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Drug Discovery And Disease Flashcards

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1
Q

What is diabetes

A

Increase blood glucose
Lack of insulin

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2
Q

What does insulin do

A

Allows muscle and fat tissue to take up glucose and use it to produce energy and store carbohydrate, protein and fat
Type 1 and type 2 diabetes, glucose uptake by these tissues is impared and so blood glucose levels rise

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3
Q

Fred Banting

A

1920
Doctor practising medicine
Understood pancreatic ducts of dogs isolate glucose in urine helped them survive
Pancreatomy, dog died from infection
Inject depancreatised diabetic dog induced drop in blood sugar

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4
Q

James B collip

A

Highly skilled in extracts, far superior to those of banting and best

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5
Q

Who started making insulin in 1922

A

Eli lilly and co

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6
Q

Charles best

A

1900-1978
Falsification about discovery
Two geniuses with no support did it all on their own

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7
Q

Future of diabetes

A

Insulin destroyed by gut so has to be injected
Injales was withdrawn because of side effects
Stem cell technology offers hope for future in repairing pancreas

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8
Q

What is pharmaclogy definition

A

Studying the effects of drugs on the function of living systems

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9
Q

Chemistry need to know for pharmacology

A

Drug and its target
Drug activity directly related to its structure

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10
Q

Pathology in pharmacology

A

Need to know how disease/ damage affects organism
Understanding of disease process/cause/progression useful for designing intervention therapy

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11
Q

Physiology in pharmacology

A

How biological organism works
Need to know what normal biological function/ activity of the organism is

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12
Q

What is Ebers Papyrus

A

Oldest egyptian text

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13
Q

What treatments were mentioned in ebers papyrus

A

Asthma - herbs heated on slate so they could inhale
Constipation - prune based mixture
Cancer - nothing
Death - hald onion and froth beer
Guinea worm - wrapping end of worm around stick and removing

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14
Q

Who is pedanius dioscorides

A

Greek physician
Surgeon in army
Wrote de materia medica - identifying and naming platns used in medicine
Info from many cultures

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15
Q

Rudolf buccheim

A

1st professer of pharmacology
Emphasised importance of drug mode of action
Develop understandings of drugs, doses etc
Developed experimental pharmacology

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16
Q

Oswald schmiedeberg

A

Buccheims student
Published outline of pharmacology
Defined pharmacologist

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17
Q

Why were opium based analgesics developed

A

Pain
Oldest human ailment
Broad class of unpleasant sensations

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18
Q

Early pain relifs ancient rome

A

Spells and incantations
Diet
Excercise
Consumptions of potions
Removal of painful limb, tissue, organ
Bleeding of painful region
Purging body (laxatives)
Burning/ scalding

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19
Q

4 fluid components humoral balance

A

Blood
Phlegm (water)
Yellow bile (liver)
Black bile (gall bladder)

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20
Q

Hippocrates 460BC

A

Used opium to treat headaches, coughs, asthma, melancholy

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21
Q

How was morphine used when frist discovered in war

A

Alendar wood invented hypodermic needle
Before morphine taken orally - less addictive
Addiction emerged
Used on wounded soldiers
Opiod addicted soldiers

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22
Q

2 primary morphine uses

A

Morphine effective pain killer
Intravenous administration (injecting) is easy and effects are almost instantaneous

