Pharmacology Flashcards
1
Q
What is the effect of corticosteroids?
A
Inhibit the production and release of many different cytokines that normally would stimulate the proliferation and function of B and T lymphocytes
Block the phospholipase 2
2
Q
What are the corticosteroids used for asthma?
A
Beclomethasone
Budesonide
Triamcinolone
3
Q
What is the toxicity associated with systemic administration of corticosteroids?
A
HPA suppression Immunosuppression - poor wound healing, opportunistic infection Cushing's syndrome Hyperglycemia Hypertension Peptic ulcers Myopathy Behavioral changes Cataracts Osteoporosis Growth retardation
4
Q
What are the therapeutic considerations for a short course of corticosteroids?
A
Insomnia and hyperactivity
5
Q
When do you use pulse therapy with corticosteroids?
A
When the person has a serious or life-threatening disease
6
Q
What is the treatment for anaphylactic reaction?
A
Epinephrine
7
Q
What are topical corticosteroids used for?
A
Dermatologic conditions
8
Q
What is a COX 2 Inhibitor?
A
Celecoxib
9
Q
What is a non-NSAIDs antipyretic / analgesic?
A
Acetaminophen
10
Q
What is the MOA of NSAIDs?
A
Non-selectively Blocks the action of COX 1 and 2 so it ultimately stops the production of prostaglandins which are involved in inflammation
11
Q
What are the 5 prostanoids?
A
- Prostacyclin
- Thromboxane A2
- Prostaglandin D2
- PGE2
- PGF2
12
Q
Where is COX1 expressed?
A
In most tissues - it is constitutively active
13
Q
What is COX2 induced by?
A
Induced by cytokines and other inflammatory mediators
14
Q
What are the contraindications to Celebrex?
A
Aspirin allergy and 3rd trimester
15
Q
What was the reason for taking COX 2 inhibitors off the market?
A
Increased risk for cardiac events
16
Q
What are some of the advantages to NSAIDs over aspirin?
A
More potent
More efficacious
Less GI problems
Have longer duration of action
17
Q
What are the disadvantages to new NSAIDs compared to aspirin.?
A
More expensive
More toxic
No CV benefit or anti-cancer usage
18
Q
What level of pain are NSAIDs effective for?
A
Low-to-moderate intensity
19
Q
What are the GI effects of prostaglandins?
A
Inhibit gastric acids secretion
Stimulate synthesis of bicarbonate and mucus
Promotes mucosal blood flow
20
Q
What are the GI effects of NSAIDs?
A
Epi gastric distress Nausea Vom Microhemorrhage Ulceration Anemia
21
Q
What does thromboxane A2 do?
A
Vasoconstrictor
Activates platelet aggregation and release
22
Q
How is aspirin good for prophylaxis of CVD?
A
It inhibits TXA2 so inhibits vasoconstriction and platelet aggregation
23
Q
How can NSAIDs cause renal failure?
A
In the setting of diseases with high levels of circulation vasoconstrictors, it can cause acute renal failure by decreasing renal blood flow because it is inhibiting prostacyclin which normally opposes vasoconstrictor action on the efferent arterioles in the kidney
Diseases to be careful with using NSAIDs: liver failure, CHF,
24
Q
What are the anti-cancer effects of COX2 inhibitors and aspirin?
A
Reduces occurrence and mets of cancer by 1/3
25
What is Reyes's syndrome?
Consequence of flu virus of chicken pox and using salicylates in children.
Liver damage and encephalopathy
26
What is indomethacin?
The most efficacious NSAID. But causes high rates of GI bleeding so not used chronically.
Used to tx patent ductus arteriosus
27
What are the side effects of NSAIDs?
Epi gastric distress, naus/vom, microscopic bleeding, ulceration, anemia, prolonged bleeding time, hypersensitivity,
28
What are the sign of salicylism?
Naus/vom, tinnitus, hyperventilation, headache, mental confusion, dizziness
29
What are the signs of overdose of a salicylate?
Fever, dehydration, delirium, hallucination, convulsions, coma, respiratory and metabolic acidosis, death
Children are especially vulnerable!!!
30
What are adverse effects of salicylates during pregnancy?
```
Low birth weight
Increased perinatal mortality
Anemia
Antepartum and postpartum hemorrhage
Prolonged gestation
Premature closure of ductus arteriosus
```
31
What is ketorolac used for?
Post op pain
| Can be given parenterally
32
What is celecoxib approved for?
