___ is the transmission of meds from the locaation of administration (GI, muscle, skin, subQ) to bloodstream.
Absorption
Enteral means...
thru the GI tract
Parenteral means...
by injection
There is no significant barrier to absorption of subQ and IM meds. Why?
Capillary wall has large spaces between cells
Rate of absorption for subQ and IM meds is determined by what 2 things?
solubility of the med in water
blood perfusion at site of injection
List the 3 major factors for distribution of drugs in the body.
blood flow to tissues
ability to exit vascular system
ability to enter cells
___ refers to the ability of a drug to reach the systemic circulation from its site of administration.
Bioavailability
Differences in bioavailability occur primarily with ___ preparations, not with ___ preparations.
oral; parenteral
Differences in bioavailability are of greatest concern for which drugs?
those w/ narrow therapeutic range
___ refers to the rapid hepatic inactivation of certain oral drugs.
1st pass effect
Explain the 1st pass effect.
When oral drugs are absorbed from the GI tract, they are carried directly to the liver via the hepatic portal vein. If the capacity of the liver to metabolize a drug is extremely high, that drug can be completely inactivated on its first pass through the liver. As a result, no therapeutic effects can occur.
How can you circumvent the 1st pass effect with drugs that undergo rapid hepatic metabolism?
Administer parenterally, which permits the drug to temporarily bypass the liver and reach therpeutic levels in the systemic blood
When plateau must be achieved more quickly, a large initial dose - or ___ - can be administered.
loading dose
The highest drug level is referred to as the ___, and the lowest drug level is referred to as the ___.
peak concentration; trough concentration
___ concentration levels are drawn just before administering the next dose; ___ concentration levels are drawn after administering the medication (depending on route, etc.)
Trough; peak
What is the time required for the amount of a drug to be reduced by 50%?
half-life
T/F Half-life is a factor in determining dosing interval.
T
A ___ is a nearly unavoidable secondary drug effect produced at therapeutic doses.
side effect
List 2 main characteristics of side effects.
predictable
dose-dependent
T/F An adverse drug rxn is a side effect.
F; side effects are considered adverse rxns
List 6 adverse rxns besides side effects and allergic rxns.
toxicity
idiosyncratic effect
iatrogenic disease
physical dependence
carcinogenic effect
teratogenic effect
___ is an adverse drug rxn caused by excessive dosing.
Toxicity
T/F Toxicity includes only those severe rxns that occur when dosage is excessive.
F; Although the formal definition of toxicity includes only those severe rxns that occur when dosage is excessive, in everday parlance the term toxicity has com eto mean any severe ADR, regardless of the dose that caused it
An allergic rxn is an ___ response.
immune
T/F For an allergic drug rxn to occur, there must be prior sensitization of the immune system
T
T/F The intensity of an allergic drug rxn is determined primarily by drug dosage.
F; determined primarily by degree of sensitization of the immune system, not by drug dosage
Most serious allergic drug rxns are caused by which drug family?
Penicillins
An ___ is an uncommmon drug response resulting from a genetic predisposition.
idiosyncratic effect
An ___ is a disease produced by a physician or drugs.
iatrogenic disease
Iatrogenic diseases are nearly identical to ___ (naturally occurring) diseases.
idiopathic
___ develops during long-term use of certain drugs, such as opioids, alcohol, barbiturates, and amphetamines.
Physical dependence
___ is a state in which the body has adapted to drug exposure in such a way that an abstinence syndrome will result if drug use is d/c.
Physical dependence
___ refers to the ability of certain medications and environmental chemicals to cause cancers.
Carcinogenic effect
A ___ can be defined as a drug-induced birth defect.
teratogenic effect
What populations are at greatest risk for med reactions, toxicity, and ADRs?
old
young
severe illness
polypharmacy
HTN
epilepsy
heart disease
psychoses
___ is that component of a drug response that is caused by psychologic factors and not by the biochemical or physiologic properties of the drug.
Placebo effect
A ___ is a preparation that is devoid of intrinsic pharmacologic activity.
placebo
T/F The placebo effect is believed to be a large fraction of the total response of any given drug.
F; a small fraction
T/F The placebo effect is always positive.
F; can be positive and negative
T/F Enough research has been done to indicate that significant gender-related differences exist in drug responses.
