D&D Unit 1 Flashcards
With enteral drug delivery (rectal), _________% of the dose will bypass the _________
50
Liver
Paraenteral drugs (sublingual or buccal) are absorbed into the _________
Superior vena cava
The best particle size for lung inhalation is _________ where particles are deposited in the _________
1-5 uM
Small airways
exhaled
>10uM -> deposited in oropharynx -> side effects
Henderson-Hasselbach equation
pH-pKa = log[ (non-protonated A- or B)/protonated Ha or BH+)]
Ion trapping means _________ drugs are trapped in _________ solutions (and also reverse)
Acidic/Basic
vs
Basic/Acidic
Acidic drugs bind to _________ and basic drugs bind to _________
Albumin
Alpha-1 acid glycoprotein
A drug binding to a protein _________ concentration of free drug, _________ metabolic degradation/excretion rate, _________ volume of distribution, _________ ability to enter CNS
Decreases all
Equation for absolute bioavailability fraction
area under curve any route (usually oral) /area under curve IV
What is the volume of distribution?
Volume of body fluid into which the drug distributes after admnistration
Equation for loading dose
Cp * Vd
peak concentration * volume of distribution
Equation for peak concentration
Dose /Vd
Equation for calcuating volume of distribution
dose/plasma concentration
Equation for backcalculating dose
plasma concentration * Vd
Calculating drug concentration in plasma
dose/Vd
A low volume of distribution means most of the drug is in the _________
Plasma, vs in other fluids
Drug metabolism produces a more _________ form of the drug
Water soluble
Milk is more _________ than plasma (pH)
Acidic, so basic things tend to be in it
_________ content of milk increases during the feeding period
Fat
Protein binding _________ drug concentration in milk
Decreases
Drug clearance equation
Vd * Ke
Volume of distribution * fraction of drug eliminated per unit time
MD*Cp/tau
Maintenance dose * peak concentration / dosing interval (hour)
What is clearance?
Volume of plasma completely cleared of a drug in a given period of time, mostly due to kidney excretion and drug metabolism
Maintenance dose equation
MD/tau = clearance * Cp
What is the elimination rate constant?
The fraction of a drug leaving the body per unit time via all elimination processes. It lets us calculate the amount of drug remaining.
What does first-order kinetics mean in terms of pharmacokinetics?
Rate of elimination is proportional to plasma concentration
What does zero-order kinetics mean in terms of pharmacokinetics?
The rate of elimination is independent of the amount of drug in the body and is constant.
What is potency?
Concentration or dose required to produce 50% of a drug’s maximal effect
What is EC50?
“Effective Concentration 50”
The drug concentration that gives half-maximal response
What is ED50?
“Effective Dose 50”
The drug dose that gives half-maximal response
What is drug efficacy?
Maximum response achievable from a drug
Therapeutic index equation
lethal dose for 50% of people / ED50
Higher is better
It is a unitless factor
Standard drug safety margin equation
100*(LD1/ED99)
Many drugs are metabolized through actions of membrane-bound enzymes of the SER called _________
CYP450
A phase 1 drug metabolism reaction renders the molecule more _________
Water soluble
A phase II drug metabolism reaction is when a the molecule is rendered highly polar so that it can be _________
Excreted (via urine)
The process by which drug metabolites in the liver are secreted into bile, stored in the gallbladder, delivered to the intestine via the bile duct, hydrolyzed by bacterial enzymes back to the parent drug and undergo reabsorption from the gut is _________
Enterohaptic recycling
Drug receptor theory assumes that binding is _________ and response is _________ to receptors
Reversible
Proportional
Pharmacokinetic factors affecting drug dose (4)
Absorption
Distribution
Metabolism
Excretion
Drug distribution can be of clinical consequence if the displaced drug has a _________, is started in _________, _________ is small, or _________ to a drug occurs more rapidly than _________
Narrow therapeutic index High doses Volume of distribution Response Redistribution
