Analgesic, Antipyretic, Anti-inflammatory Flashcards
What does inflammation start with?
Tissue Damage
What happens when histamine, kinins, and prostaglandins are released
Activation of innate & Adaptive immune cells
Vasodilation and permeability
Phagocytosis
Elimination of microbes and eventually tissue repair
What else besides injury can cause an inflammation response
Inappropriate activation or immune response, often seen in autoimmune diseases
What are the cardinal signals of inflammation?
Heat
Redness
Swelling
Pain
Loss of function
What are the main mediator systems of inflammation?
Vasoactive amines
Plasma protein systems
Eicosinoids
Platelet activating factor (PAF)
Cytokines
Nitric Oxide
What makes up vasoactive amines?
Histamine and serotonin
What makes up the plasma protein system?
Complement system
Kinin system
Clotting system
What are Eicosinoids
Prostaglandins and Leukotrienes
*Often household/OTC medications
What makes up platelet activating factors?
Acetyl Glycerol Ether Phosphocholine (AGEPC)
What do the inflammatory mediators indicate?
Tell us what we are targeting with medications to treat the present issue
What is the precursor to prostagladins
Cyclooxygenase
What does PGI2 do?
Vasodilation which inhibits platelet aggregation
What is TXA2 and what does it do
Thromboxane A2
Vasoconstriction which promotes platelet aggregation
What does PGE2 indicate?
Inflammation vasopermeability
What are the three main groups of NSAIDS
Salicylic acid derivatives
Nonselective COX inhibitors
Selective COX-2 inhibitors
What drug(s) are salicylic acid derivatives?
Acetylsalicylic acid (ASA)
Aspirin
What drug(s) are nonselective COX inhibitors?
Ibuprofen
Naproxen
Diclofenac
Ketorolac
Indomethacin
What is the brand names of Ibuprofen
Motrin or Advil
What is the brand name of Naproxen
Aleve
What is the brand name of Ketorolac
Toradol
What is indomethacin generally prescribed for?
Gout
What drug(s) are COX2 inhibitors?
Celecoxib
What’s the brand name of Celecoxib?
Celebrex
What Drug(s) are analgesic and antipyretic?
Acetaminophen (Tylenol)
What is the mechanism of action for an NSAID
They inhibit cyclooxygenase enzymes that allow for prostaglandin synthesis
What enzyme is prostaglandin generally synthesized from
Arachidonic acid
What does blocking cyclooxygenase cause
Decreased prostaglandin levels
What are the cyclooxygenase enzymes that are involved with prostaglandin synthesis
COX-1 and COX-2
Why do we avoid using drugs that are ONLY COX-2 inhibitors
They can cause cardiovascular issues
What does the production of prostaglandins do for the body?
Regulates homeostasis
what causes an increase in COX-2 in the body
oxidative stress
injury
ischemia
*Upregulates during inflammation
What is the structural difference between COX-1 and COX-2
COX-2 has a larger and more flexible substrate channel as well as a larger target space for inhibitors to bind
What is the abbreviation for asprin
ASA
What is aspirin
Acetylsalicylic acid
What is unique about aspirin as an NSAID
Aspirin irreversibly inhibits the enzymes
How long do you hold Aspirin for before surgery and why
7 days because of anticoagulation effects
What does low dose aspirin inhibit
COX-1
What do high doses of aspirin inhibit
COX-1 and COX-2
How is Aspirin metabolized
Rapidly hydrolyzed in the liver to salicylic acid and excreted by the Kidney
How long does it take an uncoated aspirin to be metabolized by the liver
about two hours
What happens with metabolism if aspirin is enteric coated
It takes longer to metabolize
What is the purpose of an enteric coated aspirin and why do you tell someone having an MI to chew it instead of swallow it whole
Enteric coating prevents the aspirin from being rapidly absorbed
You tell someone having an MI to chew the aspirin to break that enteric coating and allow for rapid absorption
What happens with metabolism at really high doses of aspirin
Turns into zero order kinetics which in turn can cause toxic side effects
What effect does aspirin have on platelets
They block prostaglandin synthesis which intern inhibits TXA2 production = low platelet aggregation
What are the side effects of aspirin
anti-inflammatory
analgesia (not for severe visceral pain)
Antipyretic
What are the adverse effects of aspirin at therapeutic dosage
GI upset
gastric/duodenal ulcers
What are the adverse effects of high dose aspirin
Salicylism (vomiting, tinnitus, decreased hearing, vertigo)
What are the adverse effects of very large doses of aspirin
Hyperpnea (Increased depth and rate of respiration)
Respiratory alkalosis
Elevated body temperature
Why does hyperpnea occur with very large doses of aspirin
ASA will have a direct effect on the respiratory centers in the medulla
why can very large doses of ASA cause an elevated body temp
It causes uncoupling of the oxidative phosphorylation which could potentially result in sever hyperthermia
What will happen with oxidative phosphorylation is inhibited
There will be a release of lactic acid from cells
What adverse effect is generally seen first with ASA
Respiratory alkalosis
What are the adverse effects of non ASA NSAIDs
Increased risk of cardiac thrombotic event
Increased risk of fatal GI upset
-> bleeding ulcer, stomach/ intestinal perf
Which cardiac patients can not be given non ASA NSAIDs
CABG patients
What is recommended when giving NSAIDs
- give at lowest effective dose
Who should not be given NSAIDs
Pregnant patients
children
hypertensive patients
hypercholesterolemia patients
What can happen in children who are given ASA during viral illness
Reye’s syndrome
What is an example of a COX-2 inhibitor
Celecoxib (Celebrex)
What is the benefit of a COX-2 inhibitor
Minimal to no GI effects
When do you never use COX-2 inhibtors
Patients with heart disease
Why is celecoxib one of the few COX-2 inhibitors still on the market
Has less thrombotic potential
Where are COX-2 inhibitors metabolized
Liver by CYP enzyme
What is the half life of COX-2 inhibitors
Roughly 11 hours
Who should not take COX-2 inhibitors
patients with severe hepatic and renal disease
What happens when COX-2 inhibits CYP enzyme
it may increase levels of celecoxib, fluconazole, fluvastatin
What else can happen when Celecoxib blocks CYP enzymes
Can lead to the elevation of beta-blockers, anti-depressants, and anti-psychotics
What does acetaminophen do
inhibits prostaglandin synthesis in the CNS
What is acetaminophen taken for
antipyretic and analgesic properties
What does acetaminophen have no effect on
platelets
Where is acetaminophen metabolized
the GI tract after first-pass metabolism and then secreted in urine
What is acetaminophen metabolized to
Gets hydrolyzed into NAPQI
What is NAPQI
potentially dangerous metabolite ( can cause quick liver failure)
At normal doses was happens with NAPQI
reacts with glutathione to form a nontoxic metabolite
How do corticosteroids work
bind to a glucocorticoid receptor and passes into the nucleus to regulate DNA translation = decreased expression of inflammatory genes
Which processes are inhibited by corticosteroids to manage inflammation
decrease COX-2 up regulation
Inhibits inflammatory cytokines
What are some adverse side effects of corticosteroids
adrenal suppression
increased blood glucose
psychiatric disturbances
Which patients do you avoid using corticosteroids on
people at risk for osteoporosis
Patients with renal impairment
