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98 Cards in this Set
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Define Tolerance
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response diminishes with time
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What is Pharmacokinetic tolerance due to?
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induction of drug metabolizing enzymes
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Alternate names for Pharmacokinetic tolerance
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Metabolic tolerance
Drug disposition tolerance |
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Give an example of Pharmacokinetic Tolerance
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Warfarin, an oral anticoagulant, dose needs to be increased in a patient taking barbiturates or Phenytoin
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Explain Pharmacodynamic tolerance
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-develops at the cellular level
-is due to changes in receptor numbers or function |
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List the 2 mechanisms of Pharmacodynamic tolerance
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Desensitization
Down-regulation |
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Explain Desensitization
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process occurs rapidly when continuous exposure to an agonist results in 1) conversion of a channel to an altered state that remains closed or 2) when a receptor-coupling element is phosphorylated to an inactive form
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What cause receptor down-regulation
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Agonists
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Explain Down-regulation
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process of ligand-induced endocytosis and degradation of receptor, caused by agonists when administered at high doses for a prolonged period
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Give 3 examples of Pharmacodynamic Tolerance
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1. continuous exposure to beta-adrenergic agonists,such as occurs in treatment of asthma with ALBUTEROL, results in a decreased responsiveness to the drug
2. tolerance to the analgesic effects of MORPHINE upon continued use 3. decreased sedation from continuous treatment with a Benzodiazepine such as DIAZEPAM |
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Explain Physiological Antagonism
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when 2 agents have opposing physiological effects
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Give an example of Physiological antagonism
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Histamine causes Vasodilation while NE causes Vasoconstriction -> when given together they counteract eachother
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Explain Competitive Antagonism
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when a receptor antagonist is administered with an agonist
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Competitive Antagonism: what does Naloxone block the effect of?
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Morphine
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Competitive Antagonism: what does Atropine block the effect of?
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ACh at muscarinic receptor
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Competitive Antagonism: what does Propranolol block the effect of?
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Isoproterenol at beta-adrenergic receptors
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Describe how Supersensitivity or Hyperactivity occurs
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due to an increase in the number of receptors
-during absence of ligand -prolonged presence of antagonist |
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Give an example of Chemically induced supersensitivity
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after prolonged treatment with Beta-blockers some individuals become supersensitive to endogenous release of Catecholamines (Epi, NE, Dopa)
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Explain Denervation induced Supersensitivity
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occurs at POST-synaptic receptors when Pre-synaptic nerve is surgically destroyed or lesioned
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What causes receptor up-regulation?
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Antagonists
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Pharmacogenetic cause of increased activity of drugs
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deficiency in degrading enzymes
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Patients with abnormal serum cholinesterase have increased sensitivity to what drug?
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Succinylcholine = muscle relaxant
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Individuals with Glucose-6-phosphate Dehydrogenase deficiency develop Acute Hemolytic Anemia after given what drug?
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Primaquine
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Explain how competition for binding sites can result in increased activity of a drug
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drugs may displace one another from plasma albumin binding sites, enhancing response to one or both agents
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T or F: If a drug is displaced from a plasma protein-binding site, response is INTENSIFIED and duration of action is PROLONGED
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False: duration is shortened
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Explain how Physiological Synergism can increase activitiy of drugs
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when 2 drugs produce the same or similar effects through different receptors or mechanisms
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Explain an additive effect
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when two drugs are given and their effect is like adding their individual effects together
5+5 = 10 |
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Classic Example of 2 drugs that act synergistically
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Diazepam + Ethanol produce severe, prolonged CNS depression
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Explain Synergistic effect
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When two drugs are added together and their effects together are greater than when adding their effects alone
5 + 5 = 15 |
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Explain Potentiation
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one drug might not have an effect alone but in combo with other drugs it
has an effect 0+5 = 20 |
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Definition: repeated administration produces altered or adaptive physiological state and physiological disturbances (withdrawal, abstinence syndrome) occur if drug is not present
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Physical Dependence
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Drugs that result in dependence (4)
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1. Alcohol
2. Barbiturates 3. Narcotic analgesics 4. Nicotine |
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Definition: Compulsive drug-seeking behavior; individual uses drug repetitively for personal satisfaction
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Psychological dependence
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Definition: cluster of symptoms indicating that the individual continues substance use despite significant substance-related problems
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Substance dependence (addiction)
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Overextension of Pharmacological response: Atropine induces _______
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Dry mouth
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Overextension of Pharmacological response: Propranolol induced _______
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Heart Block
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Overextension of Pharmacological response: Diazepam-induced _______
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Drowsiness
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Organ-directed toxicities: Aspirin-induced _______
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GI toxicity
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Organ-directed toxicities: Aminoglycoside-induced ______
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Renal toxicity
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Organ-directed toxicities: Acetaminophen-induced ______
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Hepatotoxicity
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Organ-directed toxicities: Doxorubicin-induced ______
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Cardiac toxicity
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Direct fetal toxic effects: Sulfonamide-induced ______
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Kernicterus = damage to the brain centers of infants caused by jaundice
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Direct fetal toxic effects: Chloramphenicol-induced ________
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Gray baby syndrome
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Direct fetal toxic effects: Tetracycline-induced _______
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-teeth discoloration
-Retardation of bone growth |
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When are Teratogenic effects most pronounced?