Pharmacodynamic factors affecting drug dose (3)
Antagonistic Synergistic/additive therapeutic
Synergistic/additive side effects
Indirect pharmacodynamics (a drug indirectly affects another drug)
2 ways to induce emesis
Ipecac
Apomorphine (not commonly used anymore though)
Contraindications of emetic agents (4)
Lack of gag reflex (b/c comatose) -> risk of aspiration
Ingestion of corrosive poisons
Ingestion of CNS stimulant -> risk of seizures
Ingestion of petroleum distillate -> risk of pneumonitis, pregnancy category C
4 ways to prevent drug absorption
Emesis
Gastric lavage
Chemical adsorption (activated charcoal)
Osmotic catharthics (decrease time in digestive tract)
Gastric lavage is introduction of _________ and removal with a _________
Saline
Nasogastric tube
The combination of gastric lavage and emesis removes _________% of oral poisons
30
Apomorphine is a _________ agonist and produces _________ by stimulation of _________
Dopamine
Emesis
Chemoreceptor trigger zone
4 osmotic catharthics are
Sorbitol 70%
Magnesium citrate or sulfate
Sodium sulfate
Polyethylene glycol
Contraindications for magnesium citrate or sulfate (osmotic catharthics) are (2)
Renal disease
Poisonings with nephrotoxins
4 ways to enhance elimination with toxin ingestion are
Extracorporeal removal
Enhanced metabolism
Enhanced renal excretion (now questionable)
Chelation of heavy metals
2 ways extracorporeal elimination can be done to remove toxins
Dialysis
Hemoperfusion (blood pumped through a column of absorbent material)
Dialysis is best for removal of drugs with a _________ volume of distribution
Small
2 ways to enhance renal excretion of a toxin
Forced diuresis
Block reabsorption
70-80% of acetaminophen is conjugated with _________ in adults and _________ in children
Glucuronic acid
Sulfate
Hepatocellular injury occurs with acetaminophen overdose from excessive formation of _________
Ac*
Alcohol dehydrogenase can be inhibited by _________ (drug)
Fomepizole or ethanol (competitive inhibition)
Ethylene glycol is metabolized by _________ to form _________, which causes _________ damage
Alcohol dehydrogenase
Oxalic acid
Renal
Methanol is metabolized by _________ to form _________, which causes _________ damage
Alcohol dehydrogenase
Formic acid
Retinal
What is the structure of peptidoglycan?
A polymer with repeating units of 2 hexose sugars (N-acetylglucosamine, N-acetylmuramic acid)
Where does peptidoglycan localize?
Bacterial cell walls
Bacterial capsules enhance virulence by _________
Enabling phagocytosis resistance
Peritrichous means flagella are distributed _________
All over the surface
Gram-positive bacteria have a _________ peptidoglycan layer than gram-negative bacteria
Thicker
What are the 4 phases of bacterial growth?
Lag
Exponential
Stationary
Death
Heterotrophic bacteria get carbon from _________
Organic sources
Autotrophic bacteria get carbon from _________
Carbon dioxide
_________ bacteria are deficient in at least 1 biosynthetic pathway and require addition of energy and nutrients
Fastidious
Obligate intracellular bacteria need to grow in _________
Eukaryotic cells
_________ pathogens cause disease in normal hosts and _________ pathogens cause disease in compromised hosts
Frank
Opportunistic
Aggressins are microbial products that _________ the host
Damage
Impedins are microbial products that _________ the host
Block defenses of
What is bacterial transformation?
Uptake of genetic material
What is bacterial transduction?
Transfer of genetic material by a virus
The major organ of drug metabolism is the _________
Liver
The major organ of drug excretion is the _________
Kidney
What is the difference between extension effects and side effects?
Extension effects at supra-therapeutic doses
Side effects at therapeutic doses
Size comparison between drugs that diffuse via aqueous or lipid diffusion
Lipid diffusion drugs are larger
What 2 things determine equivalency of oral drug products for FDA approval?
Rate, estimated by peak concentration
Extent (bioavailability)
They must be similar
Food _________ oral drug absorption
Delays
In pharmacokinetics, tau is the _________
Dosing interval
What is bioavailability?
