Review 1 Flashcards
Clinical Trials Phase 1
Safety. <100 healthy subjects
Clinical Trials Phase 2
Efficacy. Hundreds of patients with disease.
Compare to placebo or control group.
Clinical Trials Phase 3
> 10,000 participants.
Random Double-Blind.
Clinical Trials Phase 4
After FDA approval, post marketing.
You and me!
Schedule I drugs
Med use- no
Abuse- high
Dependence- high
Ex.- Heroin, LSD, Marijuana
Schedule II drugs
Med use- yes
Abuse- high
Dependence- high
Ex.- cocaine, meth, fentanyl, oxycodone, adderall
Schedule III drugs
Med use- yes
Abuse- mid
Dependence- mid-low
Ex.- codeine, ketamine, testosterone
Schedule IV drugs
Med use- yes
Abuse- low
Dependence- low
Ex.- Tramadol, Xanax, Ambien, Diazepam
Schedule V drugs
Med use- yes
Abuse- low
Dependence- n/a
Ex.- lomitil, robitussin, lyrica
1st order elimination
most common.
elimination proportional to concentration
constant half life
2nd order elimination
elimination rate constant/independent of concentration.
Inconsistent half life
How many half lives to “clear” a drug
5
Specificity
binds to one receptor group but not another.
all alpha receptors no beta receptors
Sensitivity
binds to a specific receptor type in a group.
only beta1 receptors, no beta 2 or 3
Competitive Antagonist
Agonist and antagonist compete to bind to receptor.
Highest concentration wins
Non-Competitive Antagonist
Near or irreversible binding to receptor
greatly diminishes/blocks agonist effect
increased agonist concentration can’t overcome it
Partial agonist
“Doesn’t fit” the receptor exactly like natural ligand
Lower dose = agonist effect
Higher dose= antagonist effect
Emax
maximal response.
receptors are saturated, may cause toxicity
ED50
Effective dose to get 50% of expected response
T/F: Lower ED50 is more potent
True
TD50
Dose that is toxic for 50%
Types of AE
Drug-Drug
Drug-Food
Allergies
Types of Pain
Nociceptive, Neuropathic, Psychogenic
2 types of nociceptive afferent neurons
unmyelinated C fibers (dull, burning, diffuse)
finely myelinated A delta fibers (sharp, intense, localized)
Pathway of pain from source
Source of pain - dorsal root ganglia - dorsal horn+substantia gelatinose - spinothalmic tracts - brain stem - thalamus - cerebral cortex
opioids MOA/AE
MOA- Bind opioid receptors in CNS to inhibit pain pathways
AE-
CNS: sedation, nausea, respiratory depression, cough suppression, miosis, truncal rigidity
PNS: Constipation, urinary retention, bronchospasm, decreased GI motility, pruritis
opioids PT concerns
Schedule therapy to maximize pain relief, increased fall risk, avoid heat and exercise in area of patch, drug seeking behavior.
NSAIDS MOA/AE
MOA: Reversibly inhibit COX-1 and 2 enzymes. Decreased formation prostaglandin precursors.
AE: GI (N/V, dyspepsia, ulcers, bleed) increased BP, nephrotoxicity, CV risk
NSAIDS PT concerns
GI, bleeding and bruising risk, DDI with cardiac drugs, increased edema with CHF, HTN, decreased cartilage repair and synthesis
Neuropathic pain
Pain associated with disease or injury to PSN or CNS
Neuropathic pain causes
Diabetes, immune deficiencies, trauma, shingles, MS, ischemia, cancer, drugs
Best treatments for Neuropathic pain
Gabapentin, Amitriptyline, Cymbalta, Lyrica
Gold Standard for RA
Methotrexate
Methotrexate MOA and AE
MOA: unknown, possibly impacts IL-1, TNF alpha, and leukotrine levels
AE: N/V/D, alopecia, malaise, increased LFTs, hepatotoxicity, nephrotoxicity, thrombocytopenia, bone marrow suppression
Biologic DMARD MOA:
Impacts mediators of inflammatory response.
Sulfasalazine (biologic dmard) AE
nausea, rash, hepatitis, pneumonitis, bone marrow suppression
Hydroxychloroquine (biologic dmard) AE
dyspepsia, nausea, abdominal pain, rashes, nightmares, visual disturbances
BIO TNF inhibitors MOA and AE
MOA: bind to TNF-alpha receptors to modulate downstream effects on inflammatory process
AE: HA, infection, antibody development, infusion reactions
BIO Non-TNF inhibitor MOA and AE
MOA: impacts inflammation process
AE: injection / infusion reactions, increased LFTs, antibody development
BIO Janus kinase inhibitors MOA and AE
MOA: impacts various components of inflammation and antibody processes
AE: infection, nasopharyngitis
DMARDS PT concerns
Review labs
DMARDS and Steroids=catabolic
stay hydrated, rash, liver effeccts, bruising, fatigue,
immunosuppression
Corticosteroids MOA
MOA- decrease inflammation and suppress immune system
Corticosteroids short term and long term AE
Short term- increased blood glucose, mood changes, fluid retention
Long term- osteoporosis, Cushing’s, thin skin, muscle wasting, adrenal suppression, immunosuppression, poor wound healing
SLE treatment
NSAIDS, hydroxychloroquine, methotrexate, immunosuppresants
OA oral, topical, and injection treatment options
Oral- acetaminophen, NSAIDS, Glucosamine chondroitin
Topical options- NSAIDS
Injections- Intra-articular hyaluronate, Intra-articular steroids (kenalog, depo-medrol)
