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Neurology > Pharmacology Of Pain > Flashcards

Pharmacology Of Pain Flashcards

1
Q

What is pain

A

Unpleasant sensory and emotional experience associated with actual or potential tissue damage

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2
Q

Function of pain

A

Protection
Alterness about problem in body
Protects from further injury
Aids with healing

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3
Q

Fibers involved in reception of noxious signals

A

A delta fibers

C fibers

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4
Q

Type of pain for C fibers

A

Polymodal, dull , diffuse, burning pain

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5
Q

A delta fibers type of pain

A

Sharp, well localized pain

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6
Q

How does tissue injury leads to pain

A

Tissue injury -> inflammatory mediators -> pain

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7
Q

What are the algogenic substances involved in nociceptor activation

A

Bradykinin in blood
Kallidin in tissues
Serotonin

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8
Q

What are the algogenic substances involved in nociceptor sensitization

A

Histamine
Prostaglandins
Leukotrienes

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9
Q

What are the algogenic substances involved in hyperalgesia

A

H+

Adenosine

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10
Q

What are the algogenic substances involved in nociceptor sensitization and stimulation

A

Cytokines

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11
Q

Neurotransmitters of nociception

A 
Neuropeptides
Tachykinins
Substance p
Calcitonin gene related peptide
Aspartate 
Somatostatin
Neurotrophins
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12
Q

Receptor involved in nociception

A

Neurotrophin receptors (tyrosine kinase receptor, transient receptor potential receptor TRPV1, TRPV3)
Tachykinin receptor
Purinergic receptor (adenosine triphosphate receptor )
Opioid receptors
Cannabinoid receptors

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13
Q

What is the pathway of pain

A

1st order neuron transmits pain signal from peripheral receptor to 2nd order neurion in dorsal horn of spinal cord

2nd order neurons crosses and ascend in spinothalamic tract to thalamus

3rd order neuron on postcentral gyrus

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14
Q

What are the steps in pain prpocessing

A 
Transduction 
Transmission
Modulation
Perception
Sensitisation
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15
Q

Medications involved in pain transduction

A 
NSAIDs 
Antihistamines 
Membrane stabilizing agenys
Local anesthetic cream 
Opioids
Bradykinin and serotonin antagonist
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16
Q

Medicatons involved in transmission of pain

A

Local anesthetics

Epidural block

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17
Q

Medications involved in modulation of pain

A 
Spinal opiods 
Alpha 2 agonists 
NMDA receptor antagonists 
Anticholinesterase 
NSAIDs
CCK antagonists
NO inhibitors 
Potassium channel opener
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18
Q

Medications involved in perception of pain

A

Parenteral opioids
Alpha 2 agonists
General anesthetics

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19
Q

Different form of classifying pain

A 
Etiology 
Mechanism 
Duration
Location
Intensity
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20
Q

Etiologic classfication of pain

A

Malignant
Benign
Idiopathic

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21
Q

Classfication of pain based on mechanism

A

Nociceptive

Neuropathic

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22
Q

Classification of pain based on duration

A

Acute
Chronic
Breakthrough

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23
Q

Classfication of pain based on intensity

A

Mild
Moderate
Severe

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24
Q

2 types of nociceptive pain

A

Somatic

Visceral

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25
Q

What causes somatic pain

A

Activation of nociceptor at surface tissue or deep tissue like bone, joint etc

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26
Q

What causes visceral pain

A

Caused by activation of nociceptor in viscera due to infection, fluid or gas, stretching, compression or solid tumor

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27
Q

What can cause neuropsthic pain

A

Structural damage and nerve cell dysfunction in PNS or CNS

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28
Q

Type of alalgesic agents

A

Opioids
NSAIDS
Antimigraine agents

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29
Q

What does opium contains

A

Morphine
Codeine
Thebaine
Papaverine

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30
Q

Semi synthetic opiods

A 
Hydromorphone 
Hydrocodone
Oxycodone 
Oxymorphone
Diacetylmorphine (heroin)
Dipropanoylmorphine
Benzylmorphine
Ethylmorphine
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31
Q