T (even though for many drugs, we don't know much about gender related differences b/c until recently, essentially all drug research was done on men)
When used to treat heart failure, digoxin may (increase/decrease) mortality in women while having no effect on mortality in men.
increase
Alcohol is metabolized more (slowly/quickly) by women than by men. As a result, a woman who drinks the same amount as a man (on a wt. adjusted basis) will become (more/less) intoxicated.
slowly; more
Certain opioid analgesics are much more effective in (men/women) than in (men/women). As a result, pain relief can be achieved at lower doses in (men/women).
women; men
women
Quinidine causes greater QT interval prolongation in (men/women) than in (men/women). As a result, (men/women) given the drug are more likely to develop torsades de pointes, a potentially fatal cardiac dysrhythmia.
women; men
women
In what year did the FDA pressure drug companies to include women in clinical drug trials?
1997
What are the major organs effected by alcohol?
CNS
cardiovascular system
respiratory system
liver
stomach
kidneys
pancreas
What 2 acute effects does alcohol have on the brain?
general depression of CNS function
activation of reward circuit
What are 2 neuropsychiatric syndromes common in alcoholics?
Wernicke's encephalopathy
Korsakoff's psychosis
Both Wernicke's and Korsakoff's are caused by ___ deficiency, which results from poor diet and alcohol-induced suppression of ___ absorption.
thiamin
A neuropsychiatric syndrome common in acoholics characterized by confusion, nystagmus, and abnormal ocular movements; readily reversible with thiamin
Wernicke's encephalopathy
A neuropsychiatric syndrom common in alcoholics characterized bypolyneuropathy, inability to convert short-term memory into long-term, and confabulation; not reversible.
Korsakoff's psychosis
T/F Low to moderate drinking helps preserve cognitive function in older people and may protect against development of dementia.
T
T/F Alcohol is a great sleep aid.
F; it actually disrupts sleep
What is the most prominent cardiovascular effect when alcohol is consumed in moderation?
Dilation of cutaneous blood vessles, which increases blood flow to the skin imparting a sensaiton of warmth, while promoting heat loss
What are two cardivascular effects of chronic and excessive alcohol consumption?
direct damage to myocardium (increasing risk of HF)
dose-dependent elevation of BP
T/F There is clear evidence that people who drink moderately experience less ischemic stroke, CAD, MI, and HF. With heavy drinking the risk of heart disease and stroke is increased.
T
Moderate alcohol consumption includes ___ drinks/day or less for men and ___ drink/day or less for women.
2; 1
Heavy alcohol consumption includes ___ or more drinks/day.
5
Like all other CNS depressants, alcohol depresses ___.
respiration
Alcohol-induced liver damage can progress from ___ to ___ to ___, depending on amount consumed.
fatty liver; hepatitis; cirrhosis
T/F Alcohol abuse is unquestionably the major cause of fatal cirrhosis.
T
___ is a condition characterized by proliferation of fibrous tissue and destruction of liver parenchymal cells.
Cirrhosis
Immoderate use of alcohol can cause ___ by (1) stimulating secretion of gastric acid, and (2) in high concentrations, injuring gastric mucosa directly.
erosive gastritis
Alcohol is a ___. It promotes urine formation by inhibiting the release of ADH from the pituitary.
diuretic
How does ADH work?
Acts on kidneys to promote water reabsorption, thereby decreasing urine formation.
About 35% of cases of acute pancreatitis can be attributed to alcohol, making alcohol the ___ most common cause of the disorder. Only ___% of alcoholics develop pancreatitis.
second; 5
What are the common social factors of drug abuse?
desire for social status and approval
peer pressure
List factors that contribute to drug abuse.
reinforcing properties of drugs
physical dependence
psychologic dependence
social factors
drug availability
individual vulnerability
___ is an intense subjective need for a drug.
Psychologic dependence
What are the drug schedules for addictive substances?
