Test 1 (Pharm) Flashcards
Pharmaco____ is how the drug affects the body (aka how the drug causes chemical and physiological effects) and Pharmaco____ is how the body affects the drug (aka ADME - Absorption/Distribution/Metabolism/Elimination)
** A pro-drug is inactive -> Active once administered
Dynamics, Kinetics
Pharmaceutical Equivalence is when a Generic name drug and Trade name drug have the SAME 1) Ingredients 2) Dosage route (Oral/IV/etc) 3) Strength (concentration)
EX: Oral Lisinopril 5mg - Zestril vs Oral Lisinopri 5mg - Generic = Same since 1, 2, and 3 are all equal
Pharmaceutical alternatives are the SAME DRUG but have either
1) A different complex (Tetracycline: hydrochloride 250mg capsule vs Tetracycline: Phosphate 250mg capsule)
2) A different dosage form (Quinidine sulfate 200mg tablet vs Quinidine sulfate 200mg capsule)
3) A different strength (Vancomycin 250mg capsule vs Vancomycin 125mg/5ml Liquid)
Along with Pharmaceutical Equivalence, Therapeutic Equivalence has all of the 3 Pharmaceutical criteria PLUS the same 1) Clinical effect 2) Safety profile
Finally, there is Bio Equivalence that is involved with the same RATE and ABSORPTION patterns
^** If ALL 3 Equivalences are met, then the Trade name drug and Generic name drug are the EXACT SAME
FDA rated drugs with an ___ rating mean generic and trade name drugs are the same
Know this concept
A
Scheduled/Controlled drugs (which are found in the Legend category) are C-1 to C-5 with C-___ being the most likely drug to be abused/addiction
C-1 (C1 is the highest risk and C5 is the lowest risk out of the Controlled substances)
Non controlled legend medications expire at either ___ months or number of refills reached
^** Is partial filling allowed? Is there a legal limit on number of refills or quantity dispensed during its 12 month life-span?
Controlled legend medications expire at either ___ months of number of refills reached
^** Is there a legal limit on number of refills? Is there a legal limit on how often you can get a refill aka quantity?
C-3 to C-5 can have ___ refills and C-2 can have ___ refills
C3-C5 must have a patient wait ____ days before they can get their next refill and C-2 drugs must have the patient wait ____ days before they can get their next refill
** Partial filling is possible for C3-C5 but not C2
** Also know docs can call in for prescriptions for all legend drugs EXCEPT for C2 (unless it is an emergency)
12
Yes, No
6
Yes, Yes
5, 0
90, 30
KNOW ABBREVIATIONS AND WEIGHT CONVERSIONS
Gm Mg (1/1000 gm) Mcg (1/1000 mg) MEq Lb Kg -> 1kg = \_\_\_ lbs
Tsp -> \_\_\_ ml Tbsp -> \_\_\_ tsp Ounce (OZ) -> \_\_\_ tsp Quart = 2 pints Pint = \_\_\_ Oz Liter = \_\_\_ ml Gallon (G) = \_\_\_ quarts or 8 pints
2.2
5ml 3tsp (aka 15ml) 6tsp (aka 30 ml) 16 1000 4
MORE ABBREVIATIONS
Qd Bid Tid Qid Qod Q"x"h M/T/W/Th(R)/F/Sa/S
Qam Qpm Qhs Prn Ac Pc
Od Os Ou Ad As Au Gtt
Po Sl ** iv Im Sq Pr NGT OGT Ut dict (Ud) Tra Kvo
KNOW THESE
Sl = sublingually aka under the tongue
Normal Saline (NS) contains 0.90% NaCl so half of NS is 0.45% etc…
D”X”W such as D5W has the X tell you the percentage of dextrose in solution so for D5W there is 5% dextrose in solution aka 5 grams of dextrose in every 100 ml of fluid
More concepts
The defining feature of ____ are the presence of the DNA-binding domains that allow them to bind to specific DNA sequences at ___ or ____ regions of the DNA that are adjacent to the coding sequences of the regulated gene; allowing them control the rate of transcription via promoting or inhibiting ____ activity
The specific DNA sequence that they bind to is called a ___
Transcription factors, enhancer or promoter, RNA polymerase
Response element (usually TATA)
Trimeric G proteins have GTPase activity (the ability to hydrolyze GTP) and ____s allow GTP to be exchanged for GDP and therefore the alpha subunit becomes active
___s allow GDP be be exchanged for GTP (aka GTP -> GDP) causing inactivation
^** So GTP hydrolysis by the Alpha subunit causes _____ activity of the GPCR
Gs family activates ___ and ___ Src tyrosine kinase
Gi family inhibits ___ and ___ Src tyrosine kinase
Gq family activates ____
GEFs
GAPs
Decreased
AC, activates
AC, activates
PLC
Inactive PKA has ___ subunits and active PKA has ___ subunits
Inactive = 2 Regulatory and 2 Catalytic
Active = 2 Catalytic
Protein Kinases phosphorylate aka activate and ____s dephosphorylate
During GPCR desensitization, a ligand (agonist) binds to the GPCR and activates the Gs subunit
