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Drug Discovery And Disease Flashcards

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USMLE® Step 1 flashcards
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Injales was withdrawn because of side effects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 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
Q

Drugs targets

A

Morphine heroin codeine have similar structure and effects - liely act on same target
Targets = receptors, enzymes, carrier molecules, ion channels

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26
Q

What does drug binding result in

A

Stimulate or inhibit target resulting in a biological response in the cell

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27
Q

What did they not know by the end of the 1800s chemistry and physiology

A

Chemistry = control effects
Physiology = morphine effects, how pain is communicated, mode of action of opiods

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28
Q

Describe descartes pain pathway

A

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

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29
Q

Modern pain pathway

A

Pain receptor connected to sensory nerve
Enters spinal cord and connected to another nerve fibre
Nerve fibre ascends spinal cord into brain (thalamus)
Connected to thalamus relays pain message to different parts of the brain
Pain is sensed and individual responds

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30
Q

Who discovered opioid receptor

A

1972
Solomon snyder

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31
Q

How do opiioids regulate the pain pathway

A

Receptors present in the brain and spinal cord
Specifically bind to morphine
Explains spectrum of opioid actions
Binding of opioid to receptor inhibits nerve ibre preventing firing

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32
Q

Opioids and pain pathway

A

Binds opioid receptors inhibits pain fibres in brain and spinal cord
Opioid receptors on thalamus blocked by morphine

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33
Q

Chemistry pathology and physiology pain and treatment things known

A

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

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34
Q

Rubbing an injury to easy pain

A

Rubbing activates another type of sensory receptor connected to a fibre that enters the spinal cord
This fibre inhibits pain signal in spinal cord -> less pain signals make it to the brain and we suffer less

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35
Q

Who was hans kosterlitz

A

German
1st professor of pharmacology at aberdeen

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36
Q

What did kosterlitz and hughes do

A

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
Q

What did kosterlitz and hughes discover

A

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
Q

WHat did kosterlitz and hughes do to the 2 enkephalins structures

A

Purify it

39
Q

How do endogenous opioids fit in the pain pathway

A

Inhibits pain transmission in spinal cord
Releases enkephalin
Binds opioid receptors
Inhibits pain fibre firing

40
Q

How do endogenous opioids stimulate the pain pathway

A

Stimulated by stress, emotions, opioid drugs = controls pain and suffering, allows us to escape stress

41
Q

Name 4 other methods of analgesia

A

Local anaesthetics + anti inflammatory drugs
TENS
General anaesthetic
Acupuncture

42
Q

How do the other methods of analgesia affect the pain pathway

A

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
Q

Cannabis original use

A

Hemp
Strong fibre extracted from stalk
Burnt it like incense and smell made them drunk

44
Q

3 main constituents of cannabis

A

Tetrahydrocannabinol
Cannabidiol
Cannabinol

45
Q

Cannabinoids effects

A

Greater THC greater activity of preparation
Regional variation in proportions of cannabinoids
Ratio differs in different parts of plants

46
Q

Psychological effects of THC central nervous system

A

Loss of STM
Increased confidence
Reduced co-ordination
Catalepsy

47
Q

Physiological digestive system effect of THC

A

Reduced nausea and vomiting
Stimulated appetite

48
Q

Psychological effectsof THC mood

A

Relaxation
Sense of well being
Sharpened sensory awareness

49
Q

How do cannabinoids work (receptor)

A

All similar structurally with similar responses
Act on same cellular target
Receptors on membrane of certain cells
Triggering effect of drug

50
Q

What are the different cannabinoid receptors

A

CB1 = brain
CB2 = periphery (outside the brain)
Cannabinoids bind to orange region -> triggers resposne inside cell via red region

51
Q

Where are the cannabinoid receptors in the brain

A

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
Q

What do endocannabinoids do

A

Regulate heart rate
Widen airways
Prevent nausea and vimittung
Stimulate appetite
Increase pain threshold
Decrease sensation of pain

53
Q

How are cannabinoid receptors activated

A

Uses THC or nabilone

54
Q

Cannabinoid drugs used to treat what

A

Nausea, vomiting
Reduce weight loss in cancer and aids
Glaucoma
Multiple sclerosis
Pain
Anxiety

