The Medicine Semester 2 Flashcards
(266 cards)
1
Q
Define kinetics.
A
Measures the rate at which the concentration of a reactant (or product) changes.
2
Q
Give three examples of protecting drugs from alteration within community pharmacy.
A
Expiry date
Light protective packaging
Moisture excluding packaging
3
Q
What are thermodynamics?
A
The factors which contribute to allowing a reaction to occur.
4
Q
How can the rate of the following reaction be defined?
aA + bB = cC + dD
A
rate= -1/a x d[A]/dt
= -1/b x d[B]/dt
=1/c x d[C]/dt
= 1/d x d[D]/dt
5
Q
How can reaction rate be expressed?
A
Rate= k[A]^m[B]^n
6
Q
Is the rate law only predicted by the reactants and their respective stoichiometry?
A
No, as it is determined experimentally and other parameters may affect it.
7
Q
How is the rate law determined?
A
Experimentally
8
Q
In the following reaction what is the order when m equals…?
rate=k[A]^m
m=1
m=0
A
m=1, first order reaction where if [A] doubles, the rate doubles.
m=0, zero order reaction, the rate remains constant.
9
Q
Define a zero order reaction.
A
Reaction that proceeds at a constant rate that is independent of the concentration of the reactant.
10
Q
What are the standard units of the rate constant in a zero order reaction?
A
mol l-1 s-1
11
Q
In a zero order reaction, how can rate be calculated using concentration of drug?
A
x= decomposed amount
x= kt
[A] remaining
[A]t= [A]o -kt
Both give straight line graphs against time where the second gives negative rate and first gives positive rate
12
Q
Define a first order reaction.
A
The reaction proceeds at a rate that is dependent on the concentration of one reactant.
13
Q
How is the rate of a first order reaction calculated?
A
dx/dt= k(a-x) a= initial concentration of reactant x= amount decomposed at t
14
Q
What are the standard units of the rate constant in a first order reaction?
A
s-1
15
Q
How can the rate of a first order reaction be accurately determined?
A
A graph of log([A]) over time gives a straight line from which the rate can be determined.
The gradient will equal -k/2.303.
log([A]t)= log([A]o)- kt/2.303
16
Q
What is a pseudo first order reaction?
A
More than one reacting species but still follows first order kinetics. For example, if a reactant is in large excess its change in concentration is negligible.
17
Q
Define a reaction half life.
A
The time it takes for the concentration of a reactant to decrease by half of its original value.
18
Q
What is the expression for half life in a zero order reaction?
A
t(1/2)= 0.5[A]o/k
19
Q
What is the expression for half life in a first order reaction?
A
t(1/2)= 0.693/k
20
Q
What are the two main barriers drugs have to cross in the body?
A
Gastro intestinal tract
Blood-brain barrier
21
Q
Define partitioning.
A
The movement or redistribution of organic compounds from one liquid to another.
22
Q
How can biological barriers be recreated experimentally?
A
Using a system containing two immiscible liquids, one aqueous and the other organic.
23
Q
How does a liquid become saturated during partitioning?
A
If an excess of an organic compound is added to a mixture of two immiscible liquids it will partition itself between the two liquids. If not in excess it will be distributed according to a definite ratio.
24
Q
What is the partition coefficient?
A
P=Corg/Caq
Where C is the concentration of the drug
The ratio of concentration of a compound in organic phase to aqueous phase and equilibrium.
25
What is the True partition coefficient?
The partition coefficient of an unionised drug.
26
What kind of drug is it if Ptrue> 1?
A hydrophobic compound because Corg>Caq.
27
What does the log of a partition coefficient show about a drug?
If LogP=1, P=10. Therefore Corg:Caq=10:1 so solubility of the compound in organic phase is ten times higher, making it hydrophobic.
28
What can be determined from the partition coefficient?
Absorption, distribution, elimination.
29
What is chemical polarity?
Describes how equally bonding electrons are shared between atoms and affects other physical properties.
30
What do the Hansch-Fujita parameters show?
They describe the contribution of various functional groups to the lipophilicity of a compound.
