PHARM block 3 without coagulation drugs Flashcards
(249 cards)
1
Q
GI drugs uses
A
most common forms of: nausea/vomiting, diarrhea, constipation, gerd
2
Q
drugs used to induce therapeutic emesis
A
ipecacuana; hypertonic saline; apomorphine
3
Q
ipecacuana
A
ipecac syrup; obsolete
4
Q
use of drugs to induce emesis
A
to empty stomach after poison ingestion; alternative to/combo with gastric lavage
5
Q
contraindications of drug-induced emesis
A
ingestion of corrosives (cleaning fluids); ingest aliphatics (petroleum -> lipid pneumonia); somnolence, unconciousness
6
Q
adverse effects of drug-induced emesis
A
aspiration, vagal syncope, hypochloremia, hypovolemia, absorption of emetic drug (NaCl, ipecac)
7
Q
antiemetic drugs
A
antihistamines (inhibit dopamine); phenothiazines; dopamine antagonists; 5-HT-antagonists; corticosteroids; cannabinoids (effective, illegal in some states); neurokinin-1-receptor antagonist; adjunct medications
8
Q
antiemetic antihistamines
A
diphenhydramine, hydroxizine
9
Q
diphenhydramine, hydroxizine adverse effects
A
sedation
10
Q
diphenhydramine, hydroxizine indications
A
pregnancy, motion sickness
11
Q
phenothiazines
A
perchlorphenazine, proemthazine
12
Q
perchlorphenazine, proemthazine adverse effects
A
epm disturbances, dyskinesias, sedation
13
Q
perchlorphenazine, proemthazine indications
A
metabolic/endocrine, cns
14
Q
dopamine antagonists
A
metoclopramide, (domperidon) - risk of arrhythmia -> used in compounds
15
Q
metoclopramide, (domperidon) adverse effects
A
s.a., but less pronounced
16
Q
metoclopramide indications
A
widely used to prevent/treat moderate nausea/emesis
17
Q
5-HT-antagonists
A
ondansetron, granisetron, tropisetron, dolasetron
18
Q
ondansetron, granisetron, tropisetron, dolasetron adverse effects
A
CONSTIPATION (contraindicated w/opiates), headache
19
Q
ondansetron, granisetron, tropisetron, dolasetron indications
A
cytostatic-induced EARLY vomiting
20
Q
antiemetic corticosteroids
A
dexamethasone
21
Q
dexamethasone adverse effects
A
none
22
Q
dexamethasone indications
A
intracranial pressure, cytostatic-induced LATE vomiting; given together w/5-HT-antagonists
23
Q
cannabinoids
A
marijuana, THC (dronabinol), nabilone
24
Q
marijuana, THC, nabilone adverse effects
A
drowsiness, confusion, amotivational syndrome (prolonged use)
25
cannabinoids indications
wasting related to AIDS, cancer
26
neurokinin-1-receptor antagonist
aprepitant
27
aprepitant adverse effects
fatigue, dizziness, diarrhea
28
aprepitant indications
cytostatic-induced; combo tx
29
adjunct antiemetic drugs
benzodiazepines, atropine, scopolamine, erythromycin (prokinetic)
30
benzodiazepines antiemetic indications
anticipatory vomiting
31
erythromycin moa
macrolide antibiotic, motilin agonist
32
erythromycin uses
diabetic gastroparesis, postoperative GI atony -> prokinetic
33
metoclopramide moa
central D2 antagonist (dopamine); peripheral M1 agonist
34
metoclopramide uses
antiemetic, gerd, diabetic gastroparesis -> prokinetic
35
metoclopramide pk
oral, im, iv, rectal
36
metoclopramide pd
antiemetic; prokinetic (GI)
37
metoclopramide adverse effects
extrapyramidal symptoms, esp in children; restlessness; drowsiness; with prolonged, high dose -> galactorrhea, gynaecomastia, parkinsonoid
38
most important therapy for diarrhea
drinking balanced fluid to maintain kidney fxn
39
diarrhea-causing drugs
adrenergic blockers ((reserpine)); antimicrobials (tetracyclines, sulfonamides, broad spectrum) - affect flora; bile acids, fatty acids, carcinoid tumor secretions; digestive enzyme blockers (acarbose, orlistat); dietary agents (OLESTRA, some sweeteners); cardiac glycosides - sign of overdose; cholinergic agonists; laxatives; prostaglandins
40
drugs for diarrhea treatment
peripheral opioid-receptor agonists (loperamide, diphenoxylate (combine w/atropine)); tinctura opii; somatostatin; alpha2 agonists (clonidine); adjunct meds - spasmolytic drugs; bile-acid induced diarrhea (colestyramine); clostridium-difficile associated enterocolitis (vancomycin; metronidazole)
41
loperamide moa
mainly peripheral; opioid receptor agonist; OTC drug
42
loperamide pk
oral
43
loperamide pd