Osteoarthritis and rheumatoid arthritis
| Menstual pain and acute post op pain
33
What is the MOA of acetaminophen?
Metabolized in the brain to COX inhibitor.
| This drug is mostly effective in the CNS - not for peripheral anti inflammatory activity.
34
What are the adverse effects of acetaminophen?
Depletes glutathione --- hepatic damage
35
What is used to treat toxicity of acetaminophen?
N-acetylcysteine (sub for glutathione)
36
What are dynorphins?
Usually associated with kappa receptor activation
| Cause dysphoria and hyperalgesia in animal studies
37
What are mu receptors important for?
```
Analgesia
Euphoria
Miosis
Respiratory depression
Physiological dependence
Reduced GI motility
```
38
What are the delta receptors for?
Euphoria
39
What are the kappa receptors responsible for?
```
Dysphoria
Psychotomimetic responses
Analgesia
Sedation
Vasodilation
Increased urinary output
Less miosis and respiratory depression than mu
```
40
What is an advantage to kappa receptors?
Less involvement in abuse potential and physical dependence
41
What is the use of opioids in analgesia?
They hit the mu and kappa receptors. They diminish the sensory and reactive component of pain, but the reactive component more.
42
What is morphine useful in treating and how does it work?
Pulmonary edema
It is a great vasodilator because it makes the brain stem less responsive to pCO2 so there is less sympathetic activation. Flid is shifted from the central to the peripheral compartment
43
How do opioids cause constipation?
They cause increased tone in the intestine
44
What are the high efficacy mu opioids?
```
Morphine
Meperidine
Methadone
Fentanyl
Oxycodone
Heroin
```
45
What are the main points about morphine?
Binds of all opioid receptors
Highest affinity for mu
Highly polar - less potent thru the oral route
High efficacy for analgesia
46
Which mu opioid has a metabolite that can cause seizures?
Meperidine
47
What is the MOA of methadone?
Blocks NMDA receptors and mono amine uptake pumps so it also acts as an antidepressant
Long Elimination half life
48
What is the mu opioid with the highest potency?
Fentanyl
49
What is fentanyl used for?
Naus/vom - lipid soluble so used as a patch
| Surgery
50
What is the side effect of fentanyl if given IV?
Truncal rigidity
51
What are the high efficacy kappa opioids?
Butorphanol
| Nalbuphine
52
What is butorphanol used for?
Post surgery because less potential for respiratory suppression
53
Who does butorphanol work better on?
Women
54
What is nalbuphine used for?
Post surgery to remove the depressant effects of mu agonists
55
What are the intermediate efficacy opioids?
Hydrocodone
Oxycodone
Pentazocine
56
What schedule drug is oxycodone?
Schedule 2
| Highly addictive
57
What are the attempts to limit abuse of oxycodone?
Add a matrix
| Add naloxone - not absorbed orally very well
58
What is the cornerstone drug for pain clinics?
Amitriptyline - an antidepressant
59
Which intermediate opioid has an effect on kappa receptors?
Pentazocine
60
What are the low efficacy opioids?
Buprenorphine
| Codeine
61
What are the characteristics of burprenorphine?
Long duration of action
Slow to dissociate from my receptors
Ideal for preventing high efficacy compounds in narcotic tx programs
62
What is the opioid of choice for cough?
Codeine
63
What is the limitation of codeine?
At higher doses it hits non-mu receptors producing unpleasant psychotomimetic effects
64
What is the MOA of codeine in analgesia?
It is converted to morphine in the liver by CYP2D6 by demethylation
65
What is CYP450 ?
A family of Microsomal enzymes located in the ER of liver cells
66
What subfamily of P450 enzymes does CYP2D6 come from?
CYP 2
67
What is CYP2D6 responsible for?
Demethylation reactions : metabolism of beta blockers and codeine to morphine
68
What is the consequence of missing CYP2D6?
High level of parent drug - codeine. No analgesic effects
69
What is the opioid that is not classified according to efficacy?
Tramadol - not a good mu agonist
70
What is the MOA of tramadol?
Weak mu agonist
Serotonin releases
Norepinephrine reuptake inhibitor
71
What are the uses of tramadol?
Good for pain in moderate range
Good for neuropathic pain
Outpatient therapy
72
What are the potential side effects of tramadol?
High doses can cause seizures
Dependence/withdrawal
Enhances respiratory depression of other drugs - be careful
73
What are the drug interactions with tramadol?
SSRIs - risk of serotonin syndrome
Alcohol
Barbiturates
74
What are the sx of serotonin syndrome?
