Exam 2 (Pharm) Flashcards
1
Q
Pharmacology
A
Study of substances interacting with living systems through chemical process
2
Q
Pharmacodynamics
A
Action of drug on body.
Used to determine drug group class and appropriateness for treatment.
3
Q
Pharmacokinetics
A
Actions of body on drug.
ADME.
Absorption
Distribution
Metabolism
Excretion
4
Q
Drug
A
Chemical or substance that causes physiologic effect when introduced to the body.
Cause a change in biological function through chemical actions
5
Q
Medication
A
Specific chemical preparation of one or more drugs for therapeutic effect
6
Q
Medical Pharmacology
A
Study of substances designed to prevent, diagnose, and treat diseases
7
Q
Toxicology
A
Study of unwanted effects of chemicals on living systems
8
Q
Receptor
A
Target of drug.
Responds to specific signaling molecules
9
Q
Ligand
A
Signaling molecule that binds to receptor
10
Q
Flycosides
A
Carbohydrate portion of plant with one or more sugar combined with hydroxy compound. Used as natural drug
11
Q
Where do essential oils come from
A
Leaves, root, bark
12
Q
Where are fixed oils and mineral oils from
A
Seeds
13
Q
Protamine Sulfate
A
Heparin antidote from fish sperm
14
Q
Heparin
A
Anticoagulant from pig intestine
15
Q
Premarin
A
Estrogen replacement from horse urine
16
Q
What are minerals often used for
A
Homeostasis
17
Q
Where all can natural drugs come from
A
Plants
Animals
Marine
Minerals
Microorganisms
18
Q
Pros of natural drugs
A
Natural affinity
Specific to binding targets
19
Q
Disadvantages of natural drugs
A
Costly
Less sustainable
May work differently than expected
20
Q
Semi-synthetic drugs
A
Naturally occurring substances that have been chemically altered (ex. paclitaxel from yew needles)
21
Q
Synthetic drugs
A
Fully man made drugs.
Majority of drugs are made this way
22
Q
Example of recombinant DNA being used to make drugs
A
Plasmid DNA of bacterium taken out and a section is cut out and replaced with part of human genome (ex. insulin).
23
Q
Covalent
A
Strong bonds.
Usually not reversible
24
Q
Electrostatic (ionic) bonds
A
More common than covalent bonds.
Vary in strength
25
Hydroohobic bonds
Very week.
Important in interactions of highly lipid soluble drugs with receptors
26
Phase 1 of drug development
Safety.
Small number of healthy volunteers
27
Phase 2 of drug development
Efficacy.
hundreds of pts with disease used.
Single blind studies
28
Phase 3 of drug development
Efficacy.
More controlled studies in thousands of pts.
Double blind and cross over
Apply for NDA
29
Phase 4 of drug development
Post-marketing surveillance AFTER drug goes to market
30
Translational research
Moving drug from science lab to clinic for screening and testing
31
Me too analog of a drug
tweaking a molecule to make it work better or have less side effects
32
Composition of matter patent
Filed for ef]ffective novel compound
33
Use patent
Filed for new and nonobvious use for a previously known chemical
34
Lifetime of a patent
20 years
35
Trademark
Drugs proprietary (brand) name
36
No-effect dose
max dose at which toxicity is not seen
37
Minimum lethal dose
smallest dose observed to kill any experimental animal
38
Median lethal dose (LD50)
dose that kills 50% of animals in test group
39
How long do clinical trials take
4-6 years
40
Crossover experiment design
Alternates periods of administration of test drug, placebo preparation, and standard treatment in each individual patient to minimize cofounding factors.
41
What factors of patients might effect study results
Presence of other diseases.
Lifestyle of subjects.
42
How soon do adverse drug rxns need to be reported
Reported within 15 days to the FDA through MedWatch
43
FD&C Act of 1938
Required new drugs to be safe and pure.
Labes should containd directions.
Mandated premarket approval by FDA.
