Pure Food and Drug Act of 1906
set standards for drug quality and purity, required drugs to be free from adulterants
19th century
drugs in the USA weren't regulated, most contained high levels of alcohol and people were dying. Led to landmark drug legislation.
Federal Food, Drug, and Cosmetic Act of 1938
regulated drug and safety, created by FDA
Harns-Kefauver Amendment of 1962
increased safety requirements and required all drugs be proven effective.
controlled substance act of 1970
established rules concerning drugs with potential for abuse.
FDA pregnancy categories
A- human studies show no risk B- Animal studies show no risk C- no studies exist, or animal studies show risks D- Evidence of human fetal harm and should only be given if benefits outweigh the risks X- contraindicated
half-life
length of time to reduce blood levels by 1 half
Pharmacokinetics
movement of drug in the body, what body does to drug
pharmacodynamics
impact of drugs on the body
direct penetration
most common passage of drugs across membranes, must be lipid soluble
pH dependent ionization
the % of drug present in charged/uncharged form depends on pH of the medium -acidic drugs ionize in basic media, bases ionize in acidic media.
Absorption
-first phase of pharmokinetics -movement of drug from site of administration into the systemic circulation
factors effecting drug absorption
lipid solubility, rate of dissolution, surface area, blood flow
bioavailability
-percent of drug that reaches systemic circulation -IV route is 100% bioavailable
Distribution
movement of drug throughout the body from the vascular space to the extravascular space
factors that effect distribution
blood flow, blood brain barrier, placental barrier. Must be lipid soluble to enter.
Vd < 9 = ? Vd > 9 = ?
Stays in plasma
Moves to extravascular space
Protein bonding
drugs are highly bonded to albumin & other blood proteins
bound/free drug:
bound= inactive free= active
patient variables effecting Volume distribution
Malnourished patients, neonates, elderly, and obese patients.
Metabolism (biotransformation)
chemical alteration resulting in enhanced excretion & inactivation. is an enzymatic process usually occurring in the liver.
cytochrome p450
-metabolizes 50% of drugs
Therapeutic consequences of drug metabolism
accelerate renal excretion of drugs, drug inactivation or increased/decreased toxicity, activation of prodrugs and therapeutic action.
first pass metabolism
the substance degradation of an orally administered drug: oral -> intestinal tract -> portal vein -> liver -> hepatic vein -> systemic circulation. low bioavailability
Excretion
drug eliminated from the body, either through metabolism or excretion
how does half-life work in the body?
4-5 half lives for drug to be gone, does not depend on dose depends on drug.
receptor theory
drug produces an effect by combining with a receptor
Lock and key concept
neurotransmitter/hormone= key agonist= bobby pin (mimics key) antagonist= stick (does not work)
agonist
a drug that mimics a natural compound by binding with receptor and stimulating a cellular response
Antagonist
a drug binds with receptor and blocks it from stimulation, prevents it from being triggered normally.
affinity
strength of attraction, tightness of bond between drug and its receptor
intolerance vs drug allergy
intolerance: adverse response to a drug that limits its usefulness drug allergy: immune system mediated response
patient variability in drug responses
allergy history, genetics, age, body size, disease states, poly pharmacy, compliance.
direct chemical interactions
usually in IV bags
pharmacokinetic interactions
altered GI absorption, altered pH, prevented absorption and distribution in general
what do cytochrome p450 drug interactions do?
