Pharmacology Of Pain Flashcards
What is pain
Unpleasant sensory and emotional experience associated with actual or potential tissue damage
Function of pain
Protection
Alterness about problem in body
Protects from further injury
Aids with healing
Fibers involved in reception of noxious signals
A delta fibers
C fibers
Type of pain for C fibers
Polymodal, dull , diffuse, burning pain
A delta fibers type of pain
Sharp, well localized pain
How does tissue injury leads to pain
Tissue injury -> inflammatory mediators -> pain
What are the algogenic substances involved in nociceptor activation
Bradykinin in blood
Kallidin in tissues
Serotonin
What are the algogenic substances involved in nociceptor sensitization
Histamine
Prostaglandins
Leukotrienes
What are the algogenic substances involved in hyperalgesia
H+
Adenosine
What are the algogenic substances involved in nociceptor sensitization and stimulation
Cytokines
Neurotransmitters of nociception
Neuropeptides Tachykinins Substance p Calcitonin gene related peptide Aspartate Somatostatin Neurotrophins
Receptor involved in nociception
Neurotrophin receptors (tyrosine kinase receptor, transient receptor potential receptor TRPV1, TRPV3)
Tachykinin receptor
Purinergic receptor (adenosine triphosphate receptor )
Opioid receptors
Cannabinoid receptors
What is the pathway of pain
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
What are the steps in pain prpocessing
Transduction Transmission Modulation Perception Sensitisation
Medications involved in pain transduction
NSAIDs Antihistamines Membrane stabilizing agenys Local anesthetic cream Opioids Bradykinin and serotonin antagonist
Medicatons involved in transmission of pain
Local anesthetics
Epidural block
Medications involved in modulation of pain
Spinal opiods Alpha 2 agonists NMDA receptor antagonists Anticholinesterase NSAIDs CCK antagonists NO inhibitors Potassium channel opener
Medications involved in perception of pain
Parenteral opioids
Alpha 2 agonists
General anesthetics
Different form of classifying pain
Etiology Mechanism Duration Location Intensity
Etiologic classfication of pain
Malignant
Benign
Idiopathic
Classfication of pain based on mechanism
Nociceptive
Neuropathic
Classification of pain based on duration
Acute
Chronic
Breakthrough
Classfication of pain based on intensity
Mild
Moderate
Severe
2 types of nociceptive pain
Somatic
Visceral
What causes somatic pain
Activation of nociceptor at surface tissue or deep tissue like bone, joint etc
What causes visceral pain
Caused by activation of nociceptor in viscera due to infection, fluid or gas, stretching, compression or solid tumor
What can cause neuropsthic pain
Structural damage and nerve cell dysfunction in PNS or CNS
Type of alalgesic agents
Opioids
NSAIDS
Antimigraine agents
What does opium contains
Morphine
Codeine
Thebaine
Papaverine
Semi synthetic opiods
Hydromorphone Hydrocodone Oxycodone Oxymorphone Diacetylmorphine (heroin) Dipropanoylmorphine Benzylmorphine Ethylmorphine
Synthetic opioids
Fentanyl Alfetanyl Remifentanil sufentanyl Pethidine Methadone Tramadol Propoxyphene Buprenorphine Pentazocine
Endogenous opioid peptide
Endorphins
Enkephalin
Dynorphins
Endomorphins
Opiod receptor types
Mu Delta Kappa ORL Nociceptin receptor
Subtypes of mu receptor
1
2
3
Location of mu receptor
Brain (cortex, thalamus, striosomes, periaqueductal gray, rostrl ventromedial medulla )
Spinal cord ( substantia gelatinosa)
Peripheral sensory neurons
Intestinal tract
Function of mu1 receptor
Analgesia
Physical dependance
Function of mu2 receptor
Respiratory depression Meiosis Euphoria Reduced GI motility Physical dependance
Function of mu3 receptor
Vasodilation
Delta receptor location
Brainn (pontine nuclei, amygdala, olfactory bulb, deep cortex)
Peripheral sensory neurons
Delta receptor function
Analgesia Antidepressant Convulsant Physical dependance Modulation of mu receptor ]
Kappa receptor location
Brain Hypothalamus Periaqueductal gray Claustrum Spinal cord Substantia gelatinosa Peripheral sensory neuron
Function of kappa receptor
Analgesia Anticonvulsant effect Depression Hallucinogenic effect Diuresis Dysphoria Meiosis Neuroprotection Sedation Stress
nociceptin receptor location
Brain ( cortex, amygdala , hippocampus, septal nuclei, habenula, hypothalamus )
Spinal cor
Nociceptin receptor function
Anxiety
Depression
Appetite
Development of tolerance to mu agonists
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
Opioids pure agonists
Endogenous or synthetic peptides
Non peptides like etorphine and methadone
Opioids pure agonist mode of action
High affinity for mu receptor
Why does methadone has wide range of effect
Has activity at other non opioid site
Opioids Partial agonist example
Codeine
Dextropropoxyphene
Considered weak compared to morphine
Opioid mixe agonist - antagonist action non what receptor
Kappa agonist
Mu antagonist
Example of opioid mixed agonist antagonist medicaitons
Nalorphine
Pentazocine
Opioid antagonist drugs
Naloxone
Naltrexone
How do admister most opioids
Sc
Po
Why should you give much higher dose of certain opioids like morphine
1st pass metabolism
Why are codeine and oxycodone effective orally
Reduced 1st pass metabolims
How are opioids metabolized
Converted to glucuronides -> excretion through kidneys
Morphine metabolism
Morphine conjugated to morphine 3 glucuronide
10% becomes morphine 6 glucuronide
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
Property of M6G and M3G
Neuroexcitatory effect
