Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

Question 1

The Endocrine system encompasses a group of organs/glands that release _______ into circulation for regulating various _________ functions.

Endocrine organs can also release _____. ____ and hormones have many similarities, but also have their differences.

Answer 1

hormones, physiological
NT, NT

Question 2

Hormones versus Neurotransmittters
Origin

Answer 2

Hormones = Glands of the endocrine system

NT = Neurons of the NS

Question 3

Hormones versus Neurotransmittters
Transport

Answer 3

Hormones = blood
NT = Neurons

Question 4

Hormones versus Neurotransmittters
Target

Answer 4

Hormones = Distal and local organs
NT = Local receptors on neurons

Question 5

Hormones versus Neurotransmittters
Action

Answer 5

Hormones = Slow (up to few days)
NT = Fast (up to milliseconds)

Question 6

Hormones versus Neurotransmittters
Duration of effect

Answer 6

Hormones = Short and long lived
NT = Short lived

Question 7

Hormones versus Neurotransmittters
Response

Answer 7

Hormones = Involuntary
NT = Voluntary and Involuntary

Question 8

Endocrine System, Glands, and Hormones

Answer 8

Different hormones from different glands with different actions

Question 9

List the similarities between hormones and NT?

Answer 9

• Chemicals
• Functions
• Receptor sites in target cells

Question 10

List the differences between hormones and NTs?

Answer 10

Regulate each other
* Feedback system

Question 11

Neuroendocrines produce ?

Answer 11

neurotransmitters and hormones.

Question 12

Hormones control the functions of ___ the organs. They affect diverse processes of ____ and ________, _______ and _____ characteristics, __________, _______.
▪ Sending _______ signals to everywhere in the body
▪ They play a role in the development of _____ and _____
▪ They are necessary for bodily changes such as _____
▪ They control _____
▪ They aid in the upkeep of ___________

Answer 12

all, growth, development, reproduction, sexual, temperature, hunger

chemical, bones, muscles, puberty, metabolism, homeostasis

There are about 20 different hormones produced in nonhuman animals

Question 13

Classification of Hormones

Answer 13

Two groups: Steroids and non-steroids
Steroids include: cholesterol, progesterone, testosterone, estrogen, cortisol.

All are lipid derived, insoluble (stay longer in blood), cross membrane and ?

Question 14

Steroids have an important role in ?

Answer 14

growth, development,
sexual differentiation and reproduction.

Question 15

Steroid hormones are produced from a lipid called ________. They can _____ cross cell membranes

Answer 15

cholesterol, easily

Question 16

Endogenous corticosteroids

Answer 16

Glucocorticoids ➢ Cortisol(metabolism and immune system)
Mineralocorticoids ➢ Aldosterone
(sodium and water retention

Question 17

Corticosteroid drugs — including (3?) —
are useful in treating many conditions, such as _______, ________ diseases, _______, _____

Answer 17

cortisone, hydrocortisone and prednisone, rashes, inflammatory, asthma, cancer

Question 18

Corticosteroids have…:
▪ Effects on ___________ metabolism
▪ Actions on ______ and ____ balance
▪ ___ effects
▪ ___________ effects
▪ ______ muscle effects
▪ Effects on ____ cells and ______ tissue
▪ ________ effects
▪ ____-_______ and ___________ effects

But these drugs also carry a risk of various ?

Answer 18

intermediary, electrolytes, water, CNS, Cardiovascular, Skeletal, blood, lymphoid, Immunologic, Anti-inflammatory, immunosuppressive, side effects

Question 19

The Synthetic analog of cortisol is?

Answer 19

Hydrocortisone

Question 20

Corticosteroids can cause unpleasant side effects, such as an _________
appetite, ____ changes and difficulty ______.

Answer 20

increased, mood, sleeping

Question 21

Common side effects of systemic steroids include:
* ________ appetite
* Weight ____
* Changes in ____
* Muscle ________
* ________ vision
* Increased growth of body ____
* Easy ________
* _______ resistance to infection

Answer 21

Increased, gain, mood, weakness, Blurred, hair, bruising, Lower

Question 22

Prolonged use of Corticosteroids is associated with:
* Adrenal ______
* Osteo_______
* Immuno________
* _________

Answer 22

atrophy, porosis, supression, Euphoria

Question 23

Inflammation is a ____-______ immune response (_____ immune system) to _______ and _____.

Answer 23

non-specific, innate, infection, injury

Question 24

Inflammation is an _____________ response of tissues injury caused by _______ trauma, ______ chemicals or __________ agents

Answer 24

immunovascular, physical, noxious, microbiologic

Question 25

Inflammation is a _______, ______ response involving ______ cells, _____ vessels, and molecular ________.

