6/12- Pharmacology of Pain Flashcards Preview

Term 5: Neuro > 6/12- Pharmacology of Pain > Flashcards

Flashcards in 6/12- Pharmacology of Pain Deck (47):
1

What is pain?

Perception of an unpleasant sensation

- e.g. nociceptors are specialized Rs for noxious stimuli (sharp pricking, slow burning)

2

What kind of receptors are nociceptors (structurally)?

Free nerve endings

3

Are nerves transmitting pain myelinated or unmyelinated?

Can be either

4

What are the other (non-nociceptor) sensation receptors?

What type of R is each?

- Meissner's corpuscle (mechanoreceptor)

- Pacinian corpuscle (pressure, vibration)

- Ruffini's ending (mechanoreceptor)

- Merkel's disk (mechanoreceptrs)

- Hair follicle receptor (mechanoreceptor)

5

How do sensory neurons modulate pain?

Sensory neurons release NTs that increase pain perception: 

- This occurs in the periphery and also in CNS

- NT in periphery dilates BVs and sensitizes nerve endings

- Releases glu, CGRP, Sub P... in SC

6

What is CGRP? What does it do?

CGRP = Calcitonin Gene-Related Peptide (37 AAs)

- acts via Gs: cAMP -> EPSP (dilates BVs)

- acts via Gq: IP3/Ca (degranulation of mast cells -> histamine, which sensitizes nerve endings)

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7

What are some different factors that facilitate pain perception?

- Prostaglandins (E2)

- Serotonin

- Histamine

- Bradykinin

- K+ from cell lysis

- ATP from cell lysis

- Substance P

- CGRP

- Endorphins (inhibit pain transmission/perception)

- Increase inhibition

8

What are some available drugs for modulating pain?

- Acetaminophen (Tylenol)

- NSAIDs (Ibuprofen, Naproxen, Indomethacin)

- Serotonin subtype agonists (Sumatriptan)

- Blockers not available; not effective but in development

- Morphine, codeine, etc. inhibit transmission/perception of pain

- Gabapentin, Pregabalin

9

Characteristics of Acetaminophen (Tylenol)?

- Functions

- Enters CNS (Y/N)

- Mechanism

Functions: analgesic and anti-pyretic, but very WEAK anti-inflammatory

Enters CNS! (good when used to relieve pain)

Mechanism: Inhibits COX (most say both, possibly just COX-2); prevents prostaglandin release that would sensitize sensory nerve endings in periphery and CNS (somewhat specific to PGs in context of inflammation without interfering much in housekeeping PGs)

10

Main ascending pain pathway?

Spinothalamic tract (STT)- sense pain, temperature, and crude touch

- Pain/temp sensed by free nerve terminals

- 1' neuron synapses in SC ipsilaterally near level of entry (in dorsal horn)

- 2' neuron decussates and ascends in lateral fasciculus to synapse in VPL of thalamus (ant white commissure)

- 3' neuron projects to primary somatosensory cortex (post-central gyrus)

11

What are some other (indirect) Spino-thalamic pathways?

- Paleo-thalamic

- Spino-reticular

- Spino-mesencephalic

Basically, pain is also relayed to:

- Reticular formation

- Periaqueductal gray (PAG)

- Amygdala

- Cingulate gyrus, etc.

12

What does the ascending pathway release in PAG? Results in?

- Glutamate and Substance P

- Activates enkephalin interneurons in PAG

13

What is enkephalin? Where/how does it work?

Enkephalin = exogenous morphine

- In PAG, enkephalin inhibits GABA neurons projecting to midline raphe magnus

- Serotonergic pathway from Raphe magnus releases serotonin in SC

- Serotonin and NE activate enkephalin interneurons in dorsal horn

Thus: more NE/serotonin -> more GABA -> less pain

Morphine works in (1) PAG and (2) Dorsal horn to inhibit pain transmission

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14

What two places does morphine work to inhibit pain transmission?

