Everything Flashcards
(220 cards)
1
Q
Is DDT lipid soluble?
A
Yes & able to undergo bio-concentration and bio-magnificatiion
2
Q
What can mercury treat?
A
Syphilis and gonorrhoea
3
Q
What is mercury used in?
A
Fungicides, production of plastics, paper and batteries
4
Q
What are the three forms of mercury?
A
Elemental - Hg0
Inorganic - Hg+, 2+
Organic - methyl mercury
5
Q
What forms of mercury cause neurotoxicity?
A
Elemental and Organic
6
Q
What does inorganic mercury target?
A
The Kidney
7
Q
What is elemental mercury used in?
A
Gold mining, scientific instruments and dental amalgams
8
Q
What does elemental mercury do at room temperature?
A
Vaporises - lipid soluble
9
Q
What does Hg0 penetrate?
A
The BBB and placenta (accumulates in the CNS)
10
Q
What happens when elemental mercury is oxidised?
A
Turns into Hg2+ & becomes trapped due to poor lipid solubility
11
Q
What is the main damage of elemental mercury and what symptoms does it cause?
A
To the CNS, resulting in personality changes, tremor and hallucinations
12
Q
What are the two forms of inorganic mercury?
A
Hg+ and Hg2+
13
Q
What is inorganic mercury used in?
A
Fur felting and electrochemical equipment
14
Q
What is exposure to elemental mercury via?
A
The oral route - bioavailability is poor
15
Q
What is inorganic mercury toxic too?
A
The GI tract
16
Q
What damage does inorganic mercury do to the kidneys?
A
Damage to epithelial cells of the proximal convoluted tubules - accumulates and binds to cysteine rich proteins called metallothioniens (buffer to toxicity)
17
Q
What are the two forms of organic mercury?
A
Methyl and diethyl
18
Q
What can organic mercury be used for?
A
Seed dressings and fungicides
19
Q
Why is organic mercury so dangerous?
A
It is lipophilic and extremely toxic to the CNS - able to cross the BBB (methyl does this via the L-type large amino acid transporter)
20
Q
What happens once alkyl mercury is metabolised?
A
Converted to Hg2+ and hence they accumulate
21
Q
When was the minimata bay incidence?
A
1954
22
Q
How many people died as a result of minimal bay?
A
1500
23
Q
What was the factory producing that had a devastating effect in minimata bay?
A
Vinyl chloride and ethanal
24
Q
What did the leakage into minimata bay contain?
A
Organic and inorganic mercury - converted to dimethyl and methyl mercury by micro-organisms, which is lipophilic and can enter the food chain.
25
What does methyl mercury bind to in the brain?
Subcellular organisms
26
What can inorganic mercury bind to?
Proteins that contain an -SH group
27
What does covalent binding to sulphydryl groups inhabit?
Glycolysis, mitochondrial electron transport chain, calcium homeostasis and induces neuronal excitotoxicity
28
What is clinical toxicology?
Diagnosis and treatment of poisoning
29
What types of poisoning causes the most amount of deaths?
Drugs, medicants and biological substances (1783)
30
How many deaths were there in the UK in 2005 due to accidental poisoning?
910
31
What can be done in correcting airways and breathing?
Recovery position
Oxygen mask/endotracheal tube
Deliver oxygen and raise the partial pressure of gas in the blood
32
What do tricyclic antidepressants do?
Block sodium channels in the myocardium leading to reduced myocardial contractility and dysrhythmias
33
What can be done to reverse TCA's?
Sodium bicarbonate infusion/vasopressor such as noradrenaline
34
What can an overdose with monoamine oxidase inhibitors cause?
Hypertension (increase in blood pressure) - reverse with a vasodilator such as nitroprusside
35
What can shock lead to?
Cardiovascular collapse - low cytosolic BP, tachycardia, cold pale skin, acidosis and low oxygen tension
36
What is the main path-physiological feature of shock?
Dilation of the venous bed causing poor venous return and fall in cardiac output
37
What drugs are used to treat shock?
Expansion of circulating volume = dextran
Increase cardiac output = glucagon, dopamine and dobutamine
Acidosis correction = sodium bicarbonate infusion
38
What is hypoglycaemia a common cause of?
Delirium and coma
| Corrected with dextrose
39
What are seizures controlled with?
Benzodiazepine administered with an anti-convulsant such as diazepam
40
What drugs cause hypothermia?
Opiates
41
What drugs cause hyperthermia?
