Pharmacology Flashcards
1
Q
What are the 5 key elements in pharmacotherapeutics?
A
- drug
- dose
- route
- frequency
- duration
2
Q
What pharmacologic principle are drug and dose based on?
A
Pharmacodynamics -
disease targets and drugregulation
3
Q
What pharmacologic principle are route and frequency based on?
A
Pharmacokinetics
route - AD
frequency - ME
4
Q
What pharmacologic principle is duration based on?
A
Disease pathophysiology
5
Q
What are 4 basic drug categories?
A
- prescriptions
- controlled substances
- OTC
- Dietary supplements
6
Q
What phase is clinical testing starts comparing drugs to placebos or existing treatments?
A
Phase II
7
Q
What phase of clinical testing do most drugs fail?
A
Phase III
8
Q
What phase of clinical testing do you monitor “does it work?”
A
Phase II and III
9
Q
If you have a drug similar to one that is already approved, what application do you use to bypass testing trials?
A
abbreviated new drug application (ANDA)
10
Q
Do structure/function claims require FDA approval?
A
No, but needs a disclaimer.
only health claims do require FDA approval
11
Q
What are the 3 different FDA categories of drug equivalency?
A
- pharmaceutical equivalents
- bioequivalent
- therapeutic equivalent
12
Q
What does signa or “sig” indicate on a prescription pad?
A
drug directions to pts.
aka dosage regimen
13
Q
Manufacturer distribution of depressants and stimulants are divided into 5 ______
A
schedules
14
Q
The 5 schedules I-V are in order from (lower to higher) abuse potential or (higher to lower) abuse potential
A
higher to lower abuse potential
Schedule I - no medical use, high abuse potential
15
Q
How many mg make 1 grain?
A
65 mg = 1 grain
16
Q
How many grams make 1 ounce?
A
28.4g = 1 oz
17
Q
how many grams in 1 lb?
A
454g = 1 lb
18
Q
how many ml make 1 tsp?
A
5 ml = 1 tsp
19
Q
how many ml make 1 tablespoon?
A
15ml = 1 tablespoon
20
Q
how many ml make 1 oz?
A
30ml = 1 oz
21
Q
What does od* and os stand for?
A
right eye, left eye
22
Q
What is the relationship between Cp and Vd?
A
inverse
more drug in plasma = less being distributed
23
Q
Higher volume of distribution = more/less lipid soluble drug?
A
more lipid soluble
24
Q
drug formulations must be more hydrophilic/hydrophobic to dissolve and release molecule?
A
hydrophilic
25
drug molecule must be more lipophilic/lipophobic to cross membrane?
lipophilic
26
after drug gets metabolized by liver it becomes more/less water soluble?
more water soluble
27
The more unionized a drug, the more/less lipid soluble it is.
More
More unionized = more lipid soluble
28
P-glycoproteins move drugs from the _______ space to the ______ space
intracellular, extracellular
| Inside-> out
29
Bioavailability is termined by comparing AUC following single/multiple dose of a drug following IV route?
single
30
What is another word for extravascular?
Interstitial
31
High Vd indicates drugs are mostly located where?
Low Vd?
High Vd = outside plasma
low vd = inthe plasma or ECF
32
What is the term for the route of drugs that are taken into the body other than through the digestive tract?
Parenteral
33
If Vd is 3L, where are the drugs mostly located?
restricted to plasma
34
Extracellular water is ~12ml. What two compartments make up that volume?
```
plasma = 3L
Interstitial = 9L
```
(highly bound to plasma proteins)
35
If Vd is 12 L, where are the drugs mostly located?
In the extracellular compartment (plasma and interstitial)
| enters cells poorly
36
If Vd is 41L, where are drugs mainly located?
Total body water
| freely enter cells
37
If Vd >? 50L, where are drugs mainly located?
sequestered in CNS, fat
38
When weak acids are protonated, it is ionized/unionized.
This means it can/cannot cross biological membranes.
unionized
can - absorbed
39
Acids become nonionized in acid/base medium.
acid
| lots of H, so it holds onto proton
40
When weak bases are protonated, it is ionized/unionized.
This means it can/cannot cross biological membranes.
ionized (ie: NH3+)
cannot (ion trapped)
41
Ion trapped means what?
Drug has been ionized and can no longer cross membrane.