After the G protein is released to cause signaling transduction, ___ regulates the GPCRs activity by binding and phosphorylating agonist-activated receptors causing ___ to bind to the receptor
The BetaArr-Receptor complex binds to coated pits (which turn into endosomes) causing internalization and dissociation of the agonistic ligand causing no more affinity for B-Arr and since it does not bind anymore, dephosphorylation occurs and the receptor moves back to the membrane to become activated once again
The problem occurs when prolonged exposure to an agonist happens which causes the internalized GPCRs in their endosomes to have enough time to merge with lysosomes causing the entire receptor to be destroyed and therefore downregulation
Phosphatase (P’ase)
GRK (G protein-coupled receptor kinase)
B-arrestin
___ ligands include Ach, NE, E, Dopa, Ser, Hist, ACTH, Bradykinin, Angiotensin, Opioids, GABA, Glutamate, Leukotrienes, TxA2, ADP, ATP, Adenosine
___ ligands include IGF-1, VEGF, EGF, NGF, PDGF, and INSULIN
^** Insulin and IGF have 2 chains (alpha and beta) and most other RTKs have 1
____ ligands include Growth hormone (somatotropin), Erythropoietin, Leptin, Interferons AKA cytokines*
____ ligands include Steroid hormones, Thyroid hormones, Vitamin D, Vitamin A, and Lipid mediators (such as free fatty acids and their products)
GPCR
RTK
JAK-STAT
Nuclear
Like trimeric GTPases involved with GPCRs, ____ is a monomeric GTPase involved with RTKs that helps phosphorylate protein targets in the nucleus, plasma membrane, and cytoplasm that causes alterations in gene transcription and protein activity
The adaptor protein (which brings signaling molecules together) called ____ contains an SH__ domain that binds to the phosphorylated RTK and an SH___ domain that binds to the proline-rich sequences
Just like in GPCRs, ___ activate the monomeric GTPase (Ras) by causing GDP to be replaced by GTP and ___ inactivate monomeric GTPases (Ras) by hydrolysis of GTP
^** The common GEF in this mechanism is called ___
Ras
Grb2 (Growth factor receptor-bound protein 2), SH2, SH3
GEFs, GAPs
Sos
So if you were to have a mutation that affects the GTPase activity of Ras (aka a decrease in GAP), you could get excessive stimulation leading to cancer and most commonly _____ are seen
^** Because remember, GTPase means hydrolysis of GTP -> GDP and therefore if you can no longer convert GTP to the inactive GDP, then excessive stimulation will occur
***GRB2 -> Sos (GEF) -> Active Ras -> Raf -> MEK -> ERK -> Changes in transcription
A point mutation in Raf often leads to ____
One way to treat a patient with a mutation causing excessive cell growth is to either inhibit the growth factor’s receptor or the growth factor ligand itself via ____ OR you could inhibit the kinase activity such as inhibiting RAF1 via _____ inhibitors
Pancreatic adenocarcinomas
Melanomas
Monoclonal Abs, Multikinase
Growth hormones and ____ molecules bind to RTKs that cause JAK to become activated causing the phosphorylation of tyrosine residues on the RTKs
Next, STAT is recruited and the JAK helps phosphorylate STAT as well and then it travels to the nucleus to regulate transcription
**JAK inhibitors can aid in allergic and autoimmune disorders
Cytokine
Steroid/Nuclear receptors have a ____ (delayed or immediate?) action on gene transcription
Nuclear receptors become activated (stabilized and converted to active configuration) when a steroid binds to the ligand-binding domain causing ___ to be dissociated
Now the receptor can translocate into the nucleus with an active DNA-binding domain that binds to the specific gene sequence and a active transcription activating domain that recruits RNA pol which are both needed for altered gene trasncription
Delayed
Hsp90 (heat shock protein)
___-gated channels are regulated by membrane potential changes and ____-gated channels are regulated by ligands binding
Voltage gated Na+ channels and voltage gated Ca2+ channels exist and ___ channels are the ones that deal with cardiac and smooth muscle cells
Name if the NT is excitatory or inhibitory for Ligand-gated channels
1) Ach
2) GABA
3) Glycine
4) Glutamate
^** Excitatory NTs open ___ channels and inhibitory NTs open ___ channels
Voltage, Ligand
Ca2+
1) Excitatory
2) Inhibitory
3) Inhibitory
4) Excitatory
Cation, Anion
Nicotinic Ach receptors allow ____ influx to ___polarize the membrane and are located at ___ muscles and ____ cells
GABA-A receptors allow ____ influx to ___polarize the membrane causing synaptic inhibition in the CNS
