Pharm 2 exam-S3 Flashcards
Conduction of electrical impulses to the CNS with major connections being in the dorsal horn of the spinal cord and thalamus with projections cingulate, insula, and somatosensory cortices?
Transmission
Process by which a noxious stimuli is converted to an electrical impulse in sensory nerve endings?
Transduction
What is the relay center in brain to cerebral cortex?
Thalamus
Process of altering pain transmission. It is likely that both inhibitory and excitatory mechanisms modulate pain impulse transmission in the PNS and CNS?
Modulation
Mediated through the thalamus acting as a central relay station for incoming pain signals and the primary somatosensory cortex serving for discrimination of specific sensory experiences?
Perception
This type of signaling takes time to reset and may only respond to a specific signal or pattern?
“All or Nothing response”
Temporal signaling
Can pain occur without one or more of the 4 steps of pain transmission?
Yes.
Phantom limb pain is an example
Type I nerve fibers?
Rapid, consistent, linear
A beta and A delta
Myelinated-polymodal fibers
Transmit thermal, chemical, and mechanical stimuli
Type II nerve fibers?
Different patterns, slower conduction
Initial pain response to heat
Saddle transmission
Rapid, consistent, linear
A beta and A delta
Myelinated-polymodal fibers
Transmit thermal, chemical, and mechanical stimuli
Type I nerve fibers
These fibers?
Different patterns, slower conduction
Initial pain response to heat
Saddle transmission
Type II nerve fibers
C-fiber afferents?
Unmyelinated
Slowest conduction
transmit burning pain and sustained pressure
These fibers are
Unmyelinated
Slowest conduction
transmit burning pain and sustained pressure
C-fibers
PGE2 and bradykinin both do what?
Modulate pain
CGRP and Substance P released from sensory nerves to do what?
Pain transmission
This is a undecapeptide that acts on NK-1 receptors and is associated with pain processing in the amygdala, hypothalamus and periaqueductal gray?
Substance P
Substance P
P stands for ?
Powder
Substance P is found with ___ in primary afferents that respond to painful stimuli?
Glutamate
Do NK-1 receptor pain relieves exist?
NO
Calcitonin gene related peptide (CGRP) causes what?
Vasodilation in blood vessels and blocks pain
This system causes receptor hyperpolarization by increasing potassium conductance?
Endorphin, cannabinoid and acetycholine receptors belong to it?
Gi/O receptor system
Also known as capsaicin or Vanilloid receptors.
provide sensations of scalding heat or pain
Similar to NMDA voltage gated receptor?
Transient V receptor-1 (TVR1)
What are the directly activated inflammatory cells?
Bradykinin
Prostaglandins
Purines
Cytokines
What are the indirectly activated inflammatory cells?
Serotonin
Histamine
Arachidonic acid
This occurs when inflammatory effects do not resolve leading to hyperalgesia due to sensitization?
Chronic pain
Allodynia?
Perception of pain from normally non-painful stimuli and response to sensitization.
What in the brain controls lower level functioning?
Rostral ventral medulla
In the SPINAL CORD white matter is?
and Gray matter is where?
White outside
Gray inside
In the BRAIN white matter is?
and Gray matter is where?
White inside
Gray outside
Where is the first place in the brain to process information and decide what to do?
Prefrontal cortex
Lamina II is called the?
Substancia gelatinosa
Which neurotransmitter is found in the locus coerelius?
Norepinephrine
Which neurotransmitter is found in the medullary Raphe?
Serotonin
Rubbing of the skin stimulates which fibers which can inhibit the gate and diminish pain?
A-beta fibers
Which fibers open the gate?
A-delta and C fibers small and open
Which fibers close the gate?
A-beta large and close the gate.
Which fibers are associated with nociception?
A-delta and C fibers
Which fibers are associated with mechanoreceptors?
A-beta fibers
Opium resin comes from Papaver somniferum first use in 100AD.
Morphine isolated in 1806
Meperidine in 1940s
Morphine name comes from what?
Morpheus, greek god of sleep
Opium means?
Juice
Which covers all agents acting on morphine receptors?
Opiods
Narcotic means?
Stupor, greek
Opioid receptor Excitation or Inhibition?