Tremor
Clonus
Hyperreflexia
Hyper pyresis
75
What are the opioid antagonists?
Naloxone - short acting, injected
Naltrexone - long acting, oral
Nalmefene
76
What is the prototype antagonist?
Naloxone
77
When does dependence become clinically relevant?
After 2-3 weeks of use
78
What is the primary triad of sign for opioid overdose?
Lethargy or coma
Depressed respiration
Pinpoint pupils
79
What are secondary signs of opioid overdose?
```
Hypotension
Hypothermia with cold or clammy skin
Pulmonary edema
Convulsions
Dilated pupils (near death)
```
80
What is the DOC for tx of opioid OD?
Naloxone
81
What is the tx for opioid OD?
Naloxone
Support of respiration and vitals
Identify drug
82
What is a non-opioid OTC drug used for cough?
Dextromethorphan
83
What are the opioids used for diarrhea?
Loperamide
Diphenoxylate
Difenoxin
84
What is the MOA of MTX?
Inhibits dihydrofolate reductase. Prevents DNA and RNA synthesis - immunosuppressive
Used in low doses for RA
85
What are the most common side effects of MTX when given in low doses?
Nausea and mucosal ulcers
86
What are the most common side effects of MTX at higher doses?
Drop in WBC
Cirrhosis
Pneumonitis
87
What are the effects of TNF-alpha?
Release of inflammatory mediators
| Kill intra cellular organisms
88
What are the TNF- alpha antagonists?
```
Inflict ab
Etanercept
Adalimumab
Golimumab
Certolizumab
```
89
What is infliximab?
A chimeric mouse/human monoclonal antibody that binds to TNF-alpha.
Given IV every several weeks
90
What is the most common side effect of infliximab?
URI
91
What is etanercept?
A recombinant protein that binds two molecules of TNF-alpha.
Injected subq twice weekly
92
What is adalimumab?
An entire human monoclonal Ab.
| An attempt to decrease the immunoreactivity of infliximab.
93
What is golimumab?
A once monthly injection approved for RA, anklyosing spondylitis, and psoriatic arthritis
94
What is leflunomide ?
What is an alternative to MTX. Mech in RA is not entirely clear - may inhibit tyrosine kinase and production of pyrimidines.
95
What are the side effects of leflunomide?
Elevated liver enzymes
GI problems
Alopecia
96
What is abatacept?
It is a drug approved for use in severe RA for patients that don't respond to TNF inhibitors
97
What is the MOA of abatacept?
Constimulation modulators that renders T cells inactive because it interferes with the process that turns them on.
It binds to CD 80 and CD 86 on the APC so that the T cell can't be activated via interaction with CD 28.
98
In what disease condition is abatacept contraindicated in?
COPD
99
What other drug can abatacept not be used with?
MTX - too many incidences of infection
100
What is rituximab?
It is a monoclonal Ab that reduces B cells.
| Approved for moderate to severe RA.
101
What are the side effects of rituximab?
Flu-like sx
| Possible breathing problems, cardiac rhythm disturbances, cardio genic shock
102
What is sulfalazine?
Drug used to treat IBD and autoimmune diseases (RA, anklyosing spondylitis, seronegative spondyloarthropathy)
103
What are the side effects of sulfalazine?
Hypersensitivity rxns
| GI problems
104
Who is sulfalazine a good alternative for?
Patients with liver disease who need MTX
105
How does sulfalazine work in the body?
It is poorly absorbed. Bacteria metabolize it to antibiotic and anti inflammatory metabolites.
106
What are hydroxychloroquines?
They are antimalarials used to treat RA that is mild to moderate.
107
What are the toxicity was associated with hydroxychloroquines?
Corneal deposits
Extra ocular muscle weakness
Loss of accommodation
Retinopathy ---loss of vision
108
How do gold salts work?
They suppress RA by inhibiting maturation and function of mononuclear phagocytes and T cells.
109
At what stage of RA, are gold salts used?
In the early active phase
110
What are the gold salts?
Gold sodium thiomalate
Aurothioglucose
Auranofin
111
Which gold salts are water soluble?
Aurothioglucose
| Gold sodium thiomalate
112
Which is the hydrophobic gold salt?
Aurofin - better tolerated, less efficacy
113
What are the most common side effects of gold salts?
Lesions on skin and mucous membranes, mostly in the mouth
Other less frequent:
Kidney damage
Severe blood dyscrasias
114
What is D-penicillamine?
An cysteine analog used in RA to slow bone destruction.
115
What are the long term effects of D-penicillamine?