42
What is the henderson hasselbach equation?
pH-pKa = log [non-protonated/protonated]
or 10^(pH-pKa)
n before p
43
What does it mean when pH of biologic compartment is < pKa of drug?
more protons are present,
there will be more protonated forms of both acid and base.
44
When pH>pKa, what does it mean?
fewer protons present
there will be more unprotonated forms of acid and base
45
greater [ ] of drug is greater on side where ionization is greater/lesser?
greater
* Acidic drugs are trapped in the more basic solutions
* Basic drugs are trapped in the more acidic solutions
46
3 types of membrane compartments that act as special barriers?
1. GI mucosa
- negligible absorption of drug into blood
2. BBB
3. Renal tubules
47
Binding of drugs to plasma proteins prolongs/reduces drug action
prolongs -
hinders metabolic degredation, and reduce rate of excretion.
48
How are plasma proteins a potential source of DDI?
They are important in drugs with narrow therapeutic index.
49
What is biotransformation?
drug metabolism
enzyme catalyzed chemical structure transormation via liver
50
What is the most frequent pathway of biotransformation (drug metabolism)?
oxidation
51
The liver makes _____ compounds converted to _____ compounds to be more readily excreted.
lipid soluble, --> water soluble
52
Phase I reactions include:
oxidation
reduction
hydrolysis
53
2 types of Phase I oxidation reactions
1. cytochrome p450 dependent
| 2. cytochrome p450 independent
54
Cyt p450 dependent oxidation
1. found where?
2. involves enzymes or cofactors?
1. rich in liver
| 2. cofactors
55
Cyt p450 independent oxidation
| -what enzymes are involved?
1. amine oxidases
| 2. dehydrogenases
56
In phase I hydrolysis, what enzymes are involved?
esterases, amidases
57
Which phase reactions are more prone to:
1. inhibition of drug metabolism?
2. DDI?
3. age related changes?
all Phase I
58
What phase reaction are more prone to saturation?
phase II
59
Inducers do what?
increases drug metabolism via cyt p450 system
60
What do inhibitors do?
decreases drug metabolism and causing decrease drug clearance
61
Name some inducers
1. phenobarbitol
2. phenotoin
3. rifampin
4. ethanol
5. carbamazepine
6. st. John's wort
62
Name some inhibitors
1. cimetidine
2. grapefruitjuice
3. HIV protease inhibitors
4. erythromycin
5. ketoconazole
6. fluoxetine
63
How does the kidney work in drug excretion?
via filtration, secretion, reabsorption
64
How fast is drug clearance in:
- filtration
- active tubular secretion
- tubular reabsorption
120 ml/min
120-600ml/min
1ml/min
65
Kidney filtration or secretion is highly affected by plasma protein binding and requires free, unbound drugs?
filtration
66
Kidney tubular secretion process/movement
drugs are transported directly from blood into urine.
67
Kidney tubule reabsorption
reabsorption of lipid-soluble drugs (via passive diffusion of the proximal and distal tubes)
(water soluble metabolite less likely to be reabsorbed. Remember that the liver makes drugs MORE water soluble to be excreted)
68
Describe the enterohepatic cycle
Drugs are excreted via bile --> bile duct --> SI --> reabsorbed into blood --> liver
69
First order kinetics rate of elimination vs Zero order
First order: rate of elimination is proportional to [ ] of drug in plasma Cp
Zero order: rate of elimination is constant and independent of amt of drug in body
70
When is first order kinetics used to eliminate drugs vs zero order?
Most drugs eliminated via first order kinetics
- drugs will be removed due to zero order kinetics when hepatic metabolic enzyme systems are saturated
71
Two types of receptors? examples
1. generalized receptors
- biological molecules
2. specialized receptors
- membrane proteins, ion channels
72
Signal transduction and amplification can activate what 3 things?
1. ligand-gated ion channel
2. GPCR
3. Kinase-linked
receptor/hormone (nuclear) receptor
73
What is response [E] of a drug proportional to?
receptors[R] occupied by drug [D]
74
Explain what a dose response curve indicate?
hyperbolic
- at low doses, drug response increases proportionally to dose
- curve levels off bc there is a limit to response achieved
75
Explain what a log dose-response curve indicate
sigmoid
can compare different drugs (and wide range of doses)
- straight line corresponds to therapeutic range
76
What is potency?