Ampthetamines
42
What does dantrolene do?
Prevents muscle contraction without exertion
43
What are the ways in stopping exposure or reducing exposure to a toxicant?
```
Gastric lavage
Emesis - administration of ipecacuanha syrup
Whole bowel irrigation
Adsorption - activated charcoal
Forced diuresis
Haemodialysis
```
44
What form of a molecule is more lipophilic and therefore more easily absorbed?
Unionised
45
What are the three groups of antidotal treatments?
Pharmacological reversal
Formation of inert complexes
Regeneration/protection of target
46
What is acetylcholinesterase inhibitors reversed with?
Atropine
47
What reverses poisoning with opiates?
Naloxene
48
What reverses poisoning with benzodiazepine?
Flumenazil
49
What is Vitamin K used for?
Reversal fo warfarin poisoning
50
What treats methotrexate overdose?
Leucovorin and folate
51
What treats methylene/ethylene glycol poisoning?
Ethanol (competitive inhibitor) and fomepizole (selective inhibitor)
52
What do fomepizole and ethanol inhibit?
Alcohol dehydrogenase
53
What is the end product in ethylene glycol?
Oxalic acid - causes acidosis and kidney damage.
| Regularly combines with calcium ions in kidney tubules and cause a blockage.
54
What is dimercaptrol and DMSA used for?
Heavy metal poisoning
55
What is calcium ETA/DMSA use for?
Lead poisoning
56
What is deferoxamine used for?
Iron toxicity
57
What is penicillamine used for?
Copper poisoning
58
What is thiosulphate used for?
Cyanide poisoning
59
What is antibodies used for?
Digoxin and snake bites
60
What is pralidoxaime used for?
Poisoning with AchE - not useful for when the AchE-organophosphate complex has aged.
It replaces the phosphate group.
61
What is methylene blue used for?
Methaemoglobin (Fe3+)
62
What do nitrates do to haemoglobin?
Prevent methaemoglobin reductase converting methaemoglobin back to haemoglobin
63
Who are at most at risk from from methaemoglobin poisoning?
Neonates as they have low levels of methaemoglobin reductase
64
What is sodium nitrate used for?
Cyanide poisoning
65
How is cyanide poisoning treated?
MetHb infusion acts as a decoy target
| Sodium thiosulphate converts cyanide to SCN- and then excreted in urine
66
What is the target of cyanide?
Cytochrome c oxidase
67
What can be used to treat a paracetamol overdose?
Methionine/N-acetylcysteine
68
What is the toxic metabolite of paracetamol?
N-acetyl-p-benzoquinine - can deplete liver cells and glutathione
69
What are the symptoms of cholinergic toxidrome?
```
DUMBBELS
Diarrhea
Urination
Miosis
Brochospasm
Bronchorrhea
Emesis
Lacrimation
Salivation
```
70
What are the symptoms of anticholinergic toxidrome?
Hot as hades, red as beets, blind as a bat, dry as a bone and mad as a hatter
71
What is the sympathomimetic toxidrome symptoms?
```
Dilated pupils
Excessive sweating
Agitation
Hyperpyraxia
Tachycardia
Hypertension
```
72
What are the symptoms of opiate poisoning?
```
CNS depression
Pinpoint pupils
Coma
Bradycardia
Hypotension
Decreased GI motility
Hypothermia
Hypoglycaemia
```
73
What are the symptoms of benzodiazepine poisoning?
Non-specific
Ataxia
Drowsiness
Coma
74
What is the TTC?
In silico predictions of various toxicological end points such as mutagenicity and knowledge of the level of exposure
75
How is the TTC calculated?
NOAEL/100
76
When was REACH established?
1st June 2007
77
What are the main principles of REACH?
Improve protection of animal health and environment
Promoter non-animal testing
Provide more transparent system for risk assessment and chemical control
78
What does opium contain?
Morphine (
79
Where is opium isolated from?
Papaver somniferum
80
What is heroin?
Diacetylmorphine
81
When was morphine extracted from opium?
1830 - Wright
82
Who was the first country to inhibit opiate import?
USA
83
When was the medical use and manufacture of heroin banned?
1920
84
What are antagonists was opiate?
Naloxene & naltrexone
85
What are the three main types of opiate receptors?
Mu - analgesia, euphoria, respiratory depression, inhibition of GI smooth muscle and miosis
Kappa - analgesia, sedation, hallucinations, maybe hypothermia
Delta - inhibition of smooth GI muscle, analgesia, respiratory depression
86
What is the treatment of heroin?