31
What are the Hansch-Fujita parameters (+pi)?
Aromatic hydrocarbons
Aliphatic hydrocarbons
Halogens
A predominance of (+pi) groups will lead to an increase in the partition coefficient.
32
What are the Hansch-Fujita parameters (-pi)?
```
Hydroxyl group
Carboxyl group
Amines
Ether
Amide
A predominance of (-pi) groups will lead to a decrease in the partition coefficient.
```
33
For partitioning to work what form should a drug be in?
It's unionised form to allow passive diffusion across a membrane.
34
What is the apparent partition coefficient?
The distribution coefficient, takes into account the pH at which it is measured.
35
How is the apparent partition coefficient calculated?
Papp= Ptrue x f(unionised)
| where f is the fraction of the drug that is unionised.
36
When are the apparent and true partition coefficient equal?
When a drug is totally unionised.
37
When can partitioning rules be applied to reabsorption in the kidneys?
If the reabsorption of the drugs occurs via passive diffusion of an unionised drug form.
38
What is forced base diuresis?
If overdose occurs and the drug is a weak acid, reabsorption can be minimised by basifying the urine, by administering sodium bicarbonate.
39
What is mass transfer?
The net movement of mass from one location to another, e.g. absorption, precipitation, dissolution.
40
What is the driving force of mass transfer?
The difference of chemical potential (change of Gibbs free energy with number of particles), down a concentration gradient.
41
Give an example of gaseous mass transfer in pharmacy.
Gas may permeate through plastic packaging and degrade formulation.
42
Give an example of mass transfer in tablet formulations.
Tablet may disintegrate causing solid dissolution to take place.
43
Describe mass transfer in terms of diffusion.
Diffusion explains mass transfer in the absence of addition forces such as flow or electric field.
44
What is the diffusion coefficient?
A characteristic of a molecule in its environment.
45
What does diffusion represent?
How rapidly molecules cover an area.
46
What is the unit of the diffusion coefficient?
area/time
47
What is permeability?
The product of the diffusion coefficient and partition coefficient of a molecule.
48
What mostly effects rate and extend of absorption?
Effective drug concentration which depends on adsorption, stability, micellar solubilisation.
49
What is drug absorption influenced by?
pKa, lipid solubility, molecular weight, number of hydrogen bonds.
50
Where does the rate of absorption of weak acids tend to be highest and why?
In the small intestine as it has a significantly larger surface area and its residence time is much longer than in the stomach.
51
What is the Stokes-Einstein relation?
Used to measure size of drug molecules and novel therapeutics.
52
What is the importance of drug stability?
Effective treatment and reduced toxicity
| Financial loss if stock expires quickly
53
What are the two reactions to consider when thinking about stability?
Free radical oxidation
| Hydrolysis
54
How is the stability of ester-containing drugs affected?
| Give examples of drugs.
Slow hydrolysis under neutral conditions
| E.g. Aspirin, procaine, warfarin (cyclic ester)
55
What are cyclic esters known as?
Lactones
56
How should ester-containing drugs be stored?
Airtight container to prevent access of moisture.
57
Why are amides and carbamates less prone to hydrolysis?
Due to resonance with the C=O bond, exception in penicillins due to steric strain within the ring.
58
How is the risk of hydrolysis reduced with penicillins?
Pharmacist adds water at dispensing.
| Stored in the fridge once made up.
59
Which drug types are more likely to undergo free radical oxidation?
Phenolic drugs e.g. paracetamol, morphine
Aromatic amines e.g. procaine
Unsaturated aliphatic compounds e.g. oils, fats, vitamin A
60
When is free radical oxidation most likely to occur?
Higher pH makes process more rapid.
61
How do free radicals form?
Exposure to light can promote electrons to an excited state.
Transition metals can accept an electron and initiate radical formation.
Oxygen forms peroxide radicals in presence of light.
62
How can free radical formation be prevented?
Stored in containers that exclude oxygen or contain another gas instead such as nitrogen.
Addition of metal chelating agent such as EDTA.
Storage in foil packaging or brown bottles.