Increase cAMP
Increase protein kinase A
Decrease K conduct
Increase Ca conduct
Increase AP
Excitation
Opioid receptor Excitation or Inhibition?
Increase K conduct
Decrease Ca conduct
Decrease AP
Inhibition
Mu receptors are mainly found where?
Brainstem, medial thalamus and spinal cord
K receptors are mainly found where?
Dorsal horn of spinal cord, brainstem and medullary reticular formation
Delta receptors are mainly found where?
Limbic system
These receptors cause analgesia, respiratory depression, physical dependence, miosis and decreased GI motility?
Mu receptors
These receptors cause supraspinal analgesia, sedation, dysphoria psychosis?
Kappa receptors
These receptors cause analgesia and diuresis?
Delta receptors
These neuropeptides are the most prevalent, bind to delta receptors and in the hypothalamus?
Enkephalins
These neuropeptides are known as endogenous morphine and bind to Mu receptors?
Endorphins
These neuropeptides are the most potent, bind to kappa receptors and associated with drug addiction, mood disorders?
Dynorphins
These neuropeptides bind with Mu receptors analgesic and antiinflammatory. Newly discovered tetrapeptide?
Endomorphines
Analgesia is mediated via receptors located where?
Dorsal horn
Periaqueductal gray matter
Thalamus
Ventral brainstem receptors mediate effects on?
Coughing, vomiting, respiration, pupillary diameter
Neuroendocrine functions controlled via the ?
Hypothalamus
Mood and behavior effects are controlled by receptors where?
Limbic system- amygdala
Primary action of opioid MOA is by doing what?
Decreasing neurotransmission by presynaptic inhibition of neurotransmitter release. Increase potassium conductance
Central or peripheral opioid effects?
Analgesia
Respiratory depression
Mood alteration
Sedation
Miosis
N/V
Cheyne-stokes resp
Central Opioid effect
Central or peripheral opioid effects?
Histamine release
Venous dilation
Smooth muscle contraction
Inhibition of ACh release
Decreased peristalsis/constipation
Peripheral Opioid effect
The main MOA of Opioid analgesia is by doing what?
Blocking Calcium influx
Increasing Potassium to hyperpolarize cell
Metabolism of opioids?
Well absorbed in GI tract, large first pass metabolism
Cross placenta well
Excreted via renal and biliary mechanisms
This chemical class of Opioids contains a 4 ring system, tertiary amine, pKa >8.
Levo isomers more active.
Morphine
Codeine
Thebain
Phenanthrenes
This chemical class of Opioids lack standard opioid activity
Papaverine
Noscapine
Benzylisoquinolines
Papaverine?
Smooth muscle relaxant, Benzylisoquinoline
PDEI increases cAMP
Noscapine?
Antitussive and anticancer
Benzylisoquinoline
Morphine, Hydromorphone, oxymorphone, Codeine, Heroin, Fentanyl are known as what?
Opioid Agonists
Morphine acts primarily at which receptors?
Mu receptors and some Kappa
Diacetylmorphine
Semisynthetic
Twice as potent as morphine
Enters CNS rapidly causing euphoria
HIGH addiction liability
Heroin
1/10th analgesic potency of morphine
Little risk of addiction
Potent antitussive
Codeine
Twice as potent as morphine
High euphoric liability
160mg XR tabs. Hillbilly heroin
Many deaths
Oxycodone/Oxycontin
Very potent synthetic 5x stronger than morphine
Less constipation
Long lasting
Levorphanol
Dextro-rotary isomer with “No” analgesic activity.
Effective antitussive
Dextromethorphan (Bromfed-DM)
Most widely used synthetic
1/10th potency of morphine
Frequently abused, NO miosis
Metabolized to nor-
Contraindicated with MAOI therapy
Meperidine (Demerol)
Same analgesic potency as morphine
Less sedation
Longer duration of action, slower elimination.
Used to counter withdrawal symptoms
Methadone
80x potency of morphine
Chemically related to meperidine
Short half life 12.5 mins
Used for continuous epidural and transdermal analgesia
Fentanyl
Selective Mu-receptor agonist
Has ester-linkage causes short DOA
Hydrolysis by esterases
Remifentanil
Veterinary use only
1000x potency of morphine
Large animal immobilizer
Toxic to humans
Etorphine
Opioid antagonists work by doing what?
