pharm (conceptual) High yield FA Flashcards
what is Km and how does it relate to substrate affinity?
Km = [S] at 1/2 Vmax. Km is inversely related to affinity of the enzyme for its substrate (high Km = low affinity and vice versa)
How is Vmax of a reaction related to the enzyme concentration?
Vmax is directly proportional to the [enzyme] (as the enzyme increases, so does the Vmax)
if an enzymatic reaction follows Michaelis-Mentin kinetics (as most do), the graph of [s] vs Vmax is what shape? What shape is the graph for reactions that follow cooperative kinetics?
Michaelis-Menten = hyperbolic, cooperative = sigmoidal (think Hgb)
What is the X axis on a Line weaver burke plot? What is the Y axis? And what is the benefit of this graph?
X axis = 1/[substrate], y axis = 1/V. The benefit of this graph is you can see how inhibitors (competetive and non-comp) affect the graph
In a Lineweaver-Burke plot, what does the Slope represent? What is the X-intercept? The Y-intercept?
Lineweaver burke plot, X axis = 1/[substrate], y axis = 1/V. so the slope = Km/Vmax, x-intercept = 1/-km, y=1/Vmax
On a Lineweaver burke plot, a higher Km (and therefore a lower affinity) crosses the X axis…. whereas a lower Km (and therefore a higher affinity) crosses the X axis…
high Km = on the left of the y intercept, but as close to it as possible (small negative numbers), low Km = as far to the left of the y intercept as possible (big negative numbers)
On a Lineweaver burke plot, a higher Vmax crosses the Y axis…. whereas a lower Vmax (and therefore a higher affinity) crosses the Y axis…
A higher Vmax crosses the Y axis closer to the X-axis, a smaller Vmax crosses the Y axis in the positive quadrant as far away from the x-axis as possible
Do competitive inhibitors: 1) Resemble the substrate, 2) Overcome by increase [S], 3) Bind active site, 4) Effect Vmax, 5) Effect Km, 6) Effect Pharmacodynamics?
competitive inhibitors: 1) Resemble the substrate = yes, 2) Overcome by increase [S] = yes, 3) Bind active site = yes, 4) Effect Vmax = no, you can add more substrate and get to the same Vmax, 5) Effect Km = increased (affinity is decreased) be you need more substrate to get to 1/2 Vmax, 6) Effect Pharmacodynamics = it makes it less potent (you need more substrate to get the same effect)
Do noncompetitive inhibitors: 1) Resemble the substrate, 2) Overcome by increase [S], 3) Bind active site, 4) Effect Vmax, 5) Effect Km, 6) Effect Pharmacodynamics?
noncompetitive inhibitors: 1) Resemble the substrate = no, 2) Overcome by increase [S] = no, 3) Bind active site = no, 4) Effect Vmax = yes, Vmax is decreased bc Vmax is directly proportional to the amt of enx avb and now there are fewer enz avb, 5) Effect Km = no, Km is unchanged, 6) Effect Pharmacodynamics = decreased efficacy ( you decrease the maximal effect a drug can provide)
How does a Competitive inhibitor compare to the normal substrate on a lineweaver burke plot in terms of where it crosses on the X and Y axis?
the competitive inhibitor crosses the x-axis further to the right of the normal substrate (the Km increases, the affinity decreases), and at the same point of the y-axis (vmax is unchanged) – competitive inhibitors cross each other competitively, noncompetitive inhibitors do not
How does a noncompetitive inhibitor compare to the normal substrate on a lineweaver burke plot in terms of where it crosses on the X and Y axis?
the noncompetitive inhibitor crosses the x-axis at the same site of the normal substrate (the Km is unchanged), and a higher point of the y-axis (Vmax is less) – competitive inhibitors cross each other competitively, noncompetitive inhibitors do not
What is the bioavailability of a drug?
the fraction of the administered drug that reaches systemic circulation unchanged
What is the bioavailability of an IV drug? An oral drug?
IV = 100% (bc the bioavailability is the fraction of the drug administered that reaches the systemic circ. unchanged). Oral bioavailability is typically <100% due to incomplete absorption and first pass metabolism
What is the Volume of Distribution of a drug (Vd), both definition and equation
The theoretical fluid vlume required to maintain the total absorbed drug amount at the plasma concentration. volume of distribution = (amount of drug in the body)/(plasma drug concentration)
The Volume of distribution (Vd) can be affected by diseases in what two organ systems?
liver and kidney- decreased protein binding increases Volume of distribution
If the Volume of distribution (Vd) is low (4-8 L), where is the drug likely contained and what types of molecules are these?