Addition of anti-oxidants such as ascorbic acid.
63
How do you determine the rate of a reaction?
Modify data so they can be tested in all integrated laws, plot graphs for zero and first order and decide which graph follows the best model.
64
Define shelf life.
The time it takes for 90% of the initial amount of drug to remain. The time during which the product retains the same properties and characteristics it possessed when manufactured.
65
What is stability testing used for?
Provide evidence as to how the quality of the drug product varies over time.
Establish the shelf life.
Determine recommended storage conditions and container closure system suitability.
66
Why is stability testing necessary?
Legally required
Chemical degradation leads to degradation of drug concentration.
A toxic product may be formed.
Assurance to the patient..
67
What stability tests are solid form drugs submitted to?
Heat, moisture uptake and physical stress.
68
What stability tests are aqueous form drugs submitted to?
pH, light, oxidation.
69
What is the most common way to achieve accelerated stability testing?
Increasing the temperature thus increasing the likelihood of collisions.
Decomposition is increased between 2 and 5 fold for every 10°C.
70
What is the Arrhenius equation?
It is used to show the effect of temperature on the reaction in stability testing.
k= A x e^(-Ea/RT)
logk=logA - Ea/(2.303RT)
71
How do you work out the shelf life from an accelerated stability testing?
Determine the rate constants of the decomposition reaction at temperatures between 30 and 60°C. Extrapolate the Ea of the system and the rate constant of the decomposition reaction at room temperature (20°C).
72
What equation can be used to determine the shelf life of a drug that follows a first order reaction?
t(90)= 2.303log(0.9)/k
where k is at T=20°C
73
What is interphase?
The boundary between two phases (i.e. solid and liquid)
74
What happens to surface tension at the interface?
Intermolecular forces between gas and liquid are weaker than in the liquid itself.
75
What is adsorption?
Describes the accumulation of molecules at the interface.
76
What is absorption?
Implies the penetration of one compound throughout the body of another.
77
What is physical adsorption?
The adsorbate is bound to the surface through weak Van der Waals forces
78
What is chemical adsorption?
Involves stronger valence forces. It is more specific and usually involves an ion-exchange process.
79
Give an example of adsorption?
The adsorption of toxins in the stomach by attapulgite and kaolin
80
What is the interface?
The boundaries of a continuous phase.
81
What is the Gibbs adsorption equation?
Relates the surface excess concentration to the change of surface tension with the initial concentration.
82
Define surface tension.
The property of the surface of a liquid that allows it to resist an external force.
83
How does surface tension work?
The surface area of the interface increases to allow forces on either side to be equal, reaching equilibrium.
84
How does temperature influence surface tension?
Liquids see decrease of surface tension with increasing temperature because cohesion between molecules decreases.
85
What does surface tension depend on?
The chemical nature of the film- change in area and length.
86
When does spreading occur?
In liquid-liquid systems where both are immiscible, such as in emulsions.
87
Why does spreading occur?
Low surface tension between the two liquids.
88
What is the spreading coefficient?
Determines whether spreading will occur. It is the difference between the works of cohesion and adhesion.
S= Cohesion- Adhesion
89
What is cohesion?
The work necessary to pull apart a column of liquid.
90
What is adhesion?
The work needed to separate immiscible liquid to form two liquid/gas interfaces.
91
What is the contact angle?
The angle between the surface tension between the solid and liquid and the liquid and gas.
92
What does the contact angle show?
If the contact angle is less than 90° then spreading has occurred.
93
What is adhesion tension used for?
To measure how well a liquid penetrates capillaries/pores of a tablet.
94
What is wetting?
The ability of a liquid to maintain contact with a solid surface.
95
What is immersion wetting?
A solid immersed in a liquid.
96
What are wetting agents?
Used for hydrophobic drugs to lower the surface tension between the solid drug and vehicle.
97
What are polymers used for in tablets?
Used as binding agents to increase tables compaction- contribute to wetting.
98
What occurs when polymers with high molecular weight are used?
A high interfacial tension will result in tick and hard polymer layers resulting in poor moisture penetrability.
99
How does tablet coating effect the appearance and surface tension?