Synthetic opioids

A 
Fentanyl 
Alfetanyl
Remifentanil 
sufentanyl 
Pethidine
Methadone 
Tramadol 
Propoxyphene 
Buprenorphine
Pentazocine
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32
Q

Endogenous opioid peptide

A

Endorphins
Enkephalin
Dynorphins
Endomorphins

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33
Q

Opiod receptor types

A 
Mu
Delta
Kappa
ORL 
Nociceptin receptor
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34
Q

Subtypes of mu receptor

A

1
2
3

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35
Q

Location of mu receptor

A

Brain (cortex, thalamus, striosomes, periaqueductal gray, rostrl ventromedial medulla )
Spinal cord ( substantia gelatinosa)
Peripheral sensory neurons
Intestinal tract

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36
Q

Function of mu1 receptor

A

Analgesia

Physical dependance

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37
Q

Function of mu2 receptor

A 
Respiratory depression 
Meiosis 
Euphoria
Reduced GI motility 
Physical dependance
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38
Q

Function of mu3 receptor

A

Vasodilation

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39
Q

Delta receptor location

A

Brainn (pontine nuclei, amygdala, olfactory bulb, deep cortex)
Peripheral sensory neurons

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40
Q

Delta receptor function

A 
Analgesia
Antidepressant
Convulsant 
Physical dependance
Modulation of mu receptor  ]
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41
Q

Kappa receptor location

A 
Brain
Hypothalamus 
Periaqueductal gray
Claustrum
Spinal cord
Substantia gelatinosa 
Peripheral sensory neuron
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42
Q

Function of kappa receptor

A 
Analgesia 
Anticonvulsant effect 
Depression 
Hallucinogenic effect 
Diuresis 
Dysphoria 
Meiosis 
Neuroprotection
Sedation 
Stress
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43
Q

nociceptin receptor location

A

Brain ( cortex, amygdala , hippocampus, septal nuclei, habenula, hypothalamus )
Spinal cor

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44
Q

Nociceptin receptor function

A

Anxiety
Depression
Appetite
Development of tolerance to mu agonists

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45
Q

Mechanism of action of oiod receptor

A 
Opioid + receptor complex
Receptor activation 
Inhibition of adenylate cyclase 
Dcreased cAMP
K+ channel opening , hyperpolarization, inhibition of Ca channels opioid response
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46
Q

Opioids pure agonists

A

Endogenous or synthetic peptides

Non peptides like etorphine and methadone

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47
Q

Opioids pure agonist mode of action

A

High affinity for mu receptor

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48
Q

Why does methadone has wide range of effect

A

Has activity at other non opioid site

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49
Q

Opioids Partial agonist example

A

Codeine
Dextropropoxyphene
Considered weak compared to morphine

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50
Q

Opioid mixe agonist - antagonist action non what receptor

A

Kappa agonist

Mu antagonist

51
Q

Example of opioid mixed agonist antagonist medicaitons

A

Nalorphine

Pentazocine

52
Q

Opioid antagonist drugs

A

Naloxone

Naltrexone

53
Q

How do admister most opioids

A

Sc

Po

54
Q

Why should you give much higher dose of certain opioids like morphine

A

1st pass metabolism

55
Q

Why are codeine and oxycodone effective orally

A

Reduced 1st pass metabolims

56
Q

How are opioids metabolized

A

Converted to glucuronides -> excretion through kidneys

57
Q

Morphine metabolism

A

Morphine conjugated to morphine 3 glucuronide

10% becomes morphine 6 glucuronide

58
Q

Co administration of what drug can cause enhancement of CNs uptake of M3G and M6G

