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62 Cards in this Set

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An ADR at normal doses may include all except: 1) Require treatment. 2) require decreased dosage or cessation of Rx. 3) suggest that the patient should avoid future Rx. 4) all are correct
all are correct
The FDA's definition of an ADR icludes all of the following except: 1) Overdose, accidental or intentional. 2) drug abuse. 3) withdrawl. 4) failure of expected resonse. 5) predictable consequences
5. Predictable consequences
According to Park and associates, which is true of type A ADR? Predictable or Unpredictable?
predictable
Are the following listed below type A or type B ADR? Idiosyncratic, hypersensitity/immunologic, pseudo-allergic/non-immunologic, intolerance
type B: Idiosyncratic, hypersensitity/immunologic, pseudo-allergic/non-immunologic, intolerance
Which ADR type includes carcinogenic and teratogenic effects?
Type D ADR include: carcinogenic and teratogenic effects, e.g., thalidimide
None
Which type of ADR includes overdose, side effects (i.e., sedation from H1), secondary effects, and drug-interactions?
Type A ADR includes: overdose, side effects (i.e., sedation from H1), secondary effects, and drug-interactions…
Which type of ADR is seen in long term therapy and is usually well known and predictable?
Type C ADR ADR are seen in long term therapy and are usually well known and predictable… e.g., withdrawl after chronic use of CNS depressants, hearing loss
Which age group see the most ADRs?
neonates
Give 4 reasons for increased likelihood to ADR in neonates.
Neonate ADR: 1) Greater proportion of body water compared to body fat --> leads to greater Vd for water soluble and decreased Vd for lipid solubility. 2) immature blood brain barrier --> greater toxicity for lipid soluble drugs in the brain. 3) inactivating P450s and conjugating enzymes are below adult levels. 4) skin is more permeable in neonates
Why is it that the fetus is less vulnerable to drug toxicity than the neonate?
the placenta offer a degree of protection
Cite 5 reasons why it is that ADR are seen more in the elderly.
5 reasons why it is that ADR are seen more in the elderly: 1) decreased hepatic and renal function 2) body fat increase and body water decreases - Vd for water soluble drugs increases, while the Vd for lipid soluble drug decreases. 3) poor compliance due to confusion. 4) elderly take more drugs - and these drugs often have a narrow therapeutic window. 5) many elderly don't like taking drugs
Cite 5 reasons why it is that ADR are seen more often in women than men.
5 reasons why it is that ADR are seen more often in women than men: 1) Receptor sensitivity and drug dispostion associated with menarche. 2) pregnancy. 3) delivery. 4) lactation. 5) menopause
Receptors, ion channels, enzymes, and immune system are associated with which of the following genetic polymorphisms? Pharmacokinetic or pharmacodynamic
Receptors, ion channels, enzymes, and immune system are associated with PHARMACODYNAMIC
Name 3 things that liver disease can do to effect drug response, both therapeutic and toxic.
1) Hepatitis or cirrhosis livers have impaired metabolizing enzyme production --> decrease metabolism and clearance. 2) decreased liver blood flow. 3) decrease plasma protein synthesis
Name 3 things that renal disease can do to effect drug response, both therapeutic and toxic.
Recalculation of dose: 1) decreased GFR will increase duration. 2) plasma protein binding is altered in uremia. 3) Dialysis tends to remove drugs in plasma, but not intracellular drugs.
Name 5 things that cardiac disease can do to effect drug response, both therapeutic and toxic.
Cardiac disease (especially CHF) effects on drugs: 1) reduces blood flow to organs of elimination. 2) reduces blood flow to target organs. 3) slower and prolonged drug response. 4) diminished BF to GI can cause reduced absorption. 5) increased risk of toxicity with poor perfusion. 6) diminished Vd
What is a likely cause of many idiosyncratic ADRs?
allergic/hypersensitivity - polymorphism is often seen with respect to idiosyncratic ADR
What are the metabolic and toxic consequences of a drug's suppression of a metabolism enzyme (CYP) on another drug?
impaired metabolism --> increased toxicity due to overdoses
None
Cimetidine is an H2 antagonist, which inhibits a P450 enzyme, which drug is affected by this and what is the result?
WARFARIN: Cimetidine inhibits P450 2C9, which normally metabolizes WARFARIN --> the result is an effective overdose
Ketoconazole (an anti-fungal) inhibits P450 3A4, which drug is affected by this and what is the result?
CYCLOSPORIN: Ketoconazole inhibits P450 3A4, wihc normally metabolizes CYCLOSPORIN --> the result is an effective overdose
With respect to drug metabolites, what does glutathione do?
glutathione is a nucleophile, which can react with electrophilic drug metabolites.
What is the mechanism of the ADR associated with acetominophen and EtOH? What is the endogenous detoxifying agent of this ADR?
1) EtOH up regulates P450 2E1 --> which increase the alternate pathway of acetominophen to a toxic electrophilic intermediate. 2) Glutathione (a nucleophile) detoxifies the metabolite
What is MPTP and what does it cause?
MPTP is a product formed in the illegal synthesis of meperidine. MPTP selectively destroys dopamine centers in the brain
How can a haptene form? And what does it cause?
A haptene can be formed by the conjugation a drug metabolite and a carrier protein --> the haptene can elicit antibody against tissues.
Halothane can become a haptene (converted by P450-2E1), which organ is targeted by the antibodies formed by this halothane haptene?
Liver -centrolobular necrosis
Which population is at risk for EtOH conversion (by P450-2E1) to a haptene which directs antibodies to the liver --> resulting in cirrhosis?