inhibits intestinal fluid secretion; inc intestinal fluid absorption; inc tonic (non-propulsive) intestinal smooth muscle tone
44
loperamide adverse effects
constipation; kids, high dose - opioid-like adverse effects
45
loperamide contraindications
ileus, subileus, fever, antibiotics-associated diarrhea, megacolon, pregnancy, lactation
46
ineffective drugs used for diarrhea
activated charcoal tablets; pektin; kaolin -> placebo, irritable bowel syndrome, 'stool freaks'; drugs w/serious adverse effects -> antibiotics/septics in OTC preps, tannin
47
constipation-causing drugs
ALL opioids - strong; anticholinergics (antidepressants, phenothiazines, antiparkinson drugs); ganglionic blockers; calcium channel antagonists; k-wasting diuretics; 'irritant'-type laxatives (chronic abuse)
48
types of laxatives
bulk-forming agents (fiber) - bran, psyllium, methylcellulose -> distend bowel -> inc peristalsis; hyperosmolar agents - sorbitol, lactulose, polyethylenglycol (for surgery prep) -> retain water in gut; stool softening/lubricating agents - docusate sodium, glycerin, mineral oil (can cause lipid pneumonia); stimulants/irritants - bisacodyl, castor oil, phenolphtalein, anthrachinones; enema - containing any of others (helps pregnant women push)
49
peptic ulcer drugs
proton pump inhibitors; H2-antagonists; antimicrobial agents; antacids; others - (anticholinergics), prostaglandins, mucosal protective agents (rare)
50
H2 receptor antagonists
cimetidine, ranitidine, famotidine, nizatidine
51
cimetidine characteristics
prototype drug; many pk interactions (cyt p450 inhibition - warfarin, phenytoin, theophylline); antiandrogenic effects; GYNAECOMASTIA
52
ranitidine characteristics
more POTENT; longer duration; no antiandrogenic effects; no gynaecomastia
53
famotidine + nizatidine characteristics
further improved potency, duration; nizatidine - 100% bioavail
54
cimetidine, ranitidine, famotidine, nizatidine pk
oral, IV
55
cimetidine, ranitidine, famotidine, nizatidine adverse effects
mild; headache, diarrhea, muscular pain, confusion
56
proton pump inhibitors (PPI)
omeprazole, lansoprazole, pantoprazole
57
omeprazole, lansoprazole, pantoprazole pk
oral, iv, prodrugs -> activated after secretion from gastric mucosal cells into acid canaliculi
58
omeprazole, lansoprazole, pantoprazole pd
IRREVERSIBLE! binding of proton pump; dose-dependent, complete inhibition of basal and stimulated acid secretion; long duration (up to 3d)
59
omeprazole, lansoprazole, pantoprazole adverse effects
mostly secondary to anacidity (gastric bacterial flora, aspiration pneumonia w/assisted resp)
60
antacids characteristics
weak base + HCL = salt + water; immediate relief from hyperacidity
61
antacids categories
absorbable/poorly absorbable - best in combos; laxative/constipative
62
antacids pd
SHORT duration (~2h); need large qty's - not suitable for ulcers; repeat at short intervals for lasting effect
63
antacids adverse effects
alkalosis (absorble antacids); interference w/absorption of other drugs (chelation, adsorption)
64
typical poorly-absorbable antacid combinations
aluminumhydroxide (promotes constipation); magnesiumhydroxide (promotes laxation)
65
simethicone
de-foaming agent; takes off surface tension -> defoam -> dec bloating
66
misoprostol moa
stable analogue of prostaglandin E1
67
misoprostol pd
cytoprotective; only clinically effective in doses that also inhibit acid secretion
68
misoprostol uses
prevention of ulcers induced by NSAIDs - protects mostly the stomach
69
misoprostol adverse effects
not well tolerated; all ae's associated w/PGs seen - nausea, diarrhea, abdominal cramps, uterine contractions
70
misoprostol contraindications
PREGNANCY
71
sucralfate characteristics
coating agent; complex of aluminumhydroxide, sulfated sucrose
72
sucralfate pk
topical action; little systemic absorption
73
sucralfate pd
coats ulcer ground in acidic environment; stimulates PG synth; ineffective when combo w/antacids
74
sucralfate uses
longterm maintenance therapy to prevent ulcer recurrence
75
therapeutic issues: peptic ulcer disease