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during organogenesis: day 20 - end of 1st trimester
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List 8 human teratogens
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1. Thalidomide
2. Antifolates 3. Phenytoin 4. Warfarin 5. Isotretinoin 6. Lithium 7. Valproic acid 8. Fetal alcohol syndrome |
VALerie is an ANTIFOLATE from THAILAND. Her country is at WAR with the PHENYTOIN's. They give their babies LITHIUM AND ISOTRETINOIN which yields FETAL ALCOHOL SYNDROME
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Definition: Abnormal response resulting from previous sensitizing exposure activating immunologic mechanism
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Drug allergies (hypersensitivity)
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T or F: in drug allergies, altered reaction occurs only in a fraction of the population
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T
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T or F: In drug allergies the dose-response is unusual: a large amount of an otherwise safe drug elicits severe reaction
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False: minute amounts elicit a severe reaction
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T or F: In drug allergies the manifestations of reaction are similar to the pharmacological and toxicological effects of the drug
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False: they are different
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T or F: Drug allergies
-Primary sensitization period occurs before the individual experiences the response |
True
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T or F: Drug allergies
-Most drug by themself are immunogenic |
False: Being small molecules, most drugs by themselves are not immunogenic; they bind covalently to self-macromolecule or alter structure of self-macromolecule to become immunogenic
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Fill in the table
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-
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Explain the Type I Hypersensitivity reaction
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-IgE molecules bind to blood basophils and tissue mast cells via Fc receptors for antibody
-When offending drug introduced into body, immediately binds to IgE bound to sensitized cells, resulting in release of mediators (histamine, leukotrienes, prostaglandins) -Mediators initiate skin and smooth muscle responses, cause tissue injury and provoke inflammatory response -Include anaphylaxis, urticaria and angioedema |
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Explain Type II Hypersensitivity reactions
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mediated by IgM or IgG binding to cells or tissues, resulting in the activation of complement and lysis of the cell
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Explain Type III Hypersensitivity reactions
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mediated by Immune complexes
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What are symptoms of Immune-complex induced serum sickness?
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-Urticarial skin eruptions
-Arthralgia -Lymphadenopathy -Fever |
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What is the name of the severe form of immune vasculitis caused by drugs?
What drug can induce it? |
Stevens-Johnson syndrome
Sulfonamides |
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Explain Type IV Hypersensitivity reaction
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cell-mediated or delayed hypersensitivity, often occurs when drugs are applied topically
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Type II reactions: Penicillin-induced _________
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hemolytic anemia
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Type II reactions: Methyldopa-induced __________
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autoimmune hemolytic anemia
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Type II reactions: Quinidine-induced _______
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Thrombocytopenia
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Type II reactions: Sulfonamide-induced ________
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Granulocytopenia
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5 drugs that can induce Type III Immune Vasculitis
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Penicillin
Anticonvulsants Iodides Sulfonamides Thiouracils **PAIST** |
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Definition: Abnormal response not immunologically mediated; often caused by genetic abnormalities in enzymes or receptors; referred to as pharmacogenetic disorders.