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23
Q

Heroin structural name

A

Diacetylmorphine

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24
Q

Why was heroin first used

A

Non addictive substrate for morphine
Ended up being more addictive

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25
Drugs targets
Morphine heroin codeine have similar structure and effects - liely act on same target Targets = receptors, enzymes, carrier molecules, ion channels
26
What does drug binding result in
Stimulate or inhibit target resulting in a biological response in the cell
27
What did they not know by the end of the 1800s chemistry and physiology
Chemistry = control effects Physiology = morphine effects, how pain is communicated, mode of action of opiods
28
Describe descartes pain pathway
1) Particles of heat activate spot on skin surface 2) ACtivation of B pulls thread connected to valve in brain 3) Allows animal spirits stores in cavity of brain to flow out 4) Withdrawal of lef grom heat
29
Modern pain pathway
Pain receptor connected to sensory nerve Enters spinal cord and connects to another nerve fibre Nerve fibre ascends into brain (thalamus) Thalamus relays pain message to different parts of brain Pain is sensed and individual responds
30
Who discovered opioid receptor
1972 Solomon snyder
31
How do opiioids regulate the pain pathway
Receptors present in the brain and spinal cord Bind to morphine receptor Inhibits nerve fibre preventing firing
32
Opioids and pain pathway
Binding of opioid receptors inhibits pain fibres in brain and spinal cord Opioid receptors on thalamus blocked by morphine
33
Chemistry pathology and physiology pain and treatment things known
Chemistry - works via opioid receotor Pathology - pain results from range of diseases and injuries, opioids highly addictive Physiology - opioid drugs work via opioid receptor, opioid receptors inhibits firing of pain fibres in pain pathway, reduce perception of pain
34
Rubbing an injury to easy pain
Rubbing activates sensory receptor connected to a fibre that enters the spinal cord Fibre inhibits pain signal in spinal cord -> less pain signals make it to the brain so we suffer less
35
Who was hans kosterlitz
German 1st professor of pharmacology at aberdeen
36
What did kosterlitz and hughes do
Intrigued by reports of wounded soldiers not feeling pain during battle Investigated whether brains can produce their own natural analgesics Began to investigate this phenomenon in animals
37
What did kosterlitz and hughes discover
Pathway of nerve fibres originating in brain that could not inhibit pain pathway in spinal cord Descending pain-inhibitory pathway Nerve fibres release own home amde opioids called enkephalins/endophins
38
WHat did kosterlitz and hughes do to the 2 enkephalins structures
Purify it
39
How do endogenous opioids fit in the pain pathway
Inhibits pain transmission in spinal cord Releases enkephalin Binds opioid receptors Inhibits pain fibre firing
40
How do endogenous opioids stimulate the pain pathway
Stimulated by stress, emotions, opioid drugs = controls pain and suffering, allows us to escape stress
41
Name 4 other methods of analgesia
Local anaesthetics + anti inflammatory drugs TENS General anaesthetic Acupuncture
42
How do the other methods of analgesia affect the pain pathway
Local anaesthetics +anti inflammatory drugs = prevent pain receptors being activates TENS = electrical impulses applied across the skin of the lower back, activates inhibitory sensory fibres General anaesthetic = induces loss of consciousness, no perception of pain Acupuncture = releases enkephalins
43
Cannabis original use
Hemp Strong fibre extracted from stalk Burnt it like incense and smell made them drunk
44
3 main constituents of cannabis
Tetrahydrocannabinol Cannabidiol Cannabinol
45
Cannabinoids effects
Greater THC greater activity of preparation Regional variation in proportions of cannabinoids Ratio differs in different parts of plants
46
Psychological effects of THC central nervous system
Loss of STM Increased confidence Reduced co-ordination Catalepsy
47
Physiological digestive system effect of THC
Reduced nausea and vomiting Stimulated appetite
48
Psychological effectsof THC mood
Relaxation Sense of well being Sharpened sensory awareness
49
How do cannabinoids work (receptor)
All similar structurally with similar responses Act on same cellular target Receptors on membrane of certain cells Triggering effect of drug
50
What are the different cannabinoid receptors
CB1 = brain CB2 = periphery (outside the brain) Cannabinoids bind to orange region -> triggers resposne inside cell via red region
51
Where are the cannabinoid receptors in the brain
Hippocamous (memory, inhibited) Cerebral cortex (consciousness, sensory awareness, altered) Cerebellum (co-ordinaiton, inhibited) Hypothalamus (appetite, inhibited) Brain and spinal cord = pain and reflex control, inhibited)
52
What do endocannabinoids do
Regulate heart rate Widen airways Prevent nausea and vimittung Stimulate appetite Increase pain threshold Decrease sensation of pain
53
How are cannabinoid receptors activated
Uses THC or nabilone
54
Cannabinoid drugs used to treat what