- PAG

- Dorsal horn of spinal cord

15

What is one of the main sites of pain modulation in the spinal cord?

Where 1' neuron relays pain signals to 2' neuron

- Raphe magnus nueuron (serotonin) an dpontine neuron (NE) release NTs onto enkephalin-containing interneuron

- Enkephalin interneuron releases onto opiate receptors on neuron synapse (this neuron also releases GABA)

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16

So, altogether, what are all of the ways (3) pain pathways can be modulated?

1. Ascending path

- 1' neuron releases glu, Sub P -> EPSP in 2' neurons and pain signals are relayed

- More NT -> more pain signals

2. Descending paths

- Serotonin and NE excite interneurons containing enkephalins -> IPSP in axon terminals of 1' neuron and dendrites of 2' neuron

- Results in less glu/Sub P released and more difficult to excite 2' neurons, so less pain is transmitted

3. Drugs given from outside

-Morphine/codeine/drugs that bind to opiate Rs and decrease relay of pain signals.

- Not a cure; problem still their, just decreased perception

17

Normally ___ depolarizes 2' neuron to ____ (allow/inhibit) pain signals.

- Normally glutamate depolarizes 2' neuron to allow pain signals

18

____ released by descending pathways (or morphine from outside) ____ (depol/hyperpol) both presynaptic and postsynaptic nerve cell membranes, resulting in _____.

Enkephalins released by descending pathways (or morphine from outside) hyperpolarize* both presynaptic and postsynaptic nerve cell membranes, resulting in reduced transmission of pain signals

*Voltage-gated Ca channels less likely to open

19

Characteristics of morphine

- Hydrophobic/phili

- Enters CNS (Y/N)

- Natural sources

- HydroPHOBIC

- Enters CNS!

- Natural sources: poppies (fruits, seeds)

20

What Rs do opiates act on?

- mu (u)*main one

- kappa (K)

- delta (d)

- (possibly also epsilon, and ORL-1)

21

What are endorphins?

Endogenous morphine-like peptides (5AAs)

22

What are some opiate receptor agonists?

- Morphine

- Fentanyl

- Codeine

- Methadone

- Heroin

- Dextromethrophan (cough suppressant)

- Loperamide (Imodium) (antidiarrheal)

23

What are some opiate receptor antagonists?

- Nalaxone

- Naltrexone

24

What are some opiate receptor ag/antags?

- Partial agonist

- Pentazocine**

- Meperidine **

Pentazocine is an agonist at Kapp Rs and a blocker of Mu Rs (administration to opioid addict will result in immediate withdrawal symptoms in the pt)

25

How do opioids work?

- Uses

- Drawbacks

Through Gi receptor, causing hyperpolarization

(40% homology to somatostatin Rs)

- Nerve terminal release less NT

- Target cells respond less

- Major pain reliever; consciousness not lost; analgesic; euphoric

- Drawbacks: addictive, dependence, tolerance

26

What clinical signs/symptoms can be seen in people on opioids?

- Pin point pupils (miosis)

(Recall: cocaine, amphetamine, and others dilated pupils)

27

Actions of mu (u) agonists?

- Analgesic: increase the pain threshold in the SC and alter brain's interpretation of pain (pain present but not so bothersome)

- Cough suppressant: dextromethorphan (d-isomer) devoid of analgesic action and codeine also commonly used

- Decrease gastric motility: can cause constipation; sometimes a side effect and sometimes used therapeutically to treat diarrhea, e.g. Loperamide/Imodium

- Respiratory depression- reduction in sensitivity to CO2

- Miosis

- Effects on mood and behavior: feelings of detachment; not a worry in the world

- Endocrine effects: decrease testosterone

- Emesis: due to stimulation of chemoreceptor trigger zone; more common in ambulatory pts

- Histamine release: itching, urticaria (hives), sweating, and local vasodilation

28

T/F: Loperamide/Imodium is absorbed systemically

False

29

What is tolerance?

Why does it occur when taking opiates?

