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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
What causes somatic pain
Activation of nociceptor at surface tissue or deep tissue like bone, joint etc
26
What causes visceral pain
Caused by activation of nociceptor in viscera due to infection, fluid or gas, stretching, compression or solid tumor
27
What can cause neuropsthic pain
Structural damage and nerve cell dysfunction in PNS or CNS
28
Type of alalgesic agents
Opioids NSAIDS Antimigraine agents
29
What does opium contains
Morphine Codeine Thebaine Papaverine
30
Semi synthetic opiods
``` Hydromorphone Hydrocodone Oxycodone Oxymorphone Diacetylmorphine (heroin) Dipropanoylmorphine Benzylmorphine Ethylmorphine ```
31
Synthetic opioids
``` Fentanyl Alfetanyl Remifentanil sufentanyl Pethidine Methadone Tramadol Propoxyphene Buprenorphine Pentazocine ```
32
Endogenous opioid peptide
Endorphins Enkephalin Dynorphins Endomorphins
33
Opiod receptor types
``` Mu Delta Kappa ORL Nociceptin receptor ```
34
Subtypes of mu receptor
1 2 3
35
Location of mu receptor
Brain (cortex, thalamus, striosomes, periaqueductal gray, rostrl ventromedial medulla ) Spinal cord ( substantia gelatinosa) Peripheral sensory neurons Intestinal tract
36
Function of mu1 receptor
Analgesia | Physical dependance
37
Function of mu2 receptor
``` Respiratory depression Meiosis Euphoria Reduced GI motility Physical dependance ```
38
Function of mu3 receptor
Vasodilation
39
Delta receptor location
Brainn (pontine nuclei, amygdala, olfactory bulb, deep cortex) Peripheral sensory neurons
40
Delta receptor function
``` Analgesia Antidepressant Convulsant Physical dependance Modulation of mu receptor ] ```
41
Kappa receptor location
``` Brain Hypothalamus Periaqueductal gray Claustrum Spinal cord Substantia gelatinosa Peripheral sensory neuron ```
42
Function of kappa receptor
``` Analgesia Anticonvulsant effect Depression Hallucinogenic effect Diuresis Dysphoria Meiosis Neuroprotection Sedation Stress ```
43
nociceptin receptor location
Brain ( cortex, amygdala , hippocampus, septal nuclei, habenula, hypothalamus ) Spinal cor
44
Nociceptin receptor function
Anxiety Depression Appetite Development of tolerance to mu agonists
45
Mechanism of action of oiod receptor
``` Opioid + receptor complex Receptor activation Inhibition of adenylate cyclase Dcreased cAMP K+ channel opening , hyperpolarization, inhibition of Ca channels opioid response ```
46
Opioids pure agonists
Endogenous or synthetic peptides | Non peptides like etorphine and methadone
47
Opioids pure agonist mode of action
High affinity for mu receptor
48
Why does methadone has wide range of effect
Has activity at other non opioid site
49
Opioids Partial agonist example
Codeine Dextropropoxyphene Considered weak compared to morphine
50
Opioid mixe agonist - antagonist action non what receptor
Kappa agonist | Mu antagonist
51
Example of opioid mixed agonist antagonist medicaitons
Nalorphine | Pentazocine
52
Opioid antagonist drugs
Naloxone | Naltrexone
53
How do admister most opioids
Sc | Po
54
Why should you give much higher dose of certain opioids like morphine
1st pass metabolism
55
Why are codeine and oxycodone effective orally
Reduced 1st pass metabolims
56
How are opioids metabolized
Converted to glucuronides -> excretion through kidneys
57
Morphine metabolism
Morphine conjugated to morphine 3 glucuronide | 10% becomes morphine 6 glucuronide
58
Co administration of what drug can cause enhancement of CNs uptake of M3G and M6G
Probenecid and other drugs that inhibit p-glycoprotein drug transporter
59
Property of M6G and M3G
Neuroexcitatory effect
60
What should you consider before administering morphine or hydromorphone
If theres renal failure
61
Phenylpiperidine (pethidine, fentanyl, alfentanil, sufentanil ) metabolism
Hepatic oxidative metabolism
62
Consequence of high concentration norpethidine
Seizures
63
Does fentanyl have active metabolite
No
64
What metabolizes fentanyl
P450 CYYP3A4 through dealkylation in liver
65
Codeine oxycdone and hydrocodone metabolism
CYP2D6
66
CYP2D5 polymorphism for codeine, oxycodone and hydrocone
Minor consequence for oxycodone and hydrocodone Oxycodone may accumulate if renal failure Codeine can lead to no repsonse or exagerated response
67
How are opioids metabolites excreted
Through urine
68
Can persistent administration of opioid analgesic like morphine , fentanyl and remifentanil lead to hyperalgesia
Yes
69
Opioïdes Effect on CNS
``` Analgesia euphoria sedation hypnosis respiratory depression cough suppression Miosis nausea vomiting temperature ```
70
Opioids cv effect
Cardiovascular effects - Bradycardia , tachycardia for pethidine
71
Opioids git effect
GIT effect- constipation
72
Ooioids biliary effect
Biliary tract - biliary colic , reflux of biliary and pancreatic secretioN ,elevated plasma amylase and lipase
73
Opioids neuroendocrine effevt
Neuroendocrine - Release of ADH prolactin somatotropin , inhibition of LH release
74
Opioid renal effect
Depression of renal function mu opioid with anti-diuretic effect enhancement of Renal tubular sodium reabsorption
75
Opioids effects on uterus
Prolong labor | reduced uterine tune
76
Opioids to affect on the skin
``` Pruritus flushing warming of skin sweating urticaria ```
77
Opioids effect on immune system
Modulate immune system with effect on lymphocytes proliferation , antibody production , chemotaxis
78
What are the clinical uses of opioids
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
Does Morrison and surrogates lose effectiveness over repeated therapeutic those
Yes
80
Why does opioids tolerance dependance occur
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
What drug is used to reverse tolerance and dependence of opioid receptor
Methadone
82
What is the treatment of opioid overdosage
``` Naloxone IV when coma due to overdose Naltrexone Therapeutic measure Methylnaltrexone Nalmefene Alvimopan ```
83
Can you give full agonist with partial agonist opioids
Should be avoided.
