using aspirin and paracetamol (acetaminophen)
Salicylic acid - tastes bad, patient vomits
Aspirin - ester derivative of salicylic acid
- less irritation to stomach, more palatable - still effective as an analgesic
- treatment of headache, toothache and sore throat
- can help reduce fever (an antipyretic) and inflammation
- used to provide relief from rheumatic pain and arthritis
- blocks synthesis of prostaglandins
- reduces blood clotting possibilities (useful in treatment of patients at risk from heart attack or strokes)
**but therefore it's also unsuitable (potentially dangerous) for people whose blood does not clot easily or after a surgery where blood clotting is necessary
- reduce risk of colon cancer (but additional data is needed)
- irritation/ulceration (possible bleeding) of stomach/duodenum
if taken with alcohol, it increases the risk of the above
- asthmatic people are also allergic to aspirin
**not for children under 12 - has been linked to Reye's syndrome, a rare and fatal liver/brain disorder
- available in various coatings/ buffering components - can delay activity until it is in the small intestine to alleviate some side-effects

Paracetamol (acetaminophen)

- reduces prostaglandin production in the brain, but not the rest of the body (so not effective in reducing inflammation)

- one of the safest analgesics if taken correctly

- does not usually irritate the stomach

- allergic reactions are rare

- overdose/ chronic use can cause severe, possibly fatal kidney/liver/brain damage

- with ethanol, toxic effect may increase

Conclusion:

D.3.3 Compare the structures of morphine, codeine and diamorphine (heroin, a semi-synthetic opiate)
Strong analgesics (narcotics)
- related to opium: codeine, morphine, heroin (increasing effects)
- acts on CNS to block pain perception
- can cause:
constipation
suppression of cough reflex
constriction of eye pupil
narcotic effects

Codeine

- 0.5% in raw opium

- used in prepation with non-narcotic drugs e.g. aspirin and paracetamol in second stage of pain management step ladder (WHO analgesics ladder above)

- used in cough medications and short-term treatment of diarrhea 

Morphine

- 10% in raw opium 

- used in management of severe pain, such as in advanced cancer

- can be habit forming and can lead to dependence, therefore use must be medically and professionally regulated

Heroin

- in opium, but usually obtained by esterification of morphine, so called 'semi-synthetic' drug

- medically used only in Britain and Belgium legally for relief of severe pain

- most rapidly acting and most abused narcotic

- produces euphoric effects, but additional use has a high chance of causing addiction and increased tolerance

- dependence can lead to withdrawal symptoms/ other associated problems

D.3.4 Discuss the advantages and disadvantages of using morphine and its derivatives as strong analgesics.
Narcotic effects
Ad:
- feeling of well-being and contentment
- dulls pain and lessens fear/tension
- euphoric feeling

Disad:
- regular use: constipation, reduced libido, loss of appetite and poor nutrition
- dependence occurs relatively quickly, therefore suffers withdrawal symptoms e.g. cold sweat, anxiety when withheld
- increasing tolerance, need higher doses for desired effect
- injections, may obtain HIV/hepatitis 

Alternative: Methadone
- taken orally and has longer duration
- can reduce drug craving and prevent symptoms of withdrawal

*****

They have a common basic structure, therefore similar properties, but has some different functional groups.

For heroin:
- Morphine's -OH esterifies into ethanoate in reaction with ethanoic acid (CH3COOH)
- loss of -OH makes the drug less polar, therefore more lipid soluble and can cross blood-brain barrier quicker (hence it's a faster acting drug)
- once in the brain the heroin hydrolyzes back into morphine by reversed esterification reaction

*****

D.2 Antacids

D.2.1 State and explain how excess acidity in the stomach can be reduced by the use of different bases.

Antacids - weak bases which neutralizes strong acids
e.g. metal oxides/ hydroxides/ carbonates or hydrogen carbonates

Acid + Metal Oxide --> Salt + Water

Acid + Carbonate --> Salt + Water + Carbon dioxide

Acid indigestion - feeling of discomfort from too much acid in the stomach

Heartburn - acid from the stomach rising into the oesophagus (acid reflux)

Ulcer - damage to the lining of stomach wall, loss of tissue and inflammation

Common antacids:

Mg: faster acting, acts as a laxative

Al: dissolves slower & provide longer-lasting relief, can cause constipation, has been linked with the development of Alzheimer's (but it's not been proven)

Metal carbonates and hydrogen carbonates produce salt, water and carbon dioxide.

- can cause bloating of stomach and flatulence (wind/gas)

- anti-foaming agents (e.g. dimethicone) added to prevent it 

Some antacids contain alginates. They float to the top of the stomach and forms a foam "raft", which acts as a barrier preventing acid reflux.

***

Because antacids change pH of the stomach, they can also alter other chemical reactions including absorption of other drugs.

***

D.1 Pharmaceutical Products

D.1.1 List the effects of medicines and drugs on the functioning of the body.
- Alters the physiological state, including consciousnesses, activity level and coordination
- Alters incoming sensory sensations
- Alters mood or emotions

*****
Analgesics, stimulants, depressants, mind-altering drugs targets the nervous system and the brain, and the perception of stimuli.
Antacids target metabolic processes
Antibacterials and antivirals aim to supplement the body's ability to fight disease causing organisms
*****

D.1.2 Outline the stages involved in the research, development and testing of new pharmaceutical products.
Discovery research (3 years)

- identify lead compounds
- synthesis of analogies
- biological testing

Development research (6 years)
Phase 1: 50-100 healthy volunteers (~1 1/2 years)
Phase 2: 200-400 patients (~ 2 years)
Phase 3: 3000+ patients, half are given placebo other half is give the drug; neither doctor/patient knows which is given (~3 years)

Application for marketing - 9th year (during phase 3)
Regulatory review (2 years, after application for marketing)

Launch of product - 11th year
Post-marketing monitoring (1 year)

D.1.3 Describe the different methods of administering drugs.
Oral - taken by mouth
e.g. tablets, capsules, pills, liquids

Inhalation - vapour breathed in; smoking
e.g, medication for respiratory conditions like asthma; drugs of abuse like nicotine, cocaine

Skin patches - absorbed directly from the skin into the blood
e.g. hormone treatments like estrogen and nicotine patches

Suppositories - inserted into the rectum
e.g. treatment of digestive illnesses, hemorrhoids

Eye/ear drops - liquids delivered directly to the opening
e.g. treatments of infections of the eye or ear

Parental (by injection)
- intramuscular e.g. many vaccines
- intravenous (fastest method of injection) e.g. local anesthetics
- subcutaneous e.g. dental injections

D.1.4. Discuss the terms therapeutic window, tolerance and side-effects.
Therapeutic window - range of a drug's concentration in the blood between its therapeutic level and its toxic level

Tolerance - when repeated doses of a drug results in smaller physiological effects

Side effects - unintended physiological effects

Therapeutic effect - the intended physiological effect