Did NOT require proof of efficacy
44
Kefauver-Harris Amendment (1962)
Required proof of efficacy
45
FDA Amendments Act of 2007
Granted FDA greater authority.
Required post-approval studies.
Made clinical trial operations more visible to the public.
46
FDA Safety and Innovation Act of 2012
Gave FDA authority to accelerate approval of urgently needed drugs.
47
Therapeutic drugs
Based on usefulness in treating disease.
ex. Antihypertensives, antidepressants, antihyperlipidemics.
48
Pharmacologic Drugs
Based upon mechanisms of action.
ex. ACEI, ARBs, Beta-blockers
49
Schedule I drugs
-High potential for abuse
-No current accepted med use
-No safety for use
50
Schedule II drugs
-High potential for abuse
-can’t be refilled
-Some accepted medical use with severe restrictions.
-Potential for severe physical and/or psychological dependence
51
Schedule III drugs
-Less potential for abuse than schedule I or II.
-can be refilled up to 5 times (6 month supply)
-Some medical use accepted.
-Potential for low or moderate physical dependence and/or high psychological dependence
52
Schedule IV
-Low potential for abuse relative to schedule III.
-Current accepted medical use
-Limited dependence to schedule III when abused
52
Schedule V drugs
-Low potential for abuse
-Current accepted med use
-Less potential for producing psychological or physical dependence
53
Pregnancy drug category A
Controlled studies show no risk (safe)
54
Pregnancy drug category B
No evidence of risk in humans, but animal research finds risk.
55
Pregnancy drug category C
Risk cannot be ruled out. Human studies are lacking and animal studies are lacking or show risk.
56
Pregnancy drug category D
Positive evidence of risk, but benefits might outweigh the risk.
57
Pregnancy drug category X
NEVER give to pregnant
58
Active receptor
Constitutive (continuous) activity without ligand.
59
Inactive receptor
Dormant until ligand binds turning it on
60
Factors that affect activation of receptors
Specificity.
Selectivity.
Affinity.
61
Specificity
Capacity of drug to cause action by binding to receptor.
If high, drug has only one intended effect.
If low, lots of side effects.
Making a certain thing happen when you open the door.
62
Selectivity
Ability of drug to discriminate between target receptors.
If high, less side effects bc not binding with similar receptors.
If low, lots of side effects
Like using the right key to open the right door.
63
Affinity
Strength of attraction between drug and receptor.
High affinity has low dissociation constant and is associated with lower dose requirement
64
Dissociation constant (Kd)
Concentration of drug that occupies 50% of available receptors
65
Agonist
Binds to and activates receptor.
Causes a change in conformation of receptor or incorporation of machinery.
Can be direct or indirect effect
66
Full agonist
Activates receptor-effector systems to max.
67
Partial agonist
Binds and activates receptor with less effect.
Acts as agonist in absence of full agonist.
Acts as antagonist in presence of full agonist.
Useful in withdrawal patients to relieve withdrawals without giving them a high
68
Inverse agonist
Binds to receptor with constitutive (constant) activity and turns off or significantly decreases activity.
69
Antagonist
Binds to receptor but no complication.
Can be competitive or noncompetitive inhibition.
Can be reversible or irreversible.
70
Allosteric Binding
Molecule binds at site other than active site and either inhibits or enhances enzyme.
71
When is it most common for duration of drug action to be over
Well after drug has dissociated (Not as soon as the drug leaves the receptor)
72
Four families of receptor
Ion channels (voltage and ligand gated)
GPCR
Enzyme linked
Intracellular
73
Ligand Gated Ion Channel
Extracellular portion has binding site.
When ligand binds, pore is open.
74
Voltage-gated ion channels
Controlled by membrane potential.
Depolarization opens the channel
Two parts: volatge sensor and pore
75
GPCR
Ligand binds to extracellular protein on extracellular portion changing shape of G protein.
Alpha subunit binds GTP and moves away from receptors.
Second messengers then activated.