Mexican-Americans… many also have defective alcohol and aldehyde dehydrogenases
What is the distribution of extensive metabolizers and poor metabolizers?
50/50
In isoniazid, which is an antitubercular drug, which patient population is susceptible to neuropathy, rapid or slow metabolizers?
slow
Name the enzyme that metabolizes codeine to morphine.
Cyp2D6
Who would receive little or no pain relief from codeine, poor metabolizers or extensive metabolizers?
poor metabolizers
Who should get a higher dose of nortriptyline (an antidepressant), poor metabolizers or extensive metabolizers? What does this indicate?
extensive metabolizers… it means that it is the pure drug (not the metabolite), confers the antidepressant benefits,
What two things does organ-specific toxicity imply?
1. Selective distribution of the drug… 2. Organ-specific mechanism for toxic activation of the drug
What two things are the organ recovery from toxicity dependent upon?
1. Reserve capacity… 2. Regenerative capacity
Which of the following is not true of ototoxicity: 1) AMINOGLYCOSIDES cause auditory and vestibular damage. 2) the t-1/2 of drugs in the perilymph and endo lymph of the inner ear is greater than the t-1/2 in the plasma. 3) auditory and vestibular function impairment is not reversible. 4) effect on the inner ear is dose dependent, so careful monitoring of the plasma levels is important.
In AMINOGLYCOSIDES, auditory and vestibular function impairment IS REVERSIBLE!!
None
Which of the following is not true of oculotoxicity: 1) most ADRs are not reversible. 2) Toxic responses due to drug accumulation may persist after drug is withdrawn. 3) digitalis can cause yellow/green vision.
all are true
What is the detrimental effect of P450 in the kidneys?
they convert drugs into toxic intermediates
What organ is does amphotericinB adversely affect?
Kidneys
What kidney physiology places the kidneys at increased risk for drug toxicity?
the toxic intermediate is concentrated along the tubules… (drugs are transported in mostly along the proximal tubules)
T/F aminoglycosides only cause ototoxicity.
false… nephrotox too
T/F drug induced aplasatidc anemia is predictable but rarely fatal.
False… it's unpredictable, idiosyncratic and often fatal
Name a drug that effects the myocardium (reversible EKG change, arrythmias, disturbances in conduction and CHF).
Doxorubicin
Which drug is limited by its potential damage to the lungs?
Bleomycin
What is the benefit of pharmacodynamics in terms of drug interactions?
drugs doses for drugs that work on same system by two different mechanism can be reduced and thus decrease toxicity
How does warfarin work?
Warfarin inhibits the synthesis of vit-k dependent plasma clotting factors synthesized in the liver
How does aspirin work in terms of reduced clotting?
Aspirin inhibits platelet aggregation (TXA2) thrombus formation.
T/F the use of aspirin and warfarin should be avoided.
false, it can cause bleeding, but it can also be a benefit for reduced risk of ischemic stroke in patients with severe atherosclerosis
T/F aspirin and warfarin work interact by pharmacodynamic interaction
true, but they also interact pharmacokinetically, aspirin displaces warfarin from plasma proteins
What word is defined by this statement: an interaction between drugs whenever one drug affects the movement of another drug
pharmacokinetic
None
Match the following: a) diazepam… b) amphoteracinB… c) PPD… 1) stick to the glass of a vial… 2) precipitate in neutral solution… 3) must be administered in glucose (precipitates)
a) diazepam = 2) precipitate in neutral solution… b) amphoteracinB =3) must be administered in glucose (precipitates)… c) PPD = 1) stick to the glass of a vial
What does allopurinol interact with? And how?
methotrexate… Allopurinol inhibits xanthine oxidase, which is needed to metabolize methotrexate
T/F MAO inhibitors block the metabolism of chatacholamines, tyramine, amphetamines, methyl dopa
TRUE
What is the activity of of Grapefruit juice?
Grapefruit it inhibits CYP3A4, which alters first pass clearance of drugs like: cyclosporine, propranolol, beta blockers and Ca blockers
What drug displaces digoxin, resulting in a possible overdose and ADR?
Quinidine, which dislaces digoxin from muscle
What type of effect does using cholestyramine in conjunction with lipitor or digoxin?
this is an example of an absorption interaction, where cholestyramine (which is a binding resin used for eliminating bile/lipids) inhibits the absorption of other drugs (lipitor and digoxin)
What type of effect drinking milk or eating iron supplements in conjunction with tetracycline?
this is an example of an absorption interaction, where calcium or iron forms a chelate with tetrayline
Give three examples of distribution
What is the problem of giving lidocaine to a CHF patient?
reduced blood flow causes the blood flow to be distributed centrally, causing psychosis.
Besides lidocaine and CHF, what is another example of a distributive interaction concerning blood flow changes?
Beta blocker and liver perfusion
How do tricyclic antidepressants alter hypertensive treatment effects?
tryicyclic antidepressants inhibit the membrane amine-reuptake pump that moves neurotransmitters and antihypertensive drugs into cell storage sites
What effect do phenobarbital, other barbiturates and other lipid soluble drugs have on Warfarin?
they accelerate the metabolism of warfarin, so if a person is taking a barbiturate and warfarin, and they stop taking the barbiturate, they will be effectively over dosed with warfarin
what effect does fluxoxetine (prozac) have on tricyclic antidepressants?
inhibits its metabolism
How could you increase the half-life of penicillin or methotrexate?
give probenecid or salicylates, which compete for tubulo transport with other organic acids --> decreasing clearance