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105 Cards in this Set
- Front
- Back
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Pharmacokinetics
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The study of what the body does to a drug: includes...
-Absorption -Distribution -Metabolism -Excretion |
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Pharmacogenomics
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The study of the genetic variations that cause differences in drug response among individuals or populations
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Pharmacotherapy
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The effectiveness of the drug therapy must be evaluated.
One must be familiar with the drug’s intended therapeutic action (beneficial) and the drug’s unintended but potential side effects (predictable, adverse drug reactions). |
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Critical Threshold
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Defined as the minimum level of drug concentration needed for the desired therapeutic effect to be present.
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Pharmacotherapy: Monitoring
Therapeutic Index |
The ratio between a drug’s therapeutic benefits and its toxic effects
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Pharmacodynamics
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The study of what the body does to the drug
Absorption Distribution Metabolism Excretion |
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Drug Forms
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Oral
-Tablet; Capsule; Pill; Liquid Injection -liquid Topical -Paste; Suppositories; Ointment; -Powder Inhalation Products -Gas; liquid aerosol; dry powder aerosol |
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Factors affecting ABSORPTION of a drug
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-Administration route of the drug
-Food or fluids administered with the drug -Dosage formulation -Status of the absorptive surface -Rate of blood flow to the small intestine -Acidity of the stomach -Status of GI motility |
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Routes of Drug Absorption
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-Enteral
-Parenteral -Topical |
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Enteral Route of Absorption
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Drug is absorbed into the systemic circulation through the oral or gastric mucosa, the small intestine, or rectum.
-Oral -Sublingual -Buccal -Rectal |
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First Pass Effect
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-The metabolism of a drug and its passage from the liver into the circulation.
-A drug given via the oral route may be extensively metabolized by the liver before reaching the systemic circulation (high first-pass effect). |
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IV administration of drug ... (and absorption)
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Drug—given IV—bypasses the liver, preventing the first-pass effect from taking place, and more drug reaches the circulation.
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Routes that Bypass the Liver
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Sublingual Transdermal
Buccal Vaginal Rectal* Intramuscular Intravenous Subcutaneous Intranasal Inhalation *Rectal route undergoes a higher degree of first-pass effects than the other routes listed. |
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Inhalation (a way of absorption of a drug)
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1 Gaseous and volatile agents and aerosols
2 Rapid onset of action due to rapid access to circulation a.large surface area b.thin membranes separates alveoli from circulation c.high blood flow Particles larger than 20 micron and the particles impact in the mouth and throat. Smaller than 0.5 micron and they aren't retained. |
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Parenteral Route
(some things that count as parenteral) |
Intravenous*
Intramuscular Subcutaneous Intradermal Intrathecal Intraarticular *intravenous is the fastest route of delivery to the blood |
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Topical Route
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Skin (including transdermal patches)
Eyes Ears Nose Lungs (inhalation) Vagina |
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Absorption:
Timeframes of absorption |
-intravenous 30-60 seconds
-endotracheal 2-3 minutes -inhalation 2-3 minutes -sublingual 3-5 minutes -intramuscular 10-20 minutes -subcutaneous 15-30 minutes -rectal 5-30 minutes -ingestion 30-90 minutes -transdermal (topical) variable (minutes to hours) |
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The elimination of drugs from the body
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Kidneys (main organ)
Liver Bowel Biliary excretion Enterohepatic circulation |
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topcial routes of absorption
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skin (incl transdermal patches)
eyes ears nose lungs vagina |
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pharmacokinetics: distribution
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The transport of a drug in the body by the bloodstream to its site of action.
Protein-binding -phenytoin Water soluble vs. fat soluble Beta blockers Blood-brain barrier psychotropics Areas of rapid distribution: heart, liver, kidneys, brain Areas of slow distribution: muscle, skin, fat |
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pharmacodynamics
Drug actions: |
The cellular processes involved in the drug and cell interaction
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pharmacodynamics:
Drug Effects |
The physiologic reaction of the body to the drug
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Absorption of a drug from fastest to slowest
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1Liquids, elixirs, syrups (fastest)
2 suspension solutions 3 powders 4 capsules 5 tablets 6 coated tablets 7enteric coated tablets (slowest) |
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Bioavailability
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Bioavailability has nothing to do with efficacy. How much will actually reach blood circulation. Measure of rate & extent drug gets absorbed into body.
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Bioequivalent
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– if you compare 2 drugs, they should have similar rates of absorption, (for a generic, it has to prove bioequivalency)
Comparing 2 medicaitons; ex: coumadin and warfarin. Generic has to be bioequivalent, same rate and distribution of absorption |
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Pharmacokinetics:
Metabolism |
The biologic transformation of a drug into an inactive metabolite, a more soluble compound, or a more potent metabolite.
