Analgesic, Antipyretic and Anti-Inflammatory Drugs Flashcards
1
Q
What does inflammation start with
A
Tissue Damage
2
Q
What chemicals are released to cause inflammation
A
histamines, kinins and prostaglandins
3
Q
Vasoactive amines
A
histamine and serotonin
4
Q
plamsa protein systems
A
complement and clotting/fibrinolysis systems
5
Q
Acetyl Glycerol Ether Phosphocholine (AGEPC)
A
platelet activating factor (PAF)
6
Q
what are the mediator systems of inflammation
A
vasoactive amines
plasma protein systems
prostaglandins and leukotrienes (Eicosinoids)
AGEPC= PAF
cytokines
Nitric oxide - vasodilation
7
Q
Eicosinoids
A
prostaglandins and leukotrienes
8
Q
What mediates inflammation
A
Vasodilation
increase permeability
chemotaxis
pain
fever
tissue damage
9
Q
what class of drugs inhibit the phospholipase
A
glucocorticoids
10
Q
What type of antihistamine inhibit the Calcium and beta2 receptors
A
second generation
11
Q
First and second generation antihistamines inhibit what
A
histamine receptors
12
Q
What do “selective inhibitors” inhibit
A
COX-1 and COX-2
13
Q
what do non-selective inhibitors inhibit
A
prostaglandins
14
Q
What does PGI2 cause
A
vasodilation, and inhibits platelet aggregation
15
Q
what does Thromboxane A2 (TXA2) cause
A
vasoconstriction, and promotes platelet aggregation
16
Q
what is part of the Prostaglandin G2 (PGG2)
A
PGI1 and TXA2
17
Q
types of nonselective COX inhibitors
A
ibuprofen (Motrin, advil)
Naproxen (Naprosyn)
Diclofenac
Ketorolac (Toradol)
Indomethacin
18
Q
Type of selective COX-2 inhibitor
A
Celecoxib (celebrex)
19
Q
what is the MOA of NSAIDs
A
inhibits COX-1 and COX-2 enzymes that break down the first step in prostaglandin synthesis. This results in a decreased prostaglandin level
20
Q
What are prostaglandins synthesized from
A
Arachidonic acid
21
Q
What are the two cycloocygenaze enzymes
A
COX-1 and COX-2
22
Q
what is the purpose of COX-1 and COX-2
A
prostaglandin synthesis
23
Q
What does COX-1 do
A
physiologic production of prostaglandins
“house keeping” enzyme
regulates homeostasis
24
Q
What does COX-2 do
A
unregulated during inflammation
induced by oxidative stress, injury, ischemia
25
Describe the physical differences between COX-1 and COX-2
larger and more flexible substrate channel and a larger space at the site where inhibitors bind
26
What NSAID irreversibly inhibits the enzymes
Aspirin
27
What does low dose aspirin inhibit
COX-1
28
what does higher dose aspirin inhibit
both COX-1 and COX-2
29
what is ASA and what are its properties
Aspirin - analgesic, antipyretic and anti-inflammatory effects at higher doses
30
where is aspirin hydrolyzed
liver
31
what is aspirin hydrolyzed into
salicylic acid
32
due to the hydrolysis of aspirin what are the plasma concentrations
always low and rarely exceed 20mcg/ml at ordinary therapeutic doses
33
describe the half life of aspirin
it is relatively short, but lengthens as the dose increases by Zero-order kinetics
34
what is aspirins antiplalet effect
8-10 days (the life of the platelet)
35
what does ASA inhibit
TXA2 production in platelets
36
what happens when TXA2 production is inhibited by ASA
decreases platelet aggregation and prevents the first step in thrombus formation
37
What is the anti-inflammatory effect of ASA
inhibits prostaglandin synthesis by inhibiting the function of COX enzymes. result in inhibiting granulocyte adherence to damaged vasculature and inhibiting the chemotaxis of PMN leukocytes and macrophages
38
What is the analgesic effect of ASA
through its effect on inflammation and probably because it inhibits pain stimuli at a subcortical(Central) site.
