Intro Flashcards
1
Q
Pharmacology
A
science of drugs including their origin, composition, pharmacokinetics, therapeutic use, and toxicology
2
Q
Pharmacokinetics
A
what the body does to a drug as it goes through absorption, distribution, metabolism, and elimination
3
Q
Pharmacodynamics
A
what the drug does to the body
4
Q
Pharmacokinetic properties determine
A
the onset
the intensity
the duration of drug action
5
Q
How can pharmacokinetic properties optimize drug regimens?
A
route of administration
dose
frequency
duration of treatment
6
Q
Absorption
A
process of a drug entering the systemic circulation
7
Q
distribution
A
process of a drug leaving the systemic circulation and entering the interstitium (ECF) and the tissues
8
Q
metabolism
A
process of a drug converting from its original chemical structure into other forms to facilitate elimination from the body
9
Q
elimination
A
process of removal of a drug from the body
10
Q
bioavailability
A
extent of administered drug that reaches systemic circulation
high >70%
low < 10%
11
Q
What affects bioavailability?
A
first pass metabolism in intestine/liver
solubility of drugs
chemical instability
nature of drug formation
12
Q
Hydrophilic drugs are poorly absorbed due to their inability to cross?
A
lipid-rich cell membranes
13
Q
enteral
A
admin by mouth
includes enteric coated, extended release, sublingual, and buccal
14
Q
Parenteral
A
admin directly into systemic circulation
includes IV, IM, SC
15
Q
Enteral Absorption is
A
variable
16
Q
Advantages of Oral admin
A
safe and common
convenient
economical
17
Q
disadvantages of oral admin
A
limited absorption of some drugs due to physical characteristics
1st pass metabolism
drug absorption affected in presence of food/other drugs
low patient compliance
18
Q
What is 1st pass metabolism?
A
Destruction of drugs by digestive enzymes or low gastric pH before reaching systemic absorption
19
Q
Enteric coated preparations
A
chemically envelope drugs
prevent a drug from causing gastric irritation
prevent a drug from dissolving in stomach acid, helps it to reach the site of action in the ileum and colon
20
Q
Extended Release preparations
A
decrease the rate of dissolution to provide slow uniform absorption > 8 hr or longer
21
Q
Advantages of Extended released preparations
A
decr frequency of dosing, incr patient compliance
maintain therapeutic effect overnight
decr incidence of adverse effects
decr non therapeutic blood levels of the drug that often occur after admin of IR dosage forms
22
Q
Sublingual admin
A
under the tongue
23
Q
buccal admin
A
between cheek and gum
24
Q
Absorption pattern of sublingual and buccal admin
A
rapid
direct systemic absorption
25
Advantages of Sublingual/ buccal admin
easy admin
rapid absorption
bypass 1st pass metabolism
26
Disadvantages of sublingual and buccal admin
limited application to certain types of drugs
only drugs with small doses
must be nonirritating
27
Parenteral Admin advantages
rapid onset of action
bypass 1st pass metabolism
useful for drugs that are poorly absorbed/ unstable in GI tract
highest bioavailability
deliver to unconscious patients
28
Disadvantages of Parenteral admin
irreversible admin not good if ADR occurs
pain, necrosis
infections at site of injection
29
IV admin
into venous blood stream directly
absorption not required
30
IV admin advantages
immediate effect
ideal for drugs with large volumes
suitable for irritating substances and complex mixes
dose titration
ideal for protein and peptide drugs
31
IV admin disadvantages
unsuitable for oily substances
irreversible admin not good in case ADR occurs
precipitation of blood constituents, hemolysis
requires slow injection
32
IM admin
into the muscle
33
IM admin absorption
depends on drug diluent
in aq solns prompt
in depot preparations slow and sustained
34
IM admin advantages
moderated drug volume
suitable for oily vehicles and some irritating substances
35
IM admin disadvantages
painful
potential IM hemorrhage
36
SC admin
beneath the skin
37
SC admin absorption
depends on drug diluents
in aq solns prompt
in depot preparations slow and sustained
38
SC admin advantages
suitable for slow-release drugs
suitable for some poorly soluble suspensions
39
SC admin disadvantages
pain/necrosis if irritating drugs
unsuitable for large volumes of drugs
40
Inhalation absorption
systemic
41
Inhalation admin advantages
rapid absorption
access to blood due to large lung surface area
ideal for gases/volatile substances
dose titration
localized effect to target lungs
fewer systemic side effects
42
Inhalation admin disadvantages
most addictive route
difficulty in regulating dose
difficulty using inhalers
43
Topical admin
local admin for local effects
44
mucous membranes
conjunctiva
nasopharyngeal
oropharynx
vagina
colon
urethra
urinate bladder
45
In mucous membranes absorption is generally ?
excellent
46
What are some examples of topical eye admin?
