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Pharmacology Flashcards

1
Q

What is pharmacology?

A

Studying the effects of drugs on the function of living systems

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2
Q

What is the definition of drug?

A

a chemical substance of known structure, which, when administered to a living organism, produces a biological effect.

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3
Q

What is a medicine?

A

chemical preparation administered with the intention of producing a therapeutic effect.

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4
Q

what is the difference between the drug and the medicine?

A

The medicine will contain the drug (active ingredient) and stabilisers, solvents, and other stuff that make the drug more effective.

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5
Q

What are the disciplines that feed in to pharmacology?

A
  • chemistry (structure and target)
  • physiology (normal biological function)
  • pathology ( disease/ damage - process/ cause/ progression)
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6
Q

What is the book that is considered one of the oldest pharmacological books?

A

The Ebers Papyrus (Egyptian)

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7
Q

What did Pedanius Dioscorides do?

A

Wrote 5 volume encyclopedia (De Materia Medica) Which contain details about medicines used by Greeks, Romans, and other civilizations.

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8
Q

What is pharmacopoeia? and what is the first pharmacopoeia?

A

reference book containing details of drugs and their use. De Materia Medica

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9
Q

What are the characteristics defining the therapies before the birth of modern pharmacology?

A
  • based on anecdotal evidence, spiritual beliefs and availability
  • no understanding of how drugs work
    -not patient friendly
  • flimsy science
  • lacked control and credibility
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10
Q

Who are the fathers of pharmacology? and what did they do?

A

Rudolf Buccheim:
- first pharmacology professor
- emphasised the importance of defining drug mode of action
Oswald Schmiedeberg
- published outline of pharmacology
- defined modern pharmacology and pharmacologist
-separated between pharmacologists and clinicians.

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11
Q

What is the difference between a pharmacologist and a clinician?

A

Pharmacologist: concerned with investigating how drugs work.
Clinicians: concerned with the use of the drugs to treat

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12
Q

What did make pharmacology a precise, mechanism-based science?

A

Critical advancements in related disciplines ( chemistry and biomedical sciences)

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13
Q

What is pain?

A

broad class of unpleasant sensations ( Stinging, burning, pinching, aching)

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14
Q

Why do we feel pain?

A
  • warning from actual or potential tissue damage
  • encourage to withdraw limb from danger
  • promote protection of damaged tissue to aid healing
  • ensures we remember the incident and learn from the experience.
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15
Q

What are some of the early ways to relief pain?

A
  • spells and incantations
  • diet
  • exercise
  • consumption of potions/ formulations
  • removal of painful limb/tissue/organ
  • bleeding
  • purging
  • burning/ scalding
    (aimed to restore the humoral balance)
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16
Q

What is opium?

A

gummy substance extracted from opium poppy plant

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17
Q

How did Hippocrates use opium?

A

used opium to treat headaches, coughs, asthma, melancholy

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18
Q

How was opium used before it was refined?

A

dissolved in alcohol (tincture of opium)

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19
Q

What were opium uses?

A

medicinal and recreational: induce analgesia, euphoria, sleep, suppress coughing and prevent diarrhoea

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20
Q

What was the first active ingredient isolated from opium? and who isolated it?

A

morphine, Friedrich Serturner

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21
Q

What are the components extracted from opium?

A

morphine, codeine

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22
Q

What is the significant that the extraction of morphine has in the history of pharmacology?

A
  • first isolation of an active ingredient for any drug
  • first proof that pure chemical in plants and natural products were responsible for biological responses.
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23
Q

What was morphine marketed as?

A

marketed by Serturner as
- analgesic
- treatment for alcohol and opium addiction

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24
Q

What was one of morphine’s first use?

A

medicine for children!!

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25
Q

Who invented the hypodermic needle?

A

Alexander Wood

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26
Q

How did the hypodermic needle changed the use of morphine?

A
  • originally morphine was taken orally ( less potent/addictive)
  • intravenous administration increased its potency
  • increased opioid abuse
  • addiction emerged as a side-effect.
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27
Q

How was morphine used as a battlefield analgesic?

A
  • ampoule of morphine with attached needle for use in WWII bc:
  • effective painkiller
  • effects are almost instantaneous
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28
Q

What is diacetylmorphine?