A

Probenecid and other drugs that inhibit p-glycoprotein drug transporter

59
Q

Property of M6G and M3G

A

Neuroexcitatory effect

60
Q

What should you consider before administering morphine or hydromorphone

A

If theres renal failure

61
Q

Phenylpiperidine (pethidine, fentanyl, alfentanil, sufentanil ) metabolism

A

Hepatic oxidative metabolism

62
Q

Consequence of high concentration norpethidine

A

Seizures

63
Q

Does fentanyl have active metabolite

A

No

64
Q

What metabolizes fentanyl

A

P450 CYYP3A4 through dealkylation in liver

65
Q

Codeine oxycdone and hydrocodone metabolism

A

CYP2D6

66
Q

CYP2D5 polymorphism for codeine, oxycodone and hydrocone

A

Minor consequence for oxycodone and hydrocodone

Oxycodone may accumulate if renal failure

Codeine can lead to no repsonse or exagerated response

67
Q

How are opioids metabolites excreted

A

Through urine

68
Q

Can persistent administration of opioid analgesic like morphine , fentanyl and remifentanil lead to hyperalgesia

A

Yes

69
Q

Opioïdes Effect on CNS

A 
Analgesia 
euphoria 
sedation 
hypnosis 
respiratory depression 
cough suppression 
Miosis
 nausea 
vomiting 
temperature
70
Q

Opioids cv effect

A

Cardiovascular effects - Bradycardia , tachycardia for pethidine

71
Q

Opioids git effect

A

GIT effect- constipation

72
Q

Ooioids biliary effect

A

Biliary tract - biliary colic , reflux of biliary and pancreatic secretioN ,elevated plasma amylase and lipase

73
Q

Opioids neuroendocrine effevt

A

Neuroendocrine - Release of ADH prolactin somatotropin , inhibition of LH release

74
Q

Opioid renal effect

A

Depression of renal function

mu opioid with anti-diuretic effect

enhancement of Renal tubular sodium reabsorption

75
Q

Opioids effects on uterus

A

Prolong labor

reduced uterine tune

76
Q

Opioids to affect on the skin

A 
Pruritus 
flushing 
warming of skin 
sweating 
urticaria
77
Q

Opioids effect on immune system

A

Modulate immune system with effect on lymphocytes proliferation , antibody production , chemotaxis

78
Q

What are the clinical uses of opioids

A

Analgesia for severe pain
acute pulmonary edema through reduced perception of shortness of breath , reduced to preload and afterload

Cough
diarrhea
shivering
preanesthetic medication

79
Q

Does Morrison and surrogates lose effectiveness over repeated therapeutic those

A

Yes

80
Q

Why does opioids tolerance dependance occur

A

Concept of receptor recycling
Failure to induce endocytosis of mu opioid receptor

Concepts of receptor uncoupling Who is dysfunction of interaction between mu receptor and G proteins

81
Q

What drug is used to reverse tolerance and dependence of opioid receptor

A

Methadone

82
Q

What is the treatment of opioid overdosage

A 
Naloxone IV when coma due to overdose
Naltrexone
Therapeutic measure
Methylnaltrexone
Nalmefene
Alvimopan
83
Q

Can you give full agonist with partial agonist opioids

A

Should be avoided.

84
Q

Can you use opioids in patients with head injuries

A

No due to carbon dioxide retention

85
Q

Can you use opioids during pregnancy

A

Can lead to dependence of fetus to opioids if dependence of mother during pregnancy

86
Q

What can you give to his fetus with mild withdrawal symptoms

A

Diazepam

87
Q

What can you give to a fetus with severe withdrawal symptoms

A

Camphorated tincture of opium

Doses of methadone

88
Q

Can you give opioids in patient with impaired pulmonary function

A

No can lead to acute respiratory failure

89
Q

Can you use opioids if impaired hepatic or renal function

A

Should be questions because of high half lives

90
Q

Can a patient with Addison’s disease or hyperthyroidism use opioids

A

No

91
Q

What are some cases of neuropathic pain

A

Trigeminal neuralgia
diabetic neuropathy
postherpetic neuralgia
phantom limb pain

92
Q

Can you use TCAs to treat neuropathic pain

A

Yes

93
Q

Type of TCAs used to treat neuropathic pain And mechanism of action

A

Amitriptyline
Nortriptyline
Desipramine
Inhibit noradrenaline reuptake

94
Q

Name of drugs that inhibits 5HT and NA uptake and is used in neuropathic pain

A

Venlafaxine

95
Q

name of drugs used to treat neuropathic pain that bind to a2d1 and a2d2 subunits of voltage activated calcium channels and reduce neurotransmitter release

