first midterm contents Flashcards
1
Q
What is Pen Tsao?
A
Ancient chinese books about medicinal and toxic plants
2
Q
What is Ebers Papyrus?
A
Ancient Egypt drug book
3
Q
What is Hippocratic Corpus?
A
Ancient Greece and Roman Empires medicine book, which rejected spirtual causes and treatment of disease
4
Q
What is De Materia Medica?
A
Ancient Green and Roman drug book
Remained used until 1600, each disease in the book has unique cause and remedy
5
Q
What is The Canon of Medicine?
A
Medieval and Islam drug book
Set the standard of medicine, foundation of experimental drug testing
6
Q
What is Digitalis?
A
The active ingredient found in digitalis Purpurea flower, which was used to treat dropsy (heart failure caused edema)
Digoxin is now extracted from Digitalis to treat heart diseases
7
Q
What is the active ingredient in Papaver Somniferum? ( used to relieve pain)
A
Morphine
8
Q
What is the active ingredient in Salix alba? And what is salix alba?
A
Salicin, which is extracted from the willow bark?
9
Q
What drug is made from salicin?
A
Aspirin, made using Salicylic acid/ acetylsalicylic acid
10
Q
Who is Rudolf Buchheim?
A
First Professor of Pharmacology
11
Q
Who is Oswald Schmiedeberg?
A
Founder of modern pharmacology
12
Q
What did Langley and Ehrlich propose?
A
Receptors mediate drug action
13
Q
What did Clark introduce?
A
The receptor occupancy model, which describe the relationship between drug concentration and effect
14
Q
How is insulin first made?
A
It is a purified pancreatic extract, that contain insulin
15
Q
Who is Gertrude Elion?
A
She won the noble prize for rational drug design
16
Q
Who is France Kelsey?
A
She worked for the FDA, helped banning Thalidomide
17
Q
What are the four classes of drug origin?
A
Natural compounds. Semi-synthetic, synthetic, Biologics
18
Q
What is a natural drug origin?
A
Active pharmaceutical ingredients that re extracted from natural source, such as plant or animal
19
Q
What is Paclitaxel?
A
It is an anti-cancer ingredient, that is first extracted from tree bark of pacific yew tree
It is now purified directly from plant cell, instead of harvesting trees
20
Q
What is semi-synthetic compounds?
A
Compound produced from chemical modification of pure compounds
21
Q
What is Hydromorphone?
A
It is semi-synthetic drug made from morphine, which has increased potency and lipophilicity, so rapid onset of action
22
Q
What is the origin of most drug?
A
Synthetic
23
Q
What is biologic drug?
A
Drug that is made from biologic process, such as extraction from tissues, tissue culture or produced using recombinant DNA technology
24
Q
What are some examples of biologic drugs?
A
Monoclonal antibodies, vaccines, recombinant protein
25
What routes of administration are included within Enteral?
1. Oral->2. Rectal->3. Sublingual (Beneath the tongue)
26
What is the definition of bioavailability
1. Proportion of administered drugs that is absorbed from site of administration and reaches systemic circulation UNCHANGED
27
What factors determines absorption in Oral administration?
1. Physiochemical, pH of GI stability and solubility of drugs in GI fluids->2. Gastric emptying rate->3. Intestian motility
28
Why are drugs taken with foods
1. Food can protect stomach from irritant drugs->2. Some drugs form complexes with food->3. Bioavailiability is increased with food
29
What is the 2 formulations for oral drugs
1. Enteric coating (does not breakdown in stomach)->2. Extended/Controlled release
30
What are the benefits of controlled release
1. Decrease frequency of dosing, therefore increasing compliance
31
Advantages of oral admin.
1. Really cheap->2. Very convenient
32
What are the major disadvantages for oral admin
1. First-pass effect->2. Subject to degredation in stomach->3. Irritant to stomach mucosa->4. Slow onset of actions, and some patients maybe unconcious/can't take orally
33
Advantages and disadvantages of rectal admin
ADVANTAGES:No first pass, larger dose is good, can be administered if vomiting/unconcious->DISADVANTAGES: Poor compliance, absorption is not regular, irritant to mucosa
34
Sublingual admin advantages and disadvantages
ADVANTAGES: No first pass, very rapid onset->DISADVANTAGES: Very little drugs can penetrate the oral mucosa, may not be convenient for large doses
35
IV advantages and disadvantages
AD: Controlled concentrations in blood, and accurate dosing is possible. large dosing is okay->DIS: Toxicity is easy, need to disinfect area readily, more expensive
36
2 types of IV injection
Slow infusion - Slow IV injection like IV drip->Bolus injection - For emergencies for fast onset, drug is pumped into the blood at a very fast rate
37
What are the 3 L's for transdermal patch
Lipophilic, low dose, low molecular weight
38
How small does a drug have to be for passive diffusion?