A
  • Heroin
  • semi-synthetic opioid
  • cough suppressant and analgesic
  • ways of intake
    *oral - converts to morphine
    *intravenous - more potent/ addictive
  • one of the most addictive drugs in the world
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29
Q

What are the four main categories of drug targets?

A
  • receptors
  • enzymes
  • carrier molecules
  • ion channels
    drug can either stimulate (agonist) or inhibit (antagonist) the target
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30
Q

How did Rene Decartes describe pain pathway in Treatise of man?

A

1) activation of a spot on the skin surface
2) Activation pulls a thread connected to a valve in the brain
3) Allows animal spirit stored in brain cavity to flow out which is responsible for:
*pain
*withdrawal of the limb from the pain source
*focusing toward the origin of the pain

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31
Q

What is the modern pain pathway?

A
  • pain source (heat)
  • pain receptors
  • sensory nerve
  • spinal cord nerve fibre
  • nerve fibre ascends spinal cord to brain
  • thalamus
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32
Q

who discovered the opioid receptors?

A

Solomon Snyder

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33
Q

What is an opioid receptor and where can it be found?

A
  • present in the brain and spinal cord
  • bind to opioids
  • has several sub-types
  • explains opioid actions
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34
Q

How do opioids work on opioid receptors?

A

inhibit the nerve fibre from firing by binding to it, hence pain relief.

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35
Q

How did the understanding of the pain pathway allow further development and discoveries in regard to drug design?

A
  • developing synthetic drugs based on morphine with subtle differences that alter the activity and the properties of the new drug.
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36
Q

What are some examples of semi-synthetic opioid drugs?

A
  • Oxymorphone: potent analgesia/ reduced euphoria
  • Oxycodone and Buprenorphine: moderate analgesia/ reduced dependence
  • Methadone: mild long-lasting analgesia/ dependence replacement
  • Pethidine: mild-moderate analgesia/ rapid onset/ short-acting
  • Fentanyl: very potent analgesia/ rapid onset/ short-acting
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37
Q

How does the pain pathway work normally to limit the sensation of pain? (without opioid intake)

A
  • Mechanism 1: rubbing
    1) rubbing
    2) sensory receptors connected to a nerve fibre
    3) spinal cord
    4) inhibition of pain signal in the spinal cord
    *less pain signals reach the brain
  • Mechanism 2: the descending pain-inhibitory pathway
    1) nerve fibre originates in the brain
    2) release endogenous opioids (enkephalins/endorphins) on the spinal cord
    3) inhibition of pain pathway in the spinal cord
    *discovered by Kosterlitz and Hughes in Aberdeen
    • Kosterlitz and Hughes purified and identified the structure of 2 enkephalins
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38
Q

How does the descending pain-inhibitory pathway get stimulated?

A
  • stress (adrenaline)
  • emotions
  • opioid drugs
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39
Q

What are some of the other methods of analgesia (other than opioid drugs)?

A
  • local anaesthetics + anti-inflammatory drugs
    (ibuprofen, paracetamol, aspirin)
    • prevent pain receptors being activated
  • TENS (transcutaneous electrical nerve stimulation)
    • activates inhibitory sensory fibres (like rubbing)
  • general anaesthetics
    • induce loss of consciousness (no memory of pain)
  • acupuncture
    • stimulates release of enkephalins
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40
Q

What is cannabis?

A

an extract from Cannabis sativa plant

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41
Q

What are some of cannabis sativa preparations?

A
  • Stalk:
    fibre used to make hemp
  • Dried flowers/leaves:
    used to make marijuana
  • Resin:
    used to make hashish
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42
Q

What was cannabis originally used for?

A

used for hemp

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43
Q

Who mentioned the medicinal/ psychoactive effects of cannabis?

A
  • Dioscordis in De Materia Medica
  • Greek historians reporting on central Asian cultures
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44
Q

what are the main constituents of cannabis?

A
  • tetrahydrocannabinol (THC): main active compound
  • cannabidiol: THC precursor
  • cannabinol: spontaneous product of THC breakdown
    *collectively termed are cannabinoids
    *lipid soluble
    *active and psychoactive effects
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45
Q

What is the most potent cannabinoid?

