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Pharmacology I - Test 2
U of D Pharm Test 2
100
Pharmacology
Graduate
10/03/2013

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Term
Pain Definitions (Three).
Definition
It is what the patient says it is.
Unpleasant sensory and emotional experience associated with actual or ptential tissue damage.
A protective mechanism that occurs when tissues are being damaged.
Term
Hyperalgesia.
Definition
Decreased pain threshold.

A hyper reactive response inappropriate to the level of stimulus. A small stimulus that causes a great amount of pain.
Term
Windup Phenomenon.
Definition
Synaptic potentials increase with amplitude with each repeated stimulus. Pain gets greater with each stimulus causing the pain.
Term
What is a nociceptor?
Definition
Pain receptor.
Term
Allodynia.
Definition
Pain evoked by a non-noxious stimulus. A stimulus that normally does not cause pain.
Term
What is preemptive analgesia?
Definition
Analgesic given prior to stimulus.
Prevents altered central processing.
Term
Define Acute Pain (4 things).
Definition
Rapid, defined onset with limited duration.

A protective mechanism.

Associated with anxiety, sympathetic hyper-activity.

Provoked (result of tissue injury).
Term
What are the two types of acute pain?
Definition
monophasic - one time cause, surgery.

Recurrent - Headaches or inflamed bowel.
Term
Define Chronic pain.
Definition
Delayed, poorly defined onset.

Unpredictable, protracted (lasting long time) duration.

Autonomus; independent of trigger.
Term
What is associated with chronic pain?

What may be associated with chronic pain?
Definition
Depression associated.

Allodynia and hyperagesia may be associated.
Term
Skeletal muscle spasm.
Definition
Pain caused by muscle spasm stimulating pain receptors.
Term
What is fast pain?
Definition
Short, well localized. Matched to type of stimulus.
Mediated by type A-Delta myelinated nerve fibers.
Term
What is slow pain?
Definition
Throbbing, burning, or aching pain.
Poorly localized and less specific to type of stimulus.
Carried by unmyelinated type C fibers.
Term
Characteristics of temperature sensation?
Definition
Follows same path as slow pain.
Pain from heat occurs at 43 deg Celcius.
Tissue damage occurs at same temp, making demonstrating pain as a protective mechanism.
Term
What are the two types of visceral pain?
Definition
Visceral and Somatic.
Term
Define Visceral Pain.
Definition
Assoicated with cramping pain caused by ischemia caused by stretching, distension, and spasm.
Term
What kinds of organs is cramping pain specific to?
Definition
Visceral pain to the hollow organs such as bowel, bladder, gastric, and uterine.
Term
What kind of organs is a sharp pain specific to?
Definition
Visceral pain to the solid organs such as liver.
Term
Define somatic pain.
Definition
A sharp stabbing pain, well localized.
Arises from skeletal muscle, skin, and peritoneum.
Term
Describe Neuropathic Pain.
Definition
Peripheral or central stimulation.
Often not responsive to opiates.
Nerve Pain.
Term
Perception of pain is a subjective experience. What three areas that compose this subjective perception?
Definition
Sensory - Intensity, location and duration.
Affective - The emotional, unpleasantness.
Cognitive - The awareness of implications, fear and anxiety.
Term
What influences pain response?
Definition
Genetics.
Chemical.
gender.
cultural.
previous perceptions/experience.
Term
What kind of activity is provoked by pain in the anatomic nervous system?
Definition
Efferent activity. Motor response to avoid or correct painful stimuli.
Term
Spontaneous firing can occur from the reusult of?
Definition
Nerve injury.
Interuptions of the peripheral nerves of the dorsal root ganglia. ie. amputation or nerve transection.
Term
Describe complex regional pain syndrom. (long)
Definition
First described in civil war "causalgia".
Consists of extreme hyperalgesia/allodynia.
Unknown physiology.
Nocioception maintained by increased sympathetic system.
Term
What does the increased sympathetic response in complex regional pain syndrome eventually lead to?
Definition
Changes at all neuraxial levels leading to sensitization of pain pathways maintaining chronic neuropathy.
Term
What is the primary receptor that is activated in the sensitization of the dorsal horn? What drug has the potential to be a antagonist to this?
Definition
N-methyl-D-Asparate (NMDA).

