Pharm Section 2 Flashcards
components/function of central nervous system
brain + spinal cord; interprets incoming sensory info, dictates motor response (integration, command center)
components/function of peripheral nervous system
spinal nerves (impulses to/from spinal cord); cranial nerves (impulses to/from brain); sensory/afferent (impulses from sensory receptors to CNS); motor/efferent (impulses from CNS to effector organs); somatic afferent (impulses from skin, skeletal muscle, joints); visceral afferent (impulses from visceral organs)
voluntary/somatic nervous system
impulses from CNS to skeletal muscle
involuntary/autonomic nervous system
impulses that regular activity of smooth muscles, cardiac muscles, and glads (“automatic”). consists of sympathetic (fight/flight) and parasympathetic (rest/digest)
ganglion and parasympathetic post-ganglionic fibers release…
acetylcholine
sympathetic post-ganglionic fibers release…
catecholamines (norepinephrine and epinephrine)
the release of catecholamines produces a _________ response
fight or flight
what enzyme inhibits the action of acetylcholine?
acetylcholinesterase
what enzymes inhibit the action of catecholamines?
monoamine oxidase (MAO) and catechol-o-methyl transferase (COMT)
What types of receptors are present in the sympathetic/adrenergic system?
alpha 1, dopaminergic, beta 1, beta 2
alpha 1 receptors (location/stimulation)
located in vascular smooth muscle; stimulation causes vasoconstriction
dopaminergic receptors (location/stimulation)
located in renal and coronary vessels; stimulation causes vasoconstriction
beta 1 receptors (location/stimulation)
located in heart; stimulation causes tremors, tachycardia
beta 2 receptors (location/stimulation)
located in lungs; stimulation causes tremors, bronchodilation
“you have one heart and two lungs” explain.
beta 1 receptors located at heart; beta 2 receptors located at lungs
What type of receptors are present in the parasympathetic/cholinergic system?
muscarinic and nicotinic
muscarinic receptors
end-receptor stimulated by the release of acetylcholine from post-ganglionic fibers in the parasympathetic nervous system. subclasses M1 (CNS), M2 (heart), M3 (smooth muscle), M4 (CNS), and M5 (CNS).
nicotinic receptors
end-receptor stimulated by the release of acetylcholine from post-ganglionic fibers in the parasympathetic nervous system. subclasses N1 (neuromuscular junction) and N2 (autonomic ganglia, CNS, adrenal medulla)
adrenergic refers to…
sympathetic nervous system (adrenaline–adrenergic. Think catecholamines.)
cholinergic refers to…
parasympathetic nervous system (think acetylCHOLINE–cholinergic.)
steps in enzymatic synthesis of catecholamines
tyrosine > dopa > dopamine > norepinephrine > epinephrine
types of sympathomimetic (adrenergic) drugs
alpha stimulants/agonists (aka alphamimetics), beta stimulants/agonists (aka betamimetics), and mixed alpha and beta stimulants/agonists
alpha 1 agonists
phenylephrine (Neo-Synephine) and norepinephrine (Levophed). potent vasoconstrictors.
what are alpha 1 agonists used for?
vasoconstrictors (hypotensive shock), treat priapism, nasal decongestant (constrict vessels @ nasal mucosa, decrease swelling, increase nasal patency)
which route of administration would you NEVER use to administer alpha 1 agonists?
Intramuscular
what do you use to reverse the effects of alpha 1 agonists?
alpha blocker phentolamine (Regitine)
beta agonists + mechanism of action
some are “preferential” or “selective” or beta 1 or 2, but none are 100% selective, so will always get some stimulation @ both. mechanism of action: activate adenyl cyclase and increase intracellular concentrations of cAMP
what are beta agonists used for?
bronchodilation for asthma/COPD, cardiac stimulant, tocolytic effect (uterine relaxation),
dobutamine and dopamine are what type of beta agonists?
beta 1 agonists (heart)
terbutaline, albuterol, levabuterol, salmeterol, formoterol, arformoterol, clenbuterol are what type of agonists?
beta 2 agonists (lungs)
mixed alpha and beta agonists
includes epinephrine (Adrenalin, Epi-pen, AuviQ), ephedrine, pseudoephedrine (Sudafed)
what are mixed alpha and beta agonists used for?