Na+, DEpolarize, Skeletal, Neuronal
Cl- HYPERpolarize
The most common absorption method of drugs is ____ driven by a concentration gradient that is a passive process that does not require energy and can not proceed against gradients
Also ionization status determines ability of a drug to passively be absorbed (ionized and unionized form = 100%)
Active transport (carrier mediated) is energy requiring and can become saturated
^** Facilitated diffusion is kind of like both active and passive because it does NOT require energy and can not move against a concentration gradient, but it has a facilitator to help it move across
Diffusion
**Ionized (aka charged) compounds have ____ lipid solubility meaning they ____ (do or do not?) diffuse across the lipid bilayer of membranes ***
Unionized compounds have high lipid solubility and therefore do diffuse across the lipid bilayer of membranes
ALL NONpolar compounds aka non water soluble, can diffuse across the lipid membrane
SMALL-POLAR-UNionoized compounds can also cross the lipid membrane but LARGE-POLAR-UNionized compounds can not
Low, do NOT
When pKa = pH, there is a 50/50 split ratio of Ionized:Unionized
As the base goes to the higher pH state (aka the more basic state) then you have a higher ____nized form
As the acid goes to the lower pH state (aka the more acidic state) then you have a higher ____nized form
***So for example, if you give someone a weak acid drug and it makes it to the stomach (which is strongly acidic) you would have more than 50% of the drug in its unionized form (since the acid is in a low pH aka acidic state) and as it moves into the intestines into a less acidic environment, it will become less and less unionized since now the acid drug is moving into a high pH aka basic state
Unionized
Unionized
For the distribution component of ADME, unbound (the free drug) is ____ (active or inactive?)
^** Alpha value is the percent of ___ (bound or unbound?) drug, so a small alpha volume means a small amount of unbound drug (large amount of protein bound drug) which means only a small amount of the drug is active because most of the drug is bound to proteins
Active
Unbound
Metabolism aka biotransformation has 2 reactions called
1) Phase 1 reactions causes drugs to become different such as the ___ system (which is part of the oxidation phase 1 reaction process)
^** A ____ is when a drug NEEDS the CYP450 system to be metabolized, inducers rev up the CYP450 system, and inhibitors also exist
So for example, lets say a substrate that uses the Cytochrome p450 enzyme system (aka 2C19) to go from an active drug to an inactive drug…
^Then lets say you give the patient a 2C19 inducer, the substrate (aka the first drug) will therefore ____ in quality and quantity **Because it is getting cleared and chewed up faster
^*Instead of an inducer, lets say you gave the patient an inhibitor of 2C19, then the 1st drug will ___ in quality and quantity **Since it does not get destroyed by 2C19 anymore
Now lets pretend like the original (1st) drug is a pro-drug (aka inactive until metabolized and then becomes active) needs to go through 2C19 to be turned on
^* If you give a 2nd drug that acts as an inducer of 2C19, the 1st drug will be metabolized faster and therefore increase in quality and quantity and vice-versa if an inhibitor 2nd drug is given
1) CYP450
Substrate
Decrease
Increase
First-pass effect tells us what % of a drug taken orally gets into the blood stream and heads straight to the ____ where it becomes metabolized
^** Think of it as an absorption killing process if dealing with a drug active from the beginning (not a pro-drug)
So a high first-pass rate of an active drug means most of it goes from the stomach -> blood -> Liver -> Metabolized to an inactive form… And therefore you would want to give it via an IV or injection rather than orally
Liver
1st order drugs have an elimination rate that is proportional to the concentration of the drug in the plasma (Cp) so for example, lets say there is 500mg/ml of drug in the plasma… After the first half-life, there will be 250mg/ml, after the second half-life there will be 125mg/ml, etc… ALWAYS
** So one more time…. The rate of elimination is ____ to the concentration*
Zero order drugs have their rate of elimination being ____ NO MATTER WHAT the concentration is
^** CAN reach a Vmax (aka a ceiling where they become fully saturated and can no longer metabolize the drug) and therefore their drug levels go up and this is seen in high levels of ethanol and aspirin overdose