What should you consider before administering morphine or hydromorphone
If theres renal failure
Phenylpiperidine (pethidine, fentanyl, alfentanil, sufentanil ) metabolism
Hepatic oxidative metabolism
Consequence of high concentration norpethidine
Seizures
Does fentanyl have active metabolite
No
What metabolizes fentanyl
P450 CYYP3A4 through dealkylation in liver
Codeine oxycdone and hydrocodone metabolism
CYP2D6
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
How are opioids metabolites excreted
Through urine
Can persistent administration of opioid analgesic like morphine , fentanyl and remifentanil lead to hyperalgesia
Yes
Opioïdes Effect on CNS
Analgesia euphoria sedation hypnosis respiratory depression cough suppression Miosis nausea vomiting temperature
Opioids cv effect
Cardiovascular effects - Bradycardia , tachycardia for pethidine
Opioids git effect
GIT effect- constipation
Ooioids biliary effect
Biliary tract - biliary colic , reflux of biliary and pancreatic secretioN ,elevated plasma amylase and lipase
Opioids neuroendocrine effevt
Neuroendocrine - Release of ADH prolactin somatotropin , inhibition of LH release
Opioid renal effect
Depression of renal function
mu opioid with anti-diuretic effect
enhancement of Renal tubular sodium reabsorption
Opioids effects on uterus
Prolong labor
reduced uterine tune
Opioids to affect on the skin
Pruritus flushing warming of skin sweating urticaria
Opioids effect on immune system
Modulate immune system with effect on lymphocytes proliferation , antibody production , chemotaxis
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
Does Morrison and surrogates lose effectiveness over repeated therapeutic those
Yes
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
What drug is used to reverse tolerance and dependence of opioid receptor
Methadone
What is the treatment of opioid overdosage
Naloxone IV when coma due to overdose Naltrexone Therapeutic measure Methylnaltrexone Nalmefene Alvimopan
Can you give full agonist with partial agonist opioids
Should be avoided.
Can you use opioids in patients with head injuries
No due to carbon dioxide retention
Can you use opioids during pregnancy
Can lead to dependence of fetus to opioids if dependence of mother during pregnancy
What can you give to his fetus with mild withdrawal symptoms
Diazepam
What can you give to a fetus with severe withdrawal symptoms
Camphorated tincture of opium
Doses of methadone
Can you give opioids in patient with impaired pulmonary function
No can lead to acute respiratory failure
Can you use opioids if impaired hepatic or renal function
Should be questions because of high half lives
Can a patient with Addison’s disease or hyperthyroidism use opioids
No
What are some cases of neuropathic pain
Trigeminal neuralgia
diabetic neuropathy
postherpetic neuralgia
phantom limb pain
Can you use TCAs to treat neuropathic pain
Yes
Type of TCAs used to treat neuropathic pain And mechanism of action
Amitriptyline
Nortriptyline
Desipramine
Inhibit noradrenaline reuptake
Name of drugs that inhibits 5HT and NA uptake and is used in neuropathic pain
Venlafaxine
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
What drug is effective in trigeminal neuralgia only by blocking voltage gated sodium channels
Carbamazepine
What are some antiepileptic agents used in neuropathic pain
Valproic acid
Lamotragine
oxcarbazepine
Topiramate
Can you use lidocaine as a patch or IV in neuropathic pain states
Yes
Can you use antidysrhythmic drugs like mexiletine taconite flecainide in neuropathic pain
Yes
What is fibromyalgia
Chronic disorder with widespread musculoskeletal pain fatigue and insomnia associated with allodynia
What is the treatment of fibromyalgia
Antidepressant drugs
Antiepileptic agents
benzodiazepines
dopamin agonist
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
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
Why does headache sometimes occur in migraine
Increased amplitude of temporal artery pulsations
What is the therapy for migraine
Triptans Ergot alkaloids NSAIDs and paracetamol beta adrenoceptor blockers calcium channel blockers tricyclic antidepressants SSRIs antiseizures agents
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
First line therapy for acute severe migraine attacks
Sumatriptan
Medication to control pain of migraine
Aspirin , ibuprofen
What do you give to patients with severe nausea and vomiting in migraine
Parenteral metoclopramide
Migraine prophylaxis
Propranolol
Amitriptyline
Calcium channel blockers
Valproic acid
Topiramate
Verapamil
Medication used to reduce severity of acute attack
Flunarizine, CCB
See table in power point
Where do NSAIDs mostly act
Peripheral nervous system
Traditional NSAIDs
Aspirin Sufasalazine Methhyl salicylate Ibuprofen Diclofenac Mefenamic acid Piroxicam Indomethacin Sulindac Ketoprofen Ketorolac
NSAIDS COX 2 inhibitors
Celecoxib
Eterocoxib
What does COX1 produces in git
Prostaglandins that are cytoprotective
Expression of Cox 2 during inflammation
Increased to produce prostaglandins to promote more inflammation
MOA of traditional NSAIDA
Non selective inhibition Cox2 and Cox 1
Most well known Side effects of traditional NSAIDs
Ulcers due to activation of cox1 leading to less prostaglandins so less cytoprotectioj
Are prostaglandins vasodilators
Yes
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
What NSAIDs can be used to close ductus arteriosus
Indomethacin by blocking prostaglandins and preventing opening of vessel
Can chronic intake of NSAIDs cause colon cancer
Yes
