MIDTERM 1 Flashcards
(62 cards)
1
Q
Drug
A
any substance that causes an change in cellular/biological effect
2
Q
Therapeutic agent
A
-drug used to TREAT disease/condition
3
Q
Prophylactic agent
A
-drug used to PREVENT disease/condition
4
Q
Pharmacy
A
the art of PREPARING, COMPOUNDING and DISPENSING chemicals for medicinal use
5
Q
Pharmacology
A
the study of drugs and their effects
- what they are, how they work, what they do
- divided into PD and PK
6
Q
Pharmacodynamics (PD)
A
- what drugs do to the body
- studying the relationship between concentration of drug + effect
7
Q
Pharmacokinetics (PK)
A
-what the body does to drugs
8
Q
Pharmacogentics/ Genomics
A
-variations in drug response due to genetics
9
Q
Toxicology
A
- study of undesirable effects of chemicals on living systems
- poisons, antidotes, unwanted side effects
10
Q
FDA Pregnancy categories
A
Category A: drug is safe for pregnancy
-penicillin, anti-histamine
Category B/C: drug MAY cause harm
Category D: drug LIKELY to cause harm
Category X: drug shown to cause harm, DO NOT USE
-interfere with pathways of fetal development
11
Q
Examples of category X drugs
A
- Ace inhibitors: fetal renal and CV damage
- Anti-epilileptic drugs: neural tube defects, CV damage
- Warfarin: anatomical malformations, CNS and CV damage
- Valproic acid: neural tube defects, anatomical malformations, CNS, CV damage
12
Q
Drug development time line
A
1) In-vitro studies
- 2 years
- chemical synthesis
2) Animal testing
- from year 2-4
- at end –> IND (Investigational New Drug)
- successful on animals, can begin testing on humans
3) Clinical trials
PHASE 1: is it safe?
-healthy volunteers, young males
-determine pharmacokinetics (what body does to drugs) and toxicity
PHASE 2: does it work in people?
- people with the condition of interest
- determine drug efficacy and dosing
PHASE 3: does it work double blind?
- large scale trials
- confirm safety and efficacy
- results determine if drug goes to market
- –> at 8-9 mark –> NDA/ New drug application
4) Marketing
PHASE 4: post marketing surveillance
- after drug approval
- withdrawn if significant problems
13
Q
Exceptions to the drug development timeline
A
- many drugs for life-threatening conditions (HIV, cancer, AIDS) skip steps to get drugs to patients faster
- may result in less info being known about a drug
- higher frequencies of adverse effects
14
Q
DIN
A
- drug identification #
- required by law in Canada
15
Q
NPN
A
- natural product number
- ex: multivitamins
16
Q
Numbers for drugs
A
- allows for tracking
- recalls
- adverse rxns
17
Q
Serendipitous discovery
A
- drug found by accident or when trying to dine something else
ex: penicillin
18
Q
Intelligent (or rational) drug design
A
- identify a target, design a drug to modulate this target
ex: reverse transcriptase inhibitors (HIV therapy)
19
Q
High throughput screening
A
test large libraries of compounds to determine “hits”
20
Q
“Me too” drugs
A
- related drugs produced after the 1st/OG discovery
- mostly just improvements, nothing new
21
Q
Canadian drug advertising regulations
A
Food and drugs Act
-prevents false advertising
Food and drug regulations
-cannot advertise benefits and or/therapeutic use
22
Q
Chemical name of a drug
A
IUPAC
23
Q
Generic name
A
- USUALLY a universal name of a drug product
- ex: ibuprofen
- acetaminophen/paracetamol
24
Q
Brand name/trade name
A
- determined by manufacturer
- different across the world
ex: over 100 diff brands of ibuprofen
- Advil
- Motrin
25
Pharmacodynamics
- what drugs do to the body
- studying the relationship between concentration of drug + effect
L + R ⇌ LR (ligand-receptor complex)
L= ligand
- binds to specific receptors
- drugs, endogenous molecules (NTs and hormones)
ASSUME: biological effect is proportional to amount of LR
-more drugs bound to receptor, the greater the effect
26
How do drugs elicit their effects?