Methadone and buprenorphine - safer in overdose and easier to withdraw
Natrexone - prevents the relapse
87
When were amphetamine synthesised?
1880s
88
What were amphetamines used in?
Benzedrine inhalers
89
What was used in WW2?
Amphetamines to help combat fatigue
| Used today as pep pills
90
What is used as a nasal decongesant?
Ephedrine and pseudophedrine
91
What is used to treat narcolepsy?
Dexamphetamine and modafinil
92
What is used to treat obesity?
Fen-Phen
93
What is used to treat ADHD?
Methylphenidate
94
What are clostridial neurotoxins responsible for?
Neurotoxic diseases such as botulism and tetanus
95
What type of bacteria is clostridium botulinum?
Gram-negative anaerobe
96
What types of exposure to clostridium botulism are there?
Food borne
Infant
Wound
97
What is the treatment for clostridium botulism?
Activated charcoal
Antibacterial drugs
Anti-toxin and human botulism immune globulin
98
What dose of BoNT is fatal?
0.1-1 ng/kg
99
What types of BoNT are there and what are humans resistant to?
A, B, C, D, E, F and G
| Resistant to C and D
100
What two chains are there in BoNT?
50kDa light chain - disulphide bone - 100kDa heavy chain
101
What is the light chain of BoNT useful for?
Zinc dependent peptidase
102
What does the heavy chain in BoNT do?
```
N = membrane translocation
C = nerve recognition
```
103
What are the four stages to intoxication with BoNT?
1) Binding to target tissues - attacks peripheral nervous system - binds to presynaptic terminal via polysialogangliosides
2) Internalisation - through endocytosis
3) Translocation - synaptic vesicles accumulate protons so that their lumen is acidic. BoNT undergoes a conformational change and L & H dissociate, the L chain translocates into the cytoplasm.
4) Enzyme modification of the molecular target - L chain is a protease which targets SNARE proteins leading to inhibition of neurotransmitter release
104
What are the ergot alkaloids?
Produced by fungi - grows on cereal grains, especially rye.
| Chemically related to LSD.
105
What are the symptoms of ergotism?
Nausea, vomiting, drowsiness, twitching muscles, itching and staggering
106
What can ergotamine treat?
Migraines
107
What can ergometrine treat?
Obsterics
108
What are amatoxins?
Heat stable, bicyclic octapeptides
| 0.1mg/kg
109
What is the target of amatoxins?
RNA Polymerase II
| Hepatocytes and renal tubule cells
110
What is the treatment for amatoxins?
Electrolyte and fluid imbalances corrected, gastric lavage and activated charcoal
111
What synthesises aflatoxins?
Aspergillum species
112
What type of aflatoxin are humans exposed to?
B1 - hepatotoxic and causes liver damage with haemorrhage, jaundice and death
113
What metabolises the aflatoxins?
Oxidatively biotransformed by the liver CYP450's - 8,9-epoxide forms covalent adduct with DNA (N7-guanine)
114
What are the two types of RIP?
```
I = single polypeptide chain
II = enzymatically active A chain - disulphide bond - B chain
```
115
What type of RIP is ricin?
Type II
116
What does ricin bind to on the cell surface?
Beta-1,4-galactose
117
How does ricin enter cells?
Through endocytosis
118
Where is ricin transported to in the cell?
Golgi and then the ER - Binds to a molecule with a KDEL sequence e.g. calreticulin etc.
119
How is ricin translocated from the ER to the cytosol?
Reductive cleavage - the L chain is treated as a misfolded protein
120
What does ricin act on?
The ribosome 60S (28S rRNA) - splits the glycosidic bond between adenine and ribose = de-adenylation causes the loss of binding of elongation factors and halt protein synthesis
121
What other activity does the A chain have?
DNA lyase activity and behaves as a polynucelotide
122
How can RIPs be used in cancer therapy?
B chain is swapped for a cell surface tumour specific antibody
123
What are the four types of snake?
Atractaspidae - side fangs and sarafotoxins
Colubridae - largest family & fangs at the back of the mouth
Elapidae - most poisonous snakes in the tropics, include Cobras
Viperidae - all continents except australia. Sub families include: viperinae and crotalidae
124
What attacks pre-synaptic neurones?
Beta - phospholipase A2 activity, block potassium channels
125
What attacks post-synaptic neurones?
Alpha - only elapid family snakes bind to nACH and inhibit channel opening
126
What does the black mamba contain?