Proportional
Constant
If you give an IV rather than oral drug, your onset would be ____ (shorter or longer?) due to the fact that you reach the MEC (Minimum effective concentration) faster
Dosing interval (aka dosing frequency) is one of the KEY things that determines ___
^** So realize that Cmin is the concentration of drug in the blood present at the time of a second dose administered, so if you give a second dose at to high of a Cmin, it can become toxic so wait a little longer and if Cmin is to low give them the second dose sooner
**Cmax is related to the AMOUNT of drug (aka the amount of the dose) given so in other words, if you want a higher Cmax give more drug and if you want a lower Cmax give less
Shorter
Cmin
IV route has an F value (bioavailability value) of ___ ALWYAS since it is not absorbed***
F values not involving IVs describe the extent of absorption aka how much of the drug actually gets into the body
**Salt factor is ALWAYS 1 so don’t worry about it on tests
Vd (Volume of distribution) represents the EXTENT of a drug’s distribution throughout the body and a ___ (bigger or smaller?) value means a large body-distribution (aka the more places it can go) so if it is around 5 liters or less, since the blood stream contains around 5 liters the drug will only be distributed in the blood but if the Vd is bigger than 5 liters (like 100 liters) it will get out of the bloodstream and go to lots of places
1
Bigger
Tau represents the dosing interval
If a pill is given once a day, then the Tau is ___
If pill is given 3 times a day, Tau is ___
If given 4 times a day, then Tau is __…etc
24
8
6
It takes ___-___ half life’s of a 1st order drug for a patients physiology to reach stead state (at least over 90% of the drug concentration at a stead state)
^** Steady state (Cpss) is rate in = rate out
Stead state is a timed process and will occur with both interval dosing and continuous infusions
So lets say a drugs half life was 4 hours… It would take between ___-___ hours until the drug reached steady state?
***Also realize that if you know the patients steady state than dosage adjustment is proportional so lets say you increased dosage by 10%, then the new steady state would be 10% higher than what it was
^* Aka if you DOUBLE the dose you will DOUBLE the level****** WILL BE A TEST QUESTION SO KNOW HOW TO SET UP THE PROPORTION
4-5
4x4 or 4x5 = between 16 to 20 hours before steady state is reached
**KNOW HOW TO CALCULATE THE CREATININE CLEARANCE (eGFR)****
EGFR = ____
((140-age) x IBW / (72xSCr))
____ is the enzymatically driven process where a substance is changed from one chemical to another
^ Often used for eliminating compounds by making them more polar, water soluble, and often larger
Biotransformation
A drug first gets absorbed into the blood stream and then undergoes phase 1 reactions which either
A) Inactivates the drug by making it more ____ aka water-____ and sometimes larger
B) Modifies the activity (such as activating a pro-drug)
^** Includes Oxidation, Reduction, and Hydrolysis reactions which are all ___bolic
After metabolism, the drugs undergo phase 2 reactions which cause the drug to undergo ____ with a polar moiety such as ___, ____, or ____ to cause the metabolite to be water soluble (less lipid-soluble) and increased molecular weight and therefore easily excreted
This is an ___bolic process
** Think of CYP450 as the initial step of phase ____ reactions ****
A) Polar, soluble
Catabolic (break down)
Conjugation, GAS (Glucuronate, Acetate, or Sulfate)
Anabolic
Phase 1
Sometimes the body is exposed to certain drugs that cause an increased transcription of CYP450 in order to make more enzymes that can break the drug down… This is called enzyme _____ because the patients are on an inducer that causes their enzyme levels to be increased (such as chronic alcoholics) so other drugs given to these patients will also be broken down faster and therefore the half-life of these drugs will ____ and their clearance will increase
^** As half life decreases, clearance is increased
^** In other words, enzyme induction leads to ____ substrate metabolism and ____ pharmacologic action of the inducer and coadministered drug
** ^Examples include phenytoin, chronic ethanol, benzo[a]pyrene (tobacco smoke), rifampin, phenobarbital, and other barbiturates used for sedation
Enzyme inhibition is another factor that affects metabolism and one great example of an enzyme inhibitor is ___ that inhibits CYP___ therefore more enzymes arent able to help in metabolism causing changes in the bioavailability of certain drugs