Liver (main organ) Kidneys Lungs Plasma Intestinal mucosa |
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metabolism of a drug depends on what factors?
(10 things) |
1Age 2Diet 3Genetic Variation
4State of Health 5Gender 6Degree of Protein Binding 7Species Variation 8Substrate Competition 9Enzyme Induction 10Route of Drug Administration |
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Some factors that decrease drug metabolism?
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Cardiovascular dysfunction
Renal insufficiency Starvation Obstructive jaundice Slow acetylator Erythromycin or ketoconazole drug therapy |
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Some factors that increase drug metabolism?
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Fast acetylator
Barbiturates Rifampin therapy |
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Factors affecting drug metabolism?
(main idea) |
Enzyme induction
Degree of protein binding substrate competition |
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Factors affecting drug metabolism
Enzyme Induction (elaboration) |
increased enzyme protein levels in the cell
ex: phenobarbital type induction by many drugs -carbamazepine |
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Factors affecting drug metabolism
Degree of protein binding (elaboration) |
conditions that displace bound drug from protein allows more of the drug to be accessible to the enzyme for which it serves as a substrate
ex: uremia, low plasma albumin |
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Factors affecting drug metabolism
Substrate competition (elaboration) |
two or more drugs competing for the same enzyme can affect the metabolism of each other; the substrate for which the enzyme has the greater affinity is preferentially metabolised
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Delayed drug metabolism results in:
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-accumulation of drugs
-prolonged action of the effects of the drugs |
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Stimulating drug metabolism causes:
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diminished pharmacologic effects
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Concept of Half-life
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the time required to metabolize 1/2 of the original dose of the drug
-determines how long a drug will remain in the body |
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Cytochrome P450 3A4 (CYP3A4)
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-Responsible for metabolism of 60% of all drugs
-It comprises approximately 28% of hepatic cytochrome P450 -Ingestion of grapefruit juice reduces expression of this enzyme -Inhibited by some regularly used drugs |
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Pharmacokinetics:
Excretion define & where does it occur? |
The elimination of drugs from the body
Kidneys (main organ) Liver Bowel Biliary excretion Enterohepatic circulation |
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Pharmacodynamics:
Critical Threshold |
Defined as the minimum level of drug concentration needed for the desired therapeutic effect to be present.
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Pharmacodynamics:
Maximal effect |
Greatest response that can be produced by a drug, above which no further response can be created (sometimes called “peak effect”
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Pharmacodynamics:
Onset |
How long before a drug is able to exert a therapeutic effect
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Pharmacodynamics:
Duration |
How long a drug effect lasts
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Pharmacodynamics:
Mechanism of Action (MOA) |
The ways by which drugs can produce therapeutic effects:
Once the drug is at the site of action, it can modify the rate (increase or decrease) at which the cells or tissues function. A drug cannot make a cell or tissue perform a function it was not designed to perform. |
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Pharmacodynamics:
Law of Mass Action |
When a drug (D) combines with a receptor (R), it does so at a rate which is dependent on the concentration of the drug and the concentration of the receptor.
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Pharmacodynamics:
Agonist |
A drug is said to be an agonist when it binds to a receptor and causes a response or effect.
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Pharmacodynamics:
Antagonist |
A drug is said to be an antagonist when it binds to a receptor and prevents (blocks or inhibits) a natural compound or a drug to have an effect on the receptor. An antagonist has NO activity
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Pharmacodynamics:
Partial Agonist |
A drug is said to be a partial agonist when it binds to a receptor and causes a partial response.
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RT = Total number of receptors
Bmax = Maximal number of receptors Bound |
As a concentration of a drug increases, the amount of drug sitting on a receptor increases until reaching a saturation point
If you increase dose of drug beyond maximum efficacy, it won’t do anything because there are not receptors for it to sit on. Can result in overdose or toxicity |
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Pharmacological Antagonists
Competitive |
Competitive
They compete for the binding site Reversible Irreversible |
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Pharmacological Antagonists
Noncompetitive |
Bind elsewhere in the receptor (Channel Blockers).
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Dose Response Curve
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Efficacy is maximum effect of drug with maximum number of receptors.
Potency ; amount of drug to produce 50% response. Drug is considered potent when it takes smaller amount of drug to get same effect. |
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Competitive Antagonists
Reversible & Surmountable |
The effect of a reversible antagonist can be overcome by more drug (agonist).
A small dose of the antagonist (inhibitor) will compete with a fraction of the receptors thus, the higher the concentration of antagonist used, the more drug you need to get the same effect. |
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Competitive Antagonists:
Irreversible & Non-surmountable |
The effect of irreversible antagonists cannot be overcome by more drug (agonist).
The antagonist inactivates the receptors. |
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RANK ORDER OF POTENCY: A > B > C > D
RANK ORDER OF EFFICACY: A = C > B > D |
Drugs B and D have a narrower dosing range.
