1) General Principles Flashcards
(108 cards)
1
Q
Pharmacology definition
A
- Science of chemicals that are utilized to prevent, diagnose, and treat disease
2
Q
Drug definition
A
- Small molecule (MW 100-1000) with particular shape that when introduced into the body will alter physiology
3
Q
3 major drug modes of action
A
- Interfere with physiological ligands that bind to receptors
- Inhibit normal body enzymes
- Replace something that is missing in the body
4
Q
Pharmacodynamics
A
- Deals with receptors, interactions, antagonists, efficacy, and toxicology
- Effect of the drug on the body
5
Q
Pharmacokinetics
A
- Study of the time course of a drug and its metabolites in the body following administration
- Effect of the body on the drug
6
Q
Three parameters of kinetics
A
- Absorption (permeation)
- Distribution (metabolism)
- Elimination (clearance)
7
Q
Duration of action
A
- For many Rx, inversely proportional to the rate at which the Rx is metabolically inactivated
- More rapidly inactivated = shorter DOA
8
Q
Dosage regimens
A
- Designed on the basis of DOA alone and does not take into consideration age, weight, renal/hepatic function, polypharmacy, etc.
9
Q
Absorption (permeation)
A
- Process of drug movement from the site of application to the systemic circulation
10
Q
Routes of administration
A
- Enteral (GI tract: buccal, rectal)
- Parenteral (injection IA, IV, IM, subcut, intrathecal)
- Other (percutaneous, inhalation, intranasal)
11
Q
Factors which affect absorption from the GI tract
A
- Physical state and solubility
- pKa of the drug and pH of the gut
- Lipid solubility
- Destruction of drug by stomach acid pH
- Blood flow/surface area
- Transit time
- Binding to food
12
Q
Unionized form of drug
A
- More lipid soluble
- Pass readily across membranes
13
Q
Ionized form of drug
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- Generally more water soluble
14
Q
Drug binding to food
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- Best to take on an empty stomach (one hour before or two hours after eating)
15
Q
Ion trapping
A
- Precipitation of a drug by gastric acid
16
Q
To increase absorption rate after injection
A
- Give IV > IM > sub q
- IV is direct to blood
- IM has increased blood flow and surface area
17
Q
To decrease absorption rate after injection
A
- Inject the basis along with insoluble salt or in an oil base
- Inject the basis along with a vasoconstrictor to decrease blood flow to the area (and thus decrease absorption and metabolism)
18
Q
Examples of skin (transdermal) absorption
A
- Nitroglycerine
- Estrogen
- Clonidine
- Scopolamine
19
Q
Examples of lung absoprtion
A
- Gaseous anesthetics
- Aerosols or volatilization “free basing” (nicotine, TCH)
20
Q
Examples of nasal absorption
A
- Decongestants
- Calcitonin
- Cocaine
21
Q
Bioavailability
A
- Rate at which and extent to which the active drug or its metabolite enters the general circulation
22
Q
Biological barriers
A
- GI mucosa
- Blood brain barrier
- Placental barrier
23
Q
Transport mechanisms across BBB
A
- Passive diffusion
- Facilitated diffusion
- Active transport
- Pinocytosis
24
Q
Passive diffusion
A
- Transport across the CM in which the driving force is the concentration gradient of the solute
25
Fick's Law of Diffusion
Flux = [(C1 - C2) x area x permeability coefficient] / thickness
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Factors affecting diffusion
- Lipid solubility
- Degree of ionization
- Molecular size
- Absorptive surface
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Lipid solubility example
- Thiopental rapid acting due to high lipid solubility vs barium sulfate (poorly lipid soluble) in normal body pH
28
Henderson Hasselbach
- Relates the ratio of pronated form of a Rx to the unprotonated form to the pKa (of the Rx) and pH of the surrounding medium
29
Degree of ionization
- Non-ionized are more lipid soluble
- Ex: NSAIDS in the pH of the stomach are non-ionized, thus more lipid soluble, thus more completely absorbed, thus more GI toxicity
30
Facilitated diffusion
- Drug molecules driven across a cell membrane with a concentration gradient with assistance of a special “carrier component” due to the drugs low lipid solubility, or large molecular size
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Plasma membrane receptors
- Polypeptides on the surface of target tissues
- Triggered by the molecule to permit uptake of glucose and amino acids and regulate metabolism of glycogen and triglycerides
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Active transport
- Allows a drug to move intra-cellularly against a concentration gradient
- Requires energy
- Must have a chemical structure similar to normal body constituents
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Factors that affect distribuiton
- Blood flow
- Plasma binding
- Membrane permeation
- Tissue solubility
34
Volume of distribution
- V = dose (mg) / plasma concentration (mg/l)
| - Related to clearance (CL)
35
Biotransformation
- Chemical alteration of drugs in the body
- Creates a more water soluble substance for excretion
- Often ↓ the activity of the drug (but not always)
36
Nonsynthetic reactions (phase I mixed function oxidases)
- All drugs: microsomal enzyme system of liver (endoplasm reticulum cytochrome P-450)
37
Common cytochrome P450 pathways
- 1A2
- 2C9, 2C19, 2D6
- 3A4
38
Types of phase I mixed function oxidases
- Aromatic hydroxylation (heparin)
- N-dealkylation (benzopiazepines)
- Desulfuration (thiopental)
- Alkyl oxidation (narcotics)
- Deamination (amphetamines)
- Sulfoxidation (cimetadine; phenothiazines)
- Epoxidation
39
Oxidations (mitochondria)
- Xanthine oxidase
- Monoamine oxidase (MAO)
- Alcohol or aldehyde dehydrogenase
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Reduction (anaerobic)
- Microsomal enzyme system of liver
41
Types of reduction reactions
- Nitro (--NO2) creates the amine (eg. chloramphenicol; dantrolene)
- Organic nitrates are reduced to nitrites
- Azo groups (-N=N-) are hydrolyzed to form two primary amines
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Hydrolysis
- Microsomal enzyme system of the liver, plasma, cytoplasm, etc.