Below 150~200 Da
39
What is partition coefficient
It is the Pow of the drug->The higher Pow, the more lipophilic, so more absorbed
40
What's a feature of facilitated diffusion at a very high conc
At a very high solute concentration it is likely to max out the speed, due to saturation of protein
41
What individuals have more water?
Leaner males that are younger
42
Volume of distribution formula
Vd = Dose/Initial concentration
43
How does larger Vd affect half life of drug?
larger Vd means that less drug can be presented to elimination organs like kidney,liver->so it would increase half-life
44
Where is potency on the drug response curve
EC50, half way to Emax
45
Therapeutic index
TD50/ED50
46
Affect on D-R curve for partial agonist
Less efficacy as drug will never produce max response
47
Which type of transport is SLC transporters involved in?
Facilitated and secondary active transport
48
How can multi drug resistance form?
Existence of wide variety of efflux transporters that can bind to variety of drugs
49
Structure of p-gp transporter
12 TM domains and 2 ATP binding domains
50
Major family of enzymes that contribute to phase I biotransformation
1. Monooxygenase->2. Oxidases and dehydrogenases->3. Reductase->4. Hydrolases
51
What is one key thing for phase I reactions
Almost all of them insert a single oxygen molecule
52
Steps for P450 oxygen cycle
1. P450 with ferric (3+) binds to drug->2. Electron from reductase reduces iron to ferrous (2+) *Only ferrous can bind to oxygen->3. Ferrous binds to oxygen->4. 2nd electron from reductase is added on to O2->5. Causes activation of oxygen->6. Oxygen is split, 1 goes into water->7. Hydrogen is pulled from RH (drug) to form OH group, producing carbocation (radical)->8. OH group on iron transffered onto drug->9. Ferric is regenerated
53
Where is POR located (NADPH p450 reductase) and which domain links it
Cytosolic side, N domain links it
54
Which is the most abundant P450 enzyme in liver and small intestine and which % of drugs does it metabolise
CYP3A4, 50% of all drugs
55
CYP1A2 And 1A1 location and what is it induced by
CYP1A2 is located in liver, induced by PAH's->CYP1A1 is located ouside
56
What drug and its reaction reaction does CYP2C9 do?
Hydroxylation of tolbutamide->Phenytoin->Warfarin
57
Which P450 is highly polymorphic in humans
CYP2D6
58
Where is CYP2C19?
Mainly in the liver
59
Where is CYP2C9 located in
Main 2C enzyme in the liver
60
Function of CYP2E1
Ethanol metabolism and small toxicants
61
Where is CYP2E1
Liver, Kidney and some other tissues
62
How is quinone/doxorubicin metabolised? which phase and type of reaction is it
Quinone → Hydroquinone via NADH/NADPH reductase->But if Quinone converted to Semiquinone via POR, it has chance to turn into OH radical
63
How is expoxide metabolised?
Epoxide → Dihydrodiol via Epoxide Hydrolase
64
All phase 2 reactions
1. Glucuronidation->2. Glutathione conjugation->3. Sulfation->4. Acetylation->5. Methylation
65
What is the glucuronidation enzyme and its cofactor and its possible substrate
Enzyme: UGT->Substrates: Hydroxyl, carboxyl, amine, thiol->Cofactor: UDPGA (Uridine diphosphate glucuronic acid)
66
What effects does genetic deficiency in glucuronidation affect the body?