allergic reactions/anaphylaxis, nasal and sinus decongestants, bronchodilation, and cadriogenic shock and bradycardia
side effects of adrenergic/sympathomimetic drugs?
increased BP, vasoconstriction, increased HR, stroke, mydriasis (dilated pupils), cardiac arrhythmias, increased BGC (hyperglycemia), intracellular movement of K+ (hypokalemia), urinary retention (males with enlarged prostate), and uterine relaxation (tocolytic effect–B2)
sympatholytic/antiadrenergic drugs
include alpha and beta blockers
alpha blockers
include phentolamine (Regitine, OraVerse) and phenoxybenzamine (Dibenzyline)
what are alpha blockers used for?
diagnosis and pre-op mgmt of pheochromocytoma (adrenal gland tumor) and to reverse the vasoconstrictive effects of alpha agonists.
how can you reverse severe vasoconstriction?
give alpha blockers
beta blockers
some of the most widely-used drugs. usually end in -olol/-alol/-ilol, esp -olol. Selective and non-selective, but selective only so for beta 1. don’t want to block beta 2 because it would stop breathing.
contraindications or precautions for using beta blockers
diabetes, asthma, COPD, peripheral vascular disease,
why would you want to use a selective beta blocker?
if you have asthma, COPD pts where you want to limit the action of the blocker @ lungs. Will still get some stimulation, but less than if use a non-selective beta blocker
benefit of using beta blockers with ISA (intrinsic sympathomimetic activity) or PAA (partial agonist activity)?
fewer side effects, esp decrease in heart rate at rest. preferred for clients who develop bradycardia with other beta blockers
when should you NOT use beta blockers with ISA?
for patients with angina pectoris, as cardiac protection during surgery, or after MI (b/c low O2 levels)
what are beta blockers used for?
cardiac arrythmias, angina pectoris, hypertension, migraine headache prophylaxis, actue anxiety reactions, prevent recurrent MIs, glaucoma (topical), chronic CHF, pre/post-op (non cardiac surgeries)
side effects of beta blockers
hypoglycemia/masks signs of hypoglycemia, bradycardia, fatigue, prevents bronchiole dilation, don’t stop abruptly or “super reactive” to sympathetic stimulation, caution with peripheral vascular disease
parasympathomimetic (cholinergic) agonists
direct-acting drugs that stimulate cholinergic receptors like acetylcholine. includes pilocarpine, mathacholine, cevimeline, and bethanechol
pilocarpine
cholinergic agonist. direct acting. eye drops for glaucoma and for dry mouth
methacholine (Provocholine)
cholinergic agonist. direct acting. inhaled for tx of bronchial airway hyperactivity
cevimeline (Evoxac)
cholinergic agonist. direct acting. dry mouth tx for pts with Sjogren’s syndrome (dry mouth, eyes, mucosa)
bethanechol (Urecholine, Duvoid)
cholinergic agonist. direct acting. tx for urinary retention.
acetylcholinesterase inhibitors
indirect acting cholinergic drugs. inhibits enzyme acetylcholinesterase, which increases body’s natural ACh activity. Includes drugs to treat alzheimer’s, myasthenia graves, etc.
tacrine (Cognex), donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne) are used to treat what?
Alzheimer’s disease. indirect acting cholinergic drugs (aka acetylcholinesterase inhibitors).
Neostigmine (Prostigmin) and Pyridostigmine (Mestinon) are used to treat what?
myasthenia gravis (muscle weakness, face droop that moves down body). indirect actin cholinergic drugs (aka acetylcholinesterase inhibitors)
organophosphates are used as what?
insecticides. poisonous to humans because they are acetylcholinesterase inhibitors. atropine is antidotal. (Scene from “The rock” where nick cage is exposed and uses atropine injection to heart to save himself)
what are cholinergic agents used for?
neurological diseases (Alzheimer’s, myasthenia gravis), glaucoma, dry mouth, stimulate GIT and GUT (tx urinary prevention)
side effects of cholinergic agents?
