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45 Cards in this Set
- Front
- Back
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Pharmacokinetics
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the effect of the body on the drug.
how the drug moves through the body: Absorption, Distribution, Metabolism, Excretion |
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Pharmacodynamics
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the effect of the drug on the body
how the drug produces an effect at the site of action leading to a cellular change |
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Phases of Drug Approval Process by FDA
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-Preclinical Testing on Animals
-Clinical Testing on Humans- *Investigational New Drug (IND) Phase I: small # of healthy subjects (up to 100), find pharmacokinetic parameters Phase II: 200-300 subjects w/disease state, assess effectiveness in treatment Phase III: 1000-3000 pts with disease are treated, do benefits outweigh risks? -New Drug Application (NDA) is submitted for FDA to approve or reject Phase IV: done by manufacturer after drug is on market, to monitor efficacy and safety, required to report adverse reactions to FDA periodically |
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What is Fast Track Approval?
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expedited drug review processs
-used when there is critical need for drug (eg: anit-HIV, cancer drug) |
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Oral Administration
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Oral drug administration
-uses GI tract -most common, easy, safe, convenient -slow entry of drug into body -may irritate stomach= nausea, vomiting -absorbed mostly in small intestine drugs must have: 1. high lipid solubility 2. stability in an acid environment and against enzymes in stomach |
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Enteral Administration
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methods using the alimentary tract
-Oral -Sublingual -Rectal |
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Parenteral Administration
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Route of administration that bypasses the GI tract
-Inhalation -Intravenous (IV) Injection -Intra-arterial (IA) -Subcutaneous (SC) -Intramuscular (IM) -Intrathercal (IT) --> CSF |
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Topical Administration
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-meant to treat a condition ON the skin
-poorly absorbed into circulatory system |
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Transdermal Systems
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-drugs applied to the skin for the purpose of systematic absorption
-must be lipid soluble -"patch" -"iontophoresis"- electric current drives ionized form of drug through skin -"phonophoresis"- ultrasound waves drive drug through skin |
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Bioavailability
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refers tot he percentage of administered drug that reaches the systemic circulation UNCHANGED
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Mechanisms to transport drugs through cell membranes
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Passive Diffusion
Active Transport Facilitated Diffusion |
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Passive Diffusion
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no energy required
1. must be a diff in conc of substances on one side than other 2. the membrane must be permeable to the diffusing substance *any drug w/high lipid solubility can gain access to many tissues |
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Active Transport
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membrane proteins work to shuttle a substance across the cell membrane
1. energy is required (ATP) 2. substances can be transported against the conc gradient 3. drug being transported in will often have a chemical similarity to a substance in the cell |
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Facilitated Diffusion
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a hybrid btw active and passive transport
-carrier protein mediates mvmt of substance WITHOUT the expenditure of energy -CANNOT move substance against the conc gradient |
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Factors that affect drug distribution
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1. Blood Flow
2. Binding to plasma proteins 3. Tissue Permeability 4. Intracellular Binding |
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How does Ionization affect a drug
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most drugs are either a weak base or a weak acid in a lipid soluble form and are unionized.
