Drug Therapy Flashcards
(105 cards)
1
Q
pharmacokinetics
A
the movement of drugs through the body
2
Q
pharmacodynamics
A
the body’s biological response to drugs
3
Q
safe and effective medications
A
balance between safety and efficacy - fine line with toxicity
4
Q
bioavailability
A
the extent and rate at which the drug enters systemic circulation, thereby accessing the site of action
5
Q
what does the effect of a drug depend on
A
- affinity
- intrinsic efficacy
- pharmalogical effect also dependent on residence time
6
Q
what can different drugs still do
A
ellicit the same response - due to different mechanisms/pathways
7
Q
What are different receptors which have the same function in different people called
A
polymorphic variation - diff sequence of genes code for same receptor
8
Q
what mechanism of binding occurs in endogenous receptors
A
lock and key - either on same site, or allosteric site
9
Q
agonist drug
A
inc proportion of activated receptors
10
Q
antagonist drugs
A
dec proportion of activated recptors - prevent activation
11
Q
what 2 mechanisms can inhibition occur by
A
competetive or non-competetive
12
Q
what is a drug steady state
A
when the quantity of drug eliminated equals the quantity of the drug that reaches the systemic circulation - kinda like equilibrium
13
Q
what are allosteric modulators
A
drug binds to different site, changing the shape of the receptor site for the endogenous ligand - can inc or dec efficacy
14
Q
Biophase
A
the effect site of the drug (physical region in which the drug target is located
15
Q
what is the bioavailability if we inject a drug directly into the circulation (e.g. IV route)
A
100%
16
Q
what is a downside of non IV routes
A
some drug is lost (e.g. gut tissues etc. and passed on for excretion)
17
Q
what is first pass metabolism
A
drug gets metabolized at a specific location in the body that results in a reduced concentration of the active drug upon reaching its site of action or the systemic circulation - amount of drug removed before it reaches systemic circulation
18
Q
Cmax
A
max plasma conc of drug achieved
19
Q
drug: half-life
A
time taked for conc in plasma to fall to 1/2 original value
20
Q
therapeutic index
A
ratio that compares the blood concentration at which a drug causes a therapeutic effect to the amount that causes death or toxicity
21
Q
where will drugs go from the plasma
A
plasma –> ISF —> ICF (or other trancellular fluid)
22
Q
what must drugs do to cross compartemnts and what are the 2 ways they go about this
A
Must cross barriers:
* Paracellular (filtration) - filter between cells
* Transcellular - through cells
23
Q
3 types of barrier, and what makes them different in terms of drug absorption
A
Continous - hard for drugs to cross
Fenestrated - more holey
Sinusoid - incomplete basement membrane with intercellular gaps
24
Q
Describe the meachanisms which drugs can use to travel from the plasma to tissues
A
- diffusion
- facilitated diffusion
- active transport
- endocytosis
25
what does the uptake of blood into tissues depend on
| Key flashcard
* Lipophilicity - can easily diffuse across cell membrane
* Blood supply (perfusion) - inc blood supply, inc rate of drug delivery
* Ion trapping? - if ionic then hard to cross capillary/cell membrane so "trapped" there
26
if drugs are lipid soluble (lipophilic) what os diffusion driven by (instead of pumps/channels etc.)
conc gradient
27
what are tissue compartments
grouping tissues that show similar conc vs time profile
28
xenobiotic
chemical substances that are foreign to animal life and thus includes such examples as plant constituents, drugs, pesticides, cosmetics, flavorings, fragrances, food additives, industrial chemicals and environmental pollutants
29
what is the purpose of drug metabolism
| + what are the steps
make the metabolite more **polar** than the parent compound and thus, more **easily excreted**
Phase 1 (functionalisation) and phase 2 (synthetic)
30
what can characteristics that facilitate absorption and diistribution do to excretion
inhibit it - lipophilic dugs more easily reabsorbed
31
How is the liver important in drug metabolism
* Main site of metabolism/excretion
* CYP450 = enzyme that helps with M/E
* polymorphic variation
* liver health impacts rate of excretion
* Liver toxicity = inc risk of toxicity (impacts safety and efficacy)
32
briefly summarise pathway of xenobiotic to excretion
Xenobiotic --Phase1--> active metabolite --Phase2--> conjugate ----> Excretion
| can skip 1, skip 2, do 2 then 1 or 1 then 2 or none ;)
33
biliary excretion
active secretion of drug molecules or their metabolites from hepatocytes into the bile
34
What are the main routs of drug administration
* IV: bioavailability = 100
* Oral (most common)
* Subcutaneous
* Intramuscular (IM)
* Nasal
* Inhaled
* Transdermal
* other GI (rectal, sublingual)
35
benefit of sublingual drug administration
bypasses first pass metabolism
36
Define each bit of ADME
**Absorption**: how a chemical enters the body. Absorption relates to the movement of a chemical from the administration site to the bloodstream.