altered metabolism: administration of 2 drugs metabolized by the same liver enzyme throws off blood levels
substrates and inhibitors
throw off balance when combined, metabolism decreases
substrates and inducers
increase metabolism
bethanecol
muscarinic agonist, direct acting: used for urinary retention adverse effects: drooling, tears, diarrhea
Donezepil
muscarinic agonist, indirect acting: used for dementia, increases acetylcholine levels
Atropine
muscarinic antagonist: anti secretory, anti spasmodic and antidiarrheal, dilates pupils
scopalamine
Anticholinergic Antiemetic and Anti-secretory: blocks AcH in inner ear preventing N/V associated with motion sickness
oxybutynin
muscarinic antagonist: used for overactive bladder adverse effects: Ach side effects
Epinephrine
adrenergic agonist: a1 B1 B2 receptors effecting vascular, cardiac and lung functions increasing HR BP and RR. treats asthma, shock, bleeds, and cardiac arrest
norepinephrine
adrenergic agonist: rarely used, intense vasoconstriction of skin resulting in high BP
isoproterenol
adrenergic agonist: treats bradycardia with high HR and low BP
Dobutamine
adrenergic agonist: increased HR and force of contraction
Dopamine
adrenergic agonist: treats cardiovascular shock through vasoconstriction
Phenylephrine
adrenergic agonist: vasoconstriction of skin, used as decongestant
Clonidine
a2 adrenergic agonist- treats hypertension, ADHD, and withdraw by decreasing epinephrine Adverse effects- hypotension, drowsiness, dry mouth, constipation, headache, impaired ejaculation
a1 adrenal blockers
end in sin- lowers BP through vasodilation adverse effects- hypotension, reflex tachycardia, fluid retention
Raynaud's disease
cut off of blood flow
Non-selective beta blockers
end in olol- treats HTN by decreasing the hearts force of contraction adverse effects- sexual impairment, hypotension, bradycardia
negative inotrope/negative chronotrope
decrease force of contraction, decrease heart rate
angiotensin converting enzyme inhibitors
end in pril- blocks ACE preventing the conversion of angiotensin I to angiotensin II to treat HTN adverse effects- angioedema, cough, elevated potassium -contraindicated in pregnancy
Angiotensin 2 receptor blockers
end in sartan similar to ACE inhibitors -contraindicated in pregnancy
calcium channel blockers
dihydropyridines end in pine, Non-dihydropyridines= verapamil and diltiazem (valentines day) -treat HTN -cause vasodilation constipation, gingival enlargement
nephron
filtration, reabsorption, and secretion
loop diuretics
block sodium reabsorption in loop of henle
hydrochlorothiazide
thiazide diuretic that treats HTN adverse effects- hypotension, orthostatic hypotension, dehydration, electrolyte imbalance
Spironolactone
potassium sparing diuretic, treats HTN adverse effects- gynecomastia
aspirin
antiplatelet
clopidogrel
anti platelet prodrug
Heparin
Anticoagulant
warfarin
oral anticoagulant to treat and prevent DVTs, causes bleeding drug interactions: Cyp2C9, highly protein bound drugs, drugs that promote bleeding INR: must be monitored (normal-1.0, therapeutic-2.0-3.0) dosing: between 2-5 mg a day anecdote: vitamin k patient education: no vitamin k, no aspirin, no alcohol
treatment vs prevention of angina
prevention: Calcium channel blockers, B-blockers treatment: nitrate sublingual
what is the importance of a nitrate free interval
avoids drug tolerance
patient instructions for nitroglycerin sublingual
dissolve one tablet under tongue, repeat every 5 minutes until pain is relieved. -up to 3 tablets can be taken
digoxin
heart failure
Dabigatran
Novel oral anticoagulant- direct thrombin inhibitor used to treat DVT and prevent stroke in A-fib patients anecdote- Idarucizumab
Rivaroxiban
novel oral anticoagulant Direct Factor Xa Inhibitor used to treat DVT and prevent stroke in A-fib patients anecdote- andexxa
Apixaban
novel oral anticoagulant- Direct Factor Xa inhibitor used to treat DVT and prevent stroke in A-fib patients anecdote- Andexxa
Thrombolytic
Converts plasminogen to plasmin used to treat Acute MI, PE, and ischemic stroke adverse effects- severe hemorrhage contraindications- Active bleeding, aortic dissection, brain cancer or aneurysm, recent surgery or trauma
*Alendronate
Bisphosphonate that treats and prevents osteoporosis by decreasing osteoclast activity.-adverse effects: poorly absorbed from GI tract, bone pain, rare esophageal ulceration and jaw necrosis -administration: take in AM before breakfast on an empty stomach with a full glass of water. remain upright for at least 30 minutes
Calcium supplements
