Lecture 10 - Over the Counter Drugs - Analgesics Flashcards
Neurons that detect sensory information in the periphery are called:
primary afferents
Primary afferent synapse onto ____ afferents in the ____ which passes sensory information up to the brain.
secondary; spinal cord
____ efferents take ____ commands from the brain and send them to the periphery (muscles or glands)
motor;motor
Pain is detected by a specific class of primary afferents called ____.
nociceptors
Where are nociceptors located?
- embedded in the epidermis.
Which channels are temperature sensitive ligand-gated ion channels?
TRP (transient receptor potential)
- TRPM8 is activated at what temperatures and give an example of a medication?
- TRPV1 is activated at what temperatures and give an example of a medication?
TRPM8 is for temperatures below 10 degrees and menthol
TRPV1 is for temperatures above 43 degrees and capsaicin
Other receptors respond to inflammatory molecules such as:
hint- there are 3, bcp
- Bradykinin
- Cytokines
- Prostaglandins
- these are released from immune cells following tissue injury or infection
Chronic use of capsiacin leads to excess calcium activation causing desensitization and ____ of ____ nociceptors.
loss of TRPV1
____ acid is a fatty acid present in phospholipids of cell membranes and is freed from the phospholipid molecule by the enzyme ____ A2.
Arachidonic; phospholipase
Which enzymes metabolize arachidonic acid into prostaglandins(PG) and thromboxanes (TX)?
Cyclooxygenase 1 and 2; COX 1 and COX 2
COX1 and COX2 metabolize arachidonic acid into what 2 components?
Prostaglandins (PG) and Thromboxanes (TX)
Which of the following are functions of prostaglandins?
1. Inflammation
2. Vasodilator
3. Pyrogenic
4. Leuokatactic
5. Gastric mucosa production (mainting low pH)
6. Platelet aggregation
7. Vasoconstriction
1-5
What are the 2 functions of Thromboxanes?
Platelet aggregation and vasoconstriction
Potent vasodilators lead to vasodilation of blood vessels and is also associated with ____ and ____.
swelling;redness
What does a pyrogenic molecule do?
associated with elevation in body temperature; fever.
Which prostagladin is associated with inflammation?
Prostaglandin E2
What signals the platelets to form a clot, causing vasoconstriction?
thromboxane A2
Arachidonic acid ia converted to ____ within blood vessels
thromboxane A2
COX _ is primarily expressed in non-imglammatory cells such as blood vessels, platelets and gastric mucosa. It is Constitutive (always on)
1
COX _ is primarily expressed in inflammatory cells such as macrophages. It is constitutive and inducible (must be activated by stimulus)
2
What is NSAIDs?
Non-Steroidal Anti-Inflammatory drugs.
NSAIDs inhibit ____ and ____.
COX1 and COX2
As NSAIDs inhibit COX1 and COX2, it results in a decreased production of what?
Prostaglandin and Thromboxanes.
Decreasing prostaglandin production inhibits inflammation and reduces ____.
Pain; aspirin reduces the production of PGH2 so its not binding to nociceptors so you don’t feel as much pain.
NSAIDs also suppress prostaglandin synthesis in the brain that is stimulated by pyrogens and reduce ____ (antipyretic action)
fever
Example of a NSAID?
aspirin
Most NSAIDs inhibit the ____ site of COX enzymes (where arachidonic acid binds).
catalytic
Acetylsalicylic acid (____) is a ________, ________ inhibitor. It permanenetly binds to the catalytic site of COX enzymes through ____ bonds.
aspirin; non-competitive, irreversible; covelent
Why does aspirin have a long half life?
due to its permanent binding to the catalytic site.
Why do immune cells (half life of 6-8hrs) recover faster than platelets (~96hrs)?
Platelets are anucleated and they make new proteins very slowly but immune cells are nucleated and they divide/recover much more quickly.
Non-selective NSAIDs are associated with ____ toxicity due to inhibiton of COX 1 enzymes in ____ mucosa.
Gastric
Chronic use of aspirin can result in gastric ____ and upper GI ____ and renal ____.
ulcers; bleeding; failure
Ketoralac (____) is a highly efficacious non-selective NSAID (comparable to morphine) which blocks COX ____ more effectively than COX ____.
Toradol; 1 and 2
Non-selective NSAIDs inhibit COX ____ more than COX ____.
1 and 2
CHronic use of Toradol results in ____ issues; recommeded for short-term use.
gastric.
To bypass gastric toxicity caused by the inhibition of COX 1 enzyme, specific ____ inhibitors are developed.
COX 2
Specific COX2 inhibitors are also associated with a higher risk of ____ toxicity.
cardiovascular toxicity such as abnormal heart rate; lethal arrythmias.
An example a specific COX2 inhbitor is:
celecoxib.
____ is a weak and reversible COX1 and COX2 inhibitor, so it doesnt work like other NSAIDs
Acetominophen
Besides COX1 and COX2, what else does acetominophen inhibit that is found in the cerebral cortex?
COX3
COX3 interfers with ____ processing and ____ synthesis.
nociceptive; prostaglandin
Which drug is an analgesic and antipyretic agent that lacks anti-inflammatory effects and does not effect the COX2 emxyme found in immune cells?
Acetaminophen.
Acetominophen will not block ____ and ____ but will reduce fever and block pain.
swelling and redness.
Acetominophen can lead to ____ damage/death if overdosed. It saturates the normal ____ enzymes that breakdown the drugs.
liver; liver
What was the first local anesthetic discovered in the late 19th century and was used as a topical anesthetic for ophthalmological surgery?
Cocaine.
What are the 3 examples of the most widely used topical anesthetics?
Hint: PIB
Procain, lidocaine and bupivivaine.
The most local anesthetics contain 3 regions, what are they?
- hydrophobic (aromatic)
- A linker region
- A substituted amine (hydrophilic)
Which region is hydrophobic, the linker region, the aromatic or the substituted amine?
aromatic
Which region is hydrophilic, the linker region, the aromatic or the substituted amine?
substiuted amine.
Procaine is really vulnerable to plasma ____ meaning it breaks down really quickly; it would also have a much shorter half-life than lidocaine or bupivicaine due to the ester connection in the linker.
Esterase.
Identify the following topical Anesthetics
Local anesthetics bind ____ to a specific site within the pore of ____ channels and block ion movement through the pore; inhibits the ability of the neurons to fire upon ____ channels blocking.
Reversibily; Na+
The site to which anesthetics bind is only accesible ____ (must cross the cell membrane).
intracellularly
Hydrophobicity ____ both the potency and duration of action because the Na+ channels binding pocket is hydrophobic and anesthetics must cross the hydrophobic cell membrane.
increases
More hydrophobic = more ____, longer ____
potent; action.
All neurons (sensory, motor) require which channels for action potential progapgation?
Sodium channels
Local anesthetics block all sensation and can cause ____ paralysis in the area.
motor
Local anesthetics have ____ affinity for the open conformation of the ____ channels so they prefentially block neurons that are active (i.e., nociceptors when there’s pain)
higher; sodium
When the voltage-gated Na+is closed is there increased or decreased anesthetic binding?
decreased
When the voltage-gated Na+is open is there increased or decreased anesthetic binding?
increased
Capsaicin is an ____ for the ____ receptor
agonist; TRPV1
