Exam 1 Pharmacotherapeutics Flashcards
Lecture 4
Pharmacotherapy relates to the use of drugs in the _____ and ____ of disease
Prevention and treatment
Pharmacotherapeutics is the art and science of:
Applying drug-related didactic knowledge (pharmacodynamics and pharmacokinetics) and making therapeutic decision that are the most likely to benefit a specific patient
True or false: drug response varies between individuals
True
Even the most selective agents evoke a spectrum of reactions rather than a single pharmacologic outcome. Why?
- target receptor is located in other organs and tissues
- Drug may be selective but not specific so may have effects at other receptors (high doses)
- Nonselective effects may cause GI upset
- A therapeutic dose for one person may ineffective or toxic to another
What factors influence drug effects?
- Patient factors
- Drug factors
Examples of patient factors
- Body weight and composition
- Age
- Genetic influences
- Sex
- Pregnancy
- Environmental factors
- Diet
- Physiologic variables
- Pathologic factors
Examples of pathologic factors
- Hepatic dysfunction
- Renal disease
Examples of drug factors
- Variables in drug administration
- Drug tolerance
- Drug interactions
- Extension effects
- Side effects
- Idiosyncratic reactions
- Drug allergy
- Drug poisoning
Vd is a function of body mass. Extremes in patient size may result in:
Significant differences in plasma concentration when given a standard adult dose
Two heavy patients, one obese and one muscular, may react ____ if given the standard dose
Differently
Adipose tissue contributes ____ to body water. So an obese person may be _____ but may also show resistance to ____
Little; More susceptible to a dose based on weight (mg drug per kg of body weight); Lipophilic agents
For children, adjustments based on ____ are helpful
Age and weight
Children often require ____ mg/kg weight doses
Larger (attributable to increased rate of elimination)
Geriatric patients are frequently ____ to drugs and have ____ metabolism and excretion
Hyperreactive; decreased
Neonates can experience drug accumulation due to:
Immature livers and kidneys
____ experience greater effects from drugs entering the CNS due to immature BBB
Neonates
Children may experience abnormal growth effects due to:
Staining of teeth
Children may experience abnormal growth effects due to:
Hormonal effects
Children may have greater sensitivity to some drugs due to:
Higher metabolic rate
Geriatric patients may be hyperreactive to drugs because of:
- reduced elimination
- existing pathology
- drug-drug interactions
For some drugs, information may be lacking due to:
Exclusion of female subjects from drug studies
Dosage adjustments may be necessary for women because:
They tend to be smaller and have a higher % body fat
For women, ____ may have possible drug interactions
Systemic contraceptives
There are decreased levels of ____ in pregnancy
Albumin
Why is renal excretion increased in pregnant women?
Elevated cardiac output and glomerular filtration
During pregnancy, what is the Pregnane X receptor?
Nuclear receptor activated by elevated estrogen and progesterone levels that increases expression of CYP3A4 (more drugs metabolized during pregnancy)
True or false: many drugs are proven to be safe for fetus
False - few if any (best to avoid medications when possible)
There is a ____ of embryonic and fetal development. Defects vary with ____
Sequential pattern; Action of drug and timing
Between fertilization to 20 days, fetus either ______ to drug insult
Survives or succumbs
Teratogenic malformations are possible from ____ to ____
21 days (somites appear) to end of first trimester (differentiation/organogenesis)
Which drugs have toxic effects during pregnancy?
- ACE inhibitors
- Cortisone
- Diazepam
- Local anesthetics
- Opioid analgesics
What toxic effect do ACE inhibitors have on fetus?
Renal toxicity
What toxic effect does cortisone have on fetus?
Cleft palate
What toxic effect does diazepam have on fetus?
- Cleft palate
- Respiratory depression
What toxic effect does local anesthetic have on fetus?
- Bradycardia
- Respiratory depression
What toxic effect does opioid analgesics have on fetus?
- Respiratory depression
- Death
True or false: there is clear data regarding the use of local anesthetics during pregnancy
False; however, even with a small risk, only urgent or emergency treatment should be provided during the 1st trimester. Regular dental care should not be postposed once patient is in 2nd trimester
What environmental factors may influence response to drugs?
Temperature, sunlight, altitude
What can happen to children taking atropine on a warm day?
Antimuscarinic, decreases saliva and sweating that can cause hyperthermia
Why would sunlight influence response to drugs?
Causes photosensitivity - skin reactions to sulfonamides/ sulfa drugs (act as photosensitizers that absorb and transfer energy)
Nitrous oxide is more or less effective in high altitudes?
Less (reduction in partial pressure of nitrous oxide)
Diet: use of insulin must be ____ to dietary intake to avoid hypoglycemia/hyperglycemia
Carefully matched
Diet: grapefruit juice contains substances that inhibit ____
CYP3A enzymes
Examples of physiologic variables
- Salt and water balance
- Exercise
- Sleep
- Body temperature
- Blood pressure
- Gastric, urinary, plasma pH
Infected tissues tend to be more ____
Acidic
Pathologic factors: altered patient reactivity most commonly involve?
