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Flashcards in Pharmacology Deck (110):
1

What are the main ion for 1) axonal transmission 2) pre-synaptic terminal

1) Na+ and K+
2) Ca2+

Ca release is triggered by Na+ and K+ wave of depolarisation

2

What are three ways of inactivating neurotransmitter

neuronal uptake (main), metabolism by glial cells and extraneuronal uptake

3

What is the function of cocaine

blocks neuronal uptake of NA, DA, 5HT

4

What is the different dose response of cocaine (high&low dose)

low dose: slow absorption, relief from fatigue, hunger, altitude sickness, some psychological dependence
high dose: rapid absorption, intense euphoria, severe psychological and physical dependence

5

What is the main cause of death from using cocaine

cardiac collapse

6

What is the main effect of amphetamine

it displaces NA from storage vesicle, so more NA can diffuse to synaptic cleft via non-exocytotic release. It can work under low concentration of NA

7

What is NA associated with in the brain?

stimulant effects, mood, appetite, cardiovascular control

8

Tyrosine is converted to L-DOPA via?

tyrosine hydroxylase

9

L-DOPA is converted to dopamine by?

dopa decarboxylase

10

dopamine is converted to NA by?

dopamine B-hydroxylase

11

NA is converted to adrenaline by?

PNMT

12

Dopamine rich area in the brain is associated with which function?

motor

13

What is the drug treatment of Parkinson's disease?

L-DOPA + peripheral DDC inhibitor (block peripheral dopamine conversion)

14

What is Huntington's disease? What is the drug treatment of Hungtinton's disease?

GABA deficiency, lack of neuronal inibition
Treatment: Baclofen, GABA agonist, or Chlorpromazine, dopamine antagonist

15

T/F Neurotransmitters can be excitatory or inhibitory, and it determines whether a synapse is excitatory or inhibitory

False, first statement is correct, but the nature of the synapse also depends on the neurotransmitter receptor

16

What are the targets of analgesic drugs

pain and sensory pathways at all levels including periphery, spinal and the brain

17

What is the main difference in target between local and general anaesthetic

local: regionalised inhibition of pain and sensory pathways

General: depresses cortical processing of pain signals, with loss of consciousness

18

Describe the neural pathway of pain

peripheral nerve picks up the signal. Signal is relayed to spinal cord to secondary neuron. Secondary neuron carries information for processing in the thalamus, then finally to tertiary neuron that relays to the cortex

19

What is the significance of adding lime to cocaine

drug formation affects pharmacokinetics. A basic environment deprotonates the drug, making it more lipid soluble

20

Cocaine is not only a CNS stimulant, it is also a _________

local anaesthetic (first)

21

Define "local anaesthetic agents"

drugs that reversibly block conduction of nerve impulses at the axonal membrane

22

local anaesthetics are often ______ with different onset, duration and _______. They serve to block _______ Channels

weak bases
toxicity
Na+

23

Give an example of an aminoester
why is it short acting (45mins)?

procaine, it is short acting because it can be rapidly hydrolysed by esterases (like AchE)

24

Lignocaine is a _________ , which is a stabilised form of _________ and is no longer affected by _________ . However, it requires ________ of the liver, so the effect of drug varies between individuals

aminoamide
aminoester
esterases
conjugation

25

What are some examples of lethal toxins that lie on the same pathway as local anaesthetics?

tetrodotoxins
saxitoxin
immobilise preys or serve a protective function

26

Give three properties of local anaesthetic that make it a clinically useful drug

1) selective binding to Na channels (except for cocaine)
2) reversible binding without damaging nerves
3) will affect all nerves and excitable tissues, so local application is crucial for limiting systemic distribution

27

What are some other excitable tissues affected by local anaesthetics?

1) peripheral motor neurons (paralysis)
2) ANS nerves (hypotension, CNS convulsion, coma)
3) heart (anti-dysrhythmic to cardiac arrest)

28

With an epidural injection, we can block 100% and only lose ________% of motor neuron function

less than 50

(if injected correctly)

29

Which part of the Na channel does the local anaesthetic bind to? How is that different to toxins?

intracellular domain (S6, to be specific)
toxins bind extracellular domains, so the effect does not dependent on channels being active

30

Why does benzocaine belong to a different class of anaesthetic

it is hydrophobic and therefore fast acting and not use-dependent (does not dependent on Na channel being open and active)

31

Why does lignocaine act slower than benzocaine

it is hydrophilic, so gets across the membrane slower than benzocaine.

Note that lignocaine is 65% protonated at pH 7.4, so does not diffuse well

32

There are two gates on a Na channel, what are they?

M gate extracellularly which opens during depolarisation
N gate intracellularly, which closes during hyperpolarisation

33

What is the effect of local anaesthetics blocking Na channels?

the neuron is unable to reach threshold potential, and action potential is therefore prevented

34

Does local anaesthetic affect resting membrane potentials?

No, the drugs can also stabilise axonal membrane

35

why are small fibres more sensitive to local anaesthetic

thinner membrane, quicker drug diffusion

36

Why does lignocaine cause cardiovascular symptoms like myocardial depression, vasomotor centre in brainstem, and hypotension?