A

Gabapentin

Pregabalin

96
Q

What drug is effective in trigeminal neuralgia only by blocking voltage gated sodium channels

A

Carbamazepine

97
Q

What are some antiepileptic agents used in neuropathic pain

A

Valproic acid
Lamotragine
oxcarbazepine
Topiramate

98
Q

Can you use lidocaine as a patch or IV in neuropathic pain states

A

Yes

99
Q

Can you use antidysrhythmic drugs like mexiletine taconite flecainide in neuropathic pain

A

Yes

100
Q

What is fibromyalgia

A

Chronic disorder with widespread musculoskeletal pain fatigue and insomnia associated with allodynia

101
Q

What is the treatment of fibromyalgia

A

Antidepressant drugs
Antiepileptic agents
benzodiazepines
dopamin agonist

102
Q

What is a textbook migraine attack consist of

A

Initial visual disturbance followed by Blindspot’s

severe throbbing 30 minutes later with headaches , photophobia ,nausea, vomiting ,prostration

103
Q

What happens during migraine

A

Trigeminal nerve release peptide neurotransmitter like calcitonin gene related peptide , substance P, Neurokinin A

extravasation of plasma and plasma proteins in perivascular space

mechanical stretching due to perivascular edema

activation of pain nerve ending in Dura

104
Q

Why does headache sometimes occur in migraine

A

Increased amplitude of temporal artery pulsations

105
Q

What is the therapy for migraine

A 
Triptans
 Ergot alkaloids 
NSAIDs and paracetamol 
beta adrenoceptor blockers
calcium channel blockers
 tricyclic antidepressants 
SSRIs
antiseizures agents
106
Q

Triptans, ergot alkaloids and antidepressant MOA

A

Activate 5HT1D/1B on presynaptic trigeminal nerve endings which prevents release of vasodilating agents

Direct 5HT agonists for vasoconstriction

107
Q

First line therapy for acute severe migraine attacks

A

Sumatriptan

108
Q

Medication to control pain of migraine

A

Aspirin , ibuprofen

109
Q

What do you give to patients with severe nausea and vomiting in migraine

A

Parenteral metoclopramide

110
Q

Migraine prophylaxis

A

Propranolol
Amitriptyline
Calcium channel blockers

Valproic acid
Topiramate
Verapamil

111
Q

Medication used to reduce severity of acute attack

A

Flunarizine, CCB

112
Q

See table in power point

A
113
Q

Where do NSAIDs mostly act

A

Peripheral nervous system

114
Q

Traditional NSAIDs

A 
Aspirin 
Sufasalazine 
Methhyl salicylate 
Ibuprofen 
Diclofenac 
Mefenamic acid 
Piroxicam
Indomethacin
Sulindac
Ketoprofen
Ketorolac
115
Q

NSAIDS COX 2 inhibitors

A

Celecoxib

Eterocoxib

116
Q

What does COX1 produces in git

A

Prostaglandins that are cytoprotective

117
Q

Expression of Cox 2 during inflammation

A

Increased to produce prostaglandins to promote more inflammation

118
Q

MOA of traditional NSAIDA

A

Non selective inhibition Cox2 and Cox 1

119
Q

Most well known Side effects of traditional NSAIDs

A

Ulcers due to activation of cox1 leading to less prostaglandins so less cytoprotectioj

120
Q

Are prostaglandins vasodilators

A

Yes

121
Q

Why do you give H1 and H2 receptor antagonist before giving NSAIDS IN systemic mastocytosis

A

Because NSAIDs can lead to mast cell degranulation causing release histamine release worsening inflammation

122
Q

What NSAIDs can be used to close ductus arteriosus

A

Indomethacin by blocking prostaglandins and preventing opening of vessel

123
Q

Can chronic intake of NSAIDs cause colon cancer

A

Yes

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