calcium carbonate, calcium citrate -no more than 500-600mg in a single dose -side effects: constipation, flatulence
*Calcitonin
treat and prevent osteoporosis by decreasing osteoclast activity and increasing osteoblast activity. -adverse effects: nasal dryness and irritation, very safe
*Raloxifene
Estrogen agonist on lipids/osteoclasts and antagonist on breast/uterine tissue that prevents osteoporosis in post-menopausal women, used as an alternative to HRT. -adverse effects: thrombosis, stopping therapy will trigger a period of accelerated bone loss
*Teriparatide
Recombinant Parathyroid Hormone that results in bone formation only used to treat severe disease -adverse effects: bone pain, weakness, leg cramps, orthostatic hypotension
*denosumab
a RANK-L inhibitor that stops the activation of osteoclasts and prevents fractures in women with osteoporosis -adverse effects: back pain, pain in extremities, musculoskeletal pain, hyperlipidemia, risk of infection
Triamcinolone & Fluticasone
intranasal glucocorticoids -most effective to reduce inflammation to treat and prevent allergic rhinitis -adverse effects: drying of nasal mucosa, burning/itching sensation, sore throat, nose bleed, headache
Diphenhydramine
First generation antihistamine -helps w/ allergic rhinitis, itchy rash, anaphylaxis, insomnia, motion sickness -adverse effects: sedation, dizziness, confusion, incoordination, AcH effects, paradoxical excitation in children
fexofenadine, loratadine, cetirizine
Second generation antihistamines -same therapeutic effects as 1st, less adverse effects
pseudoephedrine
alpha 1 receptor agonist oral decongestant
allows for nasal drainage, reduced congestion, swelling and sinus pressure through vasoconstriction -side effects: increased BP, insomnia, restlessness, anxiety -used with caution if CV disease is present
guaifenesin
expectorant -used for a productive cough to reduce mucos viscosity -adverse effects: minor drowsiness
dextromethorphan
non-opioid antitussive -opioid derivative without euphoria that works in CNS to suppress nonproductive cough
Benzonatate
non-opioid antitussive -desensitizes cough reflux -adverse effects: sedation, headache, confusion
cimetidine, famotidine, nizatidine
H2 blockers -inhibit gastric acid by blocking H2 receptors of parietal cells for healing of ulcers and treatment of GERD -adverse effects: dizziness, headache, diarrhea, confusion -drug interaction: drugs needing acidic environment -cimetidine causes gynecomastia and reduced sperm count and cytochrome p450 interactions
omeprazole, esomeprazole, rabeprazole, lansoprazole, pantoprazole
proton pump inhibitors -inhibit proton pump of parietal cells to heal ulcers and treat GERD -drug interactions: drugs needing acidic environment, inhibit absorption of calcium, iron and vitamin B12
calcium carbonate, Magnesium Hydroxide, Aluminum and Mag combos
Antacids -fast acting neutralization of stomach acid to relieve GERD and indigestion -drug interactions: drugs needing acidic environment, chelation with tetracyclines and fluroquinolones
Sucralfate
Antacid -Binds to damaged mucosa to coat & protect stomach from acid allowing healing-drug interactions: inhibit absorption of other meds
misoprostal
Antacid -replace prostaglandins that are diminished during NSAID therapy, preventing gastric ulcers -adverse effects: nausea, diarrhea, pregnancy category X
Neurotransmitters involved during signals to vomit
dopamine, AcH, Serotonin, Histamine (DASH)
Ondansetron, Granisetron
Serotonin Blockers -block serotonin receptors specific to chemoreceptor zone-used for chemo induced N/V or post-op N/V
Prochloroperazine, Promethazine, Chlorpromazine
Dopamine Antagonists -blocks dopamine receptors in CTZ and vomit center used for any N/V -adverse effects: EPSE, sedation, hypotension, AcH side effects
dronabinol, nabilone
Canabinoids -not well understood but used for chemo N/V and as an appetite stimulant in AIDS
Docusate
Stool Softener -allow water to penetrate stools making them softer and easier to pass, preventing constipation -slow onset, 1-3 days
Senna, Bisacodyl tablets, Suppositories
stimulant laxatives -stimulate peristalsis in the colon -onset of Senna=8-12 hours, tablets=6-12 hours, suppositories=15-60 min
Magnesium Hydroxide
Saline/Osmotic Laxatives -retains water in GI tract causing fecal swelling to promote peristalsis-quick onset 6-12 hours, not for long term treatment -drink plenty fluids
Loperamide OTC
Antidiarrheal (opioid) -similar structure to opioids decreasing motility and frequency -drug of choice for diarrhea
Antidiarrheal (non-opioid)
Bulk laxatives (Psyllium)