Ch 36: Non-Steroidal Anti-Inflammatory Drugs Flashcards
(88 cards)
1
Q
what are some examples of eicosanoids?
A
prostaglandins, thromboxanes, leukotrienes
2
Q
what are eicosanoids?
A
- hormones & molecules that activate receptors (PLA2)
- formed from membrane phospholipids
3
Q
what does phospholipase A2 cleave?
A
an essential fatty acid (arachidonic acid)
- which then cleaves to form lipoxogenase & cyclooxogenase
4
Q
Lipoxygenase
A
- forms leukotrienes
* * released in an autocrine & paracrine fashion
5
Q
Zileuton
A
lipoxygenase inhibitor
6
Q
Montelukast & Zaphirlukast
A
leukotriene receptor blocker
7
Q
What are the effects of LOX
A
LTC4 & LTD4 = bronchoconstrictors
- can lead to anaphylaxis
8
Q
COX
A
- activated by hormones & biomolecules when acting at receptors
- forms PGG2, converts to PGH2, then to various prostaglandins & thromboxanes
- consists of 2 isoforms
- COX-1 & COX-2
9
Q
COX-1
A
- produced in tissues for normal tissue function
- (produces prostaglandins & activates platelets and protect the stomach & intestinal lining)
10
Q
COX-2
A
-induced by inflammatory cells
used to treat inflammation, pain & fever
(release IL-6, IL-1B, and TNF-a)
11
Q
What parts of the body does COX products play key roles?
A
Smooth muscle Platelets Kidneys CNS Inflammation
12
Q
smooth muscle
A
Vascular:
- can be constrictor (TXA2 & PGF2a) or dilator (PGI2 & PGE2)
GI:
- mostly constrictors
Airways:
- PGI2 & PGE2 relax, and others constrict
Reproductive:
- PGF2a + oxytocin = parturition
- PGE2 & PGI2 = relax
13
Q
platelets
A
- aggregation that’s mostly inhibited by PG’s
- TXA2 can be released which can lead to aggregation
14
Q
Kidney
A
- TXA2 lead to renal vasoconstriction
- elevated renal inflammation
- PGI2 & PGE2 help w/ renal blood flow & function
15
Q
Inflammation
A
- PGE2 & PGI2 (prominent) inflam. agents
* * increase B.F. = edema & leukocyte infiltration
16
Q
CNS
A
- can lead to fever (PGE2)
- sleep (PGD1)
- regulation of neurotransmission
17
Q
prostaglandins & thromboxanes cause?
A
pain (sensitize pain receptors to bradykinin…)
inflammation (increased vascular permeability)
fever (hypothalamic effect)
thrombus formation (clotting)
– vasoconstriction, vasodilation, dysmenorrhea, etc
18
Q
what are some NSAID effects?
A
analgesia –> mild-mod pain
anti-inflammation –> corticosteroids
anti-pyretic –> reducing temperature in fever
anti-coagulant –> platelet aggregation
19
Q
some NSAIDS
A
aspirin indomethacin naproxen oxaprocin etodolac flurbiprofen ibuprofen diflunisal celecoxib
20
Q
NSAID adverse effects
A
CNS -- headaches, tinnitus, dizziness CV -- fluid retention, edema GI -- pain, nausea, vomiting, ulceration Hematologic -- rare (thrombocytopenia) Hepatic -- abnormal liver function Pulmonary -- asthma Rash -- pruritus Renal -- insufficiency to even failure
21
Q
aspirin
A
- acetylsalicylic acid
- cheap/ inexpensive
- irreversible inhibitor of COX1 & COX2 (esp. on platelets)
- effective due to COX2 action
- side effects due to COX1 activity
22
Q
Aspirin side effects
A
GI
(irritates upper GI)
— so take w/ meals. PG’s = mucous formation
CNS
(tinnitus, vertigo)
– possible kidney/ liver damage
Reye’s Syndrome
- children & teens
- after influenza/ chicken pox
(high fever, vomit, liver dysfunction, unresponsive, delirium, convulsions, coma, death)
23
Q
Ibuprofen
A
- similar to aspirin
- less GI side effects
- more potent
24
Q
Side effects on ibuprofen
A
- GI
- Rash, pruritis, tinnitis
- nephrotoxic
25
What area of the body is affected due to the toxicity of Ibuprofen
Stomach
Kidneys
why?