76
Gs receptor
Leads to Adenylyl cylcase which leads to cAMP that starts ac ascade that alters protein activity and increases HR
77
Gq receptor
Leads to phospholipase C that leads to IP3 and DG that trigger release of Ca and activates protein kinase C
78
Gt receptor
Leads to increase in guanylyly phosphatase that leads to
decrease in cGMP.
Uses Guanalyl Cyclades and cgmp?
Then regulates physiologic processes and has inflammatory effect and glucagon release
79
Gi receptor
Lowers adenylyl cyclase lowering cAMP.
Opening K channels lowering HR
80
Enzyme linked receptors
When ligand binds to receptor, tyrosine kinases phosphorylate the receptor.
Activated receptor then catalyzes phosphorylation of tyrosine residues on different target signaling proteins leading to cascade
81
Cytokine receptor
Require an intermediary (JAK) to phosphorylate tyrosine kinases.
Ligand binds causing cytokine receptors to dimerize.
JAKs activated and phosphorylate tyrosine residues.
Tyrosine residues initiate signaling through STATs.
STATs dimerize and dissociate from receptor to travel to nucleus and regulate transcription of specific genes.
82
Intracellular receptors
Ligands must be lipophilic.
Bind to specific DNA seq near the gene to be altered in transcription or translation.
83
Consequences of intracellular ligand-receptor binding
Lag period of 30 min to several hours.
Effects can persist for hours or days after concentration has reached zero.
84
Receptor desensitization
Receptors get overstimulated and quit responding as intensely for a period of time.
85
Down regulation of receptors
Receptors need finite time to rest after stimualtion.
Receptors internalize into cell.
86
Upregulation of receptor
Repeated exposure of receptor to antagonist results of up-regulation of receptors.
87
Enteral
Oral, sublingual, or buccal
88
Parenteral
Drug bypasses digestive system.
IV, IM, SQ, ID
More rapid and predictable absorption.
Can damage tissue or lead to infections
89
Topical
Medication is put on affected area
90
Oral
By mouth (passes through GI)
Most common
Must be able to withstand acidity of stomach.
91
SL/buccal
Rapid absorption through capillaries.
Bypasses GI
92
IV
Rapid effect and max control
93
IM
Aqueous solution.
Sustained dose over extended interval.
94
SQ
Simple diffusion
Not for drugs that irritate tissue
95
ID
Used for diagnostics (like TB skin test)
96
Intrathecal
Directly into CSF.
Local rapid effects
97
Inhalation/Intranasal
Rapid deliver.
Almost as rapid as IV.
98
Rectal
Bypasses 50% of portal circulation minimizing breakdown in liver.
Useful for vomiting pts or children.
Absorption is unreliable
99
Transdermal
Patch.
Drug seeps out at steady rate.
100
Aqueous passive diffusion
Drug moves through aqueous channels in intracellular junctions.
Drug moves down concentration gradient.
Does not involve a carrier
101
Lipid passive diffusion
Drug moves through lipid bilayer with no help.
Drug moves from high to low concentration
102
Facilitated diffusion
Uses transport proteins to move drug across membrane.
Faster than passive diffusion.
Drug moves down concentration gradient.
No energy
103
Special Carrier transport
Active transport.
Drug moves from low to high concentration
104
What factors influence absorption
pH
Blood flow
Total surface area
Contact time
Expression of P-gp
105
How does pH affect absorption
Weak acid absorbed best at acidic pH
Weak base absorbed best at alkaline pH
106
How does pH affect secretion
Weak acid excreted faster in alkaline urine
Weak base excreted faster in acidic urine
107
How does blood flow affect absorption
Increased bloodflow increases absorption
108
How does surface area affect absorption
More surface area in organ (small intestine) means faster absorption of drug
109
P-gp
Pumps drug out of the cell.
If expressed, the rate of absorption of the drug in that cell will be decreased.
Bacteria and cancer cells use this pump to their advantage
110
Bioavailability
Fraction of unchanged drug that reaches systemic circulation
111
IV drug bioavailability
100% (bc it goes straight into circulation)
112
IV dose vs PO dose size
PO dose would likely be bigger bc liver could inactivate significant amount of drug before it reaches systemic circulation.