by mimicking to blocking the actions of hormones + NTs (endogenous molecules)
27
Major classes of receptors targeted by drugs
1) Ligand-gated ion channels
- ligand binds, change in concentration of intracellular ions, leads to cellular effect
ex: Nicotinic acetylcholine receptor (milliseconds)
2) Enzyme-linked receptors
- ligand binds, protein phosphorylation, cellular effect
ex: insulin receptor (seconds- minutes)
3) G-protein coupled receptors (GPCRs)
- ligand binds, activates G protein, intracellular 2nd messengers, cellular effect
ex: B-adrenergic receptor (seconds to minutes)
4) Ligand activated transcription factors
- located inside the cell
- ligand binds, activates transcription factor, regulates gene expression
ex: estrogen receptor (hours)
28
Ligand receptor binding
- reversible
- non covalent forces:
Decreasing strength:
Ionic --> H bonds --> Hydrophobic --> Van de waals
29
Strength and number of bonds determines
- Affinity of ligand for receptor
| - functional effect of ligand on receptor
30
Lock and key model of ligand-receptor activation
Endogenous ligand= hormone or NT = key
Receptor= lock
*hormone/NT acts as a key, binds to the receptor, "unlocks it" --> induces a biological effect
Agonist= mimics NT/ hormones
- binds to their receptors, elicits the same response as endogenous ligand
- ex: bobby pin
- "picks the lock"
Antagonist
- binds to receptor
- BLOCKS NT's and hormones from binding
- inhibits receptor activation by agonists
ex: jamming a stick in the lock, other shit can't bind
31
Relationship between ligand concentration and receptor binding
- ligand binding to receptor: hyperbolic
- can also undergo semi-log transformation, same shit
Bmax= max amount of receptors bound
-all receptors are bound by ligand
B= fraction of receptors bound
kd= dissociation constant, concentration of the ligand at 1/2 Bmax, measure of affinity of receptor-ligand interaction
B= Bmax * [L] / [L] + kd
32
Graded dose response curve
- responses that have an infinite number of intermediate states
- ex: vessel dilation, blood pressure change, HR change
33
Emax
maximum effect/response achieved by the ligand
34
ED50
- ligand dose at which 50% of E max is achieved
| - POTENCY
35
Quantal phenomena
- all or none: 2 states (ex: death, pregnancy, cure, pain relief)
- useful to describe population rather than individual responses to drugs
- based on plotting cumulative frequency distribution of responders vs. log dose
36
Potency
- the amount of agent needed to produce a given effect
- ED50
- smaller ED50= higher potency
37
Efficacy
- the MAXIMUM effect that can be achieved with an agonist
- the functional impact on a receptor
- Emax (max % effect)
higher Emax= higher efficacy
38
Types of agonists
- Full agonists and partial agonists
- POTENCY DOESN'T FACTOR INTO WHETHER IT IS PARTIAL OR FULL
- ONLY EFFICACY: the functional outcome
39
Full agonist
ANYTHING WITH MAX EFFICACY
- high potency + max efficacy
- low potency + max efficacy
40
Partial agonist
ANYTHING WITH REDUCED EFFICACY
- high potency + reduced efficacy
- low potency + reduced efficacy
41
Failure of partial agonists to produce a maximal response
- not due to decreased affinity: kd can be identical for partial and full
- partial agonists have a lower functional impact on the receptor
42
Constitutive receptor activation
-going from inactive --> active via agonist or spontaneously
agonist: binding induces conformational change in the receptor from inactive --> active
- may also stabalize the active state
43
Agonist (experiment to measure constitutive receptor activation)
- has an independent effect on receptor activity: ACTIVATES
- caused vasodilation
- HAVE EFFICACY: functional impact on a receptor
44
Antagonist
- by itself, will bind to the receptor and block it
- but doesn't matter if agonist is not present
- impacts receptor activity only in the presence of agonist
- HAVE POTENCY, LACKS EFFICACY
45
Inverse agonist
- stabilizes the inactive state
- destabilizes the active state
-REDUCES CONSITITIVE RECEPTOR ACTIVATION