all tx include PPI or H2-antagonist and 2 or 3 antimicrobial agents; antimicrobials prevent recurrence (no healing); HP eradication mostly successful; antimicrobials ~10d, PPI ~6wks; symptom relief best w/PPI; healing rate same for PPI/H2-ant; no diet recs; smoking stops healing, promotes recurrence
76
aspirin clinical effects
anti-inflammatory (directly in tissue); analgesic (2ndary to anti-inflammatory); antipyretic (only if temp is inc); anti-platelet (slightly inhibit thromboxane)
77
anti-inflammatory effects of aspirin
non-selective COX inhibition - irreversible acetylation (unique), salicylate-induced reversible inhibition (like NSAIDs); interference w/kallikrein/bradykinin system (minor) - interfere w/granulocyte adherence, PMN leukos, macrophages
78
analgesic effects of aspirin
mild/moderate pain; site of pain - peripheral; 2ndary to anti-inflammation; minor 2ndary cns effect at subcortical sites; co-medication in moderate/severe pain
79
antipyretic effects of aspirin
dec high temp, normal temp unaffected; regulation at cns level (cox inhibition, IL-1 formation); vasodilation; profuse sweating
80
anti-platelet effects of aspirin
irreversible acetylation of thromboxane synthetase - low dose effect, specific for aspirin, pre-systemic effect on thrombosis in portal vein, 8-10d effect, effects add up, stop after surgery; inhibit thromboxane synthetase by salicylate - high dose effect, mild
81
aspirin combined effect on coagulation
irreversibly inhibits TXA2 for life of platelet -> inc BT; inhibits COX in endothelial cells, but can synth new COX
82
aspirin adverse effects
analgesic, short-term doses - upset GI, slight inc BT; prolonged tx - erosive gastritis, gastric/duodenal ulcers/complications -> MUST have protection; high dose (unusual) - cns syndrome - salicylism (vomiting, tinnitus, vertigo); low dose - inc urate levels -> gout -> inc dose -> dec gout; impaired renal fxn when combo w/2d nsaid; aspirin-asthma; reye syndrome -> NEVER give to kids w/fever/viral infection
83
aspirin intoxication
respiratory alkalosis, then metabolic acidosis, mixed imbalances of acid-base homeostasis
84
aspirin adverse effects on kidneys
dec renal blood flow; acute interstitial nephritis; analgesic nephropathy
85
aspirin adverse effects on kidney: dec renal blood flow
pt's w/compromised renal perfusion -> kidney synth PGE2, PGI2 (vasodilators) to balance vasoconstriction; aspirin dec PGs -> dec PGE2 -> inc na/h2o & dec PGI2 -> hyperkalemia, acute renal failure
86
aspirin adverse effects on kidneys: acute interstitial nephritis
type I hypersensitivity -> acute renal failure; almost any drug can cause interstitial nephritis, most common -> antibiotics/nsaids
87
aspirin adverse effects on kidneys: analgesic nephropathy
chronic interstitial nephritis from prolonged analgesics use, esp combos of diff agents; renal papillary necrosis after yrs -> chronic interstitial nephritis -> progressive chronic renal failure
88
aspirin clinical uses: antiplatelet dose level
prevent coronary events, transient ischaemic attacks; reduce colon ca incidence
89
aspirin clinical uses: analgesic dose level
tx mild/moderate pain; fever (not kids); moderate pain when combo w/codein; adjunct tx of severe pain w/strong opioids
90
ibuprofen characteristics
commonly used minor analgesic, otc
91
ibuprofen pk
oral, 99% protein bound
92
ibuprofen pd
nsaid
93
ibuprofen adverse effects
GI (less than aspirin); RARE: rash, pruritius, aseptic meningitis, tinnitus, dizziness, headache, fluid retention, acute renal failure, interstitial nephritis, nephrotic syndrome, hepatitis
94
diclofenac moa
potent COX inhibitor, some selectivity for COX-2
95
diclofenac pk
t1/2~1h; accums in synovial fluid (t1/2~6h); enteric-coated, sustained release available - important for chronic joint pain
96
diclofenac uses
analgesic (in combo w/codeine); antirheumatic
97
diclofenac adverse effects
like other nsaids
98
indomethacin characteristics
the more potent -> more efficacious -> more side effects
99
indomethacin moa
more potent, unselective COX inhibitor; additional anti-inflammatory effects
100
indomethacin pk
t1/2~10h
101
indomethacin adverse effects
severe nsaid-like; abdominal pain, diarrhea, GI bleeding, pancreatitis, hyperkalemia, renal failure, thrombocytopenia, APLASTIC anemia