- Esterases, amidases, and peptidases
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Phase II metabolism
- Conjugation synthesis
| - Conjugation reactions
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Types of phase II metabolism reactions
- Glucuronidation
- Amino acid conjugation
- Acetylation
- Sulfate conjugation
- Methylation
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Glucuronidations
- Most common phase II conjugation reaction
| - Then excreted in urine and bile (eg. morphine; antibiotics; acetaminophen (60%); tricyclics; narcotics)
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Amino acid conjugation with
- Glutamine and glycine
| - (eg. ASA to become salicyluric acid)
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Acetylation
- For drugs with primary amino groups (eg. sulfonamides; INH)
48
Examples of substances that undergo sulfate conjugation
- Phenolic compounds
- Alcohols
- Clinoril
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Methylation examples
- Catecholamines such as epinephrine, dopamine(COMT)
| - Griseofulvin
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Effects of age on metabolism
- Newborn infants and geriatrics do not metabolize Rx as well as adults
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Effects of genetics on metabolism
- Enzyme deficiencies
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Effects of disease on metabolism
- Liver disease will decrease the metabolism and increase the half-life of a drug
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Liver function tests
- Total protein
- Albumen
- Globulin
- Bilirubin, total
- Alkaline Phosphase
- AST
- ALT
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Inhibition of drug metabolism (drug to drug)
- Competitive inhibition of cytochrome enzyme pathways resulting in decreased metabolism of the other drug
- Increases half-life and activity of the second drug
- Will have an effect on all other drugs metabolized by the same system
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50% of all Rx are metabolized by
- CYP3A4
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CYP pathway inhibitors
- Cimetidine
- Fluoroquinolones
- Eryhtromycins
- Clarithromycin
- Azoles
- Grapefruit juice
- Ritonavir
- Ciprofloxacin (1A2)
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CYP pathway inducers
- Griseofulvin
- Barbiturates
- Rifampin
- Phenytoin
- Carbamazepine
- St. John's Wort
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Rx to Rx interaction polypharmacy
1. Hepatic Enzyme inducers vs. inhibitors
| 2. Competition for plasma binding sites
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First pass effect
- Drugs that are absorbed via the GI tract arrive at the liver via portal vein, metabolized and sometimes inactivated prior to effecting their target
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Prodrugs
- Do not become activated until after their first pass through the liver
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Eexcretion/clearance
- Process by which a drug or metabolite is eliminated from the body
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Renal clearance
- Primary organ for water soluble substances
- Only unbound drugs (ie. drugs are filtered at glomerulus (GFR 130 ml/min) and variably passively reabsorbed from the tubules)
- pH dependent
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Renal clearance and ionization
- If highly ionized and have high tubular secretion, can have renal clearance = to renal plasma flow (600 ml/min)
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Renal function tests
- BUN = 10-20 mg%
| - Creatinine = 0.5-1.5 mg%
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Cockroft equation purpose
- Calculated creatinine clearance
- Gives a good estimate of renal function
- Derived from the Cockroft-Gault equation
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Cockroft equation
Creatinine CL = (140-age x weight in kg) / (serum creatinine x 72)
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Typical creatinine clearance levels according to Cockroft equation
- Normal = > 60 ml/min
- Decreased = 30-60 ml/min
- Decreased = 10-30 ml/min
- Renal insufficiency = < 10 ml/min
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Adjusting dose for renal insufficiency
Corrected dose = usual dose x (creatinine CL / 100 ml/min)
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Enterohepatic (fecal) excretion
- Biliary secretion
- Active secretion of conjugated Rx into the bile
- Reabsorption in intestine
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Lung excretion
- Volatile anesthetics
| - Excretion proportional to the blood/air partition coefficient
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Half-life
- Time required for the plasma drug concentration of a Rx to ↓ by 50% during a constant infusion
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Half-life depends on
- Volume of distribution
| - Rate of clearance
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Half-life equation
T1/2 = (0.7 x V) / (CL)
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Designing a dosage regimen
- Amount of the drug
- Route of administration
- Interval between doses
- Period of time for which drug should be administered
75
Young's Law
age / (age + 12) = % of adult dose
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Cowling's Law
age / 24 = % of adult dose
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Clark's Rule
weight / 150 = % of adult dose