Nephritis
Aplastic anemia
Dermatological problems
116
When is D-penicillamine used?
In severe disease after every other treatment has failed
117
What are the actions of IL-1?
Stimulates own production
Causes secretions of prostaglandins, NO, metalloproteinases - promotes joint degradation
Inhibits collagen synthesis - inhibits joint repair
118
What is anakinra?
A recombinant for of human IL-1ra, IL-1 receptor antagonist
119
What drugs should anakinra not be prescribed with?
TNF inhibitors - higher rate of infection
120
What is tocilixumab/actemra?
Antibody that binds to and inactivates IL6 receptors
Approved for patients who fail TNF inhibitor therapy
121
What does IL-6 do?
Secreted by macrophages and T cells
| Stimulates immune response, osteoclasts formation
122
What are the side effects of tocilixumab?
URI, headache, high bp, liver enzyme elevation, increased LDL, decreased neutrophils and platelets.
123
What are the serious adverse side effects of tocilixumab?
Infection
GI perforation
Anaphylaxis
124
What is cyclosporine?
Complex cyclic peptide isolated from fungus
| Immunosuppressant
125
What is the MOA of cyclosporine?
Selectively inhibits T lymphocytes
126
Who is cyclosporine reserved for?
Patients who fail to respond to other therapies with severe disease
127
What are the disadvantages to cyclosporine?
Expensive
| Renal toxicity
128
What is azathioprine?
A purine anti metabolite that interferes with purine synthesis and causes DNA damage through formation of false nt substrates for DNA synthesis
Immunosuppressant
129
What are the side effects of azathioprine?
BM suppression
| Hepatotoxicity
130
What are the uses of azathioprine?
Transplant rejection
Cancer
Severe refractory RA
SLE
131
What is cyclophosphamide?
Nitrogen mustard, alkylation agent.
132
What is the MOA of cyclophosphamide?
Alkylate a DNA interfering with its synthesis and function.
| Causes t and B cell suppression
133
What is cyclophosphamide used in?
Cancer
| Severe autoimmune disease with vasculitis
134
What is capsaicin?
Derived from plants
135
What is the MOA of capsaicin?
Local depletion of substance P
136
How is capsaicin uses?
As a cream for RA and OA
137
What are the non-pharm ways to control gout?
Avoid organ means, high fructose corn syrup, alcohol
Avoid large meals with meat
Stay hydrated
138
What are the foods that are encouraged in gout?
Low-non fat dairy
| Vegetables
139
What is the DOC for acute attacks of gout?
Indomethacin
140
Which NSAIDs should not be used in gout?
Aspirin or salicylates because it inhibits phagocytosis of urea crystals and excretion of uric acid into the urine.
141
Which drug used to be used for acute gout attacks binds Tubulin in mitotic spindles causing cell cycle arrest?
Colchicine
142
How does colchicine relieve the sx of gout?
By causing cell arrest, it prevents the migration of granulomatous into the inflamed area
143
What are the side effects of colchicine?
Diarrhea
Nausea/vom
Ab pain
144
What can long term use of colchicine cause?
Myopathy
Agranulocytosis
Aplastic anemia
Alopecia
145
What are the 2 drugs used in standard care of gout?
Allopurinol and Febuxostat
146
What is allopurinol?
A purine analog that competitively inhibits the last 2 steps in uric acid production
147
What are the most common side effects of allopurinol?
Hypersensitivity rxns
148
What is Febuxostat?
A xanthine oxidase inhibitor
Better at lowering uric acid levels, but no benefit wi lesser attacks
149
Why must you begin with a low dose of allopurinol with colchicine?
Because allopurinol can precipitate a gout attack. Once uric acid levels fall, colchicine can be stopped
150
How do uricosuric agents work?
Prevent tubular reabsorption of uric acid
151
What is probenecid?
A uricosuric agent used for treating chronic gout.
152
Who is the use of probenecid contraindicated in?
Impaired renal function
| Patients prone to stone formation.
153
What is sulfinpyrazone?
A uricosuric agent.
| May induce hypoglycemia
154
What are bisphosphonates?
Pyrophosphate analogs that are not hydrolyzed
155
What is the MOA of bisphosphonates?
Inhibit bone resorption
| Prevent formation and dissolution of hydroxyapatite crystals
156
What are the side effects of bisphosphonates?
Esophagitis
| Osteonecrosis of the jaw
157
What are the bisphosphonates used?
Alendronate - weekly oral
| Ibandronate. - monthly oral
