Exam 1 Flashcards
(133 cards)
1
Q
Ch.1
How to bring a prescription drug to market?
A
1-2 years to patent, send IND (investigative new drug) to FDA, Phase 1-3; if pass all 3 phases, NDA (new drug application) - takes 1 year to get [where Thalidomide got caught up]; marketing and sent to public; TOTAL = around 9 years
2
Q
Ch.1
Monoclonal Antibodies uses in pathologic conditions?
A
cancer, autoimmune diseases
3
Q
Part of cell that engulfs the receptor and drug together?
A
Clatherin encoated pit
4
Q
4 Main Causes of Drug Variation?
A
Alteration (ADME, age, disease, sex, weight), Varied Concentration of Endogenous Ligand, Alteration in number or function of receptors, and Changes in Downstream Receptor (LARGEST AND MOST IMPORTANT)
5
Q
Ch.1
Role of Drug Carriers?
A
Carry a drug across the membrane if needed (non-lipid soluble)
6
Q
Drug Examples of Zero Elimination
A
Ethanol, phenytoin, salicylates
7
Q
What is constant in zero order elimination?
A
ROE is constant
8
Q
GCPRs Cascade
A
Know how to draw; G-PROTEIN activates cascade via ALPHA SUBUNIT
9
Q
Ch.3
Volume of Distribution (Vd)
A
The space available in body to contain the drug; how much stayed in the blood vs how much went elsewhere? Shows preference to where drug will best absorb
10
Q
Zero Order Elimination
A
ROE is constant; so much drug in body, receptors are completely saturated and you cannot get rid of the drug fast enough; Ex. Every hour, body gets rid of 150 mg of drug (ROE)
11
Q
Ch.3
Bioavailability (F)
A
12
Q
Ch.1
Pharmacodynamics
A
What the drug does to the body?
-Dose response
13
Q
2 Outcomes of Desensitization within the Cell?
A
Can be recycled or a Lysosome will degrade the receptor
14
Q
Ch.1
Toxins vs Poisons
A
Toxins - biological; puffer fish, bee, mushrooms
Poisons - non-biological; arsenic/lead
15
Q
Ch.1
Paracelsus Quote
A
“The dose makes the poison”
16
Q
Ch.1
Exogenous vs Endogenous
A
Ex - Outside body (norepi, epi, propanolol)
End - Inside body (norepi, epi)
17
Q
Ch.3
Rate of Elimination (ROE)
A
The speed at which the drug is eliminated from the body
18
Q
Ch.2
Ligand Gated Ion Channel
A
Ligand Gated - Contains ionotropic or metabotropic; ligand opens the channel, and when it leaves, the channel is shut
19
Q
What are the 4 ways drugs get across barriers?
A
Aqueous diffusion, Lipid diffusion, Special Carriers, Exocytosis (Clatherin coated pit), Endocytosis (merge of vesicle with membrane)
20
Q
Ch.1
Competitive Inhibitor
A
an inhibitor that competes to bind at the active site with an agonist
21
Q
Voltage Gated Ion Channel
A
Found in excitable cells (neurons, muscle, endocrine); closed @ RMP; based on ion selectivity; 2 gates, upper and lower; When Na+ gets close to the channel, the charge opens it up to allow Na+ in. The bottom gates shuts first after, then both gates completely shut and the whole process starts over again
22
Q
Ch.2
Desensitization Definition
A
Drug bound to receptor, but cell shuts down signaling process. Decrease effectiveness of drug; protective mechanism; if constantly being signaled, has process where cell can shut down the signals
23
Q
Ch.1
Pharmacokinetics - ADME
A
Absoprtion
Distribution
Metabolism
Excretion
24
Q
Ch.1
Father of Western Medicine
A
Hippocrates
25
Ch.1
Inverse Agonist
STRONG! Binds to same receptor as agonist, but produces opposite response: binds to inactive form of the receptor. Completely shuts down the receptor
26
Ch.1
Covalent Bond
Strongest; share same chemicals or ions; irreversible; Less specificity
27
Ch.1
Racemic Mixture
Mixture between different mirror Isomers of a drug. Ex: R-Ketamine (more toxic) and S-Ketamine (4x more potent). Done by rotating the molecules
28
How to Calculate Therapeutic Index of a Drug?