**Distribution**: drug moves from the absorption site to tissues around the body via the bloodstream, but can also occur from cell-to-cell.
**Metabolism**: biotransformation of drug by tissues/organs so the drug can be excreted.
**Excretion**: the process by which the metabolized drug compound is eliminated from the body.
37
what are the mechanisms of ADME
normal physiological mechanisms we exploit when developing mediecations
38
bulk flow
the movement of fluids down a pressure or temperature gradient
39
2 important organs in drug elimination and toxicity
Kidney and liver
40
absorption
process of mass transefer from site of administration to bloodstream
41
what does the extent and rate of drug absorption depend on
* physiochemical properties of the drug (e.g. size, **lipophilicity**, ionic...)
* Dosage form
* Anatomical/physiological factors
42
are all drugs absorbed
No, some (e.g. **topical**) arn't absorbed
43
do topical drugs reach systemic circulation
Yes, some can
44
why would we not want a drug to be absorpbed into systemic circulation
Only want to effect site of application (e.g. local anaesthetics)
45
How do we administer local anaesthetics to avoid them reaching systemic circulation
* Don't inject into circulation
* Avoid highly vascular tissues
* Co-administer with **adrenaline** - causes **vascoconstriction**
46
what is half -life
| check
tiem take for Cmax to reach half value
47
Factors to affect oral absorption
* solubility affected by gut's contents
* Gastic emptying time (e.g. poo before absorpted)
* pH change throughout gut - ionize
* Guit flora
* First pass metabolism
48
Ficks first law of diffusion
the rate of diffusion of a substance across unit area (such as a surface or membrane) is proportional to the concentration gradient
49
things affecting fick's first law (diffusion)
* Diffusion coefficient
* size etc.
* partion coefficient
* thickness of membrane
* membrane area
* **Drug concentration**
50
First order kinetics
occur when a **constant proportion of the drug is eliminated per unit time**. Rate of elimination is proportional to the amount of drug in the body. The higher the concentration, the greater the amount of drug eliminated per unit time. For every half life that passes the drug concentration is halved. - more drug in the body, the faster it is removed
51
Facilitated diffusion
for large or lipophobic molecules?
Eventually **saturable** so inc dose does not inc rate of absorption
52
What are some additional barrier to distribution
**protected** tissues: brain, testis, ovary, placenta
| BBB
53
Plasma protein binding
* Happens in **distribution**
* The bound portion may act as a reservoir or depot from which the drug is slowly released as the unbound form.
* Affects drug's half life
* Essentialy drugs bound to protein (e.g. Albumin) and circulate in bloodstream until **free drug** used. Then bound drug released and cycle continues until all is used up
54
free drug hypothesis
assumes that the unbound drug concentration in blood is the same as that in the site of action at steady state
55
Is plasma protein bound drug active
No
56
volume of distribution
apparent volume into which the drug is distributed to provide the same concentration as it currently is in blood plasma
Proportionality constant between the total amount of drug in the body and the amount in the plasma at any one time - total inc bound drugs and assumes instantaneous equilibration
57
Drugs with **low** Vd
remain in plasma (less distribution)
58
drugs with **high** Vd
leave the plasma (more distribution)
59
what does drug plasma concentration drive
the therapeutic effect
60
overall what does Vd influence
[plasma]
61
half-life property of drugs with high Vd
Drugs with high Vd tend to have longer elimination half-life
62
What can Vd be used to calculate
loading dose
63
steady state
every time administer dose, get peaks and troughs (loading dose) until steady state achieved where have **constant concentration**
64
con of inhaled medication
much is swallowed and only 5% ends up in lungs
65
Apart from dose of drugs what else can we manipulate
Dosage form: e.g. hexamers vs monomers, fast vs long acting...
| ???