84
Can you use opioids in patients with head injuries
No due to carbon dioxide retention
85
Can you use opioids during pregnancy
Can lead to dependence of fetus to opioids if dependence of mother during pregnancy
86
What can you give to his fetus with mild withdrawal symptoms
Diazepam
87
What can you give to a fetus with severe withdrawal symptoms
Camphorated tincture of opium | Doses of methadone
88
Can you give opioids in patient with impaired pulmonary function
No can lead to acute respiratory failure
89
Can you use opioids if impaired hepatic or renal function
Should be questions because of high half lives
90
Can a patient with Addison’s disease or hyperthyroidism use opioids
No
91
What are some cases of neuropathic pain
Trigeminal neuralgia diabetic neuropathy postherpetic neuralgia phantom limb pain
92
Can you use TCAs to treat neuropathic pain
Yes
93
Type of TCAs used to treat neuropathic pain And mechanism of action
Amitriptyline Nortriptyline Desipramine Inhibit noradrenaline reuptake
94
Name of drugs that inhibits 5HT and NA uptake and is used in neuropathic pain
Venlafaxine
95
name of drugs used to treat neuropathic pain that bind to a2d1 and a2d2 subunits of voltage activated calcium channels and reduce neurotransmitter release
Gabapentin | Pregabalin
96
What drug is effective in trigeminal neuralgia only by blocking voltage gated sodium channels
Carbamazepine
97
What are some antiepileptic agents used in neuropathic pain
Valproic acid Lamotragine oxcarbazepine Topiramate
98
Can you use lidocaine as a patch or IV in neuropathic pain states
Yes
99
Can you use antidysrhythmic drugs like mexiletine taconite flecainide in neuropathic pain
Yes
100
What is fibromyalgia
Chronic disorder with widespread musculoskeletal pain fatigue and insomnia associated with allodynia
101
What is the treatment of fibromyalgia
Antidepressant drugs Antiepileptic agents benzodiazepines dopamin agonist
102
What is a textbook migraine attack consist of
Initial visual disturbance followed by Blindspot’s severe throbbing 30 minutes later with headaches , photophobia ,nausea, vomiting ,prostration
103
What happens during migraine
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
Why does headache sometimes occur in migraine
Increased amplitude of temporal artery pulsations
105
What is the therapy for migraine
``` Triptans Ergot alkaloids NSAIDs and paracetamol beta adrenoceptor blockers calcium channel blockers tricyclic antidepressants SSRIs antiseizures agents ```
106
Triptans, ergot alkaloids and antidepressant MOA
Activate 5HT1D/1B on presynaptic trigeminal nerve endings which prevents release of vasodilating agents Direct 5HT agonists for vasoconstriction
107
First line therapy for acute severe migraine attacks
Sumatriptan
108
Medication to control pain of migraine
Aspirin , ibuprofen
109
What do you give to patients with severe nausea and vomiting in migraine
Parenteral metoclopramide
110
Migraine prophylaxis
Propranolol Amitriptyline Calcium channel blockers Valproic acid Topiramate Verapamil
111
Medication used to reduce severity of acute attack
Flunarizine, CCB
112
See table in power point
113
Where do NSAIDs mostly act
Peripheral nervous system
114
Traditional NSAIDs
``` Aspirin Sufasalazine Methhyl salicylate Ibuprofen Diclofenac Mefenamic acid Piroxicam Indomethacin Sulindac Ketoprofen Ketorolac ```
115
NSAIDS COX 2 inhibitors
Celecoxib | Eterocoxib
116
What does COX1 produces in git
Prostaglandins that are cytoprotective
117
Expression of Cox 2 during inflammation
Increased to produce prostaglandins to promote more inflammation
118
MOA of traditional NSAIDA
Non selective inhibition Cox2 and Cox 1
119
Most well known Side effects of traditional NSAIDs
Ulcers due to activation of cox1 leading to less prostaglandins so less cytoprotectioj
120
Are prostaglandins vasodilators
Yes
121
Why do you give H1 and H2 receptor antagonist before giving NSAIDS IN systemic mastocytosis
Because NSAIDs can lead to mast cell degranulation causing release histamine release worsening inflammation
122
What NSAIDs can be used to close ductus arteriosus
Indomethacin by blocking prostaglandins and preventing opening of vessel
123
Can chronic intake of NSAIDs cause colon cancer
Yes

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