113
Distribution
Drug reversibly leaves bloodstream and enters extracellular fluids and tissues.
IV drugs do this rapidly.
114
Factors that influence drug distribution
Lipophilicity
Cardiac output and local blood flow
Capillary permeability
Binding of drugs to plasma proteins and tissues
Volume of distribution
115
How does lipophilicity affect drug distribution
The more lipophilic a drug is the easier it can get out of the blood and into tissues.
It can be slowly released from fatty tissues.
Lipophillic molecules can also cross BBB unlike polar molecules.
116
How does blood flow affect drug distribution
The greater the blood flow to tissues, the greater the distribution.
There is greater blood flow in brain, liver, heart, and kidney.
Less blood flow in adipose tissue, skin, vescera
117
Slit junction
large, protein bound molecules can get through.
Present in liver and spleen.
118
Tight junction
Prevent large, protein bound molecules from getting through.
Hydrophilic drugs can easily get through.
Present in brain
119
Spleen and liver capillaries
Slit junctions.
Large portion of capillary membrane exposed for exchange with blood and tissues
120
Brain capillaries
NO split junctions.
Capillary structure is continuous.
Drugs must go through CNS capillaries or active transport to enter.
121
Free drug
Unbound.
Only way drug can bind to target.
122
Volume of distribution
Ratio between amount of drug in body vs amount of drug in plasma.
123
What does a high volume of distribution mean
It will leave blood plasma and go everywhere, so higher dose is needed to get desired effect.
124
High MW drugs Vd
Low. can't easily get out of bloodstream
125
Low MW drugs Vd
High. Can more easily get out of bloodstream
126
Hydrophilic drugs Vd
Low. Can't easily get out of blood stream
127
Lipophilic drugs Vd
Higher. Can easily get out of bloodstream and be absorbed into tissues.
128
If drug has High Vd how is it's duration of action
Longer
129
Ideal properties of drug to be excreted
Hydrophilic bc if lipophilic it will be reabsorbed in the kidney
130
Metabolism
Biotransformation to make a drug able to be excreted.
Usually makes the drug more hydrophilic and inactivates it
131
Prodrug
Transformed into it's more active form through metabolism.
132
Main organism of metabolism
Liver.
Drug is absorbed in small intesine and go to liver through hepatic portal vein. Liver begins metabolizes drug and drug enters systemic circulation
133
First pass effect
Biotransformation (metabolism) of drug before reaching systemic circulation (usually in liver sometimes in GI tract).
Seen in oral and rectal drugs but not with parenteral or SL/buccal
134
Phase I metabolism rxn
Introduces or unmasks hydroxyl on molecule
Often use CYP450.
Primarily in liver
135
CYP450 Enzymes
CYP1A2
CYP2A6
CYP2B6
CYP2C9
CYP2D6
CYP2E1
CYP3A4
Uses reduction, oxidation rxns or hydrolyzes drug to add hydroxyl molecule to make it more hydrophilic
136
Most important CYP450 enzyme
CYP3A4
137
CYP2D6
Used to metabolize codeine into its active form morphine.
138
What happens if CYP450 is inhibited
Drug concentration in the plasma would increase bc CYP450 would not be able to break it down as efficiently
139
Phases II metabolic rxn
Polar group is conjugated (attached) to drug to make it more hydrophilic.
UGT (a transferase) is most common enzyme used
140
First order kinetics
Rate of drug metabolism is proportional to concentration of free drug (% stays same).
Drug has specific half life.
Linear kinetics (but is curved on a graph)
MOST DRUGS
141
Zero Order Kinetics
Rate of metabolism remains constant over time.
Drug concentration does not affect rate of metabolism.
nonlinear kinetics (but is a line on graph)
ex. aspirin and phenytoin
142
Most important organ for excretion
Kidneys
143
Elimination
Inactivation or excretion of drug.