A

tetrahydrocannabinol (THC)

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46
Q

What region of cannabis sativa is higher in THC concentration?

A

Resin

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47
Q

What are the physiological and psychoactive effects of THC on the central nervous system?

A
  • loss of short-term memory
  • increased confidence
  • reduced co-ordination
  • catalepsy
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48
Q

What are the physiological and psychoactive effects of THC on the digestive system?

A
  • reduced nausea and vomiting
  • stimulates appetite
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49
Q

What are other physiological and psychoactive effects of THC?

A
  • increases heart rate
    -dilation of airways
    -reduced pressure within the eyes
50
Q

What are the physiological and psychoactive effects of THC on the mood?

A
  • relaxation
  • sense of well-being
  • sharpness sensory awareness (sight an sound)
51
Q

What is the target of cannabinoids?

A

cannabinoid receptor

52
Q

Where can the cannabinoid receptors be found?

A

membrane of certain cells

53
Q

What are the types of cannabinoid receptors?

A
  • CB1 (found in the brain)
    most effects result from this type
  • CB2 (found in the periphery)
54
Q

Where does the the cannabinoid binding occur (extracellular/ intracellular)?

A

outside the cell (extracellular)

55
Q

Where does the the cannabinoid response occur (extracellular/ intracellular)?

A

intracellular

56
Q

How does stimulation of cannabinoid receptors affect the cell?

A

inhibit cell activity

57
Q

how does the cannabinoid affect the hippocampus?

A
  • inhibits the hippocampus (involved in memory)
58
Q

how does the cannabinoid affect the cerebral cortex?

A
  • alters the cerebral cortex (involved in consciousness and sensory awareness
59
Q

how does the cannabinoid affect the cerebellum?

A
  • inhibits the cerebellum (involved in co-ordination)
60
Q

how does the cannabinoid affect the brain stem/spinal cord?

A
  • inhibits the brain stem/ spinal cord except heart rate (involved in pain, vomiting reflex, and control heart rate)
61
Q

how does the cannabinoid affect the hypothalamus?

A
  • inhibits the hypothalamus (involved in regulating appetite)
62
Q

Does the human body produce endogenous cannabinoid?

A

yes it does, called endocannabinoids

63
Q

what is the first endocannabinoid to be isolated?

A

anandamide

64
Q

how many cannabinoids discovered so far?

A

5

65
Q

What are the functions of endocannabinoids?

A

*cardiovascular: regulate heart rate
*digestion: prevent nausea/vomiting, stimulate appetite
*breathing: dilate airways
*pain: increase pain threshold (decrease sensation of pain)

66
Q

what is the name of the synthetic derivative of THC?

A

nabilone

67
Q

What are the clinical applications of cannabinoid drugs:

A
  • Activation of cannabinoid receptors
    *inhibition of cannabinoid receptors
68
Q

What can the activation of cannabinoid receptors treat?

A
  • nausea and vomiting in cancer chemotherapy
  • reduce weight loss in cancer and AIDS
  • glaucoma (decrease pressure in the eyes)
  • multiple sclerosis (increases mobility, reduce pain)
  • pain
  • anxiety
69
Q

What can the inhibition of cannabinoid receptors treat?

A
  • blocks effects of endocannabinoid (antagonist)
  • drug used called rimonabant
    -potential use in treating obesity (blocks endocannabinoid stimulation of appetite)
70
Q

What are the effects of cannabinoids in short-term?

A

Stimulation:
euphoria, drowsiness, sensory distortion, loss of short term memory
inhibition:
nausea/vomiting, diarrhoea

71
Q

What are the effects of cannabinoids in long-term?

A

stimulation:
depression, lethargy, addiction, psychological disturbance
inhibition:
anxiety, psychological disturbance

72
Q

what does the gateway theory suggest in term of cannabinoid use?

A

cannabinoid may stimulate needs for stronger, more addictive drugs

73
Q

what are the types of diabetes?

A

Type 1: body does not produce enough insulin
Type 2: body produces insulin but can’t use it well
Gestational: a temporary condition in pregnancy

74
Q

What are some of diabetes complications?