Tolerance- higher doses needed to get same effect

- Due to opioid Rs getting down-regulated

30

What does physical dependence entail?

Physical dependence means that a withdrawal syndrome will appear when the drug is stopped.

31

T/F: Withdrawal from physical dependence on opiates may be life-threatening

False; while very uncomfortable, the withdrawal from opiates is usually not life-threatening

32

What signs/symptoms are seen in pts withdrawing from opiate addiction?

- Pupillary dilation

- Sweating

- Tearing

- Runny noise

- Piloerection

- Tachycardia

- Vomiting

- Diarrhea

- HTN

- Fever

- Increased sensitivity to pain

- Abdominal cramps

- Muscle aches

33

What is the treatment for heroin addiction?

Orally active methadone (long t1/2 = 2d!)

- Long half life compared to heroin (8 min)

- Remains in system for 10-60 hrs

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34

What are some mixed opioid agonists-antagonists?

Which receptors to the work on?

Pentazocine

- K agonist

- u weak antagonist

Meperidine

- u2 agonist

- E antagonist

*Pentazocine will cause withdrawal in an opioid addict

35

What are some opiate antagonists? Uses?

Naloxone and Naltrexone

- Used to treat overdose of opiates

- Will put an addict in immediate withdrawal

36

What is a migraine? How to diagnose?

Episodic attacks of headache lasting 4-72 hrs;

Must have 2 of the following Sx:

- Unilateral pain

- Throbbing

- Aggravation on mvt

- Pain moderate to severe

And 1 of the following Sx:

- Nausea or vomiting

- Photophobia or phonophobia

(This is for migraine without aura)

37

What is though to be the underlying pathophysiology of headaches?

- Excessive dilation of cerebral BVs (by CGRP) is thought to be involved in migraine headaches

- Serotonin subtype Rs are abundant in BVs in the cranium (cerebral BVs have more serotonin Rs compared to other BVs)

38

What drugs can be used to treat migraines? Mechanism?

---triptans (Sumatriptan):

- These are serotonin (5-HT 1B/1D) R agonists that constrict cerebral BVs to help relieve migraine pain

- High success rate (70-80%)

39

What are some triptan drugs?

(5-HT1 a/d agonists)

- Sumatriptan (Imitrex)

- Naratriptan

- Rizatriptan

- Zolmitriptan

- Almotriptan

- Eletriptan

40

What is Gabapentin (Neurontin)?

- Mechanism

- Uses

- Adverse effects

Structural analog of GABA

Mechanism: more GABA synthesized and decreased Ca flux

Uses:

- Used for treating chronic, neuropathic pain and post-operative pain

- Also 2nd line (add on) drug to treat epilepsy

Adverse effects (many):

- Dizziness, ataxia

- Pregabalin appears to have fewer side effects

41

Other drugs to treat pain/headaches?

- Acetaminophen, NSAIDs to treat mild migraine pain

- Acetaminophen + codeine used short term

- DA blockers are alternates to treat pain and headaches

- Ergotamine (plant extract, contains serotonin agonists)

- Beta blockers

- SSRIs

- TCAs

42

Question:

Our body releases many signals that facilitate/increase perceptin of pain. Which of the following does NOT increase transmission of pain signals?

A. Bradykinin

B. Histamine

C. Angiotensin II

D. Serotonin (5HT)

E. Prostaglandins

Our body releases many signals that facilitate/increase perceptin of pain. Which of the following does NOT increase transmission of pain signals? 

A. Bradykinin

B. Histamine

C. Angiotensin II

D. Serotonin (5HT) 

E. Prostaglandins

(Angiotensin levels are high during emergencies; pain perception is diminished)

43

Question:

Umatriptan is a commonly prescribed drug to treat migraine headaches. What is mechanism of action of triptan class drugs?