Ketamine.
Term
What does the pathophysiology of pain involve? (four things)
Definition
Transduction.
Transmission.
Modulation.
Perception.
Term
Define Transduction.
Definition
Noxious stimuli translated into electrical activity.
Noxious stimuli activates peripheral terminals of primary afferent sensory neurons.
The action potentials are conducted to dorsal horn of spinal cord.
Term
Describe transduction as it relates to nociceptor activation.
Definition
Injury stimulates Protaglandin, serotonin, and bradykinins to activate pain fibers.
Term
During transduction what do the peripheral neurons release?
Definition
Substance P and other mediators.
Transduction activates mast cells, vasoidilates peripheral vessels and recruits other receptors.
Term
Describe nociceptors in terms of their nerve endings.
Definition
Nociceptors have open affernet nerve endings of myelinated A-delta and C-delta fibers.
Term
What are the two types of A-delta neruons?
Definition
Mechanosensitive and Mechanothermal.
Term
What kind of stimuli are polynodal C sensitive to?
Definition
Heat, mechanical and chemical stimuli.
Term
What can stimulate polynodal C type nociceptors?
Definition
Acetylcholine, bradykinin, histamine, prostaglandins, and K+.
Term
Do pain receptors adapt?
Definition
No, they act as a protective mechanism that allows for constant awareness of injury.
Term
Describe Transmission (periphery to spinal cord).
Definition
Impulse travels via axons of the primary afferent neurons to the dorsal horn of the spinal cord.
Impulses are then propagated across the dorsal horn via the interneurons where the impulse is forwarded to brain.
Term
What are the tracts called that the dorsal horn projects tot he brain?
Definition
Ascending Tracts
Term
How are pain signals transmitted to the thalmus?
Definition
Via the spinothalmic tract (ascending trat).
Term
What transmits pain informaion to reticular formation, mesencephalon, and hypothalamus?
Definition
spinoreticular, spinomesenecephalic, and spinohypothalamic tracts.
Name begins where impuls is coming from.
Term
How do opioids block the flow of information?
Definition
Opioids can inhibit sensations at the dorsal horn and can bind to sites in the brain to activate descending pathways to further inhibit.
Term
What drug mimics GABA to inhibit nociceptive transmission?
Definition
Baclofen.
Term
Where do the afferent A-Delta fibers enter and terminate in the spinal cord?
Definition
Enter - dorsal nerve roots.
Terminate - dorsal horn laminae 1, 5.
Term
After termination in 1 and 5 in the dorsal horn, what do the fibers of afferent A-Delta do?
Definition
Excite second order neurons of the spinothalamic tract then give rise to long fibers which cross to the opposite side of the spinal cord and up to the brain via the neospinalthalmic pathway.
Term
Describe A Delta Fibers
Definition
Fast transmission fiber.
Lightly myelinated.
Ascending pathway: neospinothalamic tract.
Sense: intense, sharp, stinging pain.
Can localize and stimulate withdrawl reflex.
Glutamate release.
Term
Glutamate from A Delta fibers binds to what?
Definition
AMPA receptors postsynaptically.
Term
Describe A Beta Fibers.
Definition
Large, heavily myelinated.
May release enkephalin inhibiting the spinothalmic neurons.
mediate the analgesic effects of tissue stimulation.
Term
What kind of fibers are present for slow transmission?
Definition
Type C.
Term
Describe the path of Type C Afferent fibers.
Definition
Enter via dorsal nerve.
terminate in dorsal horn laminae 2 and 3 (substantia gelatinosa).
Signals then pass through another short fiber and then to opposite side up the anterolateral column.
Some fibers may not cross and rise on the ipsilateral side.
Term
Describe Type C Fibers.
Definition
Unmyelinated, slow.
Ascend via paleospinothalamic tract.
Dull, burning, poorly localized pain.
Functions in autonomic reflex, pain memory, and discomfort.
Substance P binds to NK1 postsynaptic as major neurotransmitter.
Term
How do pain impulses travel in the brain?
Definition
Thalamus to somatosensory area of cortex.
Term
Where do afferent C fibers end?
Definition
The RAS area.
Term
Describe how pain is modulated.
Definition
Spinal interneurons release inhibitory amino acids (GABA) and neuropeptides (endogenous opioids) that bind to afferent primary and dorsal horn neurons and inhibit pain.
Descending input from brain modulates pain in DH of spinal cord.
Term
Describe the Gate Control Theory.
Definition
Dorsal horn functions as a gate.
A delta transmissions open the gates and A beta transmissions close the gate.
Small fibers open the gate wider while the larger fibers close the gate inhibiting pain.
Brain can send decending stimulus that will inhibit (spinothalmic and medullary).
Term
What do the spinothalmic and the medullary fibers release to inhibit pain responses?
Definition
GABA.
Endogenous opioids.
Serotonin.
Norepinephrine.
Term
What effect do MAO and Tricyclics have on pain inhibition.
Definition
Block the reuptake of norepi and cause an increase in concentration leading to inhibited pain responses. Ie, ANS compensation.
Term
Where does clonidine have its greatest effect?