Often gives high surface tension resulting in hindered wetting process.
A low surface tension results in 'orange peel surface'.
100
How does surface tension effect rate and extent of drug absorption?
Surface tension measurements of solids help to improve distribution, dissolution and release patterns.
Surfactants are important in favouring spreading and influencing dissolution rate of poorly soluble molecules.
101
What is the key feature of micro emulsions?
They have little or no surface tension.
102
How can surface tension be reduced?
Use of surfactants as they have hydrophobic and hydrophilic regions.
103
What happens when surfactants are added?
Accumulation of surfactants occurs at the interface and surface tension reduces.
104
What is the cmc?
Critical micelle concentration- concentration at which micelle begin to form and surface tension is no longer altered.
105
What is a micelle?
A group of surfactant molecules dispersed in the liquid phase.
106
What is the Langmuir model?
Adsorption of molecules at a relatively low concentration of solute and the adsorbate forms a monolayer.
107
What is the Freundlich model?
Adsorption of molecules at high concentration of solute and the adsorbate forms multilayers.
108
What is Lundeliu's rule?
Adsorption is inversely proportional to the solubility.
109
What factors affect adsorption in solid-liquid systems?
pH- affects solubility
Temperature- exothermic process therefore increase in temperature limits adsorption
Surface area- larger surface area results in larger extent of adsorption
110
What is an amphipathic molecules?
Exhibit double affinity- hydrophobic and hydrophillic
111
What features do hydrophobic regions usually have?
Carbon chains
| Aromatic rings
112
What features do hydrophillic regions usually have?
Anionic/cationic
| Zwitterionic
113
What is a surfactant?
Surface active agents are amphipathic molecules used to reduce surface tension.
114
What are the main uses of surfactants?
Formulation agents- for wetting, emulsifying, dispersing
| Structure forming- membrane, micelles, microemulsions
115
What are the four categories of surfactant?
Anionic, non ionic, cationic and zwitterionic
116
Common uses for anionic surfactants?
Usually combined with alkaline metal
| Used in detergents, soaps, foaming agents, dispersants, antimicrobials
117
What are the features of non ionic surfactants?
Do not ionize in solution as hydrophilic region is non dissociable at physiological pH and often polymer based.
118
Common uses for cationic surfactants?
Mostly combined with halogen type anions, often nitrogen compounds.
Used as bactericides or mouthwashes.
119
What is the most common use for surfactants?
Reduction of surface tension.
120
What are the two types of micelles?
Micelles- hydrophilic head in contact with polar solvent and hydrophobic tail inside.
Inverted micelles- hydrophobic tail in contact with organic solvent and hydrophilic head inside.
121
What is drug solubilisation?
Water insoluble substances can be brought into solution by incorporation into micelles.
122
What are liposomes used for?
Controlled release drug delivery systems
123
What is a polymer?
Member of the macromolecules family and made up of repetitive units called monomers.
124
What are homopolymers?
Polymers made up of one monomer
125
What are block copolymers?
Polymers made up of two monomers that are joined as individual chains.
126
What are alternate copolymers?
Polymers made up of alternating monomers.
127
What are grafted copolymers?
A polymer of one monomer with chains of a different monomer attached.
128
What is polydispersity?
Range of the chain length i.e. average chain length of 2000 with a range of 1500-2500.
129
What is an isotactic polymer?
All side chains point in the same direction.
130
What is a syndiotactic polymer?
Side chains point in alternating directions.
131
What is an atactic polymer?
Side chains point in random directions.
132
What is a polyelectrolyte?
A polymer made up of charged monomers.
133
What occurs with water soluble polymers?
The viscosity increases, polymers can swell or change conformation.
134
What can insoluble polymers be used for?
Create films, coating materials etc.
135
If polyacrylic acid materials are placed in contact with a basic pH, what happens to the chains?
The chains will swell and extend because the groups will become ionised, causing the monomers to repel each other and also bind to water.
136
What excipients in tablets are often polymers?
Diluents
Thickeners
Adhesive agents
Disintegrating agents
137
What excipients in semi solid preparations are often polymers?