102
indomethacin uses
ONLY in rheumatic, arthritic complaints
103
piroxicam moa
potent, unselective COX inhibitor; additional anti-inflammatory effects
104
piroxicam pk
t1/2~55h -> once daily dosing, accumulation
105
piroxicam adverse effects
severe nsaid-like; GI (~20%+); pancreatitis; hyperkalemia; renal failure; thrombocytopenia; aplastic anemia
106
piroxicam uses
ONLY for rheumatologists or not at all
107
acetaminophen characteristics
NOT an NSAID; frequently used as minor analgesic
108
acetaminophen pk
oral; t1/2~2h
109
acetaminophen pd
analgesic (like aspirin), antipyretic (like aspirin); NOT anti-inflammatory, NOT anti-platelet
110
acetaminophen adverse effects
mild inc in hepatic enzymes; RARE: hepatic failure, renal failure, dizziness, excitement, disorientation
111
acetaminophen intoxification
fatal hepatic failure, antidote - acetylcysteine
112
risk for NSAID-induced GI bleeding
low: acetaminophen, ibuprofen; intermediate: aspirin, diclofenac; high: piroxicam, indomethacin, ketoprofen
113
COX isoenzymes
COX-1 - constitutive - for homeostasis; COX-2 - induced by growth factors, tumor promoters, cytokines - major source of prostanoids in inflammation, ca
114
glucocorticoid receptor subtypes
type 1 - mineralocorticoid (misnomer) - kidney, colon, salivary glands, sweat glands; type 2 - glucocorticoid - broad tissue distribution
115
glucocorticoid response elements
effectuate all changes in gene expression - contained in ~10% of all human genes -> huge impact
116
cortisol effects, ideally
keep humoral/local inflammatory response reasonable; protect glucose-dependent tissue from starvation; switch to catabolism -> preserve electrolytes/water; improve mood
117
cortisol metabolic effects: protect glucose-dependent tissues from starvation
stimulate gluconeogenesis from AA, glycerol; stimulate liver glycogen; dec gluc use in periphery; stimulate insulin secretion - bring gluc to cells; stimulate lipolysis; NET EFFECT - inc plasma gluc
118
cortisol metabolic effects: increase nutrient availability for the brain
stim gluconeogenesis from AA, glycerol; stimulate liver glycogen storage; dec gluc use peripherally; stim insulin secretion; stim lipolysis -> NET EFFECT - inc plasma gluc/TGs -> HYPERGLYCEMIC; protein CATABOLISM, mainly muscle -> inc plasma AA
119
cortisol metabolic effects: electrolyte, water balance
aldosterone-like effects; NET EFFECTS - positive na-balance, ecv expansion, hypokalemia, alkalosis; dec body ca++ stores (dec intestinal absorption, inc renal excretion)
120
adrenal crisis metabolic imbalances
caused by abrupt discontinuation of exogenous GC; hyponatremia, hypovolemia, hyperkalemia, acidosis (low bicarb), hypoglycemia, inc BUN
121
adrenal crisis symptoms
dehydration, hypotension, abdominal complaints, "pseudo-peritonitis", hypothermia -> dehydration-related fever, delirium, coma; tx w/cortisol, cortisone
122
cortisol effects: immunosuppressive/anti-inflammatory
down-reg stress from injury; interfere w/peripheral leukocyte fxn; move leukocytes to lymphatics; suppress inflammation mediators; suppress mast cell degranulation; inhibit lipoxygenase; inhibit COX-2; inhibit complement effects (not activation); antibody production inhibited (high doses only)
123
cortisol effects: cns
variable effects on mood, behavior, excitability, insomnia, euphoria -> depression; may inc icp (large doses); improve mood, appetite in terminally ill pt's
124
cortisol effects: fetal lung maturation
critically important b4 gestational wk 34; preterm: inject 2 doses -> mature lungs, stim pulmonary surfactant production
125
corticosteroids used as aerosol inhalants
for asthma - beclomethasone, budesonide; high first pass metabolism
126
glucocorticoids adverse effects
low dose inhalant/topical - local ae's, none systemic; high dose inhalant/topical - local ae's, minor systemic; prolonged systemic use - severe -> only use if not alternatives; single ultrahigh dose bolus - inc risk of pre-existing infection, aggravation of DM, inc risk of stress ulcers
127
glucocorticoids adverse effects: prolonged systemic use