abdominal cramping, diarrhea, increased secretions, DUMBBELSS mnemonic (diarrhea, urination, mitosis–pupil constriction, bradycardia, bronchoconstriction, emesis, lacrimation, salivation, sweating)
parasympatholytics (anticholinergic/antimuscarinic)
derived from natural sources like the belladonna plant or manufactured synthetically. tertiary amines absorbed @ CNS
belladonna alkaloids
atropine (classic anticholinergic drug), scopolamine, and hyoscyamine
what are anticholinergic drugs used for?
decrease glandular secretions, pupil dilation (either mydriasis–dilation or cycloplegia–paralysis of focusing mechanism @ eye), treatment of Parkinsonism, stimulate heart for bradyarrythmias (atropine), stimulate bronchodilation (asthma, COPD), illicit central effect @ CNS to produce anti-nausea effect and somnolence (sleepiness) and “twilight sleep”, to decrease GIT/GUT actions (tx for diarrhea, enuresis–involuntary urination, IBS, and OAB), to treat hyperhidrosis (excessive sweating), and to block skeletal muscles for intubation prior to surgery.
side effects of anticholinergic drugs
classic adverse reactions: dry mouth, blurred vision (cycloplegia), urinary retention, constipation, increased temp (flushing), tachycardia (heart palpitations), central effects including confusion, amnesia, hallucinations.
anticholinergic drugs and elderly
strong evidence that they are associated with brain atrophy in elderly patients…increase risk for dementia.
two main types of incontinence
stress and urge incontinence
symptoms of stress incontinence
involuntary loss of urine, associated with sneezing/coughing/laughing/lifting
symptoms of urge incontinence
involuntary urine loss preceded by strong desire to empty bladder
causes of stress vs. urge incontinence
stress: inefficient urethral closure
urge: uncontrolled bladder contractions
receptors associated with stress vs urge incontinence?
stress: serotonin and norepinephrine receptors
urge: cholinergic muscarinic receptors
traditional treatment of urinary incontinence
alpha adrenergic stimulants
anticholinergic drugs
trycyclic antidepressants
current tx for urinary incontinence
more specific anticholinergic/ antimuscarinic agents that relax smooth muscle tissue @ bladder and decrease bladder contractions
suspected cause of overactive bladder
overactive/unstable detrusor muscles in bladder
tolterodine (Detrol LA), oxybutynin (Ditropan XL, Oxytrol transdermal), Trospium (Sanctura), Solifenacin (VESIcare), Darifenacin (Enablex), Fesoterodine (Toviaz) are used to treat what?
overactive bladder. all are anticholinergic/antimuscarinic agents that work to relax smooth muscle @ bladder
non-muscarinic agents used to treat OAB
Botox (paralyzes muscles in bladder), Mirabegron (Myrbetriq) = beta 3 (in bladder) agonist help relax bladder muscles and increase its capacity–doesn’t have anticholinergic side effects (dry mouth, blurred vision, etc)
asthma
chronic inflammatory disorder of the airways in which many inflammatory mediators (histamines, leukotrienes, prostaglandins) recruit inflammatory cells in response to triggers (esp mast cells, eosinophils, and T lymphocytes). constriction of bronchioles due to inflammation.
inflammation associated with asthma causes recurrent episodes of…
wheezing, breathlessness, increased mucous secretion, chest tightness, cough
asthma episodes generally occur at what time of day?
1-2 am (late night, early morning) and during exercise
step and severity classifications for asthma
step 1: mild intermittent(
what type of treatment approaches are recommended for asthma patients? (general)
stepwise approach to treating where doses or types of medications are stepped up as needed and stepped down when possible
asthma drugs are classified as…
1) quick relief or rescue bronchodilators for treatments (inhaled B2 agonists–SABAs)
2) long term control or anti-inflammatories for prevention (ICS, mast cell stabilizers, leukotriene inhibitors, theophylline)
oral steroids and asthma
can be used for exacerbations, but not fast enough for rescue. can be used chronically, persistent severe asthma, but has systemic side effects when used chronically.
recommended regimen for intermittent asthma
SABA as needed
recommended regimen for mild persistent asthma
low dose ICS
alternatives: leukotriene modifier like montelukast aka Singular or theophylline
recommended regimen for moderate persistent asthma
low-med dose ICS + LABA
alternatives: low dose ICS plus leukotriene modifier or theophylline
recommended regimen for severe persistent asthma
medium-high dose ICS + LABA
alternatives: same as moderate persistent
corticosteroids
anti-inflammatory agents. major role of “controllers” for asthma prevention/tx
first line therapy in the long-term management of asthma
ICS
off label use for ICS
in children with croup
actions of corticosteroids
reduce immune response and increases B2 receptors (airway smooth muscles)
why should clients taking ICS rinse and gargle with water after?
to reduce the risk of thrush (oral candidiasis)
side effects of ICS
reduce body’s ability to fight off infection (effect on inflammation, immune system); stunted growth (maybe); increased risk of glaucoma and cataracts; bone loss in young women.