Have receptor affinity but NO intrinsic activity
Blocks Mu receptors
Reverse opioid-induced respiratory depression
Which drug is a pure Mu antagonist normally given IV?
Naloxone
Which drug is similar to Naloxone, but has long half life and given orally. Used to treat alcoholics?
Naltrexone
Which drug is an oral Mu selective peripheral antagonist used for post-op ileus?
Almivopan
Analog of naltrexone, this is a nasal spray opioid antagonist. Rescue drug for opioid overdoses. Mu and delta antagonist
Nalmefene
Which drug is a partial opioid agonist, high affinity for mu receptors and weaker maximum response than other agonists. Less abuse potential, used to counteract heroine and morphine addiction.
Buprenorphine
Which drug is a mixed Opioid agonist/antagonist, veterinarian use only. Blocks mu receptor analgesia and sedation?
Nalorphine
This drug is a newer analgesic that acts to block re-uptake of serotonin and norepinephrine to decrease pain information.
Active metabolite and not entirely reversed by naloxone
less addiction
Increased bleeding if taken with warfarin
Avoid in epilepsy
Tramadol
Opioid abuse is due to?
Rapid tolerance development, euphoria and sedative effects.
Uncomfortable withdrawal symptoms
Use of butyrophenone(droperidol) and fentanyl and nitrous oxide is known as?
Neuroleptic anesthesia
Which drug class is responsible for inhibiting prostaglandin and thromboxane synthesis? Antipyretic, analgesic and anti-inflammatory properties?
NSAIDS
Which drug is similar to NSAID but bind irreversible inhibitor of COX?
Aspirin
This drug is similar to NSAIDS but NOT anti-inflammatory, will inhibit COX but not in periphery?
Acetaminophen (Tylenol)
These act through are Gi/O receptors with CB1 found in brain and CB2 found in immune system. Weak research and CBD questionable?
Cannabinoids
Alpha-2 Adrenergic Agonists function by what?
Decrease Norepinephrine release by stimulating pre-synaptic receptors to block vesicle fusion.
This drug is a partial Alpha-2 agonist used for cancer and non-cancerous pain, synergistically with opiods. Black box warning for maternal. Originally used for hypertension treatment?
Clonidine
This drug is a more potent Alpha-2 receptor agonist. Fewer side effects than clonidine, may be associated with demyelination following epidural dosing?
Dexmedtomidine
This drug is an Acetylcholinesterase inhibitor that blocks metabolism of acetycholine in synapse to keep volume high. Can stimulate muscarinic receptors for pain relief but has extensive side effects?
Neostigmine
This drug centrally acting nonopioid analgesic acts via NMDA receptor antagonist in dorsal horn of spinal cord. Side effects of sedation, headache, burning back pain, psychotic reactions.
No respiratory depression?
Ketamine
This drug is a centrally acting nonopioid analgesic acts at GABAa receptors to enhance inhibition and block pain. Lamina II, No neurotoxic effects, can also stimulate endogenous opiods?
Midazolam
This drug belongs to Conopeptides, derived from marine snail. Selective antagonist of neuronal N type voltage gated calcium channels. Blocks NE release and acts as a sympatholytic.
Side effects very common >90%, SI, dizziness, confusion, ataxia, memory impaired. Very high Costs, VERY toxic.
Ziconotide
This drug is a GABAb agonist, acts via G-protein system to activate potassium channels and hyperpolarize. Works on Lamina II and III presynaptically. Common use for back pain and cerebral palsy. Rare side effect is rhabdomyolysis.
Baclofen
Which drug is associated with Neuroleptic anesthesia?
Droperidol
Which nervous system controls skeletal muscles?
Somatic
Which nervous system controls all bodily functions required for life?
Autonomic nervous system
Which two nervous systems control homeostatic functions?
Sympathetic and Parasympathetic
Motor units are innervated by a single nerve fiber with axonal branches.
Somatic nervous system
Based on motor units, do more or less muscle fibers = more control over muscle?
Less muscle fibers have more control.
Think fingers vs thighs(poor)
Nerve fibers do not synapse until they reach what?
Motor end plate. Very long axons
Which transmitter is at the motor end plate and what receptor?