% of dose reaching systemic circulation
Absorption from the GI tract is primarily via _________
Lipid diffusion
The plasma/blood volume is
3-5 L
The extracellular water volume is
12-15L
The total body water is
42 L
What is the difference between pharmacokinetics and pharmacodynamics?
Pharmacokinetics is what the body does to the drug
Pharmacodynamics is what the drug does to the body
What are the 4 things drugs are for?
Prevention
Diagnosis
Treatment
Cure
of specific diseases
What 5 things does a prescription provide?
Drug Dose Route Frequency Duration
Drug lipid solubility is estimated by the ____________
Oil-water partition coefficient. A higher proportion in the oil phase is more lipid soluble.
Bioavailability (F) for IV drug administration is ____________
100%
Bioavailability (F) for oral drug administration is ____________
0-100%
The rate of onset for various drug administration methods ranked
Inhalation > IV > intramuscular > subcutaneous > oral
Under what condition should you not switch between different versions of the same drug?
Narrow therapeutic window
What two conditions must be met for bioavailability?
Rate and extent of absorption
What are effectors in relation to drugs?
Effectors are the components of the biologic system that accomplishes the biologic effect after being activated by the receptor
What does receptor theory allow us to do?
Allows us to make dose-response curves and quantify relationship between drug dose and effect
Most drugs are ________ agonists
full (vs. partial)
Is potency of efficacy more important clinically?
Efficacy, because we care mostly about the end result
Is the maximal efficacy of an agonist changed when an competitive agonist is added?
No. Just higher doses are needed.
Substrates for CYP450 must be ________ -soluble
Lipid
Isozyme CYP nomenclature, for example CYP1A2
CYP = human origin 1 = isoform family A = subfamily 2 = individual gene product
What is enzyme induction?
When a drug induces/enhances enzyme expression - so more enzyme is produced
Is the free drug filtered by the glomeruli?
No. Only the protein-bound
What is the normal glomerular filtration rate?
120 ml/min
Where does active tubular secretion of drugs happen?
In the proximal tubule
What sorts of compounds (drugs) are cleared by active tubular secretion?
Stronger acids and bases
3 common phase 1 biotransformations
Oxidation
Reduction
Hydrolysis
5 common phase II biotransformation
Glucuronidation
Acetylation
Glytathione/glycine/sulfate conjugation
What is the cofactor for CYP450?
NADPH
The therapeutic index compares ________ in the population and the standard safety margin compares ________ in the population
Midpoints
Extremes
FDA categories for drug use in pregnancy
ABCDX
A = no risk X = contraindicated
What is the difference between federal vs. state drug regulation
Federal government controls what drugs
State government controls who prescribes drugs
What are the 4 drug regulatory categories distinguished by? (3)
Whether or not they are evaluated for efficacy or safety prior to use in patients
Available by prescription or direct purchase
Potential for abuse
A phase I trial tests ________
If a drug is safe
A phase II trial tests ________
If a drug works in patients
A phase III trial tests ________
If a drug works in a double blind study
A ________ application is submitted to the FDA if animal studies are promising
Investigational new drug
If phase III trials or promising, a ________ application is checked out by the FDA
New Drug
An ________ can be submitted to the FDA for generic drugs rather than clinical trials and only ________ standards must be met
Abbreviated New Drug Application
Bioequivalence
A phase IV clinical trial is ________
Marketing surveillance aka submitting reports of adverse effects
What 2 drug categories should you not switch between brands?
Levothyroxine
Anti-epileptic drugs
The 3 types of drug equivalency categories
Pharmaceutical equivalence
Bioequivalence
Therapeutic equivalence
What is the difference between vitamins/minerals/amino acids and herbal meds?
The drug part is not known for most herbal medications unlike the other stuff, which has safe dosage ranges and sometimes daily allowances
For new dietary supplement ingredients (after 1994), what must the manufacturer do?
Provide reasonable evidence it is safe for human use
What FDA requirements are there for health claims?
Evaluation and authorization
What RDA requirements are there for structure/function claims?
Nothing except the disclaimer
What are the 3 things drugs are evaluated for on the schedule system?
Medical usefulness
Abuse potential
Risk for dependence (physical, psychological)
What drugs can go through endothelial call gap junctions?
