Topics by Random Chapters Flashcards

1
Q

Define prevalence

A

The number of cases of disease in a known population at a designated time.

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2
Q

Define incidence

A

The number of new cases of disease that occur in a known population over a designated period of time.

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3
Q

What muscles are involved in external hip rotation?

A

Internal and external obturator, gemellus, quadratus femoris are responsible for external rotation of the hip (insert at trochanteric fossa, antagonize the glutes).

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4
Q

The gluteal muscles (superficial, middle, deep, and piriformis) perform what motion(s) of the hip joint?

A

Abduction and internal rotation.

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5
Q

What muscles adduct the hip joint?

A

Those that run from the pelvis to the shaft of the femur: adductor, pectineus groups.

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6
Q

What is ectrodactyly?

A

Ectrodactyly, which is also known as split hand/foot malformation (SHFM), is a condition characterized by absence or malformation of one or more of the digits. Usually, the middle digits are affected.

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7
Q

What cells produce TNF-α?

A

Monocytes, macrophages, neutrophils, NK cells, and several others (T, B, fibroblasts). But Activated M1 macrophages are a major source of TNF-alpha.

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8
Q

What is stimulated by the release of TNF-α?

A

Production of proinflammatory cytokines (e.g., IL-6), reactive oxygen intermediates, chemotaxins, and endothelial adhesion molecules (all facilitate the recruitment of cells at the site of inflammation).

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9
Q

The main effect of TNF-α is stimulation of cytokines (IL-6, ROS, etc.) that facilitate cell recruitment at the site of inflammation. What are three additional effects of TNF-α?

A

Activation of natural killer cells, proliferation of cytotoxic T-cells, and T-cell apoptosis.

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10
Q

What are released from the cell surface to reduce the activity of TNF-α?

A

Tumor necrosis factor soluble receptors are found constitutively at low levels in the blood but are increased in inflammatory conditions such as sepsis. The solubilized receptors bind to TNF-α and effectively reduce the cytokine’s activity.

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11
Q

TNF-α has both beneficial and deleterious effects. Name some of each:

A

Beneficial - protects against mycobacterial infection, blocking it in septic patients increases mortality

Deleterious - causes all the classic signs of shock (hypotension, metabolic acidosis), causes inflammation (inflammatory diseases like Crohns).

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12
Q

What is TNF-α?

A

A membrane-bound surface protein, cleaved by metalloproteases, that is released in soluble form. It has two receptors, TNFR1 and TNFR2.

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13
Q

Corticosteroids and recombinant TNFR receptors (Enbrel, a treatment for RA/Crohn’s) inhibit TNF-α, which increases risk of what?

A

Recrudescence of pulmonary mycobacterial infections and infectious complications after orthopedic surgeries.

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14
Q

True or False: Activated M1 macrophages produce proinflammatory cytokines (IL-1β, IL-6, and TNF-α) and prostaglandins, enhancing the inflammatory response?

A

True.

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15
Q

True or False: M2 macrophages are activated in response to proinflammatory cytokines?

A

False. M2 macrophages are activated in response to anti-inflammatory cytokines (IL-4, IL-13, and IL-10). They then secrete growth factors like PDGF or TGF-β, which stimulate fibroblasts to produce collagen, aiding in wound healing and further dampening the inflammatory response.

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16
Q

True or False: M1 macrophages are activated by infectious agents or proinflammatory cytokines?

A

True. M1 macrophages are activated by infectious agents or proinflammatory cytokines (interferon-gamma [IFN-γ] or TNF-α). They then produce more proinflammatory cytokines and prostaglandins to increase inflammation.

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17
Q

What is something both M1 and M2 macrophages produce?

A

Both M1 and M2 macrophages secrete enzymes like collagenases and elastases to dissolve the extracellular matrix, facilitating phagocytosis and remodeling, respectively.

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18
Q

What cells produce VEGF?

A

Predominantly keratinocytes on the wound edge and also by macrophages, endothelial cells, fibroblasts, and platelets.

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19
Q

What is VEGF?

A

Vascular endothelial growth factor - it has potent angiogenic activity. and is secreted predominantly by keratinocytes on the wound edge and also by macrophages, endothelial cells, fibroblasts, and platelets.

20
Q

As the acute inflammatory response resolves, macrophages produce factors that stimulate fibroblasts to produce ________, aiding in wound repair and healing of the inflamed tissue?

A

Collagen! Fibroblasts are the most common cell that produce collagen.

21
Q

Prostaglandins are produced in the __________ pathway?

A

Prostaglandins are produced in the cyclooxygenase (COX) pathway.

22
Q

What is the starting molecule for prostaglandins?

A

Arachidonic acid (metabolized along the cyclooxygenase pathway containing COX enzymes).

23
Q

What are prostaglandins?

A

Prostaglandins mediate many inflammatory responses primarily through G protein–coupled receptors on a number of cell types. They are chemotactic agents that cause leukocyte recruitment and vasodilation, contributing to the pathogenesis of pain and fever during inflammation.

