Pharmacology Flashcards
What is the effect of corticosteroids?
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
What are the corticosteroids used for asthma?
Beclomethasone
Budesonide
Triamcinolone
What is the toxicity associated with systemic administration of corticosteroids?
HPA suppression Immunosuppression - poor wound healing, opportunistic infection Cushing's syndrome Hyperglycemia Hypertension Peptic ulcers Myopathy Behavioral changes Cataracts Osteoporosis Growth retardation
What are the therapeutic considerations for a short course of corticosteroids?
Insomnia and hyperactivity
When do you use pulse therapy with corticosteroids?
When the person has a serious or life-threatening disease
What is the treatment for anaphylactic reaction?
Epinephrine
What are topical corticosteroids used for?
Dermatologic conditions
What is a COX 2 Inhibitor?
Celecoxib
What is a non-NSAIDs antipyretic / analgesic?
Acetaminophen
What is the MOA of NSAIDs?
Non-selectively Blocks the action of COX 1 and 2 so it ultimately stops the production of prostaglandins which are involved in inflammation
What are the 5 prostanoids?
- Prostacyclin
- Thromboxane A2
- Prostaglandin D2
- PGE2
- PGF2
Where is COX1 expressed?
In most tissues - it is constitutively active
What is COX2 induced by?
Induced by cytokines and other inflammatory mediators
What are the contraindications to Celebrex?
Aspirin allergy and 3rd trimester
What was the reason for taking COX 2 inhibitors off the market?
Increased risk for cardiac events
What are some of the advantages to NSAIDs over aspirin?
More potent
More efficacious
Less GI problems
Have longer duration of action
What are the disadvantages to new NSAIDs compared to aspirin.?
More expensive
More toxic
No CV benefit or anti-cancer usage
What level of pain are NSAIDs effective for?
Low-to-moderate intensity
What are the GI effects of prostaglandins?
Inhibit gastric acids secretion
Stimulate synthesis of bicarbonate and mucus
Promotes mucosal blood flow
What are the GI effects of NSAIDs?
Epi gastric distress Nausea Vom Microhemorrhage Ulceration Anemia
What does thromboxane A2 do?
Vasoconstrictor
Activates platelet aggregation and release
How is aspirin good for prophylaxis of CVD?
It inhibits TXA2 so inhibits vasoconstriction and platelet aggregation
How can NSAIDs cause renal failure?
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,
What are the anti-cancer effects of COX2 inhibitors and aspirin?
Reduces occurrence and mets of cancer by 1/3
What is Reyes’s syndrome?
Consequence of flu virus of chicken pox and using salicylates in children.
Liver damage and encephalopathy
What is indomethacin?
The most efficacious NSAID. But causes high rates of GI bleeding so not used chronically.
Used to tx patent ductus arteriosus
What are the side effects of NSAIDs?
Epi gastric distress, naus/vom, microscopic bleeding, ulceration, anemia, prolonged bleeding time, hypersensitivity,
What are the sign of salicylism?
Naus/vom, tinnitus, hyperventilation, headache, mental confusion, dizziness
What are the signs of overdose of a salicylate?
Fever, dehydration, delirium, hallucination, convulsions, coma, respiratory and metabolic acidosis, death
Children are especially vulnerable!!!
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
What is ketorolac used for?
Post op pain
Can be given parenterally
What is celecoxib approved for?
Osteoarthritis and rheumatoid arthritis
Menstual pain and acute post op pain
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.
What are the adverse effects of acetaminophen?
Depletes glutathione — hepatic damage
What is used to treat toxicity of acetaminophen?
N-acetylcysteine (sub for glutathione)
What are dynorphins?
Usually associated with kappa receptor activation
Cause dysphoria and hyperalgesia in animal studies
What are mu receptors important for?
Analgesia Euphoria Miosis Respiratory depression Physiological dependence Reduced GI motility
What are the delta receptors for?
Euphoria
What are the kappa receptors responsible for?
Dysphoria Psychotomimetic responses Analgesia Sedation Vasodilation Increased urinary output Less miosis and respiratory depression than mu
What is an advantage to kappa receptors?
Less involvement in abuse potential and physical dependence
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.
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
How do opioids cause constipation?
They cause increased tone in the intestine
What are the high efficacy mu opioids?
Morphine Meperidine Methadone Fentanyl Oxycodone Heroin
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
Which mu opioid has a metabolite that can cause seizures?
Meperidine
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
What is the mu opioid with the highest potency?
Fentanyl
What is fentanyl used for?
Naus/vom - lipid soluble so used as a patch
Surgery
What is the side effect of fentanyl if given IV?
Truncal rigidity
What are the high efficacy kappa opioids?
Butorphanol
Nalbuphine
What is butorphanol used for?
Post surgery because less potential for respiratory suppression
Who does butorphanol work better on?
Women
What is nalbuphine used for?
Post surgery to remove the depressant effects of mu agonists
What are the intermediate efficacy opioids?
Hydrocodone
Oxycodone
Pentazocine
What schedule drug is oxycodone?
Schedule 2
Highly addictive
What are the attempts to limit abuse of oxycodone?
Add a matrix
Add naloxone - not absorbed orally very well
What is the cornerstone drug for pain clinics?
Amitriptyline - an antidepressant
Which intermediate opioid has an effect on kappa receptors?
Pentazocine
What are the low efficacy opioids?
Buprenorphine
Codeine
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
What is the opioid of choice for cough?
Codeine