Fasciculins - AchE inhibitors
127
What does crotalid venoms do?
Some have AchE and others have Beta-neurotoxins
128
What do sarafotoxins do?
Mimic the endothelium and cause vasoconstriction
129
What else does snake venom do?
Damages tissue - collagenase, hyaluronidase and metalloproteinase
130
Exposure to what can cause cancer?
Radiation
Toxins
Oncogenic viruses
Man-made
131
What are the five main groups of man made carcinogenics?
```
Alkylating agents - act directly with DNA
Polycyclic aromatic hydrocarbons
Aromatic amines
Azo dyes
Nitroso compounds
```
132
How are polycyclic aromatic hydrocarbons generated?
When organic materials are burned
133
What is the major carcinogen in coal tar?
3,4-benzypyrene (benzo(a)pyrene)
134
What do carcinogenic PAHs contain?
A penanthrene nucleus (3 fused rings) - planar molecules
135
What do PAHs not undergo?
Biomagnification
136
What is the bay region?
Free of constituents
137
What is the convex edge?
An area where groups can't be added to it
138
What is the K region?
Double bond with higher electron density
9,10 in penanthrene
4,5 in benzypyrene
139
What is more active benzo(a)pyrene or benzo(e)pyrene?
Benzo(e)pyrene
140
What are the mechanism of action of carcinogenics?
Electronic theory
K-region epoxides
Diol-epoxides
141
What is the theory behind the electronic theory?
Some double bonds have higher electron density and chemical reactivity than others present. (K region) - this exceeds the L region
142
Why does the electronic theory not add up?
It assumes that the PAH is the carcinogenic material but the metabolites have greater reactivity.
143
What basis did the K-region epoxides come from?
PAH metabolites go to a reactive intermediate capable of binding DNA
144
What are K-region epoxides metabolised by?
CYP450s
145
What diol become bound to DNA with a greater affinity than 3,4-benzpyrene?
7,8-diol
146
What CYPs form the diol?
CYP1A1, 1A2, 1B1 then mitochondrial epoxide hydrolase to trans-7,8-diol and then 7,8-diol-9,10-epoxide
147
What is the ultimate carcinogenic?
7,8-diol-9,10-epoxide
148
What does the ultimate carcinogenic bind to?
Guanine residues of DNA
149
Why does the binding of this carcinogen to DNA cause damage?
Needs replacing and this isn't always done with very high accuracy
150
What are two types of detoxificant?
Epoxide hydrolase
Glutathione-S-transferase (major)
Glucoronides and sulphates also lead to excretion
151
What do electrophilic metabolites of PAHs form covalent adducts with?
Albumin and Hg
152
How do PAHs increase their own metabolism?
Bind to AkR - translocates into the nucleus and chaperones dissociate allowing PAH to bind ARNT - this heterodimer binds to promoter sites and causes increase in the number of CYPs.
153
What do PAHs cause?
Phototoxicity
Cardiovascular disease
Reproductive health
Childhood behaviour
154
What is 80-90% of UV light dose caused by?
UVB
155
What strongly absorbs UV light?
DNA and proteins
156
What are the three types of UV light and their wavelength?
```
A = 320-400nm
B = 280-320nm
C = 200-280nm
```
157
What are the most frequent lesions in DNA?
Cyclobutane pyrimidine dimers
| Form between the 5,6 bonds of any two adjacent pyrimidines
158
What are the type of lesions that arise?
TpT, TpC, CpC, CpT
| TpT is the most common
159
What is NER specific for?
Lesions that distort the DNA helix
160
What types of methods does NER work via?
Global surveillance for helix distortion and transcription coupled repair
161
What do XP proteins do?
Recognise DNA distortions and initiate repair
Create a scaffold that enables repair
Cut out DNA base
162
What polymerases allow a new base to be put in?
Delta and E
163
What does PCNA do?
Pushes DNA polymerase along
164
What does polymerase n do?
Guesses what to put in, as it is damage from UV light it guesses at a T (TpT)
165
What did Bequeral discover in 1896?
Uranium salt emitted radiation
166
What is the law of Bergonie and Terbondeau?
Stem cells are more sensitive - Younger tissues and more sensitive - Tissue and organs with highest metabolic rate have greater sensitivity. - faster rate of division = more sensitive
167
What is radium jaw?
Caused by painting radium onto the dials of watches
168
What is radium similar to and why?
Calcium as it accumulates in bones
169
What does radium do to bones?