It’s largely distributed in the blood, and it’s large/charged molecules that are plasma protein bound
If the Volume of distribution (Vd) is medium, where is the drug likely contained and what drug types/molecules are these?
It’s largely distributed in the ECF and it’s mainly small hydrophilic molecules
If the Volume of distribution (Vd) is high, where is the dug likely contained and what drug types/molecules are these?
It’s largely distributed in all tissues, and this is mainly small lipophilic molecules, especially i bound to tissue protein
If a drug has first-order elimination, how many half lives does it take to reach a steady state [ ] of the drug?
4-5 half lives
equation for a drug’s half life
t(1/2) = (0.7 x Volume of Distribution)/CL where CL = rate of elimination of drug plasma drug concentrations = Vd (volum of distribution) * Ke (elimination constant), sp t(1/2) = 0.7 x Vd/ Vd x Ke
What is Clearance
relates the rate of elimination of a drug to the plasma concentration = Vd (volume of distrbution) x Ke (the elimination constant)
Clearance can be impaired with defects in which three organ systems?
cardiac, hepatic and renal
How do you calculate the Loading Dose for a drug?
Loading Dose = Cp x (Vd/F) where Cp = target plasma conc., Vd = volume of distribution and F = bioavailability
How do you calculate Maintenance dose?
Maintenance dose = Cp x CL/F where Cp = target plasma conc, CL = clearance (Vd x Ke (the elimination constant) and F = bioavailability
How are the maintenance and loading doses affected by renal and liver disease
the maintenance dose goes down (Maintenance dose = Cp x CL/F and clearance would decrease in renal disease and bioavailability would increase in liver disease), but loading dose is unchanged
the time to steady state depends primarily on…
t(1/2). it is independent of dosing frequency or size
endings commonly used for antimicrobial meds (4)
azole (antifungal)
cillin (penicillin)
cycline (antibiotic, prot. synth inhib)
navir (protease inhib)
antimicrobial ending “azole” - usually…
antifungal (ie ketoconazole)
antimicrobial ending “cillin”- usually…
a penicillin antimicrobial (like methicillin)
antimicrobial ending “cycline”- usually…
antibiotic, prot. synth inhib (like tetracycline)
antimicrobial ending “navir” usually…
protease inhib. like saquinavir
11 endings commonly used in CNS drugs…
- triptan (5-HT 1B/1D agonists)
- ane (inhalational general anesthetic)
- caine (local anesthetic)
- operidol (butyrophenone (neuroepileptic))
- azine (phenothiazine (neuroepileptic, antiemetic)
- barbital (barbituate)
- zolam (Benzodiazepine)
- azepam (Benzodiazepine)
- etine (SSRI)
- ipramine (TCA)
- triptyline (TCA)
ending “triptan” is what type of CNS drug?
5-HT 1B/1D agonists - migraines (ie sumatriptan)
ending “ane” is what type of CNS drug?
inhalational general anesthetic - Halothane
ending “caine” is what type of CNS drug?
local anesthetic- lidocaine
“operidol” is what type of CNS drug?
Butyrophenone (neuroepileptic)- Haloperidol
ending “azine” is what type of CNS drug?
phenothiazine (neuroepileptic, antiemetic) ie chlorpromazine
ending “barbital” is what type of CNS drug?
barbituate– ie phenobarbital
ending “zolam” is what type of CNS drug?
benzodiazepine– Alprazolam
ending “azepam” is what type of CNS drug?
benzodiazepine - diazepam
ending “etine” is what type of CNS drug?
SSRI– fluoxetine
ending “ipramine” is what type of CNS drug?
TCA - imipramine
ending “triptyline” is what type of CNS drug?
TCA- amitriptyline
3 endings in the ANS
- olol - B-agonist (propranolol)
- terol - B2 agonist (albuterol)
- zosin - a1- antagonist (prazosin)
ending “olol” is what type of ANS drug?
B agonist (propranolol)
ending “terol” is what type of ANS drug?
B2-agonist (albuterol)
ending “zosin” is what type of ANS drug?
a1-antagonist (prazosin)
3 cardiovascular drug endings
- oxin (cardiac glycoside - inotropic agent. ie digoxin)
- pril (ACE inhib- Captopril)
- afil (erectile dysfunction- sildenafil)
ending” oxin” in cardiac drugs?
cardiac glycoside- inotropic agent (digoxin)
ending “pril” in cardiac drugs?