66
medical importance of first pass metabolism
educe the total exposure of the body to drug
67
factors to affect bioavailability
* chemical composition
* how it is administered
* patient's physiology
68
effect of plasma protein binding on bioavailability
It can **limit the bioavailability of active compounds** by controlling their passage through biological membranes; however, binding to plasma proteins allows hydrophobic drugs to be transported in the aqueous environment of the human organism
69
zero order kinetics
Zero-order kinetics undergo constant elimination regardless of the plasma concentration, following a linear elimination phase as the system becomes saturated.
70
tmax
The time it takes for a drug to reach the maximum concentration (Cmax) after administration of a drug that needs to be absorbed
71
AUC
Are under curve: area under the plot of plasma concentration of a drug versus time after dosage
72
drug clearance
the rate at which a drug is removed from plasma(mg/min) divided by the concentration of that drug in the plasma (mg/mL).
73
Specific barriers (e.g. BBB, testes, placenta, ovarie)
Have continouse membranes
| (no fenestrations or sinezoids)
74
Xenobiotics
compounds other than those with a well-defined physiological role
75
what are endogenous compounds administered at concentrationsoutside the normal physiological range classed as
xenobiotics
76
Ways of physical removal of drugs from body
urine, bile, sweat, perspiration
77
Biotransformation
Processing of increasing polarity of molecule making it less likely to be reabsorbed: Phase 1 and Phase 2
78
Biotransformatio: phase 1 reactions
Creating a functional group or modifying an existing one: largely **oxidisation** and conducted by CYP450s but could also be hydrolysis
| Metabolisation
79
Where does Phase 1 of biotransformation (metabolisation) occur
**Liver** (also extrahepatic activity) and in gut/small intestine/lungs/kidney
80
Where in the cell is CYP450 found
membrane protien in mitochondria and cytosol, much in the SER
81
Toxicity of Phase 1
small number of phase 1 metabolites are toxic: **Quinones** and **quinone** analogues
Activation of **prodrugs** dec toxicity
82
what can be seen in cytochrome p450
mutations and polymorphism
83
cytochrome P450 with broad substrate specificity
3A4
84
Phase 2 biotransformation
* Products **less active**, larger and more **hydrophilic** so more likely to be **exreted**
* Tend to be weak ions - ion trapping
* More likley to bind to albumin
* Need cofactors - glucuronic acid
85
food-drug interactiong with CYP450
* CYP3A4 and grapefruit juice
* Omepraxole induces CYP3A4
Polymorhic variation
86
what is warfarin metabolised by
CYP2C9
87
Drug elimination
final removal of drug from body. Includes metabolism and excretion
88
Do drugs have to be metabolised before being excreted
not always
89
excretion
rateof drug removal from body
90
Define clearance
volume of plasma from which the drug would be totally removed per unit time
| first order process
91
factors to affect [drug] in plasma
bioavailability and clearance
92
what is total clearance
renal + hepatic + lung... etc.
93
Renal clearance includes:
| 3
* **Glomerular** filtration
* active **tubular** secretion
* tubular **reabsorption**
94
Explain the process of fibtration and the conditions which must be met
* drug must be in plasma (and free)
* Depends on Vd and protein binding as well as size and charge
95
total renal clearance
| maybe don't bother learning
No secretion/reabsorption
96
what is active renal secretion
* occurs in proximal tubule
* clears drugs too large to filter
* depends of drug flow, free drug
* **saturable**
97
what + what = renal clearance
secretion +GFR
98
passive tubular reabsorption
passive process whereby drugs are reabsorbed into the systemic circulation from the lumen of the distal tubules - depends on urin flow rate and pH - ion trapping
99
wht is renal clearance proportional to
GFR
100
briefly describbe hepatic clearance
* perfusion important here
* dependent on efficiency of removal of drug from blood
101
what does hepatic clearnce equal
hepatic clearance = hepatic blood floow x hepatic extraction ratio
102
Intrinsic clearance capacity
a measure of the maximal ability of the liver to metabolize a drug in the absence of protein binding or blood flow limitations
High: hepatic clearance is perfusion limited
103
enterohepatic recirculation
* poorly reabsorbed
* enzymes expressed bu gut microbiota can **de-conjugate** and allow its reabsorption
* **secondary** drug absorption ---> **prolonged drug action**
104
what does renal disease increase the risk of
drug toxicity
105
how can renal disease increaseing the risk of drug toxicity be accounted for
by alterations in the dosing strategy