A. Blocks serotonin receptors and dilates cerebral arteries

B. Agonist at serotonin receptors and dilates cerebral arteries

C. Agonist at serotonin receptors and constricts cerebral arteries

D. Blocks beta receptors and dilates cerebral arteries

E. Agonist alpha-1 receptors and constricts cerebral arteries

Umatriptan is a commonly prescribed drug to treat migraine headaches. What is mechanism of action of triptan class drugs? 

A. Blocks serotonin receptors and dilates cerebral arteries 

B. Agonist at serotonin receptors and dilates cerebral arteries 

C. Agonist at serotonin receptors and constricts cerebral arteries

D. Blocks beta receptors and dilates cerebral arteries 

E. Agonist alpha-1 receptors and constricts cerebral arteries

44

Question:

A 55-year-old man is admitted to the hospital with symptoms of an acute myocardial infarction. He is administered a drug intravenously for pain.

Within a few minutes he complains of abdominal pain. He is clearly agitated, his pupils are dilated, his blood pressure is increased, his temperature is elevated and he is sweating.

You specifically ask him if he has been taking any narcotic drugs. He answers that he has been taking high doses of codeine for several years, but asks you not to tell anyone.

What pain medication did this patient most likely receive?

A. Fentanyl

B. Meperidine

C. Morphine

D. Naloxone

E. Pentazocine

A 55-year-old man is admitted to the hospital with symptoms of an acute myocardial infarction. He is administered a drug intravenously for pain. 

Within a few minutes he complains of abdominal pain. He is clearly agitated, his pupils are dilated, his blood pressure is increased, his temperature is elevated and he is sweating. 

You specifically ask him if he has been taking any narcotic drugs. He answers that he has been taking high doses of codeine for several years, but asks you not to tell anyone. 

What pain medication did this patient most likely receive? 

A. Fentanyl

B. Meperidine 

C. Morphine 

D. Naloxone 

E. Pentazocine

Pentazocine is a blocker of Mu receptors and agonist at other subtype receptors

45

Question:

A 35-year-old woman suffering from migraine headache was prescribed sumatriptan (Imitrex) by her neurologist. The patient’s headache was relieved after she took the drug.

Which one of the following mechanisms is responsible for the beneficial effects of sumatriptan in treating migraine headache?

A. It dilates meningeal arteries via beta-2 adrenergic receptors.

B. It constricts meningeal arteries via alpha-1 receptors

C. It constricts meningeal arteries via 5-HT1d receptors

D. It dilates systemic arterioles via cholinergic muscarinic receptors.

E. It dilates meningeal arteries via Histamine receptors

A 35-year-old woman suffering from migraine headache was prescribed sumatriptan (Imitrex) by her neurologist. The patient’s headache was relieved after she took the drug. 

Which one of the following mechanisms is responsible for the beneficial effects of sumatriptan in treating migraine headache?

A. It dilates meningeal arteries via beta-2 adrenergic receptors.

B. It constricts meningeal arteries via alpha-1 receptors 

C. It constricts meningeal arteries via 5-HT1d receptors

D. It dilates systemic arterioles via cholinergic muscarinic receptors. 

E. It dilates meningeal arteries via Histamine receptors

46

Question:

Which of the following drugs increases GABA levels and decreases Ca influx?

A. Acetaminophen (Tylenol)

B. Codeine

C. Gabapentin

D. Indomethacin

E. Sumatriptan

Question: 

Which of the following drugs increases GABA levels and decreases Ca influx?

A. Acetaminophen (Tylenol) 

B. Codeine 

C. Gabapentin

D. Indomethacin 

E. Sumatriptan

47

Question:

When you prescribe acetominophen (Tylenol), what is the most common adverse effect(s) you will be concerned about?

A. High BP

B. Hyperglycemia

C. Liver toxicity 

D. Renal toxicity

E. Addiction, respiratory depression

Question: 

When you prescribe acetominophen (Tylenol), what is the most common adverse effect(s) you will be concerned about? 

A. High BP 

B. Hyperglycemia

C. Liver toxicity 

D. Renal toxicity 

E. Addiction, respiratory depression