What kind of agonist is Clonidine?

When are analgesia properties seen?
Definition
Clonidine works best supraspinal.

Conidine is Alpha 2 agonist.

Analgesic properties seen after one dose. Useful in augementing morphine or local blocks.
Term
WHat are the side effects of clonidine?
Definition
Sedation (alpha 2 agonist).
Hypotension.
Bradycardia.
Term
How does Ketamine effect the NMDA receptor?

What receptors does Klonidine function at other than NMDA?
Definition
Ketamine is an antagonist at NMDA receptor sites. NDMA is an excitatory neuro transmitter for pain.

Ketamine functions at opiate and muscarinic receptors.
Term
Describe effect that ketamine has on patient?
Definition
Higher BP, Higher HR.
Patient appears more responsive.
Disassoicative anesthetic - no memory of event.
Term
General Description of an NSAID.
Definition
Decrease pain receptor actiavtion from prostaglandin.
Reduce inflamation.
Inhibition of platelet aggregation.
Inhibit prostaglandin formation reducing prostaglandin induced protection of GI tract and renal function.
Prostaglandin inhibits acid in stomach and increases glomular filtration in the kidney.
Term
Listen to lecture on Eicosanoid Synthessis (inflamatory mediator cascade).
Definition
Term
Describe COX-1
Definition
Good kind.
Found in many tissues and prostaglandins formed by it are important for many normal physiologic processes.
COX-1 promotes the production of the natural mucus lining that protects the inner stomach and contribute to reduced acid secretion and reduced pepsin content.
Term
Describe COX-2
Definition
Mainly found in inflamatory cells.
Trigers inflamation/pain.
Goal with NSAIDs is to block COX-2.

Selective blockers include celebrex, which has been known to increase cardiac vulnerabilities.
Term
What NSAID is the safest for renal impairment?
Definition
Aspirin.
Term
What are the limits for both children and adult for acetaminophen?
Definition
Adults: 4 Grams.
Children: 75mg per Kg.
Term
Acetaminophen IV for analgesia DOA and onset?
Definition
Onset: < 10 min
Duration: 4-6 hours
Term
Acetaminophen IV for Antipyretic DOA and onset?
Definition
Onset: < 30 min.
Duration: > 6 hours.
Term
IV Acetaminophen.
How fast is IV infusion given?

