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117 Cards in this Set
- Front
- Back
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Atropine
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deadly nightshade
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Digoxin
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foxglove
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Morphine
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sap from poppy plant
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Quinine
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bark of cinchona tree
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Paclitaxel
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bark of Western yew tree
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Cocaine
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coca shrub leaves
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Insulin
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beef or pork pancreas
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Heparin
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porcine intestinal mucosa
bovine lung |
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Abciximab
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Monoclonal antibodies
Used in coronary bypass to prevent blood from clotting |
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Monoclonal antibody drug used for rheumatoid arthritis
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Infliximab
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Trastuzumab
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breast cancer treatment
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-olol
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beta-adrenergic antagonist
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local anesthetic
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-caine
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-dipine
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calcium channel antagonist of dihydropyridine type
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histamine-2 receptor antagonist
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-prazole
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-zosin
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alpha-1 receptor antagonist
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ACE inhibitors
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-pril
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1906 Federal Pure Food & Drug Act
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standards for strength & purity but does not check for safety
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1938 Federal Food, Drug, & Cosmetic Act
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requires testing for safety before marketing
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1962 Harris-Kefauver Amendment
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required proof of efficacy & safety before marketing and the FDA has to be notified before testing on humans
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1970 Comprehensive Drug Abuse & Prevention Control Act
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controls for manufacturers & prescribers of habit-forming drugs
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1983 Orphan Drug Act
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establishes programs & incentives for development of drugs to treat rare diseases
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1984 Drug Price & Patent Resoration Act
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required new drug applications for generic drug products
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Time frame for early research & preclinical testing
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6.5 years
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What does early research & preclinical testing assess?
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safety & biological activity
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What has to be done first before Phase 1 can begin?
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File an IND (investigational new drug) application with the FDA
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What does Phase 1 determine?
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safety & dosage
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How much time is required for Phase 1?
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1 year
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How much time is required for Phase 2?
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2 years
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What does Phase 2 evalulate?
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effectiveness, look for side effects
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How much time is required for Phase 3?
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3.5 years
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What does Phase 3 do?
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effectiveness & monitors adverse reactions from long term use
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What has to be done for pre-marketing approval?
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Need to file a NDA (new drug application) with the FDA which takes 1.5 years
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Describe the 5 categories of labeling for use in pregnant women
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A--controlled studies showing no risk
B--no risk in animal studies, no human studies done C--adverse fetal effects in animals, use only if benefit outweighs risk D--demonstrate human fetal risk, may use despite risk X--risk outweighs any possible benefit |
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What is an example of a Category X drug?
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Acutane
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FDA Modernization Act of 1997
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provides incentives, mainly patent extension, for clinical pharmacology in children
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Pediatric Rule of 1998
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studies must be done unless valid reasons not to do so
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Describe 5 categories of controlled substances & give examples of each
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1--no accepted medical use
(heroin, LSD) 2--high abuse potential (morphine, cocaine, amphetamines) 3--less abuse potential (codeine + acetaminophen, hydrocodone) 4--diazepam 5--codeine-containing cough syrups, pseudoephedrine |
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Describe filtration/aqueous diffusion
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small pores in membrane or gaps between cells, drugs are often too big to pass through
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Describe passive diffusion
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lipid soluble, unbound, and non-ionized drugs dissolve in membrane
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What is the driving force for passive diffusion?
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concentration gradient
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Properties that influence rate & extent of transport by passive diffusion
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-size of drug
-degree of ionization -lipid solubility -concentration gradient -surface area for diffusion |
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What is equilibrium partition coefficient?
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-measure of lipophilicity
-amount dissolved in oil/water |
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What determines ionization?
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pKa of drug & pH of medium
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Is aspirin a weak acid or base?
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weak acid
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What are weak acids?
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chemicals which can form salts
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In what pH do weak acids better dissolve?
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low pH
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What are weak bases?
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chemicals that form salts with acids
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In what pH do weak bases better dissolve?
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high pH
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What is ion trapping?
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weak acidic or basic drugs may concentrate to one side of the membrane when the pH of fluids on either side are different
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What is facilitated diffusion?
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carrier-mediated process carrying some chemicals across the membrane such as glucose and amino acids
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What is the driving force for facilitated diffusion?
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concentration gradient
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Is facilitated diffusion saturable?
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Yes
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What is active transport?
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requires chemical energy to drive the transport
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Does active transport depend on concentration gradient?
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transports against a concentration gradient
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Describe the multiple drug resistant P-glycoprotein
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-anti-cancer drug enters cell via passive diffusion
-when cells develop resistance, P-glycoprotein carrier pumps out the drug -concentration cannot build up in the cell |
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What is bioavailability?