A

stroke, blindness, heart attack, kidney failure, amputation

75
Q

What is diabetes?

A

increase in blood glucose

76
Q

How can urine be an indicator of diabetes?

A

diabetes mellitus - urine sweet (high concentration of glucose)
diabetes insipidus - urine tasteless (very low concentration of glucose) *rare condition

77
Q

What does insulin do?

A

allow take up of glucose into the cell

78
Q

What is the name of the condition when blood glucose rises?

A

hyperglycaemia

79
Q

where does insulin get produced?

A

Beta cells in islet of Langerhans (pancreas)

80
Q

What could happen if diabetes type I was left untreated?

A

Starvation and death

81
Q

what is the survival duration of type I diabetes pre- insulin discovery?

A

2 weeks to 18 months post-diagnosis

82
Q

What was Fred Banting idea to treat diabetes?

A

isolate pancreatic secretion to relieve glycosurea (glucose in urine; hyperglycaemia), trials on dogs

83
Q

Who did support Banting with his idea?

A

prof. John J.R. Macleod

84
Q

Who was Banting assistant?

A

Charles Best

85
Q

What was the process in which Banting achieved his first success?

A

injection of extract of degenerated pancreas injected to depancreatised diabetic dog induced a drop in blood sugar. (following Macleod advice in preparing the extract)

86
Q

Who did help Banting to make a more effective extract?

A

James B Collip

87
Q

Who were given the noble prize for insulin discovery?

A

Fred Banting and JJR Macleod

88
Q

What is the largest insulin producer in the world?

A

Novo-Nordisk

89
Q

Why is injection the best method of insulin intake?

A

Insulin gets destroyed by the gut if taken orally.
Inhaled insulin was withdrawn because of side-effects

90
Q

What is the future of diabetes treatment?

A

Stem cell technology - repairing the pancreas and restoring beta cells

91
Q

How much is spent from the NHS budget on treating diabetes?

A

over 10 billion pounds per year

92
Q

What are the phases of drug discovery and development?

A
  • Drug discovery
  • Development:
    *preclinical development (animals)
    *clinical development (5-7 years)
    #phase I (healthy volunteers)
    #phase II (patient, small-scale)
    #phase III (patients, large-scale)
    *regulatory approval (1-2 years)
    *phase IV (post-marketing surveillance) (1 year)
93
Q

what is the importance of the drug discovery phase?

A

*understanding the disease and selecting the target (enzyme, protein, receptor, etc.)
*understand how a drug molecule will act on the target (stimulation or inhibition)
*identify molecules that would bind to the target and produce the desired effect
#start with about 100 project

94
Q

what is the importance of the preclinical development phase?

A

*Assess short-term toxicology (using animal models)
*Pharmacokinetics (body effects on the drug - absorption, metabolism, secretion, etc,)
*Formulation (how is the drug taken - orally, IV, etc)
*synthesis scale-up (how is the animal trial relate to human)
#about 20% of the compounds make it to this stage (20)
#2-5 years

95
Q

what is the importance of phase I of the clinical development?

A

*pharmacokinetics
*tolerability and side-effects of the drug in healthy volunteers
#about 10 compounds
#1.5 year

96
Q

what is the importance of phase II of the clinical development?

A

*assess efficacy and dosage in small-scale trials in patients
*study long-term toxicology
#about 5 compounds

97
Q

what is the importance of phase III of the clinical development?

A

large-scaled controlled clinical trials in different places
#about 2 compounds

98
Q

What are some of the important rules applied in clinical development?

A

*Placebo controlled
*Double-blinded trials (neither the clinician nor the volunteer knows if they are giving/getting the placebo or the actual drug)
*Randomised trials (different age groups with different disease severity)

99
Q

What disease is sildenafil citrate (Viagra) used for?

A

erectile dysfunction

100
Q

What is angina? and how does it relate to Viagra?

A

*severe pain in the heart and chest wall due to insufficient blood supply to the heart by arteries
*Pfizer aimed to design vasodilation drug to relieve angina
*the target was an enzyme that brings vasodilation to an end
*inhibition of the enzyme would enhance natural vasodilation
*phase I trials showed a side-effect in male volunteers (penile erection)
*Pfizer started investigations of Viagra as a treatment for erectile dysfunction
*dropped as angina treatment due to lack of sufficient potency

101
Q

What is erectile dysfunction?