- less stomach protection (mucous production)
- less renal B.F. (nephrotoxicity)
26
symptoms of Ibuprofen toxicity
```
vomiting (w/ or w/o blood)
abdominal pain
diarrhea
black/tarry stool
loss of appetite
increased drinking
increased urination
lethargy
dehydration
seizures
```
27
Naproxen
similar to ibuprofen ( but long lasting)
28
sulindac
less toxicity for kidneys
| has greater GI affects than aspirin & ibuprofen
29
oxaprozin
50 hr half life
| - take once a day
30
acetaminophen
- inhibits cox enzymes
- anti-pyretic & analgesic (NOT a NSAID)
- less anti-coagulant * anti-inflammatory
31
side effects of acetaminophen
hepatotoxic at high doses (can be fatal)
| - no GI effects & nor Reye's
32
indomethacin
- reduce pre-term labor (under 32 weeks)
| - manage patent ductus arteriosus
33
COX-2 meds
celecoxib (Celebrex)
Rofecoxib (Vioxx)
** but removed due to strokes and MI
(for arthritis, dysmenorrhea)
34
COX-2 inhibitors
- reduce GI side effects (ulceration)
| - increased thrombosis, MI, and stroke which lead to retraction of VIOXX
35
Rheumatoid Arthritis
- chronic, systemic disorder
- synovitis, joint destruction
- morning stiffness
- arthritis in 3+ areas
- affects about 1% of population
- most often women (20-40 yrs)
- auto-immune
* * initiated from previous. infections
* * (IL's PG's LK's cause synovial proliferation, cartilage & bone destruction)
36
Treating Rheumatoid Arthritis
NSAIDS (treat inflammatory)
Corticosteroids (treat inflammatory)
DMARDS (slow disease)
37
What are some goals for Rheumatoid Arthritis
1. decrease joint inflammation
| 2. arrest disease progression
38
Glucocorticoids
- naturally cortisol (hydrocortisone) produced in adrenal cortex
- bind to receptors in cytosol (orphan receptors)
- bound to heat shock proteins
NOTE:
- once steroid binds to receptors, HSP releases receptors, it dimerizes, then moves into the nucleus
- while in nucleus, receptor/ steroid complex acts like a txn factor to initiate mRNA txn
- leads to lipocortin-1 inhibits PLA2 activity
39
corticosteroid effects
```
physiologic
metabolic
catabolic
stimulate acid & pepsin in stomach
anti-inflammatory/immunosuppressive
better than NSAIDS (inhibit leukotrienes)
efficacious
limiting side effects
```
40
when are corticosteroids used?
ONLY when NSAIDS are no longer effective
41
side effects of corticosteroids
peptic ulcer formation
muscle wasting
osteoporosis
42
Name some corticosteroids
Betamethasone
cortisol (hydrocortisone)
prednisolone
triamcinolone
43
DMARDS
disease modifying anti-rheumatic drugs
- takes 6 weeks to 6 months to work
44
methotrexate
immunosuppressive
one that's most effective
best for toxicity ratio
45
side effects to methotrexate
hepatotoxicity
GI
pulmonary effects
hair loss
46
what does methotrexate inhibit?
thymidylate synthetase
47
chloroquine, hydroxychloroquine
anti-malaria drugs
- takes 12-24 wks to work
- used when NSAIDS stop working
48
side effects to chloroquine, hydroxychloroquine
safest DMARDS
ocular damage
headaches
49
gold therapy (auranofin)
- given orally w/ less side effects
- given early on (don't reverse previous. damage)
- accumulates in lysosomes of synovial tissue (decrease lysosome & macrophages)
50
side effects of gold therapy
GI
oral irritation
common rashes, pruritis
blood disorders
51
Azathioprine
- immunosuppressant to prevent tissue damage
- FOR SEVERE CASES (cases that prevent other treat.)
- anti-metabolyte
- TOXIC & NOT well tolerated
* ** fever, sore throat, fatigue, vomiting
52
Penicillamine
- chelates heavy metals
- used for lead poisoning
- used for arthritis incase GOLDS don't work
- immunosuppressant (reduce T cell function)
53
side effects of Penicillamine
moderately toxic (fever, joint pain, pruritis)
54
Leflunomide
- NEW
- well tolerated
- works within first month
blocks RNA synthesis in lymphocytes to reduce their activity
55
side effects of Leflunomide
GI
allergy
hair loss
hepatotoxic (need monitoring)
56
Etanercept
- new & effective (binds/blocks TNF binding action)
- successful to patients unresponsive to DMARDS
- given by sub-cutaneous injection (2x weekly)
57
side effects of etanercept
risk of infections (TNF = key part of immune system)
58
osteoarthritis
- Increase viscosity of synovial fluid
1. Hyaluronan: polysaccharides injected into joints for long lasting relief
- Joint tissue precursors
1. glucosamine & chondroitin sulfate: used to reverse damage by providing precursors
59
Autonomic Pharmacology
CNS
- brain
- spinal cord
PNS
- somatic (skeletal muscle function)
- autonomic (body functions) --> HR, rest rate, etc
* sympathetic (thoracolumbar)
* parasympathetic (cranial sacral)
60
sympathetic division
1st thoracic to 3rd lumbar
pre-ganglionic neuron--> cord (ventral root) to ganglia
post-ganglionic neuron--> ganglion (dendrite & cell body) to organ
61
parasympathetic inervation
```
from brainstem (3,4,9,10 & vagus) to sacral cord
Two neurons reach the end of the organ
- ganglia found in end organ or tissue
- longer pre-gang & shorter post-gang
- 1:1 ratio of pre- to post-
```
Both pre and post neurons release ACh onto smooth muscle, cardiac muscle or glands
62
What are some ways that drugs can interfere?