ICS and growth in children
concerns that they stunt growth, but if they do it’s not by much and better to be a little shorter than dead (risk-benefit analysis).
ICS agents
generally seem to end in -one or -ide. oral prednisone, prednisolone, triamcinolone, (for severe exacerbations) + flunisolide, beclomethasone (Vanceril, Qvar), fluticasone propionate(Flovent/Flonase)/furoate (Veramyst), budesonide (Pulmicort, Symbicort), mometasone (Nasonex, asmanex), ciclesonide (Omanis, Alvesco, Zetonna)
current evidence on ICS
all ICSs show sufficient therapeutic indexes. similar efficacy and safe in low-med doses.
combination ICS therapies
ICS + LABAs. Advair Diskus (Fluticasone + LABA); Symbicort Turbuhaler (Budesonide + LABA); BreoEllipta (Fluticasone furoate + LABA) once daily
SABAs
short acting beta2 agonist. most effective drugs available for treatment of acute asthma symptoms and exercise induced asthma. prn use not recommended. not selective and selective.
epinehprine, isoproterenol (Isuprel)
non-selective SABAs
bitolterol (Tornalate), pirbuterol (Maxair), terbutaline (Bricanyl), albuterol (Ventolin, Proventil, ProAir RespiClick), levabuterol (Xopenex)
selective SABAs
LABAs
long acting beta2 agonists. long-term asthma care, prevention. also approved for COPD, chronic bronchitis, emphysema. safety concerns when used alone, but they are not used alone. Standard of care is to use in conjunction with ICS.
LABA boxed warning controversy
study of LABAs only showed risk for death due to exacerbation of asthma (which it’s used to treat…), but they aren’t used alone. Std care is ICS + LABA. when used like that no significant increase in risk for negative outcomes.
LABA agents
salmeterol (Serevent, in Advair); formoterol (Foradil, in Symbicort, in Dulera, Perforomist); aformoterol (Brovana–R isomer of formoterol for nebulizers)
LABAS and bronchospasms
LABAs are NOT recommended for acute tx of bronchospasms because they take ~1 hour to work. Clients can also take SABA b/c LABA don’t fully occupy B2 receptors.
COPD
chronic obstructive pulmonary disease. have trouble breathing out once they breath in (continually over inflated lungs). 85% caused by smoking.
COPD and asthma
COPD symptoms similar to asthma, so often misdiagnosed with asthma.
ACOS
asthma-COPD overlap syndrome. worse outcomes. combined risk factors of smoking and atopy, generally younger than COPD pts, experience more severe exacerbation more frequently than with COPD alone.
1st line treatment for COPD pts with FEV1
long acting bronchodilators–either long acting anticholinergics or LABAs or a combination of the two.
COPD drugs
long-acting anticholinergics or LABAs or combo. tiotropium, formoterol, aformoterol, fluticasone/salmeterol, roflumilast, vilanterol , olodaterol, glycopyrrolate, aclidinium, indacaterol,
anticholinergic bronchdilators (muscarinic antagonists)
short-acting muscarinic antagonists (SAMAs) and long acting muscarinic antagonists (LAMAs)
SAMAs
short acting muscarinic antagonists. blocks cholinergic response, causing bronchodilation. 10-30 minute onset, so cannot be used as rescue. used 3-4 x a day.
MDI is….
metered dose inhaler
LAMAs
long acting muscarinic antagonists. Tiotrpium (Spiriva, Spiriva Respimat) or Glycopyrrolate (Seebri)
DPI is…
dry powder inhaler
Triotropium (Spiriva, Spiriva Respimat)
LAMA. inhaled 1x a day. DPI or spray. causes more dry mouth than Atrovent. 1st line treatment for bronchospasm associated with COPD.