Answer 25

normal, protective, immune, blood, mediators

Question 26

The function of inflammation is to eliminate the ______ course of cell injury, clear out ______ cells and _______ tissues, and initiate tissue ______.

Answer 26

initial, necrotic, damaged, repair

Question 27

Inflammation is mediated by release of ________ mediators from ______ tissues such as?

Answer 27

chemical, injured, histamine, prostaglandins, bradykinins etc

Question 28

List some examples of Inflammatory Diseases in Dogs and Cats

Answer 28

Christine Sees Good Pins ▪ Chronic intestinal inflammation and intestinal disease in dogs (IBD, celiac in humans) ▪ Septic and nonseptic inflammatory diseases ▪ Gastric and peptic ulcer diseases ▪ Skin diseases ▪ Neoplastic diseases ▪ Inflammatory joint diseases ▪ Inflammatory oral diseases ▪ Primary inflammatory brain disorders

Question 29

List the classic signs of inflammation

Answer 29

* Pain * Heat * Redness * Swelling * Loss of function

Question 30

Acute Inflammation * ______ response of the body to harmful stimuli * Increases movement of _____ and ______ from the blood into the injured tissues * Biochemical events including the local ______ system, _____ system, and other cells

Answer 30

Initial, plasma, leukocytes, vascular, immune

Question 31

Chronic Inflammation * ___________ inflammation * Leads to a ________ shift in the type of cells at the site of inflammation, such as _______ cells * Simultaneous ______ and _____ of the tissue from the inflammatory process

Answer 31

Prolonged, progressive, mononuclear, destruction, healing

Question 32

Chronic Inflammation can lead to?

Answer 32

* Diabetes * Heart disease * Lung issues * Bone health * Cancer * Depression * Anger disorders and aggressive behavior

Question 33

Mechanism of inflammation represents a _____ of organized, dynamic responses including both _____ and _____ events with specific _______ secretions

Answer 33

chain, cellular, vascular, humoral

Question 34

The complex inflammatory response: ▪ Activation of ______________ (?) and release of __________ mediators of inflammation ▪** Arachidonic acid metabolism produces ? ▪ Vasoactive amines and peptides effect vascular _________ ▪ _________ produce free radicals and other reactive molecules ▪ Generation of ____-__________ cytokines

Answer 34

leukocytes (macrophages, neutrophils, lymphocytes), chemical, leukotrienes, thromboxanes, and prostaglandins, permeability, Neutrophils, pro-inflammatory

Question 35

Antipyresis = ?

Answer 35

reduction of fever

Question 36

Phopholipase A2 = important component of cell membranes. Releaed by phospholipids A2, whih is itself regualted by hormones and other stimuli such as trauma, (anything that causes inflammation). When inflammation hapens, A2 produces prostaglandins and A2 whihc collectively are called prostanoids. This process is medicated by COX enzymes COX 1 and 2. Corticosteroids which are steroids are coming from ?, have different MOA and alos inhibit prostaglandins, but mostly go through LOX pathway (lypooxygenase pathway). NSAIDs work on COX 1 and 2 inhibition whereas cortiocertoids works on LOX pathway. do prostaglandins as well, but mostly LOX pathway. Differneces dictate differences in NSAIDs.

Question 37

Same as previous slide. What to know: NSAID inhibits arachinoid acid of prostaglandins? through COX 1 and 2.

Answer 37

Different prostaglandins, in all different tissues, and different receptors. PGD2, PGE2, TxA2 Depends on cells present and site of inflammation (relisten to this part for location of each). GPCRs mostly in contrast to GABA-A = ion channel receptor

Question 38

REgulate prostaglandins and TXA

Question 39

COX-1: ______= ______ level of activity ✓ ________ and ______ of ____ mucosa ✓ ______ homeostasis and platelet _______ ✓ Maintenance of ? Regulates expression of:?

Answer 39

Constitutive, Constant, Maintenance, protection, gastric, Vascular, aggregation, renal blood flow, PGs (PGE2), TXA

Question 40

COX-2: ______ = expressed at sites of ____ Prostaglandins : ? COXs and Production of Prostaglandins ✓ Pain: ____-regulates sensitivity of __________ nociceptors ✓ __________: mediated by ✓ _______: pyrogens increase which happens mainly through ______ ✓ ________: _____ is upregulated in various carcinomas

Answer 40

Inducible, injury, PGs (PGE2) TXA2, up, peripheral, Inflammation, Fever, PGE2, Cancer, COX2 PGD2; PGE2, PGF2α, PGI2 Bradykinin, PGE2, PGI2 PGE2

Question 41

* COX-3 (AKA?): in the ______, regulates _____, discovered in ____

Answer 41

COX-1b, brain, fever, dogs

Question 42

5-LOX: ____-______________ _________ E.g.