ACE inhib- captopril
ending “afil” in cardiac drugs?
erectile dysfunction (sildenafil)
ending “tropin”
pituitary hormone (somatotropin)
ending “tidine”?
H2 antagonist - cimetidine
Sulfa Drugs (8)
Popular FACTSSS!
Probenecid o p u l a r
Furosemide Acetazolamide Celecoxib Thiazides Sulfonamide Abx Sulfonylureas Sulfasalazine
Pts w/what type of allergy shouldn’t take Probenecid because they might develop fever, UTI, pruritic rash, SJS, hemolytic anemia, thrombocytopenia, agranulocytosis, and urticaria (hives)?
sulfa allergy
pt w/what type of allergy shouldn’t take Furosemide because they might develop fever, UTI, pruritic rash, SJS, hemolytic anemia, thrombocytopenia, agranulocytosis, and urticaria (hives)?
sulfa allergy
pt w/what type of allergy shouldn’t take Acetazolamide because they might develop fever, UTI, pruritic rash, SJS, hemolytic anemia, thrombocytopenia, agranulocytosis, and urticaria (hives)?
sulfa allergy
pt w/what type of allergy shouldn’t take celecoxib because they might develop fever, UTI, pruritic rash, SJS, hemolytic anemia, thrombocytopenia, agranulocytosis, and urticaria (hives)?
sulfa allergy
pt w/what type of allergy shouldn’t take Thiazides because they might develop fever, UTI, pruritic rash, SJS, hemolytic anemia, thrombocytopenia, agranulocytosis, and urticaria (hives)?
sulfa allergy
pt w/what type of allergy shouldn’t take sulfonamide abx because they might develop fever, UTI, pruritic rash, SJS, hemolytic anemia, thrombocytopenia, agranulocytosis, and urticaria (hives)?
sulfa allergy
pt w/what type of allergy shouldn’t take sulfonylureas because they might develop fever, UTI, pruritic rash, SJS, hemolytic anemia, thrombocytopenia, agranulocytosis, and urticaria (hives)?
sulfa allergy
pt w/what type of allergy shouldn’t take sulfasalazine because they might develop fever, UTI, pruritic rash, SJS, hemolytic anemia, thrombocytopenia, agranulocytosis, and urticaria (hives)?
sulfa allergy
pt with sulfa allergies may dvp what symp to sulfa drugs (8)?
- UTI
- fever
3.pruritic rash - stevens johnson syndrome
- hemolytic anemia
- thrombocytopenia
- agranulocytosis
- uticaria (hives)
symptoms range from mild - life threatening
p-450 inducers (8)
- Modafinil (narcolepsy)
- Barbituates
- St. John’s Wort
- Phenytoin
- Rifampin
- Griseofulvin
- Carbamazepine
- Chronic ETOH use
“momma barb steals phen-phen and refuses greasy carbs chronically”
how does Modafinil affect p-450?
inducer
how does Barbituates affect p-450?
inducer
how does St. John’s Wort affect p-450?
inducer
how does Phenytoin affect p-450?
inducer
how does Rifampin affect p-450?
inducer
how does Griseofulvin affect p-450?
inducer
how does Carbamazepine affect p-450?
inducer
how does Chronic ETOH use affect p-450?
inducer
what are the p-450 inhibitors? (12)
- Macrolides
- Amiodarone
- Grapefruit juice
- Isoniazide
- Cimetidine
- Ritonavir
- Acute ETOH abuse
- Ciprofloxacin
- Ketoconazole
- Sulfonamides
- Gemfibrozil
- Quinidine
MAGIC RACKS in GQ
How do macrolides affect p-450?
inhibitor
How does amiodarone affect p-450?
inhibitor
How does grapefruit juice affect p-450?
inhibitor
How does isoniazide affect p-450?
inhibitor
How does cimetidine affect p-450?
inhibitor
How does ritonavir affect p-450?
inhibitor
How does acute ETOH abuse affect p-450?
inhibitor
How does ciprofloxacin affect p-450?
inhibitor
How does ketoconazole affect p-450?
inhibitor
How does sulfonamides affect p-450?
inhibitor
How does gemfibrozil affect p-450?
inhibitor
How does Quinidine affect p-450?
inhibitor
Zero-order elimination of a drug
the rate of elimination is constant regardless of the plasma concentration (constant amt of drug elim per unit time)
on a graph, zero-order elimination of a drug is…
linear (the rate of elimination is constant regardless of the plasma concentration (constant amt of drug elim per unit time))
3 common examples of zero-order elimination drugs?