A and C have larger dosing range. |
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Receptor Reserve or
SPARE RECEPTORS |
-Maximal effect does not require occupation of all receptors by agonist.
-Low concentrations of competitive irreversible antagonists may bind to receptors and a maximal response can still be achieved. -The actual number of receptors may exceed the number of effector molecules available. |
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Therapeutic Index
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the ratio between a drug's therapeutic benefits and its toxic effects
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Tolerance
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a decreasing response to repetitive drug doses
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Dependence
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a physiologic or psychological need for a drug
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Pharmacotherapy
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The effectiveness of the drug therapy must be evaluated.
One must be familiar with the drug’s intended therapeutic action (beneficial) and the drug’s unintended but potential side effects (predictable, adverse drug reactions). |
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Pharmacotherapy: Monitoring
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Therapeutic index
Drug concentration Patient’s condition Tolerance and dependence Interactions Side effects/adverse drug effects |
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Pharmacotx:
Interactions in general |
Interactions may occur with other drugs or food
Drug interactions: the alteration of action of a drug by: Other prescribed drugs Over-the-counter medications Herbal therapies |
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Pharmacotx:
Interactions can have a.... |
Additive effect
Synergistic effect Antagonistic effect Incompatibility |
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Example of an Additive effect of drug interactions:
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presurg meds, make someone relaxed, not more so than normal effect
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Example of a Synergistic Effect of drug interactions:
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effect is exaggerated from norm – ex: pt with depression, pt with serotonin syndrome (much stronger than by itself)
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Example of an Antagonistic Effect in drug interactions
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usually with overdose. Morphine and naloxone
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Example of Incompatibility in drug interactions
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alcohol and illicit drugs used with meds
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Adverse Drug Reactions
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An undesirable response to drug therapy: includes
-Idiosyncratic -Hypersensitivity reactions -Drug interactions |
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Side Effects (a part of adverse drug reactions)
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--Some adverse drug reactions are classified as side effects.
-Expected, well-known reactions that result in little or no change in patient management -Predictable frequency -The effect’s intensity and occurrence is related to the size of the dose. |
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Medication Misadventures:
Adverse Drug *Events* |
ALL are preventable
Medication errors that result in patient harm |
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More on Adverse Drug Reactions
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-Inherent, not preventable event occurring in the normal therapeutic use of a drug
-Any reaction that is unexpected, undesirable, and occurs at doses normally used |
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Iatrogenic Responses
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Unintentional adverse effects that are treatment-induced
Dermatologic Renal damage Blood dyscrasias Hepatic toxicity (are in side effects profile of med) |
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Pharmacogenomics
(in more detail) |
Genetic factors that affect enzyme levels
Slow acetylators = autosomal recessive trait occurs in about 50% of blacks and whites in the US CYP2C9 2 variants of the enzyme, each with amino acid variations that lead to changes in how it is metabolized Warfarin = CYP2C9*3 ; has a 10% clearance , increase bleed risk |
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ANS
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ANS anatomy
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pns/ans
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note nerve differences in pns/ans
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Autonomic Nervous System
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--Sympathetic Division
(thoracolumbar division) – pre-ganglionic fibers exit spinal cord from first thoracic (T1) to second lumbar (L2) level --Parasympathetic Division (craniosacral division) – pre-ganglionic fibers originate in the brain and sacral region of the spinal cord |
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Mass Activation in ANS
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--Sympathetic system activated as a unit – affects all effector organs at same time
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Mass Activation in the ANS
--Divergence |
–pre-ganglionic fibers branch to synapse with numerous post-ganglionic neurons located in ganglia
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Mass Activation in the ANS
--Convergence |
– the post-ganglionic neuron receives input from a large number of pre-ganglionic fibers in the ganglia
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neurohormonal transmission
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Cholinergic receptors:
Nicotinic Muscarinic Adrenergic receptors: Alpha Beta |
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Acetylcholine
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Biosynthesis of acetylcholine occurs in peripheral nerves and nerve endings
Choline + Acetyl coenzyme A --> Acetylcholine +coenzyme A b. Released into synaptic cleft during neural stimulation by exocytosis c. Interact with specific receptors d. Hydrolysis or destruction by cholinesterases |
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Norepinephrine
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Biosynthesized from Tyrosine from Dopa, to dopamine to Norepinephrine (can also proceed further to epinephrine)
Storage in and release from vesicles (formed in the cell bodies, axoplasmic flow to nerve endings); neural stimulation promotes exocytosis Disposition of norepinephrine – enzyme destruction by catechol-O-methyltransferase (COMT) and monoaimine oxidase (MAO), reuptake by neuronal ending |
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Cholinergenic Receptors
2 types |
Nicotinic receptors – (ligand gated ion channels) stimulated by acetylcholine; present in autonomic ganglia and in CNS. Blocked by curare.