Thickeners
Suspending agents
Flow property enhancers
138
How can polymers contribute to controlled drug release?
Using gels
Bioadhesives
Prolong duration of permeation activity
Implants
139
What is carboxypolymethylene?
Carbomer- suspending/binding agent and in formulation of prolonged action tablets.
140
What is methylcellulose used for?
Low viscosity grades used as emulsifiers for liquid paraffin.
High viscosity used for jellies or thickeners for suspensions.
141
Give two examples of natural gums?
Gum arabic- polyelectrolyte used as an emulsifier and for its adhesive properties.
Gum tragacanth- highly viscous and mostly used as a thickener, emulsifier or suspending agent.
142
What is polyvinylpyrrolidone used for?
Suspending and dispersing agents as well as tablet vending and granulating agent.
143
What is PEG?
Polyethylene glycol is hygroscopic and used as a solvent for drugs.
144
What are water insoluble polymers used for?
Fabrication of membranes, containers and tubings.
145
What properties must be considered for water insoluble polymers?
Crystallinity
Permeability to drugs and gases
Affinity of drugs for plastics
Ion exchange properties
146
What are gels?
Made of cross linked networks and do not flow when in the steady state. They are made of a liquid phase contained between polymeric chains.
147
What are hydrogels?
Hydrophillic gels.
148
How are gels prepared?
Dispersion of polymers in a solvent where they will form a network.
149
What are Type 1 gels?
Irreversible systems of covalent bonds, chains are cross linked.
150
What are Type 2 gels?
Held together by intermolecular bonds, they are reversible and often heat reversible.
151
How much of a gel is made up of its liquid phase?
90%
152
What is the third type of gel?
Gels induced with cations e.g. Ca2+ binding to negatively charged polymers.
153
What are heterogels?
Gels prepared using polymers with different properties.
154
What is syneresis?
Used in drug delivery and laxatives, swelling of gels linked to cross linking and solvent affinity to backbone.
155
What is the most common type of gel?
Type 2- reversible gels
156
What factors affect type 2 gels?
```
Hydrophillic polymer concentration
Molecular weight
Nature of solvent
pH of solvent
Ion concentration of solvent
Temperature
```
157
What are colloidal dispersions?
Heterogeneous systems made up of a dispersed phase and a dispersion medium
158
What size are colloidal dispersions?
Less than 1mm- hardly visible
159
What shapes do colloids present in?
```
Spherical
Ellipsoid (proteins)
Discs
Rods (large micelles)
Coils (DNA)
```
160
Are colloids stable?
They are inherently unstable
161
What affects the stability of colloids?
Repulsion between short ranged particles
Attraction- van der waals
Steric forces
Solvation forces
162
What is the DLVO theory?
Considers forces of attraction and repulsion to predict stability of colloids
163
What relationship do attractive forces and distance between colloids have?
The energy of attraction is inversely proportional to the distance between colloids.
164
What relationship do repulsion forces and distance between colloids have?
The repulsive force decays as an exponential force with distance.
165
What is an emulsion?
A fluid obtained through interspersion of two or more immiscible liquids
166
What are the different types of emulsion?
Oil in water
Water in oil
Multiple emulsions
Microemulsions
167
What are the main characteristics of emulsions?
Inherently unstable
Droplets are between 0.1-100um in diameter
Appearance is affected by droplet size
168
What defines a coarse emulsion?
Droplet size 10-100um
| White/milky appearance
169
What defines a fine emulsion?
Droplet size 0.1-5um
| Cloudy appearance
170
What defines a micro emulsion?
Droplet size 0.01-0.1um
| Transparent
171
What methods can be used to determine the type of emulsion?
Phase dilution
Dye solubilisation
Conductivity
Filter paper wetting
172
What is a phase dilution?
Adding drops of emulsion to water results in either dilution of o/w emulsion as droplets disperse in water
Or a continuous oily phase that doesn't disperse for w/o emulsion
173
What is dye solubilisation?
The use of an oil soluble dye will lead to coloured droplets for an o/w emulsion or clear droplets for a w/o emulsion.