Td50/Ed50: Wider = safer; narrow = more toxic
29
Competitive Inhibitor vs Allosteric (non-competitive) Inhibitor
Competitive - Blocks @ the active site [A+B]; surmountable; Countered by increasing agonist
Allosteric - Blocks @ site other than active site [A+D]; insurmountable; irreversible
30
Ch.3
Concentration (C)
Sub-defined to: C in blood, C in plasma, C in H2O (unbound)
31
Ch. 1
Electrostatic Bond
Most common; bond based on ionic charges, hydrogen, Van der Waals
32
Ch.1
Regulation of Prescription Drugs
Have to have licensed provider; viewed by public as "more effective"; increased risk for toxicity
33
What is constant in 1st order elimination?
CL is constant
34
Ch.1
Regulation of OTC Drugs
Able to get freely; less risk for toxicity due to usually wider TI
35
Allosteric
Bind not @ active site of the receptor. Non-competitive; Insurmountable; Irreversible
36
Ch.2
Inotropic Ion Channel
More common; ligand binding and channel on same protein; nAch receptor in skeletal muscle; Sux binds to this receptor
37
Ch.3
4 different ways a drug gets across barriers
Aqueous Diffusion, Lipid Diffusion, Special Carriers, Endocytosis (Clatherin Coated Pit) and Exocytosis (merge vesicle with membrane)
38
Ch.1
Allosteric Inhibitor
Binds outside of Active Site on Receptor Protein
39
1st Order Elimination
Drug slowly leaves body; CL remains constant (Ex. Every hour, 12% leaves the body)
40
Agonist
Activator; bind to similar ligand endogenous in the body
41
Ch.1
Partial Agonist
Weaker than a full agonist; Antagonist in presence of full agonist. Lower intrinsic activity than full agonist
Ex: Epi with Partial Agonist = Decreased effect of Epi
42
Ch.2
Metabotropic Ion Channel
Ligand activates GCPR --> 2nd messenger opens channel (cAMP binds to channel and opens)
43
Receptor
Component that interacts with drug and initiates a chain of events that lead to drug observed effect
44
Ch.3
Target Concentration (TC)
45
Ch.3
Half-Life (T1/2)
The time it takes for 50% of the drug to be eliminated from the body
46
Ch.1
How can a partial agonist also be an antagonist?
Partial agonist, when in presence of agonist, turns into an antagonist. This is because the 2 compete, thus decreasing the desired effect of the med. The partial agonist prevents the agonist from accessing the receptor
47
Ch.1
Pharmacogenomics
Study of genetic profile to see how body will respond to certain drug given
48
Ch.2
The Molecular Components of Desensitization in the
GPCR
Betaerestin
Clatherin Coated Pit
49
Ch.2
Types of Ligands that Bind to Receptors Inside the Cell
Gas (NO activated within cell to dilate smooth muscle and decreased BP) and Lipid Soluble Agents (Steroids)
50
Ch.1
Role of the FDA
To regulate drugs and make sure they are safe and effective; reviews claims and makes recommendations
51
Ch.1
Most common drug carriers in the blood
Albumin - acid drug binding
A1-Acid Glycoprotein - basic drug binding
Lipoproteins - neutral drug binding
52
Elimination of the drug is based off of what?
Clearance of the drug
53
Metabotropic Ion Channel
Ligand activates GCPR; 2nd messenger opens up ion channel' Ex. cAMP binds to ion channel to open up
54
Ch.1
Precursor to Pharmacology
Materia Medica
55
Ch. 2
Cell signaling process
Signaling Molecule --> Receptor --> Signal Transduction Protein --> 2nd Messenger--> effector protein (change in the cell)
56
Ch.1
First Recorded Physician
Imhotep
57
What is Clearance (CL)?
The ability of the body to clear the drug; elimination is based off CL; remains constant in 1st order elimination
58
4 Transmembrane Signaling Methods
(1) Intracellular Receptors (lipid soluble)
(2) Cell Surface Receptors: Ions, Catalytic, GCPRs
59
Ch.1
Father of Toxicology
Paracelsus
60
What does a high CL mean?
61
What is a clatherin coated pit?
Part of the cell wall that engulfs the receptor/drug combo and either recycles it or lysosomes will come digest the receptor
62
Stereoisomerism and Drug Effects
Same chemical makeup, just different arrangement of the atoms; can cause greater desired effect, but may contain more adverse effects
63
Ch.2
Most Common Second Messenger (per Lecture)
cAMP and IP3
64
Ch.1
Physiologic Antagonism
Drugs opposite effect @ different receptors
Ex: Epi @ B1B2 to increase HR
Acetylcholine @ M1M2 to decrease HR
65
2 types of ligands that bind to receptors within the cell?