Glycopyrrolate (Seebri)
LAMA. long acting anticholinergic form of glycopyrrolate approved for COPD tx. Also used in combination tx with LAMA glycopyrrolate and LABA formoterol fumarate. For COPD, but not asthma or acute bronchospasm relief.
mast cell stabilizers
reduce the release of histamine, serotonin, leukotrienes, etc. (precipitate asthma attack). Similar mechanism to ICS, but with fewer side effects. Less effective than ICS. cromolyn (Intal)
LTRAs
Leukotriene receptor antagonists. prevents breakdown of prostaglandins, leukotrienes. reverse bronchoconstriction, mucus hypersecretion, and airway inflammation. less effective than ICS. e.g. monolukast (Singular)
methylxanthine agents
theophylline and amniophylline. inhibits phosphodiesterase to cause bronchodilation. theophylline notorious for fluctuations in blood levels due to drug interactions. narrow therapeutic index. side effects similar to large doses of caffeine. chocolate.
IgE antagonist
Omalizumab (Xoliar) = 1st biotech product for asthma caused by allergies and chronic hives. for people who ICSs don’t work for. disables IgE. side effects = injection site reactions, viral/URT infections, headache. Black box warning for possible delayed reaction. wait @ office 2+ hours.
Interleukin-5 (IL5) antagonist
mepolizumab (Nucala) and Reslizumab (Cinqair). work to lower levels of blood/circulating eosinophils. expensive.
how many people does in the FDA predict have eosinophilic phenotype for asthma
1 in 20.
exercise induced asthma or bronchospasm (EIA/EIB)
bronchial spasm, edema, and mucus secretion brought on by exercise (esp in cool, dry climates). Recovery usually within 90 min. 10-15% reduction in FEV1 confirms diagnosis
tx for EIA/EIB
inhaled SABA 15 minutes before workout.If that doesn’t work, daily LABA + ICS, but some of these banned by athletic regulatory agencies. Tailor regimen for athletes. Don’t use ICS just before exercise (takes 2-4 weeks to work) and don’t take LABAs alone.
preferred SABA for use in pregnancy
albuterol
preferred ICS for use in pregnancy
budesonide
LABAs and pregnancy
appear to be safe
montelukast and pregnancy
appears to be safe
PAH
pulmonary arterial hypertension. tx with vasodilators.
standardized tx for PAH
warfarin (Coumadin) and furosemide (Lasix)
CFC vs. HFA inhalers
CFC inhalers banned in 2009. Most manufacturers switched from MDI to DPI systems, but some now make hydrofluoroalkane (HFA) inhalers to propel meds out of container and into lung. equally as effective. Need to clean HFAs more often, but don’t have to prime as often.
DPI
dry powder inhaler. requires deep, rapid force inhalation because doesn’t have propellents. don’t shake. clean with brush/dry cloth.
nebulizers
aerosolize a liquid
chronobiology of asthma
asthma attacks late at night/early AM (1-2am) because cortisol drops, airway reactivity/inflammation peaks, sympathetic tone trough, vagal tone peak, airway/cilia function trough.
Mucolytic/Expectorant agents
Guaifenesin (combo expectorant and anti-tussive); N-acetylcysteine (Mucomyst)
cough suppressants
aka anti-tussives. Codeine (central suppression), dextromethorphan (DX,DM central suppression), Guaifenesin, diphenhydramine (Benadryl-histamine blocking +CNS), Benzonatate (Tesslon, Perles, Zonatuss–peripheral action…anesthetizes stretch receptors @ resp passages), hydrocodone (central suppression)
anti-tussives in children
no longer recommended. honey before bed instead.
anti-tussives in adults
antihistamine-decongestant combos recommended for 1st line tx for acute coughs due to colds, postnasal drip. Don’t use DX or guaifenesin for cold-realted coughs. Atrovent if cough persists 3-8 weeks after URI.
sympathomimetic amines (nasal + sinus decongestants)
vasoconstrictors in nasal mucosa, sinus, ear via alpha 1 adrenergic receptors. decrease blood supply, improve nasal patency. Short-term therapy, if longer = rebound congestion.
topical sympathomimetic amines
phenylephrine (Neo-Synephine) and oxymethazoline (Afrin)
oral sympathomimetic amines
pseudoephedrine, phenylephrine (Sudafed PE)
are sympathomimetic amines effective as decongestants?