similar to cushing's syndrome - affects skin, bone, sk muscle, eyes, GI, cv system, blood, electrolytes, endocrine sys, immunological status, mental status
128
interactions during prolonged systemic tx: cardiac glycosides
inc toxicity due to hypokalemia
129
interactions during prolonged systemic tx: loop diuretics, thiazides, irritant laxatives
inc potassium loss
130
interactions during prolonged systemic tx: NSAIDs
inc peptic ulcers, GI bleeding
131
interactions during prolonged systemic tx: antidiabetics
dec antidiabetic effects
132
interactions during prolonged systemic tx: ACE-inhibitors
inc risk of blood dyscrasias (unspecified blood disorder)
133
interactions during prolonged systemic tx: chloroquine, mefloquine
inc risk of myopathy, cardiomyopathy
134
interactions during prolonged systemic tx: atropine, anticholinergics
inc rise in intraocular pressure
135
how to minimize GC toxicity
use topical when possible; adapt systemic use to diurnal rhythm (8am); vary daily dose; taper dose asap; use other immunomodulator as sub or in combo
136
glucocorticoids indications
allergic rxn (asthma, angioneurotic edema, drug rxns, envenomations); collagen disorders (rheumatoid arthritis, polymyosistis); ophthalmologic (allergic uveitis, conjunctivitis); GI (bowel inflammatory dz); hematologic (acute allergic purpura, leukemia); infections (gram- septic shock); joint, bone (arthritis, bursitis, tendosynovitis); neurologic (cerebral edema, MS); pulmonary (COPD, infant RDS); renal (nephrotic syndrome); dermatologic (atopic dermatitis); thyroid (subacute thyroiditis); surgery/EM (acute severe trauma)
137
drugs used to minimize glucocorticoid use
leukotriene-receptor antagonist (asthma, allergy); lipoxygenase inhibitors; anti-IgE-antibodies; cyclosporin (bowel inflammatory dz); tacrolimus (rheumatism, dermatology); methotrexate; azathioprine; etanercept; remicade (BID); thalidomide; activated protein C (septic shock)
138
gouty attack clinical features
sudden onset; nocturnal; precipitating factor; monoarticular; small, peripheral joint; fever
139
gout differential diagnosis
critical: bacterial infection of joint; other: pseudogout, aseptic monoarthritis, trauma; plasma urate level unreliable predictor of gouty attack
140
gout risk factors
OBESITY; high purine (PROTEIN) diet; metabolic factors; excessive alcohol; drug therapy; kidney failure;
141
pathophysiology of gouty attacks
plasma urate - ONE determinant of gouty attack, but inc levels may persist for years w/o attack; slight rise could cause attack
142
deposition of monosodium urate crystals depends on
'solubilizers' in plasma; plasma pH (alcoholics -> acidotic); tissue perfusion/temp
143
summary of gout treatment
aspirin competes w/urate for secretion -> inc urate in predisposed ppl! inc fluid intake -> inc excretion; allopurinol - don't give if prone to attack -> slight inc in purines at start
144
colchicine characteristics
plant alkaloid w/cytostatic properties
145
colchicine pk
oral
146
colchicine pd
binds to tubulin (inhibit microtubule assy) -> depolymerization -> cytostatic effect on leukocytes, inhibit inflammation -> pain relief; NO EFFECT on msu crystals or plasma urate levels
147
colchicine uses
tx acute gouty attack
148
colchicine adverse effects
related to cytostatic properties; acute: GI complaints, pain, DIARRHEA (frequent); chronic: no longterm tx -> alopecia, agranulocytosis, aplastic anemia, myopathy, neuropathy
149
colchicine contraindications
pregnancy
150
uricostatics: allopurinol pk
oral; converted to oxypurinol (alloxanthine) by xanthine oxidase
151
allopurinol pd
competitively inhibit xanthine oxidase -> large dec urate, large inc hypo/xanthine -> more soluble than urate -> dec risk of urate precipitation, inc hypo/xanthine renal excretion
152
allopurinol adverse effects
GI upset; may inc urate at onset; rare: erythema multiforme, stevens-johnson syndrome
153
allopurinol uses
manage chronic gout; NOT in first 1-2 wks after acute episode
154
uricosuric agents
probenecid, sulfinpyrazon, (benzbromarone)
155
probenecid, sulfinpyrazon, (benzbromarone) pd
block tubular reabsorption of urate at therapeutic conc
156
low doses of uricosuric agents...