Schedule 1: high tendency for abuse, no accepted medical use; marijuana, ecstasy, LSD, GHB; not sold by pharmacies, not available w/ physician prescription
Schedule 2: high tendency for abuse, may have accepted medical use, can produce dependency/addiction; cocaine, opium, morphine, fentanyl, amphetamines, methamphetamines; may be available w/ physician prescription
Schedule 3: less abuse/addiction potential, accepted medical use; anabolic steroids, codeine, ketamine, hydrocodone w/ aspirin, hydrocodone w/ acetaminophen; may be available w/ prescription
Schedule 4: low abuse potential, accepted medical use, limited addictive properties; valium, xanax, phenobarbital, rohypnol; may be available w/ prescription
Schedule 5: lowest chance of abuse, accepted medical use in US, lowest chance of dependence; cough suppressants w/ codeine; regulated but don't generally require prescription
What medications interact with alcohol?
CNS depressants: intensifies psychologic and physiologic manifestations of CNS depression, and greatly increases risk of death from respiratory depression
NSAIDs: significant gastric bleeding
Acetaminophen: poses risk of potentially fatal liver injury
Disulfiram: variety of potentially dangerous adverse effects
Antihypertensives: alcohol counteracts (since it raises BP when consumption is high); in moderation, may aid antihypertensives
What are the underlying causes of malnutrition in the chronic alcoholic?
poor diet
malabsorption of nutrients and vitamins
Malabsorption in the chronic alcoholic results from...
alcohol induced damage to the GI mucosa
Why does poor diet occur in the chronic acoholic?
Meet up to 50% of caloric needs w/ alcohol, and therefore consume subnormal amounts of foods w/ high nutritional value
B/c of their poor diet, alcoholics are in need of ___, ___ and ___.
fat; protein; vitamins
The ___ vitamins are especially needed in alcoholics.
B
T/F Alcoholics frequently require fluid replacement therapy and antibiotics.
T
What drugs are used in the rehab of alcoholism?
benzodiazepines
disulfiram
naltrexone
acamprosate
topiramate
In theory, any drug that has cross-dependence with alcohol (any CNS depressant) should be effective in facilitating withdrawal, however in actual practice, ___ are the drugs of choice.
benzodiazepines
T/F Benzodiazepines are most effective at facilitating alcohol withdrawal, but are not always safe.
F; are safe
How do benzodiazepines facilitate alcohol withdrawal?
Decrease withdrawal symptoms, stabilize vitals, prevent seizures and delirium tremens
What benzodiazepines are used most often to facilitate alcohol withdrawal?
chlordiazepoxide (Librium)
diazepam (Valium)
oxazepam (Serax)
lorazepam (Ativan)
T/F To facilitate alcohol withdrawa, benzodiazepines are only administered around around the clock on a fixed schedule.
F; PRN administration is just as effective and permits speedier withdrawal
What are some other drugs that may be combined with a benzodiazepine to improve alcohol withdrawal outcome?
carbamazepine (antiepileptic)
clonidine (alpha adrenergic agonist)
atenolol, propranolol (beta adrenergic blockers)
In the US, what 3 drugs are approved for maintaining alcohol abstinence?
disulfiram (Antabuse)
naltrexone (ReVia, Vivitrol)
acamprosate (Campral)
___ works by causeing an unpleasant rxn if alcohol is consumed; disrupts alcohol metabolism.
Disulfiram
___ blocks the pleasurable effects of alcohol and decreases craving.
Naltrexone
___ reduces some of the unpleasant feelings (tension, dysphoria, anxiety) brought on by alcohol abstinence.
Acamprosate
Of the 3 alcohol abstinence drugs, which appears to be the most effective?
Naltrexone
This alcohol abstinence drug has no applications outside the treatment of alcoholism.
Disulfiram
The constellation of effects caused by alcohol plus disulfiram is referred to as ___ syndrome, a potentially dangerous event. In its mild form manifestations include: n/v, flushing, palpitations, headache, sweating, thirst, chest pain, weakness, blurred vision, hypotension; the rxn can be brought on by as little as ___ mL of alcohol. Severe manifestations are life threatening and include: respiratory depression, cardiovascular collapse/dysrhythmias, MI, acute CHF, convulsions, death.
acetaldehyde; 7
T/F Alcoholics who lack the determination to stop drinking should not receive disulfiram.
T
What are some key points in disulfiram patient education?
Avoid ALL forms of alcohol
Effects will persist about 2 weeks after last dose
Carry identification indicating status
Naltrexone falls under what drug class?
Pure opioid antagonist
What happens if naltrexone is given to an opioid dependent individual?
Since it's an opioid antagonist, it precipitates withdrawal
T/F Unlike disulfiram, patients are not required to stop drinking before starting naltrexone.
