pharm- hypertension, anticoagulants, antiplatelts, thrombolytics

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Pure Food and Drug Act of 1906

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Pure Food and Drug Act of 1906

set standards for drug quality and purity, required drugs to be free from adulterants

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19th century

drugs in the USA weren't regulated, most contained high levels of alcohol and people were dying. Led to landmark drug legislation.

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Federal Food, Drug, and Cosmetic Act of 1938

regulated drug and safety, created by FDA

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Harns-Kefauver Amendment of 1962

increased safety requirements and required all drugs be proven effective.

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controlled substance act of 1970

established rules concerning drugs with potential for abuse.

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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

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half-life

length of time to reduce blood levels by 1 half

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Pharmacokinetics

movement of drug in the body, what body does to drug

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9

pharmacodynamics

impact of drugs on the body

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direct penetration

most common passage of drugs across membranes, must be lipid soluble

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11

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.

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  1. Absorption

-first phase of pharmokinetics -movement of drug from site of administration into the systemic circulation

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factors effecting drug absorption

lipid solubility, rate of dissolution, surface area, blood flow

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bioavailability

-percent of drug that reaches systemic circulation -IV route is 100% bioavailable

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  1. Distribution

movement of drug throughout the body from the vascular space to the extravascular space

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factors that effect distribution

blood flow, blood brain barrier, placental barrier. Must be lipid soluble to enter.

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Vd < 9 = ? Vd > 9 = ?

  1. Stays in plasma

  2. Moves to extravascular space

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Protein bonding

drugs are highly bonded to albumin & other blood proteins

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bound/free drug:

bound= inactive free= active

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20

patient variables effecting Volume distribution

Malnourished patients, neonates, elderly, and obese patients.

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  1. Metabolism (biotransformation)

chemical alteration resulting in enhanced excretion & inactivation. is an enzymatic process usually occurring in the liver.

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cytochrome p450

-metabolizes 50% of drugs

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Therapeutic consequences of drug metabolism

accelerate renal excretion of drugs, drug inactivation or increased/decreased toxicity, activation of prodrugs and therapeutic action.

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first pass metabolism

the substance degradation of an orally administered drug: oral -> intestinal tract -> portal vein -> liver -> hepatic vein -> systemic circulation. low bioavailability

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  1. Excretion

drug eliminated from the body, either through metabolism or excretion

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26

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.

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receptor theory

drug produces an effect by combining with a receptor

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Lock and key concept

neurotransmitter/hormone= key agonist= bobby pin (mimics key) antagonist= stick (does not work)

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agonist

a drug that mimics a natural compound by binding with receptor and stimulating a cellular response

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Antagonist

a drug binds with receptor and blocks it from stimulation, prevents it from being triggered normally.

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affinity

strength of attraction, tightness of bond between drug and its receptor

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intolerance vs drug allergy

intolerance: adverse response to a drug that limits its usefulness drug allergy: immune system mediated response

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patient variability in drug responses

allergy history, genetics, age, body size, disease states, poly pharmacy, compliance.

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direct chemical interactions

usually in IV bags

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pharmacokinetic interactions

altered GI absorption, altered pH, prevented absorption and distribution in general

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what do cytochrome p450 drug interactions do?

altered metabolism: administration of 2 drugs metabolized by the same liver enzyme throws off blood levels

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substrates and inhibitors

throw off balance when combined, metabolism decreases

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substrates and inducers

increase metabolism

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39

bethanecol

muscarinic agonist, direct acting: used for urinary retention adverse effects: drooling, tears, diarrhea

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Donezepil

muscarinic agonist, indirect acting: used for dementia, increases acetylcholine levels

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Atropine

muscarinic antagonist: anti secretory, anti spasmodic and antidiarrheal, dilates pupils

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scopalamine

Anticholinergic Antiemetic and Anti-secretory: blocks AcH in inner ear preventing N/V associated with motion sickness

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oxybutynin

muscarinic antagonist: used for overactive bladder adverse effects: Ach side effects

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44

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

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norepinephrine

adrenergic agonist: rarely used, intense vasoconstriction of skin resulting in high BP

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isoproterenol

adrenergic agonist: treats bradycardia with high HR and low BP

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Dobutamine

adrenergic agonist: increased HR and force of contraction

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Dopamine

adrenergic agonist: treats cardiovascular shock through vasoconstriction

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Phenylephrine

adrenergic agonist: vasoconstriction of skin, used as decongestant

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Clonidine

a2 adrenergic agonist- treats hypertension, ADHD, and withdraw by decreasing epinephrine Adverse effects- hypotension, drowsiness, dry mouth, constipation, headache, impaired ejaculation