A

inability to obtain or sustain an erection (often an indication of underlying disease/ problem)

102
Q

Why is Viagra effective at promoting penile vasodilation and erection but not at dilating heart arteries to treat angina?

A

Because there are many subtypes of the target enzyme, and Viagra turned out to be more potent at inhibiting the enzyme subtype in penile arteries.

103
Q

What are the side-effects of Viagra?

A

-headache, hot flushes, indigestion
- not advisable to take with certain heart conditions

104
Q

How did Viagra indirectly save lives?

A

detection of underlying diseases earlier, as males with ED seeked medical help

105
Q

What is drug addiction?

A

the human condition where drug taking becomes compulsive

106
Q

What is drug abuse?

A

recurrent use of illegal or harmful substances

107
Q

what is drug tolerance?

A

decrease in pharmacological effects of a drug with repeated use

108
Q

what is the withdrawal syndrome?

A

adverse physical and psychological effects upon stopping taking a drug

109
Q

What were some of the substances that caused addiction through history?

A

Mushroom (stone age)
Frog/toad venom (ancient tribes)
Cojobano seeds (prehistoric)

110
Q

What are the drugs of today?

A

Alcohol
Opium
Cannabis
Cocaine

111
Q

what are the drug types of today drugs?

A

*opioid analgesics
Morphine (VS), diamorphine (VS)
*nervous system depressants
Ethanol (S), Barbiturates (S), Anaesthetics (M), solvents(S)
*nervous system stimulants
Amphetamine (S), Cocaine (VS), Nicotine (VS),
Caffeine (W)
*others
Cannabis (W), LSD (W)

112
Q

What is the link between the addictive drugs knowing that they are very different pharmacologically and structurally and they don’t bind to the same target?

A

they are called hedonic drugs (their effects are associated with pleasure). all of the addictive drugs activate the reward pathway in the brain.

113
Q

What is the reward pathway?

A

Reward pathway (mesolimbic/pleasure pathway) is responsible for the feel of pleasure or reward by releasing dopamine.

114
Q

What does keep down the activity of the mesolimbic pathway?

A

inhibitory nerve cells which prevent the release of dopamine.

115
Q

How can the pleasure pathway be activated naturally?

A

pleasurable social activities (sex, shopping, etc) that stimulate the release of endogenous opioids (enkephalins) which inhibit the inhibitory input.

116
Q

How can the pleasure pathway be activated unnaturally ?

A

drugs of abuse affect the reward pathway in two ways:
1) inhibit the inhibitory inbut
2) directly stimulate the reward pathway

117
Q

How does the brain react to repeated substance abuse?

A

down regulates the mesolimbic pathway (less sensitive to drug stimulations)

118
Q

what are the consequences of the protective mechanism of the brain?

A

*larger doses needed to experience similar effects
*pathway rarely activated without the drug
*withdrawal effects (depression, etc) when drug absent

119
Q

How do the non-chemical addictions affect the pleasure pathway?

A

Engaging in those activities excessively and repetitively but to a lesser degree compared to their chemical counterpart.

120
Q

Does the effects vary with different drugs of abuse?

A

yes, more potent> more addictive> more severe withdrawal effect> more likelihood of relapse

121
Q

What is the difference between physical and psychological dependence?

A

*physical D: associated with down regulation of the reward system and other drug targets, varies from drug to drug, lasts days-weeks.
*psychological D: brain learned to connect drug with reward, produces craving, stimulated by association, long-lasting, main reason for relapse

122
Q

What are some of addiction treatments?

A

1) short-term substitution
methadone (opioid), diazepam (alcohol)
2) long-term substitution
methadone (opioid), nicotine patches/chewing gum
3) blocking response
blocking drug’s target, prevent relapse, giving for addicts who show good progress
4) aversion therapies
produce unpleasant response to drugs
alcohol aversion therapy> induce violent nausea/ vomiting in response to alcohol
5) psychological therapy

Medical sciences (5 decks)

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