Metabolism can also be decreased by a ____ hepatic blood flow
Induction, decrease
Increased, decreased
Grapefruit juice, CYP3A4
Decreased
Enzyme ___ like ethanol (chronic alcoholics) can increase acetaminophen toxicity since phase ____ metabolism is increased more than phase 2 (since the body runs out of phase 2 conjugates), and phase 1 metabolism can convert acetaminophen into toxic byproducts
Inducers, Phase 1
CYP450 is an example of pharmaco____ because it is what the body does to the drug aka the variation in the rate at which the body absorbs, transports, metabolizes, or excretes a drug/metabolites
** Polymorphism is the variations in the DNA sequence that is present at an allele frequency of 1% or greater in a population
G6PD defects is an example of pharmac____ because it is what the drug does to the body aka an allelic variation in a drugs downstream target such as the receptor, enzyme, or metabolic pathway
^**G6PD will cause hemolytic anemia due to the fact that ____ is reduced and this is needed to reduce ROS so blood in urine occurs
If one is given Sulfa drugs, then the G6PD needs increase and patients with defects can’t keep up and this will lead to the hemolytic anemia
^***Also VCORC1 (Vitamin K epoxide reductase) is an example of pharmacodynamics
Variations at multiple gene loci is called ___ effects such as mutations in VCORC1/CYP2C9 that inactivate Warfarin aka Coumadin ( aka there are changes in the biotransforming enzymes AND changes in the drug targets)… Since the enzymes are mutated Warfarin’s action does not get properly decreased if given to a patient leading to an increased risk of bleeding
Pharmacokinetics
Pharmacodynamics
NADPH
Polygenic
Succinylcholine, a depolarizing neuromuscular blocking drug, can be associated with defects in the enzyme that breaks it down called Pseudo___ that metabolizers the succinylcholine and therefore these patients have a 50% slower rate compared to normal individuals and therefore it would take longer for a patient to come out of a paralysis state
^** This would be considered a genetic factor due to ___ in xenobiotic-metabolizing enzymes
Another example of a genetic defect can be from pharmacogenetic differences in enzyme expression levels like in patients with slow acetylator phenotypes that have a decreased N-acetyltransferase level and therefore can not metabolize certain compounds like caffeine
Pseudocholinesterase
Polymorphisms
___ bonds are irreversible and ____ bonds are reversible
From strongest to weakest, Ionic > Hydrogen > Hydrophobic > Van der Waals
Covalent, Non-covalent
A ____ curve describes the relationship between a drug’s dose and its effect
The maximum effect that can be produced by the drug is called ____ aka ____y
The dose of that drug that produced 50% of the maximum effect (Emax) is called ___ aka ____
*** The smaller the ED50, the _____ potent the drug (because think about it, less drug is needed to produce 50% of the maximum effect)
Dose-response curve
Emax, efficacy
ED50, potency
More
Instead of a dose-response curve that tells us the relationship between a drug’s dose and its effect, one can also plot a dose-binding curve which shows us the relationship between a drug’s dose and how many receptors it binds to (aka the affinity)
The concentration of a drug when 50% of the receptor sites are bound is denoted ___
^** The smaller the Kd, the _____ the affinity (because think about it, a small Kd means a small drug dose will still allow 50% of the receptors to be bound
Drugs with a smaller Kd aka higher affinity for a receptor are ____ potent
** One can also determine Bmax (the total number of receptors in a system) if they know how many binding sites on each receptor exists
Bmax represents efficacy and therefore related to the total number of receptors available to bind a drug so drugs with a high Bmax aka more receptors able to bind have ____ efficacy
**** So once again it is important to realize the difference between drug effect (Emax/ED50) and drug-receptor binding (Bmax/Kd) and realize that ED50 DOES NOT ALWAYS EQUAL KD because it depends on the coupling of receptor occupancy and response to a drug
^** If the ED50 is LESS than the Kd, then ___ receptors are said to exist which means that the maximum drug dose aka Emax will be obtained at LESS than 100% receptor occupancy aka Bmax
Kd
Greater
More
More (aka higher)
Spare