174
What is conductivity of emulsions?
Water has a higher conductivity than oil therefore conductivity of o/w is higher than w/o emulsions.
175
What is filter paper wetting?
O/w emulsions spread rapidly whereby w/o spread slowly.
176
What is the fraction of internal phase?
The volume of the internal phase divided by the total volume of the emulsion and expressed as a percentage.
177
What is coalescence?
Process by which two smaller droplets come together to form a larger droplet, eventually resulting in phase separation if left.
178
How can stability of emulsions be increased?
Addition of a surfactant to reduce surface tension
| Reduction of surface area
179
How are coalescence and surface tension related?
If a droplet comes into contact with another droplet, coalescence occurs.
This results in a larger droplet forming and therefore a reduction in surface tension.
180
What is the critical value of the fraction of internal phase in o/w emulsions?
74%
| In practice- 50%
181
What is the critical value of the fraction of internal phase in w/o emulsions?
40%
182
What does the critical value of the fraction of internal phase show?
The lower the volume of the internal phase, the lower the probability of coalescence.
183
What affect do surfactants have on emulsion stabilisation?
Charged surfactants lead to charged stable droplets.
Non-ionic surfactants stabilise by the formation of a hydrophilic layer around oil droplets.
Overall a hydrophobic droplet is converted into a hydrophilic droplet.
184
What is the Hydrophile Lipophile Balance?
The volume ratio between hydrophilic and lipophilic part of the surfactant.
185
What is the HLB used for?
To find the most effective emulsifier for a given oil.
186
What is the general rule for the HLB?
The higher to hydrophilicity of a surfactant, the higher its HLB value.
187
Give examples of other emulsion stabilisers.
Macromolecules- adsorb at the surface and prevent coalescence by steric hindrance e.g. gums, proteins and synthetic polymers
Solid particles- at the interface may be preferentially wetted by either oil or water e.g. carbon particles (w/o), magnesium hydroxide (o/w)
188
What is tagrisso?
A potent selective EGFR tyrosine kinase inhibitor
189
What does tagrisso inhibit?
It has irreversible activity against growth factor receptor mutation and T790M resistant mutations.
190
What is tagrisso used in?
Patients with the EGFR T790M mutation in metastatic non-small lung cell carcinoma.
191
What are the top elements found in the human body by weight?
```
Oxygen (65%)
Carbon (18%)
Hydrogen (10%)
Nitrogen (3%)
Calcium (1.5%)
Phosphorus (1%)
```
192
How much sodium should be in the body?
Serum levels are around 140mM- there are 4 moles of sodium ions in the body
193
How does high salt intake affect the body?
Leads to high blood pressure
194
What are the recommended and actual daily intakes of sodium?
Recommended 1.6g of sodium or 4g of sodium chloride
| Average is actually around 9g of sodium chloride
195
How much potassium should be in the body?
Serum levels of 4-5 mM but intracellular levels of 150mM
196
What is the recommended daily intake for potassium?
4-5g of potassium chloride
197
What does potassium deficiency lead to?
Muscle weakness
198
What is lithium carbonate used for?
Treating bipolar disorder and depression- mode of action remains unclear but likely to be related to membrane transport of metal ions
199
What is calcium used for in the body?
Strength in bones and teeth, blood clotting, transmission of nerve signals and muscle contraction.
200
What are calcium channel blockers used for?
Hypertension
| Angina
201
What is the recommended daily intake of calcium ions?
Around 700mg, value is higher for children and pregnant women
202
How can tetracyclines and quinolones affect calcium intake?
Can chelate calcium so should be taken well-separated from food. Can affect bone and tooth development in children and foetuses.
203
How is magnesium used in the body?
Required for the activity of most of the kinases in the body
204
How much magnesium is there in the body?
Around 25g, half in the bones and half in cells
205
Why is magnesium used as a laxative?
Magnesium sulphate is used because the magnesium is slowly absorbed from the gut.
206
What is a common treatment for indigestion?
Magnesium carbonate
207
What is barium used for in medical terms?