BLOCK tubular secretion of urate! don't use after first few weeks of attack
157
probenecid, sulfinpyrazon, (benzbromarone) interactions
probenecid inhibits tubular secretion of penicillin, naproxen, ketoprofen, indomethacin (nsaids) -> can't tolerate co-tx
158
probenecid, sulfinpyrazon, (benzbromarone) adverse effects
mild; sulfinpyrazone - GI
159
treatment of chronic hyperuricemia
dec of the body urate pool takes months/yrs; maybe lifelong therapy; ensure high fluid turnover; start in symptom-free interval; dec purine-rich food; tx w/uricosuric/static drug; can use nsaid/low dose colchicine at onset of therapy - prevent recurrence; weight loss; urine alkalinization may help -> if overdue -> calcium oxalate stones
160
diagnosis of rheumatoid arthritis
at least 4 of these: morning stiffness for >1hr, arthritis of >=3 joints for >6wks, arthritis of hand joints, symmetric arthritis for >6wks, rheumatoid nodules, serum rh factor positive, radiographic changes typical of RA; FOGGY to diagnose
161
treatment modalities for rheumatoid arthritis
rest, motion exercise, physiotherapy, diet, heat, cold; symptomatic tx w/nsaid; dz modifying drugs (dmard); immunosuppressant drugs (w/flair up); corticosteroids, surgery, novel/experimental
162
NSAIDs clinical effects in rheumatoid arthritis
anti-inflammatory; analgesic
163
risk for NSAID-induced GI bleeding
low: acetaminophen (not used in RA), ibuprofen; intermediate: aspirin, diclofenac, diflunisal; high: piroxicam, indomethacin, ketoprofen
164
disease modifying anti-rheumatic drugs (DMARDs) uses
to reduce/prevent joint damage (nsaids relieve symptoms, no real effect on destruction)
165
DMARDs features
poorly understood mech's; none effective in >60% pt's -> unpredictable efficacy; therapeutic effects take 2-4 mths; if ineffective in pt once, not considered in future for same pt
166
important DMARDs
methotrexate (MTX), gold compounds, cytotoxic agents
167
methotrexate characteristics
aminopterin analogue; cytostatic drug
168
methotrexate pk
oral, subQ, im, iv
169
methotrexate pd in rheumatoid arthritis
low doses DMARD -> module immune system; inhibit AICAR transformylase, thymidilate synthetase pathway (higher conc) -> dec PMN chemotaxis; inhibit DHFR -> dec lymphocyte, macrophage fxn
170
methotrexate moa1
-> inc AICAR -> AICAR inhibits ADA, AMP deaminase -> AMP, adenosine inc, AMP -> adenosine -> inc inc adenosine -> act on A2b receptors -> suppress NF-kappaB activation induced by TNF, other inflammatory mediators
171
methotrexate interactions
nsaid reduce Cl; combo w/sulfonamides potentiates bone marrow toxicity
172
methotrexate adverse effects
GI, stomatitis, hair loss, mild inc liver enzymes; RARE: leukopenia, thrombopenia, severe inc liver enzymes, cns disturbances
173
methotrexate contraindications
teratogen in pregnancy
174
combine methotrexate with:
folic acid daily (stomatitis)
175
methotrexate effects at (time)
6-8 weeks
176
methotrexate advantages vs other DMARDs