Gilbert's syndrome, usually survivable, may cause jaundince->Crigler-Najjar syndrome, very severe, causes jaundice
67
Glutathione Conjugation Enzymes, Substrates, and Cofactors
Enzymes: GST (Glutathione-s-Transferase)->Substrates: Epoxides, Nitro groups and hydroxylamines (Highly electrophilic groups)->Cofactor: GSH (remember SH - thiol group)
68
Sulfation enzymes, substrates, and cofactors
Enzyme: SULT->Substrates: Phenols, aliphatic alcohols->Cofactor: PAPS (SO3-)
69
How can metabolism of acetaminophen cause liver cell death?
1. If glucuronidation or sulfation pathways are saturated too much (too much drug)->2.If converted by CYP2E1 or CYP3A4, then it forms NAPQI->3. NAPQI is a radical and it can bind to proteins, causing cell death
70
Acetylation enzymes, substrates, cofactors
Enzyme: NAT (N-acetyltransferase)->Substrates: Aromatic amines, hydrazines->Cofactor: Acetyl CoA
71
Methylation enzymes, substrates, cofactors
Enzyme: MT (Methyltransferase)->Substrates: Phenol, catechol. aliphatic and aromatic amine, N-heterocyclic, thiol->Cofactors: SAM
72
Explain induction
Induction is when certain compounds boost the transcription of P450 enzymes->This causes rapid degredation of drug molecules, causing less therapeutic effects (in most cases)
73
How does the aryl hydrocarbon receptor work (AHR)
1. Inducer binds to AHR, along with bunch of other proteins forming a complex->2. this complex moves into the nucleus, boosting transcription of P450 enzymes->3. This increases biotransformation
74
Which enzymes/reactions/P450 does AHR effect
Phase I: CYP1A1, 1A2, 1B1, 2S1->Phase II: GST, UGT
75
How does St.John's wort effect biotransformation
CYP3A4 is induced, increasing its transcription rate therefore decreasing drugs that are metabolised by it
76
how can induction be a potential benefit
Cabbage induces CYP1A2, reducing the levels of 17B-estradiol (Bad estrogen)
77
How did seldane (Terfenadine) get banned?
If taken with ketoconazole erythromycin, it can inhibit CYP3A4 (normal pathway)->This causes build up of terfenadine, leading to arrhythmia
78
How can grapefruit be bad?
It inhibits CYP3A4 so it inhibits metabolism for CYP3A4 drugs
79
How do you test for P450 inhibition?
Get a cDNA sample to express the enzyme->Put it together with various chemicals
80
Which P450 should pharmaceutical companies avoid?
CYP3A4 - Too busy since it metabolises majority of drugs->CYP2D6 - High polymorphism in humans
81
What does agonist drug do?
It mimics the natural compound/ ligand, by binding to the receptor and initiate signaling cascade
82
What does Emax tell us? What about E50?
Emax= drug efficacy, the max response achieved by agonist
E50= potency, measure the drug concentration needed to reach 50% max response
83
What happend to the DR curve of a more potent drug?
It is left shifted
84
What is partial agonist?
Agonist that cannot produce the full response, so max efficacy cannot be reached even when all receptors are bound
85
What is diazepam? In term of agonist
Positive allosteric modulator of GABAa receptor, , shift DR curve to the left
Used to treat anxiety, insomnia and seizures
86
What is competitive antagonist?
It bind to the same site on receptor as agonist, bock the agonist/ ligands from binding to the site of action, shifting DR to the right
87
How to counter competitive antagonist?
Increase the concentration of the agonist
Potency is decrease, but same efficacy can be reached eventually
88
What is non-competitive antagonist?
Can be either irreversible binding to site of action, or negative allosteric modulator
Reduce both potency and efficacy, the same efficacy can never be reached
SHift DR to the right and downward
89
What is the usual size of drug?
200-500 Da
90
What is the permeability of ionized and unionized drug?
Ionized= charged, less permeable due to lower lipophilicity
91
What drugs are substrate to OATs
Penicillin
diuretics
92
What drugs are substrate of OATPs
digoxin
ciprofloxacin
fexofenandine
93
What are some parenteral drug administrations?
IV= into vein
IM= into muscle
SC= subcutanous, under skin
94
How are drugs excreted? In term of water/ lipid soluble drug
Water soluble: directly eliminated
Lipid soluble: need to be biotransformed into polar and water soluble drug, then get excreted
95
What is cyclophosphamide?
It is a chemotherapy pro drug, used to treat cancer
It will be metabolized to phosphoramide mustard, which bind to DNA and kill cancer