oral pheylephrine = same as placebo
oral pseudopephedrine = nasal congestion only
intranasal like oxymethazoline = effective, less likely for systemic adverse effects
ICS = most effective drugs for prevention and relief of nasal congestion and other seasonal allergic rhinitis symptoms
cromolyn sodium as decongestant
anti inflammatory. prevents the degranulation of mast cells. used for nasal allergies and allergic rhinitis. NasalCrom = OTC.
anticholinergics as decongestants
used for drying effects in the nasal mucosa
antihistamines/histamine blockers
H1 = increases bronchial smooth muscle contraction and nasal/eye secretions H2 = increases G1 secretion. Diphenhydramine (Benadryl) = still gold standard histamine blocker.
traditional/1st gen vs second gen antihistamines
1st gen: penetrate blood brain barrier, nonspecific, many side effects (drowsiness, anticholinergic effects), every 4-6 hours; 2nd gen: decreased movement across BBB–fewer side effects but not better, usually 1x a day, use more now
side effects of antihistamines
competitive inhibition of histamine activity, CNS depression/drowsiness, anti-vertigo, anticholinergic
indications for use of antihistamines
immunotherapy (allergic rhinitis), allergic disorders, acute anaphylaxis, sedation
1st gen antihistamines (list)
generally end in -ine/ -amine. oral, intranasal.
2nd gen antihistamine agents (list)
loratidine (Claratin), desloratidine (Clarinex), Certizine (Zyrtec), Fexofenadine (Allegra), levocertirzine (Xyzal)
comparing antihistamines
efficacy (1st/2nd gen same), sedation (1st gen more sedating), onset (cortisone/levocertizine = 1 hour, others = 1-3 hours), allergy type (all effective for outdoor and indoor allergies), price (OTC cheapest. pts respond diff so try others if needed)
allergy meds and driving
may impair driving more than alcohol. 25mg Benadryl can cause more impairment than legal alcohol limit
Benadryl in elderly, infants
linked to dementia. may stimulate infants
NSAIDSs
pain relief. no systemic review for NSAID relief of common colds.
children’s cold medicine
2008 = cold meds should not be used for kids under 2 2011 = cold meds taken off market, the rest not labeled for kids under 4-6
allergic rhinitis
“Asthma of the face” chronic IgE mediated respiratory illness that causes inflammation of the membranes lining the nose…nasal congestion, rhinorrhea, sneezing, itching of the nose, and post-nasal drip.
Treatment for allergic rhinitis
first line = nasally inhaled corticosteroids, as well as oral antihistamines and intranasal antihistamines
others = oral decongestants, oral corticosteroids, intranasal cromolyn, intranasal anticholinergics, oral anti-leukotriene agents
Tx of allergic rhinitis during pregnancy
nasal cromolyn or beclomethasone
avoid oral decongestants in 1st trimester (infant gastroschisis). don’t initiate immunotherapy during pregnancy, but can continue if already on it.
Tx allergic rhinitis in athletes
oral decongestants banned by USOC
oral and parenteral steroids banned
oral antihistamines allowed by USOC but not international federation.
e.g. advil cold and sinus and UT track athlete. Must disclose (exactly) all meds on before testing.
Alternative therapies for common cold
echinacea, goldenseal, green tea, zinc, airborne
echinacea possible benefits
shorter, less severe cold (not proven)
goldenseal benefits
contains berberine salts, which may have antibacterials and ant-iinflammatory properties. present in small amounts in goldenseal.
green tea benefits
polyphenols in green tea have antiviral effects. may help prevent cold and flu symptoms (1-5 cups a day in kids, need more research)
zinc benefits
thought to assist t cells, which kill virus infected cells. mechanism unknown. adverse effects: GI upset, altered taste/smell. conflicting results. metaanalysis…12/ say it works, 1/2 say it doesnt.
airborne
no proof that it can prevent or treat colds
what sort of immunotherapy is available for people who are afraid of needles?
new sublingual immunotherapies (Oralair, Grastek) have been approved to treat multiple grass pollens and ragweed allergies (Ragwite). More expensive than allergy shots, but sublingual is safer, more convenient, and almost as effective as shots.