Answer 42

pro-inflammatory leukotriens LTB4 Called housekeeping enzyme? COX2 is inducible at the sites of injury

Question 43

PGs control processes such as ? PGs promote ?

Answer 43

inflammation, blood flow, the formation of blood clots inflammation, pain, and fever

Question 44

Lipid compounds have diverse ________-like effects

Answer 44

hormone

Question 45

What is produced in almost every tissue in animals (lungs, GI, kidney, liver, blood vessels)?

Answer 45

Prostaglandins

Question 46

Different PGs have ______ effects in different tissues depending on the ______ of receptor they interact with.

Answer 46

various, type

Question 47

High concentrations of prostaglandins cause ______ by ______ action upon ______ endings

Answer 47

pain, direct, nerve

Question 48

COX2 is inducible

Question 49

Thromboxane A2 (TXA2) activation mediates several physiological and pathophysiological responses ▪ Platelet _______ and _____, ________ muscle contraction, and activation of __________ ________ responses ▪ TXA2 is predominantly derived from ?

Answer 49

adhesion, aggregation, smooth, endothelial, inflammatory, platelet COX-1

Question 50

Potential benefits in inhibiting LOX pathway: ▪ Higher ? ▪ Greater _______ efficacy

Answer 50

GI safety, analgesic

Question 51

The Stunning Complexity of Prostanoids in Inflammation ▪ Different molecules have ____________ effects on both the _______ and __________ of inflammation ▪ The same product is formed by different enzymes –COX-1 and COX-2 – may either ______ or ______ inflammation ▪ Products of the _____ enzyme may promote or resolve inflammation in ______ models ▪ Different cell types that predominate at varying stages of disease progression generate _______ that have _______ effects on inflammation ▪ Individual prostanoids ________ considerably in their biological effects with other mediators

Answer 51

conflicting, promotion, resolution, promote, resolve same, different, prostanoids, contrasting, overlap

Question 52

Given this complexity, how we can develop drugs that are reasonably well tolerated and reasonably effective?

Question 53

What are the three Main Functions of NSAIDs?

Answer 53

❖ Analgesia - reduction of perception of pain ❖ Antipyresis - reduction in fever ❖ Anti-inflammation – reduction of inflammation

Question 54

Non-Steroidal Anti-Inflammatory Drugs (“______” analgesics) Uses: ▪ _______________ ▪ ___________ arthritis (AKA?) ▪ ______________ ▪ _______ pain ▪ ____ inflammation Adverse Effects: ▪ Increase risk of ___ complications ▪ Deteriorate __________

Answer 54

weak, Osteoarthritis, Rheumatoid, Ankylosing spondylitis, Pancreatitis, Dental, Skin, GI, osteoarthritis

Question 55

True or False: There are more NSAIDs available for dogs than there are for cats?

Answer 55

True.

Question 56

No NSAIDs are approved for long-term in ______.

Answer 56

cats

Question 57

NSAID Overdose in cats can lead to: ▪ Stomach ______ with bleeding into the _____ tract ▪ Kidney _____ and _______ ▪ _____ problems ▪ _____ damage

Answer 57

ulcers, GI, damage, failure, Liver, Brain

Question 58

There are 2 FDA-approved NDAIDS for short-term use in cats:

Answer 58

Robenacoxib Meloxicam

Question 59

NSAIDs: PK properties ▪ Well ___________, and _____ does not substantially change their bioavailability ▪ Circulating NSADs are bound by ______ which ________ volume of distribution ▪ Displacement from albumin due to _________ by other drugs for the albumin binding sites or ___________ can lead to _____ levels of unbound drug, which can predispose the patient to drug-induced adverse effects on the _____-term basis ▪ Highly metabolized in the ____ ▪ _____/______ elimination ▪ Very little PK information is available in ____. Since cats have inefficient _______________ _____ and __________ conjugation system; the extrapolation of dosages from other species needs to be carefully considered ▪ ______ and ____ patients may require smaller doses of NSAIDs due to weak ____ and _____ status, which may result in _____ elimination rates

Answer 59

absorbed, food, albumin, decreases, competition, hypoalbuminemia, higher, short, liver, Urine/feces, cats, cytochrome P450, glucuronidation, Young, old, liver, kidney, lower