55
Q

How was cannabis used in 1940s

A

Truth serum in ww2

56
Q

Inhibiting cannabinoid receptor using cannabinoid drugs effects

A

Rimonabant
Blocks endocannabinoid stimulation of appetite

57
Q

Short term effects of STIMULATING cannabinoid receptors

A

Euphoria
Downsiness
Sensory distortion
Loss of STM

58
Q

Short term effects of INHIBITING cannabinoid receptors

A

Nausea/ vomiting
Diarrhoea

59
Q

Long term effects of STIMULATION of cannabinoid receptors

A

Depression
Lethargy
Addiction
Psychological disturbance

60
Q

Long term effectsof cannabinoid receptor INHIBITION

A

Anxiety
Psychological disturbance

61
Q

Drug discovery

A

Target selection
Lead optimisation
Pharmacological profiling

62
Q

Drug development preclinical development

A

Pharmacokinetics
Short term toxicology
Formulation
Synthesis scale up

63
Q

Drug clinical development phase 1, 2, 3

A

1 = healthy volunteers
2 = small group patients, dosages, long term toxicology studies
3 = large scale

64
Q

How long does it takke to discovery and develop a drug

A

Discovery = 2-5yrs
Development = 10 ish years

65
Q

What is angina

A

Severe pain in heart and chest wall
Artieries dont supply heart with enough blood

66
Q

How is angina treated

A

Vasodilation
Opens arteries supplying more blood to heart

67
Q

What are the arteries like in an angina patient

A

Partially blocked = blood reaches heart -> chest pain
Vasodilator = increase blood flow to heart -> relivees angina

Enzyme brings natural vasodilation to an end

68
Q

Erectile dysfunction underlying disease

A

Diabetes, vascular disease, heart disease, spinal damage, prostate cancer, psychological problems, side effect of drug abuse/ smoking

69
Q

What is UK-92480

A

Inhibits target enzyme
Prlongs natural vasodilation

70
Q

Physiology of an erection flaccid and erect

A

Flaccid = spongy with spaces
Erect = penis stiffens and engorges, arteries dilate, penile blood flow

71
Q

Drug addiction/ dependence definition

A

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
Q

Drug abuse/ substance abuse definition

A

Recurrent use of illegal or hamrful substances
Often centred around pleasure seeking
Can develop into addiction

73
Q

Drug tolerance definition

A

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
Q

Withdrawal syndrome

A

Adverse physical and psychological effects upon stopping taking a drug
Can last days, months or indeed years

75
Q

Hedonic drugs

A

Associate effects of these drugs with pleasure
Designed to reinforce basic survival behaviours
Pleasurable effects of these drugs drive humans to repeat it

76
Q

Names of reward pathway

A

Mesolimbic
Pleasure pathway

77
Q

How to control the reward pathway

A

Inhibit nerve cells
Prevents releasing dopamine

78
Q

Natural rewards stimulate what

A

Endogenous opioids
Inhibit the inhibitory inputs
Activate pleasure pathway

79
Q

Unnatural reward stimulates what

A

Inhibits inhibitory input or directly stimulates pleasure pathway

80
Q

Unnatural reward - breeds addiction

A

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
Q

Non-chemical addictions

A

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
Q

Physical dependence opioid withdrawal

A

Downregulation of reward pathway
Depends on targets of drug
Wtihdrawal varies from drug to drug

83
Q

Psychological dependence opioid drug waithdrawal

A

Craving
Brain learned to connect drug with reward
Stimulated by association
Long lasting, main reason for relapse

84
Q

Short term substitution addiction treatment

A

Designed to lessen withdrawal and make it more bearable
Helps break habit and re establish control
Reduces chance of relapse

85
Q

Long term substitution addiction treatment

A

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
Q

Blocking responses addiction treatment

A

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
Q

Aversion therapies addiction treatment

A

Designed to produce an unpleasant response to drug
Discourages relapse
Helps to associate drug with unpleasantness
Unlearns association with pleasure

88
Q

Psychological therapies addiction treatment

A

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

Medical Sciences (5 decks)

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