pharm- hypertension, anticoagulants, antiplatelts, thrombolytics

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.

1. 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

2. 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 = ?

1. Stays in plasma
2. 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.

3. 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

4. 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)