best response rate; less ae's; well-tolerated longterm; well tolerated in dmard combo tx
177
gold compounds moa
taken up by macrophages -> suppress phagocytosis, enzyme activity -> slows bone/articular destruction in ra
178
gold compounds effects at (time)
after 4-6mths of tx, with ae's acting immediately
179
gold compounds toxicity
dermatology, hematology, kidneys -> infrequently used
180
cytotoxic agents
alkylating agents; antimetabolites; others
181
alkylating agents
chlorambucil, cyclophosphamide
182
chlorambucil, cyclosphosphamide moa
cross-link dna -> prevent replication
183
chlorambucil, cyclophosphamide toxicities
bone marrow suppression; infertility; carcinogenic risk (most cytostatics); hemorrhagic cystitis (characteristic)
184
chlorambucil, cyclophosphamide contraindications
teratogen - pregnancy
185
antimetabolites
azathioprine (azt)
186
azathioprine characteristics
purine metabolite; prodrug of 6-mercaptourine
187
azathioprine pd
converted to 6-mercaptourine -> convert to additional metabolites -> inhibit de novo purine synth -> suppress B, T cell fxn, Ig synth, IL-2 secretion
188
azathioprine interactions with allopurinol
xanthine oxidase metabolizes active material of azt b4 excretion in urine -> pt's on allopurinol need to reduce azt dose
189
azathioprine toxicities
bone marrow suppression; GI disturbances; inc infections/malignancies
190
leflunomide pd
arrest cells in G1 phase -> inhibit autoimmune T cell prolif, autoantibody synth by B cells; other cells not affected -> use salvage pathway whereas activated lymphocytes need de novo since need is 8x
191
biological response modifiers
anti-cytokine (anti-TNF); anti-IL1; others (abatacept, rituximab)
192
anti-cytokines (anti-TNF)
adalimumab; etanercept; infliximab
193
anti-IL1
anakinra
194
biological response modifiers uses
in combo with low dose mtx; in earlier tx
195
biological response modifiers contraindications
when pt has history of immunosuppression i.e. TB
196
asthma abnormality
insufficient expiration
197
drugs used in asthma symptom relief
symptom relief: beta2 agonists (fast/long-acting), ipratropium, theophylline (less often)
198
drugs used in asthma long term control
corticosteroids; cromolyn, nedocromil; leukotriene modifiers; anti-IgE antibody
199
adjunct drugs used in asthma
antibiotics; mucolytics; oxygen (sedatives ci'd)
200
asthma last resort drugs
general anesthesia; muscle relaxation; controlled respiration; bronchial lavage; ketamine
201
short-acting beta2 agonists
albuterol, levalbuterol, pirbuterol, terbutaline, metaprotenerol - for acute episodes
202
long-acting beta2 agonists
salmeterol, formoterol - for prophylaxis, long term therapy
203
beta2 agonists adverse effects
selectivity is relative; beta2 - muscle tremor, diabetogenic; beta1 - tachy, arrhythmogenic; loss of responsiveness; high dose continuous use - hypokalemia;
204
beta2 agonists uses
NOT anti-inflammatory; can be for preventative i.e. b4 going to gym
205
beta2 agonists and theophylline moa
can have over-additive effect!