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fraction the dose of the drug that reaches the systemic circulation
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What does the rate & extent of absorption depend on?
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-blood flow to the site of administration
-surface area of diffusion -ionization state of the drug -lipophilicity of the drug |
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What is the most important & commonly used route of administration?
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oral
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What are the 10 different routes of administration?
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-oral
-sublingual -rectal -intravenous -subcutaneous -intramuscular -inhalation -intraperitoneal -intrathecal -topical |
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What is the first pass effect?
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removal of significant portion of a drug dose by metabolism during the first pass of the drug through the GI mucosa & liver, only fraction of the oral dose reaches peripheral circulation
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What does intrathecal mean?
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entry of drug into CNS (spinal anesthesia)
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What properties of oral mucosa favor absorption?
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thin epithelium, rich vascularity
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What property of oral mucosa do not favor absorption?
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small surface area
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What factors influence absorption from the stomach?
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-properties of the drug (degree of ionization, lipophilicity, molecular weight, solubility in aqueous GI fluids, stability in acid & digestive enzymes)
-binding of drug to food particles -surface area -blood flow -gastric emptying time |
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What is a main feature of the small intestine to help with absorption?
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largest GI surface area
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What are some properties of the small intestine that affect absorption?
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-surface area
-pH environment variation (more acidic in duodenum than ileum) -GI flora may inactivate certain drugs -drug transit slow |
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What are the factors that influence absorption in the small intestine?
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-properties of the drug (degree of ionization, lipophilicity, molecular weight, susceptibility to digestive enzymes & GI flora, solubility in aqueous GI fluids)
-binding of drug to food particles -surface area -blood flow |
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Describe how L-Dopa is absorbed?
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-NOT by passive diffusion
-carried across by same carrier that carries phenylalanine |
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What compounds besides L-Dopa are not absorbed by passive diffusion?
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toxic compounds such as lead & the herbicide paraquat
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What is a big difference between large and small intestine that affects absorption?
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no villi
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What are 2 different routes of drug once it enters the gut lumen?
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1--goes right through liver & into systemic circulation
2--metabolized in liver |
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What are some ways to increase the amount of drug found in the peripheral circulation?
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-administer via IV
-increase drug -change drug |
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What are 4 reasons why most drugs are administered orally in tablets or capsules?
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-convenience
-economy -stability -patient acceptance |
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Why are drug tablets designed to dissociate?
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increases drug surface area
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How can you reduce the dissolution of drugs into GI fluids?
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coating particles with wax or other water-insoluble material & embedding drug into a matrix
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What is parenteral?
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-direct placement of drug into the blood stream to ensure bioavailability
-still has to penetrate through membranes |
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What determines the rate of entry into capillaries?
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-hydrophobicity of drug
-rate of capillary blood flow |
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How can you slow absorption of local anesthetic drugs injected SQ for local pain relief?
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administer vasoconstrictors (epi), heat or cold
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What happens when salts of poorly soluble acids & bases are injected IM?
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absorption may be delayed or erratic
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Describe what happens with phenytoin (an anti-convulsant)
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-water soluble only as the Na salt in a solution with a pH of ~12
-injected IM -> tissue fluids act as buffers & pH decreases -> shift to produce more free acid (HA), which precipitates at the site of injection & absorbs very slowly |
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What are some advantaes of prolonged release dosage forms of drugs?
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-reduce frequency of dosing
-can maintain more uniform plasma drug concentration -may improve drug compliance |
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Describe the procaine salt of penicillin
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-poorly soluble, slowly absorbed
-prolonged by suspending penicillin in oil containing aluminum stearate -oil prevents contact of salt with aqueous medium, retarding dissolution -aluminum stearate further delays dissolution by increasing viscosity |
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About how much total body water is in a 70 kg person? How much of that is plasma? Interstitial fluid? Intracellular fluid? Extracellular fluid?
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-60% of ody weight, 42 liters
-Plasma: 4%, 3 liters -Interstitial Fluid: 16%, 11 liters -Intracellular Fluid: 40%, 28 liters -Extracellular Fluid: 20%, 14 liters |
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Which are more permeable--cell membranes or capillary walls?
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Capillary walls because they have large pores allowing ultrafiltration of smaller molecules to take place
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What is the primary plasma binding protein?
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albumin
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What is the function of plasma binding proteins?
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-keeps concentration of free drug in plasma low
-enhances drug absorption since the rate of absorption by non-ionic diffusion is proportional to the concentration gradient of free drug from the site of administration into the blood stream -if drug is actively transported, movement across membranes is NOT reduced |
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What happens with people that have hypoalbuminemia?