F; like disulfiram, patients must stop
Which alcohol abstinence drug should be used only as part of a comprehensive management program that includes psychosocial support?
Acamprosate
T/F Combining acamprosate with naltrexone is more effective than acamprosate alone, but no better than naltrexone alone.
T
Which 2 alcohol abstinence drugs are oral, and which is oral and IM?
disulfiram, acamprosate
naltrexone
What are 2 drugs that are less commonly used for alcohol abstinence, and what are they currently approved for?
topiramate (Topamax); epilepsy and migraine
ondansetron (Zofran); n/v in cancer patients
___ is the principle methylxanthine employed in asthma.
Theophylline (Uniphyl)
What are the 2 most prominent actions of the methylxanthines?
CNS excitation
bronchodilation
This drug has a narrow therapeutic range, is usually administered by mouth, and is not administered by inhalation b/c it is not active by this route.
theophylline
In the past, this drug was a first line med for asthma and nearly all patients with chronic asthma took it. However, use of this drug has declined sharply. Why?
theophylline; we now have safer, more effective meds (inhaled glucocorticoids, inhaled beta2 agonists)
Benefits of theophylline derive primarily from ___.
bronchodilation
Oral theophylline is used for maintenance therapy of...
chronic stable asthma
Although (more/less) effective than beta2 agonists, theophylline has a (longer/shorter) duration of action.
less; longer
Becasue its effects are prolonged, theophylline may be most appropriate for patients who experience what?
nocturnal attacks
T/F Theophylline is metabolized in the liver, and rates of metabolism are fairly consistent.
F; rates of metabolism vary widely
What is the therapeutic drug level range for theophylline?
5-15 mcg/mL
___ is a methylxanthine with pharmacologic properties like those of theophylline, and should thus be avoided.
Caffeine
What drugs reduce theophylline levels?
phenobarbital
phenytoin
rifampin
What drugs increase theophylline levels?
cimetidine
fluoroquinolone antibiotics (ciprofloxacin)
___ (formerly available as Truphylline) is a theophylline salt that is considerably more soluble than theophylline itself.
Aminophylline
T/F Pharm properties of aminophylline and theophylline are identical.
T
Which route is most often used for aminophylline?
IV
Because of its relatively high solubility, ___ is the preferred from of theophylline for IV use.
aminophylline
The usual loading dose for aminophylline is ___; the maintenance therapeutice range is ___.
6mg/kg
10-20 mcg/mL
This asthma inhalation device is small, hand-held, pressurized and delivers a measured dose of drug with each actuation. Hand-lung coordinaiton is required. Only 10% of the dose reaches the lungs; about 80% impacts the oropharynx and is swallowed, and the remaining 10% is left in the device or exhaled.
MDI (metered dose inhaler)
This asthma inhalation device delivers drugs in the form of a dry, micronized powder directly to the lungs. No propellant is employed and they are breath activated (don't require lung-hand coordination). About 20% of dose reaches the lungs.
DPI (dry powder inhaler)
This asthma inhalation device is a small machine used to convert a drug solution into amist. Takes several minutes to deliver, but may be most effective.
Nebulizer
What are the 2 major classifications of asthma drugs?
anti-inflammatories
bronchodilators
What are 4 anti-inflammatory drug classifications for asthma?
glucocorticoids
leukotriene modifiers
cromolyn, nedocromil
omalizumab
What are 3 brochodilator drug classifications for asthma?
montelukast (Singulair)
zafirlukast (Accolate)
zileuton (Zyflo)
What are these?
anti-inflammatories, leukotriene modifiers
cromolyn (Intal)
nedocromil (Tilade)
What are these?
anti-inflammatories
omalizumab (Xolair)
What is this?
anti-inflammatory, IgE antagonist
albuterol (AccuNeb, ProAir, Proventil, Ventolin)
bitolterol (Tornalate)
levalbuterol (Xopenex)
pirbuterol (Maxair)
What are these?
bronchodilators, inhaled short acting beta2 adrenergic agonists (SABAs)
arformoterol (Brovana)
formoterol (Foradil, Perforomist)
salmeterol (Serevent)
What are these?
bronchodilators, inhaled long acting beta2 adrenergic agonists (LABAs)
albuterol (VoSpire)
terbutaline (Brethine)
What are these?
bronchodilators, oral beta2 adrenergic agonists
theophylline (Theo24, Theochron, Uniphyl, Elixophyllin)
What is this?
bronchodilator, methylxanthine
ipratropium (Atrovent)
tiotropium (Spiriva)
What are these?
bronchodilators, anticholinergics
This med class is the foundation of asthma therapy, is taken daily for long-term control, and addresses the underlying disease process (inflammation).
anti-inflammatories
What are the principle prophylactic anti-inflammatories used for asthma?