39
What is the antipyretic effects of ASA
probably mediated by both COX inhibition in CNS and inhibition of IL-1
40
What is aspirin not effective for
severe visceral pain
41
when is IL-1 released
released by macrophages during episodes of inflammation
42
What are the adverse effects of theraputic doses of ASA
GI upset and ulcers
43
What are adverse effect of higher doses of ASA
vomiting, tinnitus, decreased hearing and vertigo (reversible)
44
define Salicylism
vomiting, tinnitus, decreased hearing and vertigo that is reversible
45
what are adverse effects to very large doses of ASA
hyperpnea (hyperventilating) through a direct effect on respiratory centers int he medulla resulting in respiratory alkalosis
and
elevated body temperature due to uncoupling of oxidative phosphorylation which can result in sever hyperthermia
46
What is the primary concern with ASA toxicity
Respiratory alkalosis - early
47
what occurs with ASA toxicity
lactic acidosis and hyperpyrexia
metabolic acidosis
ketone bodies - wide anion gap
respiratory alkalosis
48
what are the common signs of ASA toxicity
nausea, vomiting, diaphoresis, tinnitus, deafness, vertigo, agitation, delirium, hallucinations
49
what does increased renal bicarbonate exceretion due to ASA lead to
metabolic acidosis
50
What does the inhibition of oxidative phosphorylation lead to with ASA
lactic acidosis hyperpyrexia
51
What does the increase in fatty acid metabolism with ASA lead to
ketone bodies and wide anion gap
52
What is an anion gap
a larger space in the NMJ space
53
what is the effect of renal and cardiovascular disease
decreased renal blood flow
54
what is the effect of cirrhosis, nephrosis, heart failure and diuretics
decreased blood volume
55
What patients should you avoid NSAIDs in
Kidney disease, Cardiovascular disease, Liver disease and those on a diuretic
56
what are the FDA black box warnings for non-ASA NSAIDS
increased risk of serious and potentially fatal cardiovascular thrombotic event and increased risk of serious or potentially fatal GI adverse events including bleeding, ulcer, stomach or intestine perforation
57
What cardiac patients have a contraindication for NSAID use
CABCG peri-operative pain
58
AHA NSAID recommendations
lowest effective dose
avoided in patients with cardiovascular risk factors
avoid in patients with history of hypersensitivity to NSAIDs
no recommended during pregnancy or children with viral diseases
59
What is the risk of ASA in kids with viral diseases
it increases the risk of Reyes Syndrome
60
what is Reyes Syndrome
a rare but serious illness thought to be preciptated by aspirin that causes cognitive impairement
61
what is the effect of ASA on a fetus
damages fetal vasculature
62
what cardiovacular risk factors for NSAID use
hypertension, hypercholesteremia, angina, edema, recent cardiac bypass surgery and a history of MI or other CV events
63
What do COX-2 inhitors bypass
most side effects of COX -1 inhibitors
- less GI adverse effects
64
what is an example of a COX-2 inhibitor
Celebrex (celecoxib)
65
Where are COX-2 inhibitors metabolized
Liver (CYP2C9)
66
what is the half life of COX-2 inhibitors
about 11 hours
67
when do you avoid COX-2 inhibitor use
severe renal and hepatic disease and patients with anaphylactoid reactions to ASA and NSAIDs
68
what are common drug type interactions with Celebrex
elevation of beta-blockers, antidepressants and antipsychotic drugs
69
What is the mechanisms of action for ASA
irriversibly inhibits both COX-1 and COX-2, which decreases TSA2 and prostaglandin synthesis
70
what is the clinical use of low dose aspirin
decreased platelet aggregation
71
what is the clinical use for intermediate dose ASA
antipyretic and analgesic
72
what is the clinic use for high dose ASA
Anti-inflammatory
73
what are the most common NSAIDS
ibuprofen, naproxen, indomethacin, ketorolac, diclofenac
74
what is the mechanism of action for NSAIDs
reversibly inhibits both COX-1 and COX-2. blocks prostaglandin synthesis
75
what is the clinical use for NSAIDs
antipyretic, analgesic, anti-inflammatory, gout (indomethacin)
76
what are signs of NSAID toxicity
interstitial nephritis, gastric ulcer and renal ischemia
77
What is the MOA for Celebrex
reversibly inhibits COX-2. mediated inflammation and pain. spares COX-1 which helps maintain gastric mucosa. spares platelet function as TXA2 production is dependent on COX-1.