24
Q

COX-2 expression is induced by what?

A

Trauma, growth factors, proinflammatory cytokines, and other mediators.

25
Q

True or False: COX-1 is constitutively expressed (always present)?

A

True. It is involved in homeostasis and is present
in the majority of mature cells.

26
Q

What is the precursor to all prostaglandins and thromboxanes?

A

PGH2 (Prostaglandin H2).

27
Q

Describe the arachidonic acid pathway?

A

AA -> through COX -> PGG2 -> releases free oxygen radicals to become -> PGH2 -> ENZYMES = Thromboxane A2 and B2, PGE2, PGF2, and PGI2 (prostacyclin).

28
Q

What is the unstable endoperoxide that degrades/releases oxygen radicals to become PGH2, precursor to all prostaglandins and thromboxanes?

A

PGG2 (prostaglandin G2).

29
Q

What is the hepatotoxicity of carprofen?

A

Acute hepatic necrosis.

30
Q

What is the incidence of hepatotoxicity in dogs taking carprofen?

A

Of 1 million dogs receiving carprofen, an incidence of 0.2% suspected side effects was reported, with 0.02% involving the liver.

31
Q

What was the most affected age group in dogs with suspected carprofen hepatotoxicity?

A

At least 70% of affected animals were considered geriatric.

32
Q

What lab abnormalities would suggest a carprofen hepatotoxicity?

A

increased ALT, aspartate transaminase (AST), alkaline phosphatase (ALP), and bilirubin.

33
Q

What frequency of monitoring is advised for carprofen administration?

A

Monitoring for hepatic damage and hepatic function (bile acids) at weekly or biweekly intervals for the first month is recommended, particularly in predisposed (e.g., geriatric) animals. Monitoring should continue at intervals of 2 to 4 weeks for 3 months and perhaps longer in patients at risk for liver disease.

34
Q

What medication can increase risk of carprofen hepatotoxicity?

A

Animals receiving phenobarbital have been anecdotally reported to be more susceptible to hepatotoxicity.

35
Q

How do you treat carprofen hepatotoxicity?

A
  1. Stop the drug
  2. Use of hepatoprotective agents such as N-acetylcysteine (a glutathione precursor) or SAMe may be beneficial during initial or continued hepatic damage.
36
Q

How long does oral carprofen take to reach steady state?

A

1 hour. Oral carprofen is rapidly and almost completely absorbed; greater than 90% bioavailability.

37
Q

What is the half life of carprofen?

A

About 10 hours, long enough to be approved for once daily dosing.

38
Q

How is carprofen excreted?

A

Between 70% and 80% of carprofen metabolites are excreted in the feces, with the remainder in the urine.

39
Q

Where is carprofen metabolized?

A

All NSAIDs undergo hepatic metabolism so the liver is exposed to a high concentration of parent drug and metabolites.

40
Q

Is NSAID hepatotoxicity dose-dependent?

A

No. Reactions to drugs other than aspirin and acetaminophen tend to be idiosyncratic- unpredictable and non-dose related.

41
Q

True or False: Prior hepatic disease predisposes a patient to NSAID induced liver injury?

A

False. There is no evidence that prior hepatic disease predisposes a patient to NSAID induced liver injury.

42
Q

True or False: Giving liver protective supplements reduces risk of NSAID induced liver injury?

A

False. No supplements help protect against liver injury. May actually decrease liver metabolism and clearance. (But after/if injury occurs can use as therapy).

43
Q

What is the direct effect of NSAIDs on the GI?

A

Irritation of the GI mucosa:
Acidic NSAIDs become more lipophilic in the stomach acid which allows them to diffuse into gastric mucosa cells and damage them. They can also directly damage intestinal villi. (Decreased cytosolic bicarb).

44
Q

What is the indirect effect of NSAIDs on the GI?

A

From systemic inhibition of endogenous prostaglandin production (COX-1, COX-2): Inhibition causes decreased cytoprotecting effect on the mucosa from the prostaglandins, decreased mucosal blood flow, decreased epithelial mucus production, bicarbonate secretion, decreased mucosal epithelial cell turnover.
Platelet function inhibition can also lead to bleeding.

45
Q

What are the protective mechanisms for the GI mucosa?

A

The natural mechanisms for gastric mucosal protection from gastric acid secretions are threefold:
(1) secretion of a bicarbonate-rich mucus
(2) gastric epithelial cell apical membrane and cytosolic bicarbonate
(3) increased blood flow, which readily releases bicarbonate and acts as a sink for gastric acid, quickly neutralizing and removing excess acid. A rich blood flow is also important for epithelial repair.

46
Q

What is Tepoxalin (Zubrin)?

A

An older NSAID that was used in Europe.
Tepoxalin is a nonselective inhibitor of COX that also inhibits 5-lipoxygenase. It’s effect on leukotriene activity may be responsible for some protection against GI toxicity, preventing leukocyte adherence to the endothelial lining of mucosal blood vessels and hence maintaining blood flow. It is not commonly used in the US/was not extended in EU as of 2017.