What is concentration?
Definition
Given: 15 min.
Concentration: 100ml amp, 10mg/ml.
Term
What are the effects of using a non-selective NSAID?
Definition
Renal impairment, blocks prostaglandin in stomach, and platelet inhibition.
Term
What are the concerns related to toradol?
Definition
GI bleeding > than aspirin.
Renal concerns (no use > 5 days).
Post op bleeding (check with surgeon).
Term
What may be a relative contraindication to a patient getting toradol?
Definition
Asthma
Term
What is the max dose of toradol for an adult.
Definition
120mg over 24 hours.
Term
WHat are the potential side effects of NSAIDS?
Definition
Bleeding.
GI irritation.
Renal.
Cardiac tox (cox-2 selective)
Shouldn't take aspirin and ibuprofen at same time.
Term
What kind of receptor is an opiate receptor?
What is seen with activation or agonist activity of an opiate receptor?
Definition
G-protein.

Agonist activity includes: Analgesia, sedation, miosis (pupil constriction), bradycardia, respiratory depression, euphoria/dysphoria.
Term
Activation of the opiate receptor causes the inhibition of
Definition
Adenylyl Cyclase, which in turn causes a decrease in CAMP.
Term
Where are opiate receptors located?
Definition
Brain and spinal cord.
Term
How is classification opioid receptors accomplished?
Definition
Classified by receptor affinity for opioid peptides.
Term
Activation of a Mu1 receptor causes?
Definition
Bradycardia.
Euphoria.
supraspinal analgesia.
Sedation.
pruritis.
Urinary Retention.
Term
Activation of a Mu2 receptor causes?
Definition
Spinal analgesia.
Respiratory depression.
sedation.
dependence.
constipation.
Term
What kind of agonist are highly specific to Mu receptors?
Definition
Opioid Receptors.
Term
Spinal anesthesia is mediated by primarily what receptor?
Definition
Mu-2
Term
Supraspinal anesthesia is mediated by what receptors?

What is the only receptor that does not mediate supraspinal analgesia?
Definition
Mu-2
Term
What receptors cause respiratory depression?
Definition
All except Mu-1.
Term
What receptors causes dependence?
Definition
Delta and Mu-2.
Term
Supraspinal analgesia is primarily mediated by what receptor?
Definition
Mu-1.
Term
What receptor causes Euphoria?
Definition
Mu-1.
Term
What receptor causes dysphoria?
Definition
Kappa.
Term
What receptor is most important for peripheral pain?
Definition
Delta.
Term
What receptors cause sedation?
Definition
Mu-1, Mu-2, and Kappa.
Term
What does the term neuraxial analgesia refer to? What is it based on?
Definition
Epidural and suarachoid opiates. Based on opioid receptors in the spinal cord.
Term
What results in systemic absorption in regards to spinal anesthesia
Definition
Venous Plexus.
Term
What complication can be caused by cephalad migration of a drug interacting with the trigeminal nucleus?
Definition
Herpes Simplex.
Term
What accounts for differences in synthetic opioids?
Definition
Receptor affinity, potency, duration.
Term
Is there a ceiling affect with opioids?

Is there a celing affect with NSAIDS?
Definition
No ceiling affect with opioids.

Yes, there is a ceiling affect with NSAIDs.
Term
Where do synthetic opioids act?
Definition
At the opiate receptor pre and post and at primary afferent neurons.
Term
What are the CNS effects of morphine like drugs?
Definition
decreased stress respons to surgical stimulation, decreased MAC of volatile agents, analgesia, euphoria (in presence of pain), dysphoria (when not in pain), sedation, respiratory depression.
Term
What are the GI effects of morphine like drugs?
Definition
Biliary tract-spasm of sphincter of Odi, pancreatic ducts (reversible by
Narcan or glucagon 2mg IV)
Constipation (delayed empty)
Nausea and vomiting
Term
What are the Gu effects of morphine like drugs?
Definition
Urinary retention, urgency, difficulty voiding (increase tone of ureter,
increased detrussor muscle tone, enhanced vesicle sphincter tone)
Term
What are the cutaneous effects of morphine like drugs?
Definition
Vessel dilation, localized histamine release, pruitis, erythema.
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