Acetycholine transmitter
Nicotinic N1 Receptor (Ionophore pentameric system)
This system is critical in maintenance of body homeostasis, regulating hormonal secretions and smooth muscles?
Autonomic Nervous sytem
Heart rate is controlled via which predominant system?
Parasympathetic nervous system
Pre-ganaglionic transmitter/receptor of both sympathetic and parasympathetic are?
Nicotinic
Acetycholine
Post-ganglionic Sympathetic transmitter/receptor?
Adrenergic
Norepinephrine
Post-ganglionic Parasympathetic transmitter/receptor?
Muscarinic
Acetycholine
This system controls mainly sedentary functions, Exits spinal column at Cranio-Sacral regions.
Synapses to ganglia close to innervated tissue.
1:1 ratio. Fine control
increased GI secretion, Miosis(constriction) of eyes, Accomidation of eyes.
Pre- acetycholine (N)
Post-acetycholine (M)
Parasympathetic nervous system
This system controls Fight or Flight.
Exits spinal column at Thoraco-lumbar regions.
Synapses ganglia close to spinal cord
1:10 to 1:100 ratio Wide control
Mydriasis(dilation), BP up, Glucose up, temp up.
Pre-acetycholine
Post- Norepinephrine
Sympathetic Nervous sytem
What secretes epinephrine and norepinephrine?
Adrenal Medulla
Ratio of EPI to Norepi secreted by Adrenal Medulla?
80:20
EPI : Norepi
What structure receives pre-ganglionic fibers then outputs transmitter into bloodstream instead of a synapse in the SNS?
Adrenal Medulla
Why are Ganglionic Blockers not used anymore?
A lot of side effects due to nonspecific blocking of predominant tone. Blocks both PNS and SNS.
Only _____ ganglionic blockers can completely block the transmission through ganglia?
Nicotinic
Which Ganglionic blocker is a non-depolarizing blocker that doesn’t stimulate the receptor but acts by competing for binding site?
Hexamethonium
Which Ganglionic blocker is a non-depolarizing blocker that acts on a secondary site via NON-competitive to decerease ACh binding?
Mecamylamine
Hexamethonium blocks the ion channel by acting as a plug which is often unpredictable in its affects such as?
Nicotine can increase HR via SNS or depress HR by PNS.
Can also trigger release of epinephrine from adrenal medulla to increase HR and Blood pressure.
Decreased sweating, salivation, mydriasis, decreased GI tone, hypotension, urinary retention, constipation, hypoglycemia.
Primary controller of heart rate is?
Veins
Mecamylamine has orphan drug status and is used today for?
Treating Tourette’s syndrome and cocaine and nicotine addictions
Decreases dopamine and norepinephrine release
Succinycholine?
Depolarizing NMBA
Dual Ester structure
Very short duration 1-2 mins
Onset very short 30 secs
Fasiculations, Increased potassium, MH, Bradycardia
Histamine release
Short acting steroidal non-depolarizing NMBA?
Rocuronium
20-60 mins
Intermediate acting NMBA?
Atracurium, Cisatracurium, Vecuronium
30-60 mins
Long acting NMBA?
Pancuronium
60-120 mins
Which drug is metabolized by esterases and Hofmann elimination to produce toxic CNS excitatory laudanosine that causes seizures?
Atricurium
Cisatricurium metabolized by what?
Hoffman elimination
Mivacurium metabolized by what?
Plasma esterases
What causes Hoffman elimination to speed up?
Increase in temp
Increase in pH
What causes Hoffman elimination to slow down?
Decrease in temp
Decrease in pH
Which NMBA not to give to renal patients?
Pancuronium
Steroidals
Which NMBA not to give to hepatic disease patients?
Rocuronium and Vecuronium
Steroidals
Which NMBA have moderate histamine releasing potential and should be avoided in asthma or cardiac patients?
Succinycholine
Atracurium
Best NMBA to give for asthmatic or cardiac patient?
Rocuronium
Avoid this NMBA in patients with Myasthenia gravis as it can cause prolonged block?
Pancuronium
Tachycardia is most common with which NMBA?
Pancuronium
Malignant hyperthermia is caused and triggered by what?
Succinycholine and Volatile gas agents
Caused by uncontrolled release of Ca from SR in skeletal muscle.