Gas - Shearing forces in vessel cause NO to open the vessels and lower BP
Lipid Soluble Agents - Steroid hormone binds to steroid receptor, then increases transcription and translation in nucleus
66
Ch.3
Pharmacokinetic Variables (ADME)
Adsorption, Distribution, Metabolism, Excretion
67
What does a high Vd mean?
Less concentration in blood, as it distributes elsewhere in the body (Hydroxychloroquine likes to spread to adipose tissues, so high Vd)
68
6 Types of Antagonist Receptor Interactions
Competitive, Non-Competitive (Allosteric), Partial Agonist, Inverse Agonist, Opposite Charge, Physiologic Antagonism
69
GDP, GTP, GPCR Definitions
GDP - Guanosine Diphosphate (inactive)
GTP - Guanosine Triphosphate (active)
GPCR - G-Coupled Protein Receptors
70
Ch.2
Role of Second Messengers
Relay the message sent from the effector protein to create cellular response
71
Antagonist
inhibitor; blocks ligand; does not activate response
72
GCPR Structure and Components
7TM structure; A,B,Y subunits: A is most important as sends GTP over to effector protein and starts cascade, B and Y are structural
73
Orthosteric
Bind @ active site of the receptor
74
Monoclonal Antibodies and How they Are produced?
Drugs extracted from living organisms; taken from a single clone of a single plasma cell
Recombinant DNA technology; isolate antigen, inject into mouse, mouse makes antibodies, take plasma cells from mouse, mix plasma cell with myeloma cell to create immortal cell; inject back into mouse ( see how it responds, and now you have unlimited copies)
75
Ch.1
Toxicology
study of undesired effects of chemicals on living systems
76
Ch.3
Clearance (CL)
The ability of the body to clear the drug; elimination is based off clearance
77
Protein that blocks OH group during desensitization
Betaerestin
78
GPCR Signaling
Signaling Molecule - Receptor - Signal Transduction Protein - Secondary Messenger - Effector Protein
79
What is Concentration (C)?
Concentration of drug in blood (Cb), plasma (Cp), or H2O/unbound (Cu)
80
Phosphorylation Cascade
Know how to draw; RECEPTOR activates cascade
81
Ch.1
Hydrophobic Bond
Weakest; no charge; more specificity to lock and key. Lipid soluble
82
Ionotropic Ion Channel
Part of Ligand gated ion channels; more common; ligand binding to site and channel on same protein; Ex. nACh receptor in skeletal muscle (SUX binds to this receptor)
83
What is Volume Distribution (Vd)?
How much drug stays in the blood vs how much goes to other parts of the body
84
Ch.1
Pharmacokinetics
What does body do to the drug?
- 1/2 life: BBB
85
Ch.1
Potency vs Efficacy
Potency - Amount of drug needed to produce desired effect (EC50 and Emax)
Efficacy - Drugs capacity to produce desired effect (Kd and Bmax)
86
2 Types of Ligand Gated Ion Channels
ionotropic and metabotropic
87
Receptor Site
Protein on cell membrane that binds with ligand
88
Explain CYP450 Metabolism
The drug (RH) binds to CYP450. CYP450 has an Iron group attached which goes through various oxidation reactions.
89
Hepatic Portal System Blood Flow
GI - Local Veins - Hepatic Portal Vein - Sinusoids - Hepatic Vein - Vena Cava - Systemic Circulation
90
Tylenol Normal Dosage Pathway
Phase 2 reaction: Glucuronidation and sulfation are added to tylenol to help it be excreted easier from the body
91
Hepatic Enzyme Induction
Some drugs enhance synthesis or inhibit degradation: If metabolism deactivates the drug, then DECREASED drug effect. If metabolism activates the drug, then INCREASED drug effect
92
Most common CYP450s?
CYP3A4*1 (50%), CYP2D6 (20%), CYP2B6 (8%)
93
What is the "Wild Type" CYP enzyme?
CYP3A4*1; occurs most often in the population
94
Hepatic Enzyme Inhibition
If metabolism deactivates the drug, then INCREASED drug effect; if metabolism activates the drug, then DECREASED drug effect
95
What is a Prodrug?