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-more free drug is in plasma -> enhanced absorption to concentration level that is toxic
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What are the 3 things that characterize plasma protein binding?
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-Reversibility
-Saturation -Competition |
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Describe reversibility
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-free drug leaves circulation, remaining complexes dissociate -> release more free drug for diffusion
-protein-bound drug may be depot |
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Describe saturation
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plasma concentration increases -> available protein binding sites decreases
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What kinds of drugs are able to distribute to the CNS?
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highly lipid soluble drugs, due to BBB
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What factors of the CNS limit diffusion?
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-endothelial cells of capillaries much more firmly joined
-capillaries sheathed with processes of astrocytes |
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What are some things that can increase the permeability of the BBB?
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-infants
-inflammation |
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Describe the distribution through the placenta
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-placenta is rather permeable
-there is a time lag between drug concentration in maternal blood & that in fetal blood -rate of maternal blood limits availability of drug to fetus -placenta slow drug movement, but does not prevent distribution |
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What determines differential distribution?
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-binding of drugs to plasma proteins or tissue
-storage of drugs by body fat, BBB -active transport in the liver, kidney, & other organs |
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Describe saturation
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plasma concentration increases -> available protein binding sites decreases
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Describe saturation
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plasma concentration increases -> available protein binding sites decreases
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What are targeted drug?
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drugs designed to achieve high concentrations at the site of action
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What kinds of drugs are able to distribute to the CNS?
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highly lipid soluble drugs, due to BBB
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What kinds of drugs are able to distribute to the CNS?
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highly lipid soluble drugs, due to BBB
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What is redistribution of drugs and what is a good example?
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-initial distribution of drugs often follows distribution of blood flow, then drug redistribute according to affinity
-example: thiopental -> first goes to brain & later redistributes to adipose tissue & muscle (lower blood flow) |
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What factors of the CNS limit diffusion?
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-endothelial cells of capillaries much more firmly joined
-capillaries sheathed with processes of astrocytes |
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What factors of the CNS limit diffusion?
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-endothelial cells of capillaries much more firmly joined
-capillaries sheathed with processes of astrocytes |
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What are some things that can increase the permeability of the BBB?
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-infants
-inflammation |
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What is the volume of distribution (Vd)?
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-volume of fluid needed to maintain a drug in the same concentration as in the plasma
-Vd = A / CPo -A=amount of drug in body -CPo=plasma concentration of the drug following distribution of the drug to tissues & before elimination of the drug occurs |
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What are some things that can increase the permeability of the BBB?
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-infants
-inflammation |
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Describe the distribution through the placenta
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-placenta is rather permeable
-there is a time lag between drug concentration in maternal blood & that in fetal blood -rate of maternal blood limits availability of drug to fetus -placenta slow drug movement, but does not prevent distribution |
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What determines differential distribution?
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-binding of drugs to plasma proteins or tissue
-storage of drugs by body fat, BBB -active transport in the liver, kidney, & other organs |
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Describe the distribution through the placenta
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-placenta is rather permeable
-there is a time lag between drug concentration in maternal blood & that in fetal blood -rate of maternal blood limits availability of drug to fetus -placenta slow drug movement, but does not prevent distribution |
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What determines differential distribution?
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-binding of drugs to plasma proteins or tissue
-storage of drugs by body fat, BBB -active transport in the liver, kidney, & other organs |
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What are targeted drug?
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drugs designed to achieve high concentrations at the site of action
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What are targeted drug?
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drugs designed to achieve high concentrations at the site of action
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What is redistribution of drugs and what is a good example?
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-initial distribution of drugs often follows distribution of blood flow, then drug redistribute according to affinity
-example: thiopental -> first goes to brain & later redistributes to adipose tissue & muscle (lower blood flow) |
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What is redistribution of drugs and what is a good example?
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-initial distribution of drugs often follows distribution of blood flow, then drug redistribute according to affinity
-example: thiopental -> first goes to brain & later redistributes to adipose tissue & muscle (lower blood flow) |
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What is the volume of distribution (Vd)?
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-volume of fluid needed to maintain a drug in the same concentration as in the plasma
-Vd = A / CPo -A=amount of drug in body -CPo=plasma concentration of the drug following distribution of the drug to tissues & before elimination of the drug occurs |
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What is the volume of distribution (Vd)?
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-volume of fluid needed to maintain a drug in the same concentration as in the plasma
-Vd = A / CPo -A=amount of drug in body -CPo=plasma concentration of the drug following distribution of the drug to tissues & before elimination of the drug occurs |