It is opaque to x-rays so barium sulphate is used to provide contrast in x-rays of the gut.
208
What is strontium used for?
In toothpastes for sensitive teeth.
209
What transition metal is present in vitamin B12?
Cobalt
210
What gives blood its bright red colour?
Complex of Iron 2+ ions with a porphyrin ring.
211
How much iron should be present in the blood?
In adult males 13-18g/dL
| In adult females 11/5-16.5g/dL
212
How much iron does the body contain?
Around 4g
213
What is prescribed to treat iron-deficient anaemia?
Ferrous Sulphate
| Ferrous Gluconate
214
What is the typical action of cytochrome P450 enzymes?
They generally oxidise compounds to make them more soluble and easily excreted
215
Where is Haem found other than the blood?
In cytochromes in the electron transport chain as well as cytochrome P450 enzymes
216
How much zinc is present in the body?
Around 2g of Zn2+ ions
217
Where in the body is zinc found?
In the active site of many enzymes
218
What are ACE inhibitors used for?
Treatment of hypertension by inhibiting the angiotensin converting enzyme
219
Give three examples of precious metals used in medicines?
Silver salts have been used to treat warts
Sodium aurothiomalate can be used to treat rheumatoid arthritis
Cisplatin and related compounds used in cancer treatment
220
Where is phosphorous found in the body?
Present in nucleic acids and is available as a radioisotope, both isotopes are relatively safe beta-emitters
221
Where is sulphur found in the body?
In cysteine and methionine residues in proteins, the S(35) isotope is a beta-emitter but at a slightly different energy to phosphorus(32)
222
What is the normal valence state of phosphorus in living systems?
P(V)
223
Are phosphates able to get through cell membranes?
Very hydrophilic so transport through membranes is difficult
224
What is INX-189?
An experimental phosphate drug used to treat hepatitis
225
What are thiols?
Compounds where sulphur exists in its -2 oxidation state as RSH, often foul smelled e.g. captopril
226
What oxidation state is sulphur in when forming disulphide bridges?
0
227
What are sulphonamides?
Drugs where sulphur is in its +4 oxidation state, used as antibacterials.
228
What are pharmaceutical suspensions?
Made of solid particles with low solubility dispersed in another phase.
229
How big are the dispersed particles in suspensions?
0.5mm-100mm
| Although coarse, treated as colloidal systems
230
How much drug is used in a suspension?
High concentrations- more than 2% w/v
231
What are the desirable qualities of pharmaceutical suspensions?
Should sediment slowly
No caking or clumping
Should be pourable
232
What is caking of suspensions?
Particles sediment over time and those at the bottom are gradually compressed by the weight of those above.
233
What is Stokes law?
Controls the rate of sedimentation of suspensions relating to the densities of components, the square of the particles diameter and the gravity and viscosity of the solution.
234
What is flocculation?
Spontaneous formation of a cluster of particles held together in a loose open structure
235
What is deflocculation?
Particles do not form loose open aggregates in normal suspensions, particles sediment independently due to potential of repulsion being high.
236
How can controlled flocculation be achieved?
Using electrolytes or polymers to form loose open aggregates that can be re-dispersed.
237
What polymers can be used to control flocculation?
Stach alginates, cellulose derivatives, tragacanth, carbomers, silicate.
238
How can polymers be used to control flocculation?
Linear-branched chains form a gel-like network within the system and become adsorbed on the dispersed particles forming protective colloids.
239
What is the Schultz-Hardy rule?
Ions are arranged in order of their capacity to aggregate hydrophobic colloids
240
What must be considered in pharmaceutical formulations?
Particle size
| Wetting properties of the therapeutic agent
241
What is the Bophal gas leak?
15 tons of methyl isocyanate was released from a pesticide factory in India, instantly killing 4000 residents and ultimately killing around 15000 people due to long term health problems such as oedema.
242
What are the 12 principals of green chemistry?
```
Prevent waste
Maximise atom economy
Design less hazardous chemical synthesis
Design safer chemicals and products
Use safer solvents/reaction conditions
Increase energy efficiency
Use renewable feedstocks
Avoid chemical derivativisation
Use catalysts
Design for degradation
Analyse in real time to prevent pollution
Minimise the potential for accidents
```
243
Why is preventing waste a principle for green chemistry?