Phenytoin
Ethanol
Aspirin (at high or toxic concentrations)
- think a PEA is round, like a “0” in zero-order
capacity limited elimination is another way to say..
zero-order elimination
zero-order elimination is another way to say…
whereas first-order elimination is another way to say…
zero-order: capacity-limited elimination
firt-order: flow-dependent limited
first order elimination of a drug
the rate of elimination is directly proportional to the drug concentration (ie a constant fraction of drug is eliminated per unit time)
in zero-order elimination, the plasma concentration of the drug decreases
linearly with time
in first order elimination, the plasma concentration of a drug decreases
exponentially with time– the rate of elimination is directly proportional to the drug concentration (ie a constant fraction of drug is eliminated per unit time)
if a species is ionized in the urine what happens?
they are trapped in the urine and clear quickly
if a species is neutral in the urine, what happens?
neutral forms can be reabsorbed
what are three examples of weakly acidic drugs?
phenobarbital, methotrexate, aspirin
what happens to weak acids (like phenobarbital, methotrexate, aspirin)?
they get trapped in basic environments
RCOOH —> RCOO- + H+, where RCOOH is lipid soluble and RCOO- is trapped
how do you treat overdoses of weak acids? why?
with bicarbonate
- weak acids get trapped in basic envts
(RCOOH —> RCOO- + H+, where RCOOH is lipid soluble and RCOO- is trapped)
add bicarb, neutralize the acid, the non-ionized drug = excreted in the urine
what is an example of a pharmacological weak base?
Amphetamines
what happens when a weak base (like amphetamines) enter the body?
they get trapped in acidic envts (RNH2 + H+ —> RNH3+) where RNH2 = lipid soluble and RNH3+ is trapped
how do you treat overdoses of weak bases? Why?
ammonium Chloride
weak bases get trapped in acidic environments. (RNH2 + H+ —> RNH3+, where RNH2 = lipid soluble and RNH3+ is trapped)
Ammonium Chloride neutralizes the acid —> drug is back to being lipid soluble,and can be eliminated by the body
drug metabolism has how many phases?
2
phase I of drug metabolism?
reduction, oxidation, hydrolysis with cytochrome p450
phase 1 of drug metabolism (reduction, oxidation, hydrolysis with cytochrome p450) usually yields metabolites that are…
slightly polar, water-soluble and often still active
geriatric pt often lose which phase of metabolism first?
Phase I (reduction, oxidation, hydrolysis with cytochrome p450 that yields slightly polar, water-soluble and often still active metabolites)
** Geriatric pt have GAS (Glucuronidation, Acetylation and Sulfonation - ie phase II metab)
phase II of drug metab?
conjugation (Glucuronidation, Acetylation, Sulfonation)
phase II metab (conjugation (Glucuronidation, Acetylation, Sulfonation)) usually yields metabolites that are…
very polar, inactive and renally excreted
in terms of side effects from certain drugs, patients who are slow acetylators…
have greater side effects bc there’s a decreased rate of phase II metab, and usually phase I metab creates active metabolites
what does the mnemonic “Geriatrics have GAS” refer to?
Geriatrics have Glucuronidation, Acetylation and Sulfonation (ie phase II metab), bc they lose phase I metab. reduction, oxidation, hydrolysis with cytochrome p450 that yields slightly polar, water-soluble and often still active metabolites) first
efficacy
maximal effect a drug can produce
4 high-efficacy (in terms of maximal effect a drug can produce) drug classes
- analgesic (pain)
- abx
- antihistamines
- decongestants
which has a higher efficacy (maximal effect a drug can produce) a full or partial agonist?
a full agonist
potency
amt of drug needed for a given effect
increased potency implies a higher or lower Km?
lower Km (a higher affinity for the receptor) and therefore a lower amt of drug needed for given effect
Which 3 drug classes are highly potent (in terms of amt of drug needed for given effect)
- Chemotherapeutic drugs
- anti HTN drugs
- antilipid (cholesterol) drugs
if you plot “agonist dose” against the percent of maximum effect on a graph, and then plot the same thing with the presence of a competitive antagonist, what happens to the curve?
the curve is the exact same shape but it is shifted to the right (more of the agonist is required for every effect)
if you plot “agonist dose” against the percent of maximum effect on a graph, and then plot the same thing with the presence of a noncompetitive inhibitor, what happens to the curve?