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Drug Idiosyncrasies
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Classical idiosyncracy: patients with abnormal serum Cholinesterase develop _____ when given normal doses of succinylcholine
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Apnea = temporary suspension in breathing
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"Slow" acetylators of Isoniazid are homozygous autosomal recessive for this gene's protein
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N-acetyltransferase
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What are "slow" acetylators of isoniazid more prone to?
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isoniazid-induced Vitamin B6 deficiency which may produce:
-anemia -various neuropathies **Supplement with B6 when treating TB with Isoniazid |
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Hemolytic anemia in patients with G-6-P Dehydrogenase can be induced by these 3 drugs
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1. Primaquine
2. Sulfonamides 3. Nitrofurantoin |
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_______-induced Porphyria occurs in individuals with abnormal ______ biosynthesis
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Barbiturate
Heme |
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Explain how Barbiturates can induce Porphyria
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-the Barbiturate acid moeity mimics part of the Heme structure, occupying a portion of the heme site on the protein that regulates production of ALA synthetase
-Heme is a repressor, inhibiting production of ALA synthetase and reducing porphyrin production = without Heme present inhibiting the production of ALA synthetase, Porphyrin production will increase |
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Definition: Application of the principles of pharmacokinetics, pharmacodynamics and adverse effects to the treatment of patients
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Pharamcotherapeutics
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The incidence of a placebo response is constant between what percents in clinical trials?
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20 and 40%
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Drug whose resin binds with other drugs and prevents their
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Cholestyramine
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Antacids have metals that chelate with these 2 drugs and prevent their absorption
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Tetracyclines
Fluoroquinolones |
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Group of drugs that decrease GI motility and slow absorption of many drugs
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Anticholinergics (Atropine)
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GI motility alteration may alter absorption of some of this group of drugs
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Weak organic acids
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3 groups of plasma protein binding drugs that can displace drugs from albumin
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1. Oral hypoglycemic agents (tolbutamide)
2. Oral anticoagulants (warfarin) 3. Antimetabolites (methotrexate) |
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Digoxin can be displaced from its tissue binding sites by this drug
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Quinidine
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Alkalinization of urine (Sodium Bicarb) enhances excretion of ________
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Weak organic acids
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Acidification (ammonium chloride) of urine enhances the excretion of _______
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weak organic bases
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What drug blocks the tubular excretion of penicillin?
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Probenicid
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Administration of these two nephrotoxic drugs can produce kidney damage even when dose of either agent alone may have been insufficient to produce toxicity
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Aminoglycoside
Vancomycin |
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What 2 properties of drugs are regulated by the FDA?
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Safety
Efficacy |
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What is filed with the FDA once a potential drug is judged ready to be initiated for Human studies
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Investigational New Drug (IND) exemption
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What is the goal in Phase 1 of Human Testing?
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to find the maximum tolerated dose = "Is it safe?"
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What is always the first dose in Phase 1 human testing?
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Placebo
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T or F: testing is never double-blind in Phase 1 testing
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True
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What is the definition of Phase 2 human testing?
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first attempt to determine clinical effectiveness of test agent = "Does it work?"
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T or F: Phase 2 tests may be single-blind or double-blind and involve hundreds of patients
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True
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What is the definition of Phase 3 human testing?
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extensive testing of a drug's efficacy and toxicity = "How well does it work, and what are the common side effects?"
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Phase 1 and 2 studies are usually conducted by __1__, but Phase 3 may include __2__
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1. Clinical scientists
2. physicians in private practice |
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After completion of Phase 3 testing, company files _________with the FDA
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New Drug Application
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Fewer than how many subjects are usually tested before Phase 4?
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10,000
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What is Phase 4 human testing?
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post-marketing surveillance = when adverse effects and toxicity become most evident
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During which Phases is informed consent required?
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Phase 1-3
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Informed consent must be in writing for which Phases?
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1 and 2
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Who protects the interest of the subjects in Phase testing?
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Peer review (Committee on Human Experimentation)
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