When drugs have Intrinsic activity, they can change a receptors function to produce a response upon binding
One example is an ___ which changes a receptors conformation and usually activates it
^** This ____ (does or does not?) have intrinsic activity
Another example is an ____ which binds to the receptor, does NOT change the function, but prevents the receptor from being activated aka inhibiting it from binding to an agonist so no affect can be produced
^** This ____ (does or does not?) have intrinsic activity (aka intrinsic efficacy)
Agonist
Does
Antagonist
Does NOT
There are also FULL and PARTIAL agonists
Full agonists have MAXIMAL intrinsic activity and fully activate receptors
Partial agonists have a sub-maximal effect (intrinsic efficacy) and only partially activate the receptor upon binding
^** In other words, they bind to the receptor but have a ___ Emax (aka effect/efficacy) at full dosage than a Full agonist
In the presence of a full agonist, a partial agonist acts as an _____ and results in a neutral antagonist
Smaller
Inhibitor
___ agonists have intrinsic activity due to the fact that they bind to a receptor (specifically, the inactive Ri state of the receptor) and change the conformation causing NO constitutive activity, aka activity in the absence of a ligand, to occur
Inverse
___ receptors include competitive and non-competitive antagonists that have their action at the same receptor as endogenous ligands or agonist drugs
___ antagonism is when there is interaction directly with the drug being antagonized to remove it or to prevent it from binding to its target
___ antagonism is when the antagonist binds to a different receptor molecule to produce an effect that is opposite to that produced by the drug it is antagonizing (**So for example, if one drug causes bronchoconstriction, and you gave someone a drug that caused bronchodilation, it would negate the original drug’s actions via different receptors and pathways and therefore is a physiologic antagonist)
Pharmacologic
Chemical
Physiologic
As we just said, pharmacologic antagonists can be competitive or non-competitive
Competitive antagonists bind to the agonists receptor site in a reversible way without activating the effector system for that receptor and therefore the dose-response curve is shifted to the ____ leading to a increased ED50 but NO increase in Emax since the competitive antagonist can be overcome
Non-competitive antagonists decrease the Emax, but ED50 does NOT change
A) Irreversible at the active binding site
B) Allosteric and Irreversible
C) Allosteric Reversible
^** Allosteric means that it binds to a site other than the agonist’s binding site
So just to recap, competitive has an ___ ED50 and ____ Emax
And noncompetitive has a ____ ED50 and ____ Emax
Right
Irreversible
Increased, No change
No change, Decreased
Potency is related to the drug’s ____ whereas efficacy is related to the drug’s _____
^** Related to Kd and Bmax for what it comes down to
Dose, Maximal effect
Grade dose response curves tell us about the ____ aka “how much”
Quantal response curves tell us about the RESPONSE of individual dugs aka “does the response occur? Or In how many people does it occur?”
^** Quantal dose response curves can be either Cumulative or Non-Cumulative. A non-cumulative quantal dose response curve shows how many people respond to a drug as a SPECIFIC dose (aka ONLY at that dose) whereas a cumulative quantal dose response curve shows how many people respond to a drug at a specific dose and ALL DOSES LOWER
^** Using the ____ quantal dose response curve, one can calculate the ED50 which would show the ___ effective dose at which 50% of a population will respond to that drug at a certain dose
Effect
Cumulative, median
Therapeutic index (TI) is calculated by ____ / ____ and the ___ the TI, the SAFER the drug
So if drug A has a TD50 aka becomes toxic at 500 mg and the Therapeutic effect works at 10 mg, then the TI = 500/10 -> 50
Now lets say drug B has a TD50 of 250mg and a Therapeutic effect at 10mg, the TI = 250/10 -> 25
So since drug A has a higher TI, it is more safe which makes sense since the therapeutic effect is further away in concentration to the toxic effect in drug A compared to drug B
A narrow therapeutic window is when the effective aka therapeutic (ED50) effect is close to the Toxic effect (TD50) and a wide window is when they are far away so in the example above, drug A would have a WIDE window and drug B would have a NARROW window
TD50/ED50 (aka Toxic effect / Therapeutic effect), higher