A drug that is inactive until converted by the body's metabolic process (Plavix)
96
Phase 1 Metabolic Reactions
Convert drug to more polar; Oxidation (CYP450), Reduction, Hydrolysis, Dehydrogenation [these turn drug lipo-hydrophilic for excretion]
97
Phase 2 Metabolic Reactions
Adding larger molecules to a drug, making it more hydrophilic; conjugation to endogenous substrate (Glucuronidation) and (Glutathione - GSH)
98
Glucuronidation (UDP Glucuronic Acid)
Phase 2 Reaction; Adding a glucose molecule to a drug to make it easier to excrete (makes more hydrophilic)
99
Glutathione (GSH)
Phase 2 Reaction; binds to drug to make easier to excrete (hydrophilic)
100
Hepatic Artery Blood Flow
Systemic Circulation - Hepatic Artery - Sinusoids - Hepatic Vein - Vena Cava - Systemic Circulation
101
What is an Active Drug?
102
What test determines kidney function?
Creatinine Clearance (mL/min)
103
IBW for Men
52 + (1.9 kg x inches over 5 ft)
104
IBW for Women
49 + (1.7 kg x inches over 5 ft)
105
What is Peak? When do you draw it?
Highest concentration of drug in blood; 5-10 min after IV administration
106
What is Trough? When do you draw it?
Lowest concentration of drug in blood; 30 min prior to next dose
107
7 Routes of Drug Administration?
IV, IM, SC, PO, Rectal, Inhalation, Transdermal
108
What is 1st Order Elimination?
Drug slowly leaves body, as CL is constant; Sigmoidal
109
What is 0 Order Elimination?
So much drug in your body, your receptors become saturated and you cannot get rid of it fast enough. Occurs when body ability to eliminate has reached max capacity. ROE is constant, as you can only get rid of so much at a time; Linear
110
What Remains Constant in 1st Order Elimination?
Clearance (CL)
111
What Remains Constant in 0 Order Elimination?
Rate of Elimination (ROE)
112
3 Drugs that can easily get to 0 Order Elimination?
ethanol, phenytoin, salicylates
113
Parts of the BBB?
ABC Transporters, Vascular Epithelium (primary site of exclusion), Other Cells (Astrocytes and Podocytes)
114
What are High Extraction Drugs?
Drugs that are sensitive to 1st pass metabolism; large portion are extracted in the liver
115
What is a high extraction ratio? How does this compare to Blood flow and CL?
(0.7-1); High blood flow (Q) and High CL
116
Tylenol OD pathway
Phase 1 Reaction; Non Lethal when CYP3A4 goes through GSH-conjugation, which adds Mercapturic Acid (swept out of the body)
Lethal - Glutathione runs out and Nucleophilic structures bind to cell macromolecules (leads to liver cell death)
117
Capacity Limited Elimination
Think of 0 order elimination
118
What are Drug Efflux Transporters?
Bind to drugs to send in or out of the cell; important when protecting barriers, such as BBB (prevent things from coming into BBB)
119
Most Important ABC Transporters? 3
B1, C, G2
120
ABCB1?
Broadest specificity, Critical to BBB (pumps drugs back into blood, instead of brain)
121
ABCC?
Largest Class, but does not transport as much as B1
122
ABCG2?
Breast cancer resistance, folate transport, antineoplastics
123
The role of Drug Transporters in the Cell?
To Transport Endogenous Substances (hormones, glucose, amino acids, etc)
124
Steady State 1/2 Lives?
4 Half-Lives to reach steady state
125
What is steady state?
Time at which concentration of drug in the body stays consistent
126
What are 2 drug interactions with ABCB1?
Loperamide with Quinidine (increased respiratory distress like opioid OD)
Digoxin with Cyclosporin (increases Dig levels = Dig toxicity)
127
3 Drugs that might require dosage changes in specific genetic populations?
Warfarin, 6-mercaptopurin, Trastuzumab (Herceptin)
128
What enzyme metabolizes Warfarin?
CYP2C9
129
What enzyme metabolizes 6-Mercaptopurin?
TPMT
130
Which variants show that a Patient needs less warfarin to avoid bleeding out?
CYP2C9 *2, *3
131
What test is done to see if patient has Warfarin mutation?
Simple Trial and Error and Genetic Testing
132
What test is done to see if patient has TPMT enzyme mutation?
Simple blood test (if deficient, give lower dose of 6-mercapto)
133
Importance of Pharmacogenomics in Personalized Medicine?
5 rights of medication