Contains radium-222 which has an alpha particle in it and kills osteoblasts and other cells necessary for the maintenance of bone
170
What does oxygen do to radiation?
Enhance the cell-killing effect of ionising radiation resulting in hydrolysis of water and generation of damaging free radicals
171
What is the electromagnetic spectrum divided up into?
Ionising and non-ionising (
172
What do alpha particles consist of?
2 protons and 2 neutrons
173
What do beta particles consist of?
Electrons and positrons
174
What do X-rays and gamma rays consist of?
Very high energy, no charge
175
How can DNA be damaged?
Stripped of electrons directly or by inducing ionisation of the atoms that compromise this molecule or indirectly through radiolysis of water molecules
176
What is radiation measured in?
Grays
177
What does 1Gy equal?
Release and absorption of 1 joule of energy per kg of tissue
178
What is exposure expressed in?
Sieverts
179
What does one SV equal?
Sv = Gy x (radiation weighing factor)
180
What are the radiation weighing factors?
X-rays, gamma and beta: 1 Sv=1 Gy
| Alpha = 20
181
What is LET?
Rate at which energy is released when ionising radiation passes through passes through matter
182
What type of LET do X-rays and gamma rays have?
Low
183
What do alpha rays have for thereir LET?
High LET = greater chance of interaction and mor likely to cause damage
184
What are the sources of radiation?
Anthropogenic and natural
185
What do natural ionisation sources consist of?
Cosmic rays, solar rays and terrestrial radiation in rocks and ground water
186
What is Rad-222 a decay product of?
Rad-226
187
Where is Rad-222 found?
Near granite (lots of uranium and radium)
188
How is most radon absorbed?
Inhaled
189
What does 222 release?
Alpha-particles
190
What is the half life of potassium-40?
13 billion years
191
What are the anthropogenic sources?
X-rays, exposure to radioactive waste - accidents at nuclear power stations
192
What happened in Windscale?
Fire at plutonium reactor
Iodine-131 and Polonium-210
5-60mSv
Ban on milk sales
193
What happened in Three mile island?
Meltdown of nuclear reactor core - no one is killed and little was released
Radiation released was less than background radiation so little damage
194
What happened in Chernobyl?
Reactor went out of control (explosion and fire)
Iodine-131, Strontium-90 and caesium-137
28 people died and increase thyroid cancer
195
What is a deterministic effect?
Threshold dose and severity increased with dose
196
What is stochastic effect?
No threshold dose - probability increases with doe but severity doesn't
197
What are the doses for different types of cancer?
```
100mSv = solid tumours
200mSv = leukaemias
```
198
What do high doses of radiation lead to?
Death within a few hours
199
What does of radiation causes damage to the GI tract?
10-50Gy
200
What does 2.5Gy cause?
Nausea, vomiting and diarrhoea
201
When did and why Ramazzini published?
1700 & disease of workers
202
What did Sir George Baker do?
Lead poisoning and devonshire colic
203
When were the first medical inspectors introduced?
1898
204
When did the workmens compensation act come in?
1897
205
When was the national insurance act introduced?
1911
206
What is the structure of asbestos?
Crystalline structure - silicon dioxide bonded to a metal oxide such as (MgO)
207
What are the two forms of asbestos?
Serpentine and Amphibole
208
What are the types of serpentine asbestos?
Chrysotile (white) - very flexible
209
What are the types of amphibole?
Crocodile (blue) - very flexible
| Amosile (brown) - too brittle so used in the construction industry
210
Who identified asbestos damage in the lung?
Lucy Deane
211
When was the link between pulmonary fibrous and asbestos workers?
1920
212
When were inadequate asbestos regulations?
1931
213
When was Alice: a fight for life released?
1982
214
When was the EU ban on import and use of asbestos?
April 2006
215
What type of cancer does asbestos cause?
Mesothelium
216
Why does asbestos fibres biopersist?
Slowly cleared from the lung as the fibres are poorly soluble and too long to be removed by phagocytes and the militated epithelium
217
How do chyryostile fibres split?
Longitudinally
218
What happens when asbestos fibres interact?
Triggers chronic inflammatory reaction that leads to pulmonary fibrosis - phagocytes rupture releasing fibre and destructive enzymes
219
What can asbestos fibres trigger the release of?
Reactive oxygen species - mutagenesis and carcinogenesis
220
What do asbestos fibres contain and what damage does this lead to?
Iron - catalyse hydroxyl radical formation that leads to lipid preoccupation and DNA damage