Because it blocks Na channels on all excitable tissues, so there is direct blocking of myocardial fibres and vasomotor centres, and there is hypotension because of SNS block

37

Why does cocaine cause hypertension instead of hypotension?

it does block the sympathetic nerves, but it also blocks the reuptake of NA, hence increase cardiac output

38

The CNS and CV side effects of lignocaine are proportional to blood drug concentration. Which side-effect is not proportional?

hypersensitivity / allergic response

39

In a dental wound, why does a dentist need to clean it up as much as possible before using anaesthetic?

Inflamed areas tend to be acidic, and local anaesthetics are more in the charged, protonated form in acid. Cleaning up the wound lower the dose required

40

Describe the four stages of general anaesthesia

I) amnesia/euphoria, pre-excitement stage
II) excitement (last about 20 seconds)
III) surgical anaesthesia, unconsciousness but regular breathing
IV) medullary depression, one you want to avoid as there is CV/Resp arrest

41

All general anaesthetic increase likelihood of respiratory and CV side effects. What is often given in conjunction in order to prevent obstruction of airways

anti-muscarinics to block secretions, as secretions are retained

42

What should we consider if general anaesthetic is applied to a patient undergoing surgery sitting up?

must monitor CV function, as there is sometimes inadequate response to fall in BP and CO

43

What is Meyer-Overton Lipid Theory? What makes this theory plausible?

anaesthesia is caused by volume expansion of membrane lipids, impinging on the normal protein function. This is possible because drug effect can be reversed by pressure

44

What do anaesthetics do to the effects of neurotransmitters?

enhance inhibitory receptors (GABA) and inhibit excitatory (glutamate) receptors

45

What is propofol?

IV general anaesthetic

46

What is the problem with most CNS drugs?

the drugs are somewhat empirical. SSRI for example, the effect varies based on individual

47

On a biochemical level, what is the treatment for epilepsy

reduce excitation from glutamatergic neurons
increase inhibition from GABA neurons

48

What is an example of glutamatergic epileptic drug? How does it work?

Phenytoin - it inhibits Na channel on glutamatergic neurons to reduce action potential triggering glutamate release

Note that it only works when the channel is open

49

What is an example of GABAergic epileptic drug? How does it work?

Benzodiazepine, enhances GABA receptor activity by binding the allosteric site

50

T/F different neurotransmitter receptor in the CNS can have similar desirable effect

True, for example, serotonin, NA and NPY all have effect on anxiety

51

What is the use of benzodiazepine? Why is it used less in the market nowadays

it is use to treat epilepsy, anxiety, sleep disorders, sedative. It is used less because it affects coordination

52

What are some clinically recognised anxiety disorders?

generalised anxiety states
panic disorder
phobias
PTSD

53

How can beta-antagonist be used as an anxiolytic

it blocks the physical manifestation of anxiety like increased heart rate and resp rate

54

What class of drugs is barbituate

general depressant, very good anaesthetic

55

What is it becoming obsolete

it is exceeding toxic with low therapeutic index. It can induce liver enzyme and abrupt withdraw can cause death

56

Why can you overdose on barbituate but not benzodiazepine

Because of the way drugs open the GABA channels
with benzodiazepine, there is a ceiling effect on how frequent the channel can open.

Barbituate binds GABA receptors and keep them open, so there isn't a ceiling effect

57

What pharmacological term can be used to describe barbituate and benzodiazepine? (the way they affect GABA channels)

they are both allosteric modulators that increase the effect of endogenous agonist effect at GABAa channels

58

What is efficacy in pharm term?

the strength of the receptor activation

59

T/F The current treatment for Parkinson's is very new

False, the therapy hasn't changed for 50 years

60

Where is dopamine produced in the motor system? What is its effect on the target site?

from the substantia nigra, and it tonically inhibits the corpus striatum

61

What effect does the corpus striatum exert on the cortex?

GABA, so inhibition

62

What are some motor signs of Parkinson's related to muscles?

Tremor, rigidity of limbs
bradykinesia, impairment of postural reflexes
decreased manual dexterity

63

What are the facial signs of Parkinsons?

impassive and no blinking

64

what are the symptoms of Parkinsons associated with speech?

monotonous
hypophonic

65

There are non-motor signs in Parkinson's - what is usually the first presenting symptom? Which symptom usually follows shortly after?

Olfactory deficiencies
bowel and bladder control

66

which protein mutation will predispose to Parkinson's?

alpha synuclein

67

What do motor symptoms present at the later stage of Parkinsons

you need to lose up to 80% of motor neurons before symptoms occur

68

What does a MRI scan of a Parkinson's patient look like

There is asymmetric degradation of DA neurons

69

What is the role of L-DOPA in terms of managing the patient?

the drug provides symptomatic relief, but it's not curative

70

Why do we need to add cholinergic antagonist along with dopamine?

movement relies on the balance of DA and Ach
when there is less DA, there is less inhibition, so neurons are hyper-excitable

anti-cholinergics are added to reduce effect of Ach, hence restore normal movement

71

What happens if we ingest dopamine

vomit violently

72

What needs to be co-administered with levodopa to ensure its efficacy?