Nausea, vomiting Reduce weight loss in cancer and aids Glaucoma Multiple sclerosis Pain Anxiety
55
How was cannabis used in 1940s
Truth serum in ww2
56
Inhibiting cannabinoid receptor using cannabinoid drugs effects
Rimonabant Blocks endocannabinoid stimulation of appetite
57
Short term effects of STIMULATING cannabinoid receptors
Euphoria Downsiness Sensory distortion Loss of STM
58
Short term effects of INHIBITING cannabinoid receptors
Nausea/ vomiting Diarrhoea
59
Long term effects of STIMULATION of cannabinoid receptors
Depression Lethargy Addiction Psychological disturbance
60
Long term effectsof cannabinoid receptor INHIBITION
Anxiety Psychological disturbance
61
Drug discovery
Target selection Lead optimisation Pharmacological profiling
62
Drug development preclinical development
Pharmacokinetics Short term toxicology Formulation Synthesis scale up
63
Drug clinical development phase 1, 2, 3
1 = healthy volunteers 2 = small group patients, dosages, long term toxicology studies 3 = large scale
64
How long does it takke to discovery and develop a drug
Discovery = 2-5yrs Development = 10 ish years
65
What is angina
Severe pain in heart and chest wall Artieries dont supply heart with enough blood
66
How is angina treated
Vasodilation Opens arteries supplying more blood to heart
67
What are the arteries like in an angina patient
Partially blocked = blood reaches heart -> chest pain Vasodilator = increase blood flow to heart -> relivees angina Enzyme brings natural vasodilation to an end
68
Erectile dysfunction underlying disease
Diabetes, vascular disease, heart disease, spinal damage, prostate cancer, psychological problems, side effect of drug abuse/ smoking
69
What is UK-92480
Inhibits target enzyme Prlongs natural vasodilation
70
Physiology of an erection flaccid and erect
Flaccid = spongy with spaces Erect = penis stiffens and engorges, arteries dilate, penile blood flow
71
Drug addiction/ dependence definition
The human condition where drug taking becomes compulsive Drug taking becomes more important than other basic needs Often has serious knock on consequences Involves physical and psychological dependence
72
Drug abuse/ substance abuse definition
Recurrent use of illegal or hamrful substances Often centred around pleasure seeking Can develop into addiction
73
Drug tolerance definition
Decrease in pharmacological effects of a drug with repeated use Results in requirement for increased doses to achieve same effect Often accompanies dependence/ addiction
74
Withdrawal syndrome
Adverse physical and psychological effects upon stopping taking a drug Can last days, months or indeed years
75
Hedonic drugs
Associate effects of these drugs with pleasure Designed to reinforce basic survival behaviours Pleasurable effects of these drugs drive humans to repeat it
76
Names of reward pathway
Mesolimbic Pleasure pathway
77
How to control the reward pathway
Inhibit nerve cells Prevents releasing dopamine
78
Natural rewards stimulate what
Endogenous opioids Inhibit the inhibitory inputs Activate pleasure pathway
79
Unnatural reward stimulates what
Inhibits inhibitory input or directly stimulates pleasure pathway
80
Unnatural reward - breeds addiction
Repeatedly taking drug = brain down regulates reward pathway Protective mechanism against abnormal levels of stimulation = means larger doses of drug required to stimulate the pathway
81
Non-chemical addictions
excessive stimulation of reward pathway brain down regulates the pathway (tolerance) more and more of these activities needed to gain reward (addiction) not continuing with these activities means little or no pathway activity depression and illness (withdrawal)
82
Physical dependence opioid withdrawal
Downregulation of reward pathway Depends on targets of drug Wtihdrawal varies from drug to drug
83
Psychological dependence opioid drug waithdrawal
Craving Brain learned to connect drug with reward Stimulated by association Long lasting, main reason for relapse
84
Short term substitution addiction treatment
Designed to lessen withdrawal and make it more bearable Helps break habit and re establish control Reduces chance of relapse
85
Long term substitution addiction treatment
Designed to gradually and progressively reduce drug dose Uses controlled, prescribed form of drug Allows brain to slowly adapt to lower doses of the drug Re establishes natural balance
86
Blocking responses addiction treatment
Designed to prevent the problem drugs having an effect Tends to involve blocking specific target od rug Helps prevent relapse (taking drug little or no effect) Tends to be used when addict is making good progress
87
Aversion therapies addiction treatment
Designed to produce an unpleasant response to drug Discourages relapse Helps to associate drug with unpleasantness Unlearns association with pleasure
88
Psychological therapies addiction treatment
Therapies 1-4 are all pharmalogical Psychological therapy also vitally required Helps unlearn drug taking behaviour Helps to understand and deal with craving Effectively addresses the long lasting psychological dependence Aims to help with moving forward and recucing chances of relapse

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