EC50 or ED50
concentration or dose required to produce 50% of drugs maximal effect
-more potent, takes less to bring about EC50 or ED50
77
What is efficacy?
ability to initiate response
| -most important determinant of clinical usefulness
78
Competitive reversible antagonist affects potency/efficacy
it decreases potency
| doesnt affect# of receptors available to contribute to response
79
Non competitive "reversible" antagonists affects potency/efficacy
It decreases efficacy (Emax goes down)
80
Two types of noncompetitive antagonist
1. binds to active site
| 2. binds to allosteric site
81
Two types of noncompetitive active site antagonist?
1. irreversible
| 2. pseudoirreversible
82
What are reversible antagonists that bind to the active site of the same receptor?
competitive "reversible" antagonist
83
Two types of noncompetitive allosteric site antagonist?
1. reversible
| 2. irreversible
84
What is ED50 for graded dose-response curve?
dose that produces 50% of maximal response possible
85
What is ED50 for population dose-response curve?
effective dose that initiates target response in 50% of pop
86
Higher therapeutic index indicates what?
safer drug
| usual clinical drugs between 10-20
87
FDA categories for Drug use in pregnancy: description of -
| A
shows no risk
88
FDA categories for Drug use in pregnancy: description of -
| B
no evidence of risk
89
FDA categories for Drug use in pregnancy: description of -
| C
risk cannot be rule out
90
FDA categories for Drug use in pregnancy: description of -
| D
positibe evidence of human fetal risk
91
FDA categories for Drug use in pregnancy: description of -
| X
contraindicated in pregnancy
DO NOT USE
92
What are the 4 pharmacokinetic interventions preventing drug overdoses and poisoning?
1. Prevent absorption of toxin
2. Inhibit toxication
3. Enhance metabolism
4. Increase elimination of toxin
93
4 ways to prevent absorption of toxin
1. Emesis
2. Gastic lavage
3. Chemical adsorption
4. osmotic cathartics
94
Important drugs for emesis
1. Ipecac
| 2. Apomorphine
95
Contraindications for ipecac or apomorphine
§ Patient comatose / stuporous (lack of gag reflex à risk of aspiration)
§ Ingestion of corrosive poisons (i.e., strong acids or alkalis)
§ Ingestion of CNS stimulant such as strychnine (risk of seizures)
§ Ingestion of petroleum distillate (risk of pneumonitis)
§ Pregnancy Category C: (weigh benefit vs risk, unknown if drug can cause harm)
96
What is chemical adsorption
an emesis intervention used to prevent absorption of toxin:
binds drug in gut - limits adsorption
97
What is osmotic cathartics?
an emesis intervention used to prevent absorption:
decreases time of toxin in GI tract if ingestion is >60
98
Recommended drugs for osmotic cathartics?
sorbitol,
Mg citrate or sulfate
polyethylene glycol
99
3 methods used to inhibit toxication (pharmacokinetic interventions)
1. inhibit rate limiting enzyme
2. hemodialysis
3. sodium bicarb (corrects metabolic acidosis)
100
4 methods used to increase elimination of toxin
1. extracorporeal removal
2. enhanced metabolism
3. enhanced renal excretion
4. chelation of heavy metals
101
how is 70-80% of Acetaminophen (AC) metabolized?
conjugated with glucuronic acid or sulfate (phase II)
102
5-10% of acetaminophen is metabolized how? describe
5-10% of AC proceeds through cytochrome P450 oxidation (phase I)
AC → becomes chemically reactive NAPQI (Ac*)
→ becomes detoxified by phase II GSH
transferase
→ excreted as mercapturate
103
Describe mechanism of acetaminophen overdose toxicity
= hepatocellular injury due to saturation
- Saturation of Phase II conjugation pathways ←glucuronide + sulfate→
- This leads to excessive formation of Ac* by phase I pathway
- Glutathione (GSH?) gets depleted
- Ac* builds up
104
Describe acetaminophen treatment.
N- acetylcysteine (mucomyst)
| -glutathione synthesis
105
What is methanol (CH3OH) metabolized to?
| poisoning leads to what?
formic acid
○ Visual disturbance (snowstorm) soon after acidosis → cant breath → die
106
What is ethylene glycol (HOCH2CH2OH) metabolized to?
| Leads to what?
oxalic acid
○ Acute renal failure
107
What is the rate limiting enzyme in methanol and ethylene glucol metabolism?
-how can you inhibit it?
alcohol dehydrogenase
ihibit with fomepizole