Glucocorticoids
These are 1st line drugs used for asthma, are considered very safe, are not administered PRN, and have adverse effects of oropharyngeal candidiasis and dysphonia.
Inhaled glucocorticoids
When are oral glucocorticoids indicated for asthma?
When severe; only when symptoms can't be controlled w/ safer meds (inhaled glucocorticoids, beta2s)
Toxicity of oral glucocorticoids (increases/decreases/stays the same) with duration of use.
increases
Although alone these are less effective than glucocorticoids, they are very effective when combined with glucocorticoids.
Leukotriene modifiers
Although used for prophylaxis of chronic asthma, this class of anti-inflammatories should not be used as 1st line therapy.
Leukotriene modifiers
This class of anti-inflammatories for asthma is only administered orally.
Leukotriene modifiers
This is the safest of all antiasthma meds; used for prophylaxis of chronic asthma, EIB, allergic rhinitis; must be administered on a fixed schedule.
Cromolyn
This anti-inflammatory asthma med is no longer available in the US.
Nedocromil
Cromolyn is AKA a ___
mast cell stabilizer
This anti-inflammatory med is a 2nd line agent indicated only for patients whose asthma is caused by specific allergen, and when preferred options have failed. It's very expensive, viscous, and is only administered subQ. It's long-term safety is unknown.
Omalizumab
This major class of asthma meds provides symptomatic relief but does not alter the underlying disease process (inflammation).
Bronchodilators
T/F Unless attacks are mild/infrequent, patients taking a bronchodilator should also be taking inhaled glucocorticoids for long-term suppression of inflammation.
T
There is evidence that this class of bronchodilators can increase risk of asthma related death when used alone.
Beta2 adrenergic agonists
Beta2 adrenergic agonists are most effective for...
relieving acute bronchospasm and preventing EIB
What are the 3 subclasses of beta2 adrenergic agonists?
SABAs
LABAs
oral
These beta2 adrenergic agonists are used to abort an ongoing attack, are adnministered PRN or before exercise.
SABAs
These beta2 adrenergic agonists are used to abort an ongoing attack and for prolonged prophylaxis (though not 1st choice), are administered on a fixed schedule, and should never be used alone.
LABAs
These beta2 adrenergic agonists are used for long-term control of asthma (though not 1st choice) and should never be used alone.
Oral
This class of bronchodilators is only approved for COPD, but is used for asthma. They block muscarinic receptors in bronchi, and are only administered by inhalation. Contraindicated in those with peanut allergy.
Anticholinergics
Combination asthma meds combine what two classes of drugs? What are 2 examples?
Sulfonamides: n/v/d, allergy, decrease in white blood cell and platelet counts, sensitivity to sunlight, possibly increased tendency to bleed if used with warfarin
Tetracyclines: GI upset, sensitivity to sunlight, staining of teeth in the fetus if used late in pregnancy or in children under 8 years of age
Without this - consisting of immune system and phagocytic cells - successful antimicrobial therapy would be rare.
Host defenses
T/F In most cases, the drugs we use do not cure infection alone. Rather, they work in concert with host defense systems to subdue infection.
T
When treating immunocompromised, the only hope of treating infection lies w/ drugs that are rapidly ___, and even those may prove inadequate.
bactericidal
What class does gentamycin belong to?
Aminoglycosides
Gentamicin treats serious infections caused by what kind of bacteria?
Gran-negative bacilli (Pseudomonas aeruginosa, E. coli)
In hospitals where resistance isn't a problem, ___ is often the preferred aminoglycoside for use agains E. coli. Why?
gentamycin
Cheaper
Gentamicin is cross-resistant to ___.
tobramycin
For infections that are resistant to gentamicin and tobramycin, ___ is usually effective.
amikacin
What med can be combined with vancomycin, a cephalosporin, or a peniccilin to treat serious infections caused by certain gram-positive cocci (Enterococcus, streptococci, Staph)?