206
theophylline characteristics
methylxanthine, related: caffeine, theobromine
207
theophylline pk
oral, sustained release; iv; many drug interactions; low therapeutic margin
208
theophylline adverse effects
cns - nervousness, tremor; cv - catecholamine release, +inotropy/chronotropy; arrhythmogenic; GI - hyperacidity, nausea
209
theophylline toxicities
convulsions, coma
210
theophylline uses
controversial -> dec in US (seizure risk - last choice); considered safe/useful in Europe esp in emergencies; more used for intermittent claudication
211
theophylline molecular moa
induce histone deacetylase -> dec inflammatory gene expression -> promotes corticoid action (unrelated to phosphodiesterase) -> controller/preventer drug
212
anticholinergics
ipratropium, thiotropium
213
ipratropium characteristics
polar compound; mostly local effect when used as inhalant; ineffective in 30% of asthma pt's
214
ipratropium adverse effects
rare w/usual doses; dry mouth; NO tremor, tachy, dyskrinia (thickening mucous)
215
ipratropium uses
esp COPD w/vagal components; asthma in kids/old; psychogenic exacerbations of asthma; combo with beta2 agonists
216
thiotropium characteristics
much longer half-life; limited absorption from bronchial mucosa into system; some selectivity for M1, M3 receptors; labeled for COPD (combo tx)
217
corticosteroids inhalants
beclomethasone, budesonide, flunisolide, fluticasone
218
corticosteroids systemic
any e.g. prednisone, dexamethasone
219
corticosteroids adverse effects
depends on dose/asthma severity; inhalant low dose - local ae's, insig systemic ae's; inhalant high dose - local ae's, minor systemic (avoid in kids); oral/systemic - severe systemic ae's; single high dose (emergencies) - no systemic except risk of infection, aggravate DM
220
beclomethasone, budesonide, flunisolide, fluticasone pd
dec asthma symptoms; dec hyperreactivity; improve bronchial/pulmonary epithelial fxns
221
beclomethasone, budesonide, flunisolide, fluticasone pk
10% inhaled deployed into bronchial tree
222
beclomethasone, budesonide, flunisolide, fluticasone application
use application aids (e.g. spacer); in combo - apply 10 mins after b2 agonist inhaled
223
beclomethasone, budesonide, flunisolide, fluticasone local adverse effects
oral/esophageal candidiasis, hoarseness -> apply b4 meals
224
beclomethasone, budesonide, flunisolide, fluticasone systemic adverse effects
little bioavail -> minor ae's compared to systemic corticosteroids
225
cromolyn, nedocromil characteristics
mast cell stabilizers
226
cromolyn, nedocromil pk
topical aerosol (for other indications - nasal spray, eye drops, oral)
227
cromolyn, nedocromil pd
inhibit early/late response by stabilizing mast cells, eosinophils -> dec hyperreactivity
228
cromolyn, nedocromil uses
preventative tx of antigen/exercise-induced asthma; INEFFECTIVE in acute exacerbation
229
cromolyn, nedocromil adverse effects
cough, airway irritation; RARE: drug allergies, gastroenteritis
230
leukotriene modifiers pd
effective in antigen/exercise-induced asthma, esp aspirin-asthma
231
leukotriene modifiers adverse effects
inc LFT, headache, dyspepsia
232
leukotriene modifiers
zileuton, montelukast, zafirlukast
233
zileuton moa
5-lipoxygenase antagonist; rarely used
234
montelukast, zafirlukast moa
LTD4 anatagonist, also blocks LTE4
235
leukotriene modifiers characteristics
less effective than inhaled corticosteroids, but used to dec cort. dose; definite position in asthma therapy not established
236
mucolytics pd
facilitate expectoration by dec viscosity of bronchial mucus
237
mucolytics
water (most important); acetylcysteine
238
acetylcysteine pd
disrupts S-S bonds in mucoproteins
239
mucolytics application
nebulizer, oral, iv, endotracheal lavage; tastes, smells like rotten eggs -> oral is best
240
mucolytics adverse effects
mechanical airway irritation, GI disturbances; allergic rxns; use w/CAUTION in severe acute asthma, gastric ulcer pt's
241
asthma absolute contraindications
ALL beta-blockers; cholinergic drugs; centrally-acting anticholinergic drugs; codeine, dextrometorphane; aspirin, other nsaids
242
asthma relative contraindications
diuretics; ace-inhibitors; cns depressants; sedatives
243
treatment of mild intermittent asthma
reliever - inhaled short-acting beta2 agonist as needed - less than 1x/day; controller - none or cromolyn b4 allergen exposure
244
treatment of mild persistent asthma
reliever - inhaled short-acting beta2 agonist as needed, but less than 4x/day; controller - inhaled low dose corticosteroid or cromolyn, nedocromil
245
treatment of moderate persistent asthma
reliever - inhaled long-acting beta2 agonist; controller - inhaled corticosteroid
246
treatment of severe persistent asthma
reliever - (plus oral theophylline); controller - oral corticosteroid
247
asthma prevention of acute exacerbation
short oral prednisolone 'rescue' at anytime
248
emergency treatment of asthma
1. oxygen, monitor
249
NO-NO'S in asthma emergency treatment
nedocromil, cromolyn; uncritical sedation