the curve shifts down (it has decreased efficacy at every dose that can’t be overcome by adding more substrate)
What is an example of a noncompetitive antagonist of NE on alpha receptors? what does it do to the potency? the efficacy?
phenoxybenzamine (used in pheochromocytoma), decreases efficacy of NE– can’t be overcome by increasing NE
what is an example of a competitive inhibitor of Diazepam on the GABA receptor?
flumazenil
decreases potency of Diazepam but no change in efficacy- can overcome flumazenil by increasing GABA
if you plot “agonist dose” against the percent of maximum effect on a graph, and then plot the same thing with the presence of a partial agonist, what happens to the curve?
The curve shifts down, and can go to the right or left? the efficacy is decreased because it acts at the same site, but with reduced maximal effect. The potency can be increased or decreased with a partial agonist.
What is an example of a partial agonist at the opioid mu receptors of Morphine (a full agonist)
buprenorphine
therapeutic index- conceptual definition and mathematical definition
measurement of drug safety (LD50/ED50) = median lethal dose/median effective dose
do safer drugs havea higher or lower therapeutic index?
higher (LD50/ED50)
4 drugs that have a very low Therapeutic index:
- digoxin
- lithium
- theophylline
- warfarin
what is the therapeutic window?
the range from the minimum effective dose to the minimum toxic dose. (a measurement of clinical drug safety)
what are the two classes of local anesthetics?
esters and amides
as a class, benzodiazapines, such as alprazolam, diazepam and lorazepam, are sedative-hypnotic agents that exert what 4 effects?
anxiolytic, muscle-relaxant, anticonvulsant and amnestic effects
Benzos enhance the effect of what neurotransmitter?
GABA
if you want to reverse the effects of a benzo (alprazolam, diazepam, lorazepam, etc) what drug should you give?
Flumazenil– it’s an agonist at the benzodiazepine receptor and has no effect on other CNS depressants
Nicotinic AcH receptors are what kind of channels?
ligand gated Na+/K+ channels
muscarinic ACh receptors are what kind of receptors
GPCR- act through second messengers
5 subtypes of muscarinic receptors?
M1, M2, M3, M4, M5
QISS $ QIQ til you’re SIQ of Super Qinky Sex
alpha 1- Q
alpha 2- I
Beta 1- S
Beta 2- S
M1- Q
M2- I
M3- Q
D1 - S
D2- I
H1- Q
H2- S
V1- Q
V2- S
which receptor/GPCR class is responsible for…increased vasc SM contraction, increase pupillary dilator contraction (mydriasis), increase intestinal/bladder sphincter muscle contraction (no peeing)
alpha 1- Gq
which receptor/GPCR class = responsible for decreased sns outflow, decreased insulin release, decrease lipolysis, increase platelet aggregation?
alpha 2 = Gi
which receptor/GPCR class = increase HR, contractility, renin release, lipolysis
B1 = Gs
which receptor/GPCR = responsible for vasodlation, bronchodilation, increase HR, increase contractility, increase lipolysis, increase insuin release, decrease uterine tone (tocolysis), ciliary muscle relaxation, increas acqueous humor production?
B2= Gs
which receptor/GPCR class = resp for CNS/entric nervous sys
M1= Gq
which receptor/GPCR class = resp for decrease HR and contractility of atria?
M2= Gi
which receptor/GPCR class = resp for increase exocrine gland secretion (lacrimal, gastric acid), increase gut peristalsis, increase bladder contraction, bronchoconstriction, increase pupillary sphincter muscle contraction (MIOSIS), ciliary muscle contraction (accomodation)
M3 =Gq
which receptor = the major muscarinic receptor in the periphery?
M3 = Gq
Major muscarinic receptor/GPCR class in the heart?
M2=Gi
Major muscarinic receptor/GPCR class in the CNS?
M1= Gq
5 Gq receptors
HAVe 1 M&M H1 A1 V1 e
M1
M3
Gq path:
phospholipase C —> cleaves PIP2 into DAG and IP3.
DAG —> protein Kinase C
IP3 —> increase Ca2+ release from SR —> Smooth muscle contraction
Gs receptors
B1, B2, D1, H2, V2
Gs mech
activate adenylyl cyclase —> atp becomes cAMP —-> activates prot. kinase A —-> increase Ca2+ in the heart and inhibits myosin-light chain kinase (smooth muscle)