Better to prevent that treat waste once formed. Hazards associated with storage, transportation and treatment are minimised.
244
What is love canal?
In Niagara Falls, a plastics company used an old canal bed as a chemical dump, the land was then used for a new school, them chemicals leaked through a clay cap that sealed the dump, it was contaminated and lead to high incidences of birth defects and seizure inducing nervous disease among children in the area.
245
What happened in Cuyahoga River?
Gasoline, oil, paint and metals were dumped in the lake, this caused fires to erupt on the lake.
246
Why is maximising atom economy a principle for green chemistry?
Evaluates the efficiency of chemical transformation, incorporating most of the starting materials into the product minimises waste
247
Why is designing less hazardous chemical synthesis a principle for green chemistry?
Choosing reagents that pose the least risk reduces chance of toxicity to human health and the environment..
248
Why is designing safer chemicals and products a principle for green chemistry?
Chemical products should be designed to affect their desired function whilst minimising their toxicity.
249
Why is using safer solvents/reaction conditions a principle for green chemistry?
Use of solvent and separation agents leads to considerable waste. Purification steps also generate large quantities of waste.
250
How should solvents for industry be chosen?
Chemical efficiency
Avoid low boiling point, risk of peroxides
Acute and long term health
Biodegradability, ecotoxicity, solubility in water
Quality
Cost and recyclability
251
Give examples of recommended solvents for industry?
```
Alcohols- methanol, ethanol, propanol
Ketones- propane, butanone
Esters- ethyl/propyl/butyl acetate
Methoxybenzene
Acetonitrile
Water!
```
252
Give examples of banned solvents for industry?
Ethers- fire hazard
Hydrocarbons
Halogenated solvents
Nitromethane- high energy of decomposition
253
Why is increasing energy efficiency a principle for green chemistry?
Synthetic and purification methods should be designed for ambient temperature and costs. Requirements should be recognised for their environmental and economic impacts.
254
What chemical processes involve energy?
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Heating
Cooling
Stirring
Distillation
Filtering
Equipment
Photochemistry
Microwave chemistry
```
255
Why is using renewable feedstocks a principle for green chemistry?
Use of raw materials and feedstocks that are renewable would help with depletion of fossil fuels
256
Why is avoiding chemical derivatisation a principle for green chemistry?
Adding or removal of protection groups should be minimised or avoided, require additional reagents and generate waste.
257
Why is using catalysts a principle for green chemistry?
Catalytic reagents are superior to stoichiometric reagents. Can enhance selectivity, reduce required temperature, reduce reagent based waste.
258
Why is designing for degradation a principle for green chemistry?
Prevents persistence in the environment and reduces hazards.
259
Give some examples of environmental damage due to chemicals?
Sulfonated detergents lead to foam in sewage plants, rivers and streams due to long alkyl chain.
Chlorofluorocarbons do not break down, contribute to destruction of ozone layer.
DDT bioaccumulates and caused thinning of eggshells.
260
What strategies can be used to alter lead compounds?
```
Vary alkyl substituents
Extra functional groups
Isosteres
Simplification
Rigidification
```
261
How does varying alkyl substituents improve lead compounds?
Lipophilic alkyl group may interact with lipophilic pockets in binding site, making them more specific.
262
How does adding functional groups improve lead compounds?
Using all available binding sites for maximum activity.
263
What are isosteres?
Lead to more controlled changes in steric properties of lead compounds, can be used to identify which atoms are responsible for activity.
264
How does simplification improve lead compounds?
Makes synthesis of analogues easier, quicker and cheaper. May fit the binding site easier and increase activity.
265
What are the disadvantages of simplifying lead compounds?
Oversimplification may result in decreased activity and specificity, more conformations may lead to interaction with wrong binding site or side effects.
266
How does rigidification improve lead compounds?
Simple, flexible molecules with multiple conformations can be limited to give more chance of desired active conformation being present.