78
what are toxicity concerns with Celebrex
increased risk of thrombosis, avoid in sulfa allergy and renal ischemia
79
APAP
Tylenol/acetaminophen
80
what does APAP inhibit
prostaglandin synthesis in CNS
81
what does APAP have minimal effect on
antiiflammatory effects
82
what are the primary effects of APAP
antipyretic and analgesia
83
what is APAPs effect on platelets
none
84
Where is APAP absorbed
GI tract - rapidly
hepatocytes and luminal cells of intestines
85
what type of metabolism does APAP go through
first pass metabolism
86
where is APAP conjugated
in the liver to form inactive metabolites
87
what is the potentially damaging metabolite that APA is hydroxylated into
N-acetyl-p-benzoquinoneimine (NAPQI)
88
at normal doses what does NAPQI react with
glutathione and forms a nontoxic metabolite
89
where are APAP and its metabolites excreted
urine
90
what happens when there is not enough glutothione
NAPQI does not react and lead to covalent binding of amino acids in proteins and enzymes leading to cell death
91
what is the MOA of acetaminophen
reversibly inhibits cyclooxygenase in CNS. inactivated peripherally
92
what is the clinical use for APAP
antipyretic, analgesic but no anti-inflammatory effect. used instead of ASA in children with viral infection
93
what does overdose of APAP produce
hepatic necrosis and cell death
94
Most common oral corticosteroids (4)
prednisone
methylprednisolone
dexamethasone
hydrocortisone
95
most common IV corticosteroids (3)
Methylprednisolone
hydrocortisone
dexamethasone
96
most common inhaled corticosteroids (4)
beclomethasone
fluticasone
budesonide
triamcinolone
97
most common opthalmic corticosteroids (3)
dexamethasone
prednisolone
fluorcinolone
98
most common topical corticosteroids (10)
hydrocortisone
triamcinolone
fluocinolone
desonide
fluticasone
mometasone
fluorandrenolide
fluorcinonide
betamethasone
clobestasol
99
what is corticosteroids considered
immunosuppressive
100
what do corticosteroids bind to
glucocorticoid receptor
101
what do corticosteroids regulate
Translation of DNA as it is passed into the nucleus
102
what do corticosteroids decrease
the expression of genes involved in inflammatory response
103
what does the decrease in gene expression cause
decrease COX-2 up-regulation and inhibits various inflammatory cytokines
104
What effect do corticosteroids have on inflammatory cells
decrease numbers of eosinophils (apoptosis)
decrease cytokines from T lymphocytes
decrease number of mast cells
decrease cytokines from macrophages decrease number of dendritic cells
105
What effects do corticosteroids have on structural cells
decrease cytokines and mediators of epithelial cells
decrease leakage of endothelial cells
increase B2 receptors and decrease cytokines in smooth muscle (airway)
and decrease mucus secretion in the mucous glands
106
why is tapering a corticosteroid necessary
it may cause adrenal suppression with prolonged use with greater than 20 mg/day being at higher risk
107
what affects do corticosteroids have on blood glucose
increase blood glucose
108
What can corticosteroids cause
insomnia, mood swings, psychiatric disturbances including euphoria, personality changes, severe depression or frank psychotic manifestations
109
what patients require caution when using corticosteroids
renal impairment and osteoporosis
110
what is the correlation between osteoporosis and corticosteroid use
high doses and/or long-term use of corticosteroids have been associated with increased bone loss and osteoporotic fractures
111
what is the correlation between renal impairment and corticosteroids
fluid retention may occur