Free drugs, charged and uncharged
Not protein-bound drugs
Inputs from the body for Phase I oxidation reactions
Oxygen
NADPH
Why are phase II reactions more likely to saturate?
Because metabolites are more scarce, so you run out faster.
1st order -> 0 order kinetics
Chronic alcoholics are fast _________ metabolizers
CYP2E1
_________ is a CYP450 genetic polymorphism that metabolizes codeine
CYP2DG makes codein more active (into morpheine)
Alcohol dehydrogenase is a phase _________ reaction
I
Glucaronyl transferase is a phase _________ conjugation enzyme
II
How do you tell by drug nomenclature is a pain drug is an amide?
-caine means they are local anasthetics and work on sodium channels
Amides have an extra I in the prefix
How long does it take for drug induction to occur?
2-3 days and max effects are 7-10 days
Same time frame for effects to dissapate
Phase I enzymes are _________ prone to inhibition than phase II enzyme
More
How does Rifampin affect oral contraceptive metabolism?
Increases clearance due to induction
How does erythromycin affect lipitor metabolism?
Decreases clearance due to inhibition
2 phases of the log concentration vs time graph for IV drug input
Distribution
Elimination
How to calculate fold fluctuation in multiple drug boluses
2^x where x=# half-lives that occur in the dosage interval
What are the 2 types of dose response curves?
Graded - measure amt of response
Quantal - measure % of people responding
FDA drug-labelling rules for specific populations - what are the 3 populations of note?
Pregnancy
Lactation
Females and Males of Reproductive Potential
2 methods of pharmacodynamic drug-drug interactions
Drugs have same target
Drugs enhance/antagonize the other drug’s effector system
No changes in plasma concentration!
Glomerular filtration is decreased by _________ and increased by _________
Nephrotoxic drugs
Displacement from plasma proteins
Tubular secretion is decreased by _________
Competition for active transport like penicillin
Tubular reabsorption is increased for _________ drugs and decreased for _________
Weak bases
Weak acids
Tubular reabsorption increases by _________
Increased urine pH
What 4 things are needed to demonstrate pharmaceutical equivalence?
Active ingredients
Dosage formulation
Route of administration
Strength/concentration
Do generics need to demonstrates therapeutic equivalence?
No. It is assumed if they are pharmaceutically equivalent and bioequivalent
When is it advisable (in terms of drug properties) to avoid switching between drugs?
Narrow therapeutic index
Zero order pharmacokinetics
Poor bioavailability
Contraindication for sodium sulfate osmotic cathartic
Congestive heart failure
Hypertension
b/c will cause systemic Na+ absorption, leading to edema
What drug is used to correct metabolic acidosis?
NaHCO3
How does acetaminophen toxicity happen?
Saturation of phase II pathways so more goes by phase I
Increases formation of phase I hepatotoxic metabolite
What drug is used for management of acetaminophen intoxication?
N-acetylcysteine
A precursor for glutathione synthesis
Inactivates the hepatotoxic metabolite
3 classes of drugs limited to prescription use
Controlled substances (habit-forming)
Not safe w/o supervision
Limited to prescription only under an NDA
Generalized scheme of drug action
Drug binds to receptor
Signal transduction via effectors
Amplification
Physiological effect
Without an agonist, what are the effects of antagonists?
No effects
What are rules in a patient getting a schedule II drug in terms of prescriptions (3)?
In ink in prescriber’s handwriting
Cannot be telephoned to a pharmacist
Cannot be refilled
ac on a prescription means _________
Before meals
bid on a prescription means _________
Twice a day
hs on a prescription means _________
At bedtime
pc on a prescription means _________
After meals
prn on a prescription means _________
When needed
qam on a prescription means _________
Every morning
tid on a prescription means _________
3x/day
a on a prescription means _________
Before
c on a prescription means _________
With
gtt on a prescription means _________
drop
p on a prescription means _________
after
qs on a prescription means _________
Sufficient quantity
s on a prescription means _________
without
Sig on a prescription means _________
label
_________ is a CYP450 genetic polymorphism that metabolizes acetominophen to Ac*
CYP2E1