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Prescription construction
1. Patient's full name, address, age
2. Date
3. Superscription (Rx)
4. Inscription (name and amt of each medicinal ingredient)
5. Subscription (directions for pharmacist)
6. Transcription (directions to pt to be written on label)
7. Refill information
8. Substitution information
9. Physicians signature
10. Med license # (DEA # if controlled substance)
79
Components of inscription
- Basis
- Adjuvant
- Corrective
- Vehicle
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Basis (inscription)
- The principle ie responsible for the chief therapeutic action
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Adjuvant (inscription)
- A drug that assists or increases the action of the basis
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Corrective (inscription)
- Modifies or corrects the undesirable effects of the basis
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Vehicle (inscription)
- The agent used to carry the basis
| - eg. as a solvent, to increase the bulk, or to dilute
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FDA pregnancy category A
- Safe
| - Adequate studies in pregnant women have not demonstrated risk to the fetus
85
FDA pregnancy category B
- Believed to be safe
- Animals studies have not demonstrated risk to the fetus
- Not adequate studies on pregnant women
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FDA pregnancy category C
- Believed to be harmful
- Animals studies have demonstrated adverse effect on the fetus
- No adequate studies in humans
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FDA pregnancy category D
- Harmful
- Positive evidence of human fetal risk but potential benefits may warrant use of the drug in pregnant women despite potential risks
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FDA pregnancy category X
- Absolute contraindication
- Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal harm
- Risks involved in use of the drug in pregnant women clearly outweigh potential benefits
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FDA pregnancy category N
- FDA has not classified the drug
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Dependence
- Adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus
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Physical dependence
- Involves persistent physical-somatic withdrawal symptoms (e.g. fatigue; delirium tremens)
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Psychological dependence
- Involves emotional-motivational withdrawal symptoms (e.g. dysphoria; anhedonia)
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Substance abuse
- The use of any substances for non-therapeutic purposes or use of medication for purposes other than those for which it is prescribed
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Addiction
- A condition that results when a person ingests a substance (e.g. alcohol, cocaine, nicotine) or engages in an activity (such as gambling, sex, shopping, eating) that is pleasurable, but the continuation of which becomes compulsive and interferes with ordinary responsibilities and concerns, such as work, relationships, or health
95
Tolerance
- The diminishing effect of a drug resulting from repeated administration at a given dose
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Drug sensitization/reverse tolerance
- The escalating effect of a drug resulting from repeated administration at a given dose
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Schedule I
- Research only
- Not currently for medical use in U.S.
- High potential for abuse
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Schedule II
- High potential for abuse
| - High propensity for physical and psychological dependence
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Schedule II Rx writing rules
- Rx must be written and signed in ink
- Automatic no refill
- No telephone Rx
- Fl: max 3 days supply and must sign consent in office
100
Schedule III
- Moderate potential for abuse
- High propensity for psychological dependence
- Low or moderate for physical dependence
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Schedule IV
- Mild potential for abuse
| - Low propensity for physical or psychological dependency
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Schedule III Rx writing rules
- May be written or oral
| - May be refilled up to five times in six months
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Schedule IV Rx writing rules
- May be written or oral
| - Refill up to 5 times in 6 months
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Schedule V
- Low abuse potential
105
Schedule V Rx writing rules
- No restrictions
- No need for Rx
- May go directly to the pharmacy
- Must be an adult, in limited quantities
- Cannot make another purchase in 48 hrs
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Schedule V "exempt narcotics"
- Antitussives (codeine containing) such as Robitussin
| - Antidiarrheals such as Lomotil, tincture, or Paragoric
107
E-FORSCE Rx drug Monitoring Program
| Electronic-Florida Online Reporting of Controlled Substance Evaluation Program
- Must have 2 hours of CME every 2 year license renewal
- Violations may result in a $10,000 fine and loss of license
- Pharmacists must register and consult with PDMP web site any time a controlled substance is prescribed
108
Hospital orders for Rx
- Inscription (name of drug)
| - Subscription (directions to the nurse: drug, strength, route, how often, how many days, all on one line)