Organs of absorption, distribution, metabolism, and excretion
Hepatic dysfunction can ____ the metabolism and biliary excretion of drugs
Dramatically reduce
Characteristics of hepatic dysfunction
- Reduced blood flow slows delivery of drugs to the liver
- Reduced transport can inhibit the uptake of drugs and export of metabolites
- Altered CYP450 expression
In renal disease, plasma half-times of drugs eliminated in the urine are ____ by renal failure
Greatly prolonged
True or false: even if a drug is inactivated by the liver, inadequate excretion of metabolites may increase incidence of side effects
True
Renal status is measured by:
Endogenous creatinine clearance (indicator of GFR)
A 50% decrease in creatinine clearance indicates:
2x increase in half-time of a drug that is removed solely by glomerular filtration
What should you do to avoid excessive drug accumulation in patients with renal disease?
- Lengthen the dosage interval in accordance with degree of impaired elimination
- Or, reduce dose
Memorize table for dosage adjustments in renal failure
You can minimize significance of side effects if an agent is given before:
Sleep (ex. nausea associated with opioids, sedative properties of antihistamines)
Agent producing CNS stimulation is best given when?
During the day
Drugs dosed with meals is to limit:
GI upset
Duration of therapy should be limited when capable of producing:
Dependence or have potential for cumulative effects (chemotherapy)
____ is a state of decreased responsiveness that develops on repeated or continuous exposure to the drug
Drug tolerance
Two major categories of drug tolerance
- Pharmacokinetic (effective drug conc is diminished)
- Pharmacodynamic (reaction to a dose of a drug is reduced, receptor downregulation = cellular tolerance)
Pharmacokinetic tolerance involves:
Induction of enzymes
Pharmacodynamic tolerance involves:
Cell tolerance due to receptor changes and/or other cell changes
Immune tolerance involves:
Antibodies bind to drug and inactivate
Cellular tolerance involves:
Therapy results in changes in cells of a tissue
Learned tolerance involves:
Individual uses coping skills to compensate for drug effects
Drug interactions occur when:
The effect of one drug may be increased or decreased when administered with another drug
Minimum number of medicines taken daily by 30% of patients aged 75 and older
10
Adverse drug reactions: serious outcomes include?
Hospitalization, disability, congenital anomaly, life-threatening and/or other serious outcome
Extension effects: prescribed dosages generally provide an intensity of effect that is ____
Submaximal (often the maximum effect is dangerous)
Any adverse effect arising from an “extension” of the therapeutic effect is ____
Dose related and predictable (adjust the dose to avoid the effect without loss of therapeutic benefit)
Furosemide is used for ____. The therapeutic effect is ____, but the toxic extension is _____
Edema and hypertension; diuresis; hypovolemia and hypotension
Heparin is used for ____. The therapeutic effect is ____, but the toxic extension is _____
Thromboembolic disorders; inhibition of coagulation; spontaneous bleeding
Insulin is used for ____. The therapeutic effect is ____, but the toxic extension is _____
Diabetes mellitus; reduction of blood glucose concentration; hypoglycemia
____ are predictable, dose-dependent reactions unrelated to therapy but occur at therapeutic doses
Side effects
Side effect of diphenhydramine
Xerostomia
Side effect of phenytoin
Gingival enlargement
Side effect of amoxicillin
Dermatitis
Side effect of lidocaine
Convulsions
Side effect of erythromycin
Nausea, vomiting
Side effect of morphine
Constipation
Some side effects are due to the ____ tissue-receptor interaction, but in ____
Same; different tissue or organ
(example is atropine which results in xerostomia as a side effect - but can also be used to control excessive salivation during dental procedures)
Amphetamine original use and subsequent use
CNS stimulant; ADHD
Diphenhydramine original use and subsequent use
Antihistamine; sedative
Lidocaine original use and subsequent use
Local anesthetic; antiarrhythmic
Methadone original use and subsequent use
Analgesic; heroin substitute
Metronidazole original use and subsequent use
Antiparasitic; antibacterial
What is an idiosyncratic reaction?
A genetically determined abnormal response to a drug, unique or specific to the individual
Genetic trait for idiosyncratic reaction is often ____ in the absence of the drug. Often appears as ____
silent; abnormal drug sensitivity
Extension effects, side effects, and allergies are often falsely described as:
Idiosyncratic
Example of idiosyncratic reaction
Genetic abnormality of low plasma cholinesterase + procaine or other ester local anesthetics –> local anesthetic toxicity
Drug allergy is of ____ origin
Immunologic
Distinguishing characteristics of drug allergy
- Prior exposure to drug or related compound
- Severity of response is dose independent
- Nature of the effect is not a function of the drug but is of the immune mechanism involved
- Unpredictable, may follow multiple doses without consequence
Patients complaining or local anesthetic “allergy” are most often experiencing:
Pain, anxiety, or tachycardia - not a true allergic reaction
American Association of Poison Control Centers
- In 2019, more than ____ human poison exposures in US
- Most poisonings were ____
- 13% of all poison exposures were believed to be ____
- 2,000,000
- children under 5 yers (43%)
- suicide attempts