Gentamycin
Like all other aminoglycosides, gentamicin is toxic to what 2 things?
kidney
ear
Gentamicin is inactivated by ___ and should not be mixed with these drugs in the same IV.
penicillins
Drug or chemical damage to the inner ear.
Ototoxicity
T/F Only some aminoglycosides can accumulate w/in the inner ear, causing cellular injury that can impair both hearing and balance.
F; all
How do aminoglycosides cause impairment of hearing?
By damaging sensory hair cells in the cochlea
How do aminoglycosides cause disruption of balance?
By damaging sensory hair cells of the vestibular apparatus
The risk of ototoxicity is r/t primarily excessive ___ levels of drug.
tough
Is cellular injury from ototoxicity d/t prolonged exposure or brief exposure at high levels?
Prolonged exposure
In addition to high trough levels, the risk of ototoxicity is increased by wht 3 things?
renal impairment
concurrent use of ethacrynic acid
aminoglycosides in excessive doses or form more than 10 days
What is the first sign of impending cochlear damage?
High-pitched tinnitus
What's the first sign of impending vestibular damage?
Headache
What are later signs of damage from ototoxicity?
nausea
unsteadiness
dizziness
vertigo
Ototoxicity is largely (reversible/irreversible).
irreversible
What's the most serious adverse effect of vancomycin?
Ototoxicity
Renin Angiotensin Aldosterone System
What 4 drug classes are associated w/ RAAS?
ACE (angiotensin converting enzyme) inhibitors
ARBs (angiotensin II receptor blockers)
DRIs (direct renin inhibitors)
aldosterone antagonists
For many of the RAAS related meds, aldosterone release is inhibited, which may result in ___, especially when combined with potassium supplements, salt substitutes, potassium-sparing diuretics, or other RAAS meds. Why?
hyperkalemia
With inhibition of aldosterone, instead of reabsorbing sodium/water and excreting potassium, the body reabsorbs potassium and excretes sodium/water.
What is the major vasoconstricort of the RAAS, and how does volume increase to increase BP?
angiotensin II
With stimulated production of aldosterone, kidneys then retain sodium/water and excrete potassium, increasing fluid volume.
What meds cause vasodilation and a decrease in afterload? How do they work?
All of these drugs dilate resistance vessels (arterioles), causing a decrease in cardiac afterload (the force the heart works against to pump blood). By decreasing afterload, arteriolar dilators reduce cardiac work while causeing cardiac output and tissue perfusion to increase.
These block beta adrenergic receptors.
Beta adrenergic antagonists (beta blockers)
What makes the difference between a beta blocker being therapeutic vs nontherapeutic?
Selectivity...therapeutic effects result from blockade of beta1 receptors of the heart only; nontherapeutic effects result from blockade of both beta1 and beta2 receptors
What are the 3 major consequences of blocking beta1 receptors in the heart?
reduced HR
reduced force of contraction
reduced velocity of impulse conduction through the AV node
What are beta blockers used for?
angina pectoris
HTN
cardiac dysrhythmias
MI
HF
hyperthyroidism
migraine
stage fright
pheochromocytoma
glaucoma
What are the 2 "c's" associated with beta blockers?
conduction
contraction
What's the most important factor of success of thrombolytic drugs?
Time b/w onset of symptoms and delivery of the med
How long do you have to administer a thrombolytic med for it to be effective following a stroke?
3 hours
What's the chief use for low-molecular wt heparins?
prevention and treatment of DVT
The most significant adverse effects of alpha adrenergic antagonists result from blockade of (alpha1/alpha2) receptors.
alpha1
What are the main side effects of pts on alpha blockers?
orthostatic hypotension
reflex tachycardia
nasal congestion
inhibition of ejaculation
sodium retention, increased fluid volume
What are the main side effects of pts on beta blockers?
Beta1: bradycardi, reduced CO, precipitation of HF, AV heart block, rebound cardiac excitation
Beta2: bronchoconstriction, inhibition of glycogenolysis
What med would you give if the pt's fluid volume increased after giving an alpha blocker?
Diuretic
Why is heparin not administered orally? What is used instead?
It's too large and too polar to permit intestinal absorption