144
Clearance
Volume of plasma cleared over time (mL/min).
Does not tell amount of drug cleared from body.
Can't be directly measured.
Represents body's ability to eliminate drug and predict rate to decide right dosage.
145
Systemic clearance
Sum of clearance at each organ
146
What happens to person's clearance as they get older
Decreases
147
Liver role in excretion
Excrete unchanged drug into bile
148
What all processes does a drug pass through in the kidney
Glomerular filtration
Active tubular secretion (proximal)
Passive tubular reabsorption (distal)
149
Glomerular filtratino
Afferent arterioles carry drug to nephron.
Hydrostatic pressure pushes free drug into bowmans capsule.
Low GFR causes drug to not be pushed out so its stuck in blood.
High protein binding makes it hard for drug to go through filter.
Lipid solubility and pH NOT a factor.
150
Proximal tubular (PCT) secretion
Drugs secreted from efferent arteriole into PCT through ACTIVE transport with anion and cation transporters with low specificity
151
Distal tubular (DCT) reabsorption
Passive.
Nonpolar drug diffuses out of lumen back into circulatoin.
Changes lumen pH
152
First order elimination kinetics
Depends on blood flow of drug to elimination organ.
153
Zero order elimination kinetics
Same amount eliminated over time.
Blood flow doesnt matter.
154
Half life
amount of time needed for plasma concentration to decrease 50% after drug is discontinued.
155
Accumulation
Takes 4-5 half lives after drug is first administered to achieve steady state
156
How long does it take to get rid of 95% of drug
4-5 half lives
157
Steady state
Rate of drug elimination equals rate of drug adminstration
158
Loading dose
First dose of medication given is larger dose to get to desired effect more quickly. However, can be dangerous with regards to toxicity and plasma concentration could take longer to decrease.
159
Should IV meds be given fast or slow
Slow
160
What method can be used to prevent the highs and lows of the effect of the drug
Smaller doses at shorter intervals
160
What happens to steady state when clearance is incresased
Steady state will decrease, Inverse relationship.
161
Vd in elderly
Vd is lower
Less body mass, so less tissue for drug to escape to
162
Vd in obese
Vd is higher.
More tissue for drug to escape to
163
When does absorption typically occur
2 hours after administration of the drug.
But some drugs take longer
164
When is the best time to take samples to test concentration once steady state has been reached
At midpoint of dosing interval.
165
Potency
Concentration of drug producing 50% of max effect.\
Depends on Kd of receptors and efficiency of drug-receptor interaction
166
Efficacy
Measure of Magnitude of response.
167
Intrinsic activity of antagonist
0
168
Intrinsic activity of full agonist
1
169
Intrinsic activity of partial agonist
Between 0 and 1
170
Intrinsic activity of inverse agonist
less than 0
171
Intrinsic activity
Drug's ability to fully activate receptor
172
Therapeutic index
Ratio of drug dose that produces toxicity in halg population devided by the dose that produces a desired or effective response in half the population
TI=TD50/ED50.
High TI values needed for must drugs bc it shows it takes much higher dosage to become toxic than the dosage to get desired effect.
173
WHO
The degree to which the person's behavior corresponds to the agreed recommendations from health care provider.
174
Adherence
Pt and provider collaborate to find the best way to get care.
175
Primary non-adherence
non-fulfillment.
Can't afford meds.
Didn't get sent to pharmacy.
Pharmacy is out.
Pt never picked up from pharmacy.
176
Secondary non-adherence
non-persistence.
Pt stops taking dose without instruction or consultation with provider.
177
Tertiary non-adherence
non-conforming.
Skipping doses
Taking at wrong time (ex. with/without food)
Taking more/less than perscribed.
178
non adherence rate
10-92%
average of 50%.
half of those are intentional
179
Does chronic or acute have better adherence
acute
180
What often causes non-adherence in elderly
Have to remember to take lots of drugs.
181
How quickly should you follow up after changing meds
Month