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51

a1 adrenal blockers

end in sin- lowers BP through vasodilation adverse effects- hypotension, reflex tachycardia, fluid retention

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Raynaud's disease

cut off of blood flow

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Non-selective beta blockers

end in olol- treats HTN by decreasing the hearts force of contraction adverse effects- sexual impairment, hypotension, bradycardia

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negative inotrope/negative chronotrope

decrease force of contraction, decrease heart rate

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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

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Angiotensin 2 receptor blockers

end in sartan similar to ACE inhibitors -contraindicated in pregnancy

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calcium channel blockers

dihydropyridines end in pine, Non-dihydropyridines= verapamil and diltiazem (valentines day) -treat HTN -cause vasodilation constipation, gingival enlargement

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nephron

filtration, reabsorption, and secretion

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loop diuretics

block sodium reabsorption in loop of henle

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hydrochlorothiazide

thiazide diuretic that treats HTN adverse effects- hypotension, orthostatic hypotension, dehydration, electrolyte imbalance

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61

Spironolactone

potassium sparing diuretic, treats HTN adverse effects- gynecomastia

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62

aspirin

antiplatelet

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63

clopidogrel

anti platelet prodrug

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64

Heparin

Anticoagulant

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65

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

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66

treatment vs prevention of angina

prevention: Calcium channel blockers, B-blockers treatment: nitrate sublingual

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67

what is the importance of a nitrate free interval

avoids drug tolerance

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68

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

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69

digoxin

heart failure

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70

Dabigatran

Novel oral anticoagulant- direct thrombin inhibitor used to treat DVT and prevent stroke in A-fib patients anecdote- Idarucizumab

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71

Rivaroxiban

novel oral anticoagulant Direct Factor Xa Inhibitor used to treat DVT and prevent stroke in A-fib patients anecdote- andexxa

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72

Apixaban

novel oral anticoagulant- Direct Factor Xa inhibitor used to treat DVT and prevent stroke in A-fib patients anecdote- Andexxa

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73

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

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74

*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

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75

Calcium supplements

calcium carbonate, calcium citrate -no more than 500-600mg in a single dose -side effects: constipation, flatulence

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76

*Calcitonin

treat and prevent osteoporosis by decreasing osteoclast activity and increasing osteoblast activity. -adverse effects: nasal dryness and irritation, very safe

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*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

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78

*Teriparatide

Recombinant Parathyroid Hormone that results in bone formation only used to treat severe disease -adverse effects: bone pain, weakness, leg cramps, orthostatic hypotension

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79

*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

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80

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

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81

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

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82

fexofenadine, loratadine, cetirizine

Second generation antihistamines -same therapeutic effects as 1st, less adverse effects

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83

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

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84

guaifenesin

expectorant -used for a productive cough to reduce mucos viscosity -adverse effects: minor drowsiness

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85

dextromethorphan

non-opioid antitussive -opioid derivative without euphoria that works in CNS to suppress nonproductive cough

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86

Benzonatate

non-opioid antitussive -desensitizes cough reflux -adverse effects: sedation, headache, confusion

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87

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

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88

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

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89

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

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90

Sucralfate

Antacid -Binds to damaged mucosa to coat & protect stomach from acid allowing healing-drug interactions: inhibit absorption of other meds

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misoprostal

Antacid -replace prostaglandins that are diminished during NSAID therapy, preventing gastric ulcers -adverse effects: nausea, diarrhea, pregnancy category X

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92

Neurotransmitters involved during signals to vomit

dopamine, AcH, Serotonin, Histamine (DASH)

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93

Ondansetron, Granisetron

Serotonin Blockers -block serotonin receptors specific to chemoreceptor zone-used for chemo induced N/V or post-op N/V

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94

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

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95

dronabinol, nabilone

Canabinoids -not well understood but used for chemo N/V and as an appetite stimulant in AIDS

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96

Docusate

Stool Softener -allow water to penetrate stools making them softer and easier to pass, preventing constipation -slow onset, 1-3 days

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97

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

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98

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

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99

Loperamide OTC

Antidiarrheal (opioid) -similar structure to opioids decreasing motility and frequency -drug of choice for diarrhea

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100

Antidiarrheal (non-opioid)

Bulk laxatives (Psyllium)

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