```
block synthesis
block uptake
block storage
displace transmitter
prevent exocytosis
agonist mimetic
block receptor
inhibit breakdown
```
63
cholinergic receptor
nicotinic receptors
Nn--> neuronal
- post-ganglionic neurons
- pre synaptic cholinergic terminals
- open Na+ or K+ channels
Nm--> muscle
- skeletal muscle neuromuscular junction
- open Na+ or K+ channels
64
muscarinic receptors
from a mushroom (amanita muscarina)
G protein coupled receptors
- activate ion channels, adenyl cyclase, PLC
at least 4 subtypes
- agonist: muscarine
- antagonist: atropine
(location: sm muscle, glands, heart, brain)
65
muscarinic receptors & locations
```
M1
M2
M3
M4
M5
```
66
M1
CNS & Symp. post-gang neurons
67
M2
heart & smooth muscle
68
M3
glands, smooth muscle
69
M4
glands, smooth muscle
70
M5
?? (cloned?? )
71
Muscarinic effects
- depolarization of ganglia
- decreased chronotropic & inotropic response
- smooth muscle contraction & glandular secretions
72
cholinergic stimulants
A. Direct-Acting: active receptors
1. choline esters: similar to ACh
- Bethanechol
- Pilocarpine
- Methacholine
2. Alkaloids: from plants
- muscarine
- nicotine
- pilocarpine
73
what are the effects of direct acting cholinergics
eye:
pupil constriction, accommodation, increased lacrimation & decreased intraoccqular pressure
CV system:
bradycardia, decreased contractility, relax peripheral vessels
Respiratory System:
airway constriction, increased secretions
GI- increased motility
CNS- hypothermia, tremors, convulsions
Bladder- stim detrussor, relax trigone (urination)
74
SLUD
```
poisoning by cholinergics
salivation
lacrimation
urination
defecation
```
75
indirect- acting cholinergics
inhibit AchE
similar effects as direct acting
Reversible:
edrophpnium, neostigmine, physostigmine
Irreversible:
insecticides (malathion, parathion)
nerve gases
76
what are cholinergics used for?
glaucoma
GI and bladder
Heart
Atropine intoxication
77
Glaucoma
pilocarpine, physostigmine
| - to reduce intraocular pressure
78
GI and bladder
bethanechil, neostig
| - for post-op atony
79
Heart
edrophorium
| - for tachycardia
80
Atropine intoxication
physostigmine
81
side effects/ toxicity of cholinergics
contraindications
- asthma, peptic ulcer, bradycardia, hypotension
SLUD
Cholinesterase inhibitor poisoning
- give heroic doses of atropine
- for organphosphatases, use 2-PAM
82
muscarinic receptor blockers effect:
heart:
tachycardia by clocking vagal input
resp. system:
bronchodilator & less secret
eye:
dilate & accomodate
Urinary & GI:
reduce activity/motility
CNS:
sedative, then excitement
83
muscarinic blocker uses
respiratory: Ipratropium (Atrovent)
- for asthma & pre- anesthesia
eye: Cyclopentylate
- for mydriasis & Cyclopegia
urinary/GI: Dicyclomine
- for incontinence or irritable bowel
motion sickness: Scopolamine
heart: Atropine
- for bradycardia
others: mushroom poisoning
84
muscarinic blockers are contraindicated for
glaucoma patients
prostate hypertrophy patients
anti-depressant patients
85
Ganglionic blockers
autonomic selective inhibitors
| pirenzepine
86
pirenzepine
- for peptic user
- - specific for muscarinic gang.
- - have less side effects
87
autonomic selective inhibitors
- Hexamethonium, trimethaphan: used in hypersensitive emergencies
88
what does autonomic selective inhibitors cause?
tachycardia, mydriasis, constipation, urinary retention, decreased sweat & saliva