has an independent impact on receptor activity
produces effect opposite to agonist
-INACTIVATES THE receptor
46
Types of antagonism
chemical antagonism, physiological antagonism, pharmacological antagonism
47
Chemical antagonism
DIRECT interaction of two chemicals/substances
-effect of one or both is lost
ex: acidic + basic= loss of activity of both drugs
48
Physiological antagonism
- INDIRECT interaction of two substances with opposing physiological actions
ex: Histamine decreases bp through vasodilation, epinephrine increases bp through vasoconstriction
49
Pharmacological antagonism
-blocking substances from interacting with its receptor by another substance
- bind to receptors, but do not activate signalling
- the decreased biological effect is the result from agonists being unable to bind the receptor
50
Types of pharmacological antagonists
1) Competitive antagonist
- REVERSIBLY binds receptor
- inhibition can be overcome by increasing the concentration of the agonist
- affects potency/ED50
* does not decrease the # of receptors available for activation*
2) Non-competitive antagonist
- IRREVERSIBLY (covalently) binds to receptor
- or irreversibly binds to allosteric site
- inhibition can't be overcome by increasing concentration of agonist
- decreases efficacy/ Emax
* DO DECREASE THE # OF RECEPTORS AVAILABLE FOR ACTIVATION*
51
ID50/ IC50
- inhibitory dose/ inhibitory concentration
- concentration dose at 1/2 Emax
- AKA POTENCY FOR ANTAGONIST
52
Emax (antagonist)
max biological effect achieved by antagonist
| -NOT A MEASURE OF EFFICACY, only agonists have efficacy
53
Drug desensitization
AKA: resistance, refractoriness, tolerance, tachyphylaxis
-diminished effect of drug due to continuous exposure
two types, receptor mediated and non-receptor mediated
54
Receptor mediated desensitization
1) Loss of receptor function
- receptor stops working (change in conformation)
- rapid desensitization/ decreased response
- due to feedback of agonist
ex: phosphorylation of a.a in GPCRs block coupling to G proteins
2) Reduction of receptor #
- decrease in # of receptors
- slower, long term
- due to feedback of agonist
ex: phosphorylation of a.a in GPCRs causes removal from cell surface
55
Non-receptor mediated desensitization
1) Decreased receptor coupled signalling components
- decrease in signalling molecules required for response
- prolonged GPCR stimulation, decreases 2nd messengers
2) Increased metabolic degradation
- increased metabolism + increased elimination of drug
ex: barbiturates induce metabolic enzymes that degrade the drugs
3) Physiologic adaptation
- decrease in drug effects due to homeostatic responses
56
Adverse drug effects
side effects, toxic reaction, allergic reaction
57
Side effect
- action of drug at OTHER SITES to produce undesirable effects
- depends on does
- not directly related to the desired effect of drug
58
Toxic reaction
- excessive action of drug at intended target site
- depends on dose
- directly related to the desired effect of drug
59
Allergic reaction
- immune response to drug
- does not depend on dose
- not related to desired effect of drug
60
Discuss the adverse effects of cyclosporine
Benefits: promotes survival of transplanted organs
-dose dependent, result of immunosuppression (so that organs don't get rejected)
ADVERSE EFFECTS
Side effect
- kidney damage
- not related to intended pharmacological activity
- magnitude of effect is dose dependent
Toxic effect
- increased risk of infection due to immunosuppression
- consequence of intended pharmacological action (immunosuppression)
Allergic effect
- rash, hives, itching, breathing difficulties
- not related to intended pharmacological activity
- not dose dependent
61
Therapeutic index (TI)
TI= Toxic ED50/ Beneficial ED50
- relative measure, not absolute
- if outcome = death, need large TI
- if outcome = headache, can have a lower TI
62
Therapeutic window
-RELATIONSHIP TO DOSE
the range of DOSAGES of a drug
-associated with: adverse effects, therapeutic benefit, lack of effect in a population