*drugs that are in ionized form have poor permeability to cell membranes *pH plays an important role in absorption, distribution and excretion of drugs |
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Metabolite
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when a drug is chemically altered from its original compound to an less active form to be more easily excreted
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Prodrug
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where the parent drug has no pharmacologic activity until it is biotransformed in the body to an active metabolite
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Phase I Metabolism
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1. Oxidation= addition of oxygen or removal of hydrogen from original compound
*predominant method *enzymes that do this are located on smooth ER of specific cells 2. Reduction= removing oxygen or adding hydrogen to original compound *enzymes that do this are in the cell cytoplasm 3. Hydrolysis= compound is cleaved into parts *enzymes that do this are located in several sites of the cell |
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Cytochrome P450 Microsomal Enzymes (CYP450)
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enzymes involved in phase I metabolism (oxidation, reduction, hydrolysis)
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Phase II Metabolism
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1. Conjugation= when either the parent compound of metabolite is combined with an endogenous substance (ACh, amino acid) forming a larger, more water soluble substance that can be excreted renally
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Methods of Drug Excretion
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-Renal excretion
-Clearance -Half-Life |
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Renal Excretion
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-Kidney is primary organ
Three mechanisms: 1. Filtration -ionized drugs stay in nephron and are lost in urine -unionized drugs can be reabsorbed from nephron back into systemic circ 2. Tubular Secretion -drug is ACTIVELY secreted into nephron 3. Tubular Reabsorption -reabsorption of drug from urine back into systemic circ -may be active, but is primarily passive |
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Clearance
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describes the ability of the body to eliminate a drug from the systemic circulation
-Can be total body clearance or clearance by a particular organ |
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Half-Life
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the amount of time required to eliminate 50% of the drug remaining in the body
*important in describing the length of activity of a drug *after 5 half-lives 97% of drug is out of body |
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Mechanisms of Drug Interaction
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1. Pharmacodynamic Interactions
*one drug interfering with the activity of another drug -by blocking receptors for another drug -by preventing clearance of another drug 2. Pharmacokinetic Interactions *one drug alters the disposition of another drug -alteration of plasma levels (causing either toxicity or loss of efficacy) -interactions related tot he four individual processes (ADME) |
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Types of Pharmacokinetic interactions
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*Absorption Interactions
-Physiochemical -Altered GI Motility *Drug Distribution Interactions -altered plasma and tissue protein binding *Liver Based Interactions -changes in blood flow -alteration in enzyme activity *Kidney Based Interactions -increased filtration -interference with tubular secretion -interference with tubular reabsorption |
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Kinase
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an enzyme that catalyzes the conversion of a pro-enzyme (inactive) to an active enzyme through a phosphorylation reaction
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Receptor-Gated Ion Channels
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proteins act as a pore with a gate. drug binds to extracellular part, gate opens and ions flow down the gradient
eg: Ach receptors on post-synaptic neurons eg: GABA receptors in the CNS |
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Receptors as Enzymes
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can catalyze biochemical reactions when drug binds to cell receptor.
Drug binds --> protein changes shape --> exposes catalytic domain eg: receptors for peptide hormones that modulate growth (insulin, GH) |
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Receptor G-protein Effector System
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drug binds to receptor,which causes an intermediary G-protein to stimulate enzyme activation inside the cell
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Intracellular Receptors
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drug passively diffuses through cell membrane and binds to receptor
-receptor changes shape -translocation to nucleus where it causes gene transcription and protein synthesis (alters expression of genes) eg: steroids and thyroid hormones, anti-inflammatory drugs |
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Efficacy
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the degree of response that can be produced by a drug
eg) morphine has a higher efficacy than tylenol |
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Potency
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the does of a drug required to elicit a given response
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ED50
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dose that produces a given response in 50% of subjects = effective dose
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TD50
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does that produces a given toxic effect in 50% of subjects = toxic dose
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LD50
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does that is lethal in 50% of subjects (animal studies) = lethal dose
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Therapeutic Index (TI)
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refers to the relative safety of a drug (calculated by the ED50 and TD50)
-the higher the therapeutic index, the safer the drug |
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Pharmacodynamic Drug Interactions
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When one drug interferes with the pharmacodynamic activity of another drug
-competing with each other for receptors |
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Adrenergic Receptors
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NE and EPI --> activate alpha & beta receptors
-NE has a greater affinity for alpha -EPI excites both |
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Alpha receptors
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alpha 1 and alpha 2
-mainly a1 receptors on post-synaptic membrane and effector cells -a2 located on pre-synaptic membrane agonists: EPI, NE, dopamine, isoproterenol antagonists: terazosin |
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Beta receptors
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beta 1 and beta 2
-both b1 and b2 on post-synaptic membranes and effector cells agonists: EPI, NE, dopamine (DA) and isoproterenol (ISO) antagonists: propranolol, atenolol, metoprolol |
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Cholinergic Receptors
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ACh --> activates muscarinic and nicotinic receptors
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Muscarinic Receptors
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found in all effector organs stimulated by the postganglionic neurons of the parasympathetic NS and those stimulated by cholinergic neurons of the sympathetic nervous system
stimulation = increased secretion of exocrine glands (sweat, salivary, mucous, etc) -smooth muscle contraction of bronchi, GI tract, gallbladder, bile duct, urinary bladder, ureters -slowing of heart and respiratory rate -relax sphincters |
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Nictonic Receptors
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found in the synapses btw pre and post-ganglionic neurons of both symp and parasym NS, also in skeletal muscle at neuromuscular junction and adrenal medulla
stimulation = propagates impulse transmission -stimulates adrenal medulla to discharge EPI and NE -contraction of skeletal muscle |