Muscarinic receptors – (G-protein receptors) stimulated by acetylcholine; present in smooth muscle, glands, cardiac muscle, in CNS; blocked by atropine. |
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Adrenergic Receptors
2 types |
--All adrenergic receptors act via G-proteins
-Alpha receptors – stimulated by norepinephrine; blocked by phenoxybenzamine or phentolamine - second messenger: Ca2+ (alpha1) Beta receptors – stimulated by norepinephrine, blocked by propranolal - second messenger: cAMP |
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ADRENERGIC RECEPTOR SUBTYPES
4 in all |
-alpha1 (constriction of vascular smooth muscle)
-alpha2 (many targets, incl. receptors in the brain and smooth muscle) -beta1 (increase cardiac pumping) -beta2 (dilation of pulmonary bronchioles, relaxation of smooth muscle in walls of GI tract) |
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Contents of the Prescription
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Under Texas State Law, all prescriptions should have the following essential elements:
-Date of the order -Patient Name and Address -If the drug is prescribed for an animal, the species of the animal -Name of the drug -Strength of the drug -Quantity of the drug -Directions for use -Intended use of the drug, unless practitioner feels indication is not in best interest of patient -Practitioner Name, Address, -Telephone number |
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Classifications of Drugs:
Prescription Drug |
--A Drug that requires a prescription because it is considered potentially harmful if not used under the supervision of a licensed health care practitioner
--Known synonymously as a legend drug because the label of the drug bears the legend, “Caution: Federal Law Prohibits Dispensing without a Prescription” or “Rx only.” |
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Classifications of Drugs:
Controlled or scheduled drug |
Controlled or scheduled drug
a prescription drug whose use and distribution is tightly controlled because of its abuse potential or risk Controlled drugs are classified into schedules Schedules CI, CII, CIII, CIV, and CV Prescriptions for controlled substances have additional requirements by law |
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Pregnancy Category A
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Controlled studies in women fail to demonstrate a risk to the fetus in the first trimester (and there is no evidence of a risk in later trimesters), and the possibility of fetal harm appears remote.
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Pregnancy Category B
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Either animal-reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women, or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the first trimester (and there is no evidence of a risk in later trimesters).
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Pregnancy Category C
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Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women, or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.
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Pregnancy Category D
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There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
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Pregnancy Category X
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Studies in animals or human beings have demonstrated fetal abnormalities, or there is evidence of fetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.
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Schedule I (C-I) Drugs
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– Highest abuse risk. No safe medical use in U.S. Examples: heroin, marijuana, LSD, PCP, and crack cocaine.
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Schedule II (C-II)
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– High abuse risk but have safe and accepted medical use. Examples: morphine, oxycodone, methylphenidate, dextroamphetamine.
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Schedule III (C-III)
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– Abuse risk less than C-II and safe and accepted medical use. Examples: Acetaminophen/Codeine (Tylenol #3), acetaminophen/hydrocodone (Vicodin), propoxyphene (Darvon).
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Schedule IV (C-IV)
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– Abuse risk less than C-III and safe and accepted medical use. Examples: diazepam (Valium), alprazolam (Xanax), phenobarbital, chloral hydrate.
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Schedule V (C-V)
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– Abuse risk less than C-IV and safe and accepted medical use. Mainly consist of preparations containing limited quantities of certain stimulant and narcotic drugs for antitussive and antidiarrheal purposes.
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Drug R&D Time frame
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Time span- approx 10-15 years from idea to marketable drug.
-a drug patent expires 20 years after filing the NDA. (new drug application) |
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Drug R&D
Chemistry/pharmacology stage |
Discovery Phase
-the search for active substances -toxicology, efficacy studies on various types of animals lasts from 2-4 years |
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Drug R&D
IND stage (investigational new drug) |
Discovery Phase
- undergoes regulatory review - application for permission to administer a new drug to humans lasts 2-6 months |
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Drug R&D
Phase I |
Early Clinical Phase
efficacy studies on healthy volunteers -50-100 persons from phase I to III lasts 4-9 years |
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Drug R&D
Phase II |
Early clinical Phase
-clinical studies on a limited scale -100-200 patients from phase I to III lasts 4-9 years |
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Drug R&D
Phase III |
Development Phase
comparative studies on a large number of patients 500-5000 pts from phase I to III lasts 4-9 years |
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Drug R&D
NDA (New Drug Application) |
Development Phase
NDA - application for permission to market a new drug -regulatory review from NDA to Phase IV lasts 1-3 years |
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Drug R&D
Phase IV |
Development Phase
continued comparative studies -registration market introduction from NDA to Phase IV lasts 1-3 years |