Dopa-decarboxylase inhibitor in order to prevent metabolism in the periphery

73

T/F You need functional neurons for levodopa to work

True, hence there is a debate on when to start the drug. When you start using the drug, you increases degeneration of DA neurons

74

T/F Levodopa has a long half life

False, the half life is only about 1-2 hours, so patients need to constantly medicate

75

What happens if you take too much levodopa?

experience tardive dyskinesia, which is involuntary, repetitive body movements

76

What kind of central side effects does levodopa cause?

visual and auditory hallucinations
abnormal motor movements
mood changes
depression
anxiety

77

What is the function of levodopa?

increase dopamine synthesis

78

What is the function of bromocriptine? Why is it preferred in younger individual?

dopamine agonist
the disease is more aggressive in younger people

79

T/F bromocriptine has more CNS side effects than levodopa

True, it floods the whole brain with dopamine

80

What is the function of the drug Entacapone?

inhibits COMT, therefore inhibit the breakdown of DA

81

What is the function of selegiline?

it's a Mao-inhibitor, reduce metabolism of dopamine

82

What is the new therapy for Parkinson's, said to be available within 10 years?

phototherapy, turn on receptors in response to light

83

How does levodopa accelerate DA neuron death?

levodopa stimulates DA production. For DA to be produced, you need iron. The increased iron level creates reactive oxygen species, and the increased oxidative stress on mitochondria ultimately kills the neuron

84

What is MPTP?

a by-product of a party drug, which accelerates the death of DA neurons and Parkinson's

85

What are the key areas in the brain involved in addiction

nucleus accumbens
ventral pallidum
amygdala
hippocampus

86

T/F Only monoamines are involved in addiction/reward

False, GABA, glutamate, and opioids can be involved as well

87

How does overdose on amphetamine cause death?

In general, it's not the CNS effect. Death is caused by CV related issues like tachycardia, increased BP, and eventually vascular collapse

88

What are the symptoms of withdrawal of amphetamine

lethargy, sleep, desire for food, depression

89

MDMA (Ecstasy) is both a _______ and a _________. Structurally, it is similar to ________, but it is considered safer. There is strong ________ dependence as well as CV side effects. __________ can also be disrupted, leading to chills and sweating. MDMA in linked to production of ROS, and may cause ________ of 5HT and DA neurons

stimulant
hallucinogen
amphetamine
psychological
Thermoregulation
degeneration

90

What is the primary effect of LSD

visual, auditory and tactile hallucinations due to disruption of sensory processing

91

Is LSD addictive?

not usually, because the effect can be aversive

92

How does tolerance development differ between ethanol and LSD

the tolerance of LSD comes from cross tolerance with other drugs (pharmacodynamic), while ethanol tolerance comes from increased metabolism (pharmacokinetics)

93

What class of drug is caffeine?

adenosine antagonist and phosphodiesterase inhibitor

94

What adverse effect on the tissue level can ethanol cause?

liver damage, neurodegeneration, foetal impairment

95

T/F Ethanol is a CNS stimulant

False, it is a CNS depressant

96

What are the actions ethanol in the CNS

inhibit Ca channel opening = stop exocytosis of transmitters
enhance GABA action
inhibit NMDA

97

What class of drug is flumazenil

GABA receptor antagonist

98

What are the subjective effects of D9-THC

sharpened sensory awareness
relaxation, feeling of well being

99

What class of drug is D9-THC

cannabinoid receptors agonist, a GPCR that inhibit adenyllate cyclase

100

What is the endogenous substance activating cannabinoid receptors

anadamide

101

What are the central effects of D9-THC

binding to CB1 to cause impaired short term memory, impaired motor coordination, catalepsy, analgesia, anti-emetic, increased appetite

102

What are the peripheral effect of D9-THC

binding to CB2 to cause tachycardia, vasodilatation, reduced intraocular pressure, bronchodilatation

103

what's the pharmacological action of tricyclic antidepressant

inhibit neuronal uptake of NA and 5HT
adrenoceptor, muscarinic receptor, histamine and serotonin receptor antagonist

very non-selective

104

What are the clinical effects of tricyclic antidepressant

takes a few weeks to take effect because there is long term anti-depressant activity

105

T/F tricyclic antidepressant has a high therapeutic window

False, it has a narrow window and must be prescribed with care

106

T/F tricyclic antidepressant has a long half life

True, so there may be late on-set side effects. Patients need to start first on a low dose and increase if it's working

107

What's cheese reaction

when taking MAO-inhibitor, the tyramine contained in cheese cannot be neutralised, which can lead to a hypertensive crisis

108

What's the advantage using Moclobemide

It's a selective MAO-A inhibitor, so patients are less likely to get cheese reaction

109

What are the side effects of SSRI

nausea, insomnia, agitation, weight change, loss of libido, suicidal tendencies in adolescent

110

What's an example of SSRI

Fluoxetine