Drug loaded contact lenses
ocular inserts
47
Transdermal admin
admin to skin
48
Transdermal admin absorption
slow and sustained
dependent on surface area and lipid solubility of drugs
49
Transdermal admin advantages
convenient
painless
bypass 1st pass effect
50
Transdermal admin disadvantages
irritation
only highly lipophilic drugs
delayed drug delivery to site of action
only drugs with small daily doses
51
rectal admin
drug absorbed via rectal mucosa
52
rectal admin absorption
erratic and variable
53
Rectal admin advantages
partially bypass 1st pass metabolism
ideal for drugs that cause gastric irritation, nausea and vomiting
ideal for patients that are comatose
54
Rectal admin disadvantages
irritation to rectal mucosa
lack of patient acceptability
55
intra-arterial admin
delivers drug to a particular tissue, or as a diagnostic agent
accidental admin here cause serious complications
56
Intrathecal admin
injection directly into the cerebrospinal fluid
bypass blood-brain barrier
used for treatment of brain tumors and for spinal anesthesia
57
What affects drug absorption?
pH
blood flow to the absorption site
total surface area available for absorption
contact time at the absorption surface
expression of a transmembrane transporter protein
58
Can charged drugs (A^- or BH^+) diffuse through biological membranes?
no
59
For drugs to cross biological membranes what do they need?
to be lipid soluble/ have a specific transporter
60
What affects drug distribution?
blood flow
capillary permeability
binding of drugs to plasma proteins and tissue proteins
lipophilicity of the drug
volume of distribution
61
Which organs receive most of the administered drug?
liver
kidney
brain
other well-perfused organs (lungs)
62
Which organs have slow drug distribution?
muscle
visceral organs
skin
fat tissues
63
Does plasma protein binding increase or decrease the amount of drug that can enter tissues from the blood?
decrease
64
Albumin
binds to acidic drugs
65
alpha1-acid glycoprotein
binds basic drugs
66
Fat tissue reservoirs
where lipid soluble drugs accumulate
prolongs half-life of drug and duration of action
67
Bone tissue reservoir
mostly seen with divalent metal-ion chelating agents and heavy metals accumulate into bone crystal lattice
slow release of toxic agents
68
What do the tight junction in brain capillary endothelial cells prevent?
The diffusion of hydrophilic drugs from the blood into the CNS
69
What do the membrane transporters in brain capillary endothelial cells of the blood brain barrier do?
remove drugs from the CNS
decr effectiveness of protease inhibitors for treating HIV in the CNS
70
What do pericapillary glial cells in the blood brain barrier do?
Form and maintain the blood-brain barrier
establish a diffusion barrier
71
Placental barrier
placenta has a [high] of metabolic enzymes and export transporters to decrease the [drugs] that enter fetal circulation
to some degree the fetus is exposed to all drugs taken by the mother
72
Can uncharged drugs diffuse through biological membranes?
yes, so HA will diffuse through acidic environments, and bases will diffuse through basic environments
73
Distribution of the drug between ionized and non-ionized forms is dependent on?
pH and pKa of the drug
74
When pH = pKa what is the behavior of acids and bases?
[HA] = [A^-]
[BH^+] = [B]
75
When pH
[HA] > [A^-]
[BH^+] > [B]
protonation is favored
76
When pH>pKa what is the behavior of acids and bases?
[HA] < [A^-]
[BH^+] < [B]
deprotonation is favored
77
What is the henderson - hasselbalch equation
ratio of nonionized to ionized drug at given pH
log (protonated form/unprotonated form) = pKa - pH
78
What percentage of drugs are eliminated unchanged in the urine?
25-30%
79
What are the primary organs of metabolism?
liver
GI tract
kidneys
lungs
80
Biotransformation
process by which lipophilic, xenobiotic, or endobiotic chemicals are converted in body by enzymatic reactions to products that are more hydrophilic.
81
Metabolism Phase 1 reaction
oxidation, reduction, hydrolysis
drug may be activated, unchanged, or often inactivated
done by cytochrome P450
converts lipophilic drugs in to polar molecules
result: loss of pharmacologic activity, can sometimes prolong/enhance it
82
Metabolism phase 2 reaction
conjugation
conjugated drug is usually inactive
drugs are bound covalently to polar water soluble molecules which are then removed in urine or feces
83
Prodrugs
drugs that are inactive in the original structure but activated by phase 1 metabolism
84
What reactions are included in phase 2 metabolism?
glutathione conjugation
sulfation
acetylation
glucuronidation
85
Which is eliminated more rapidly, water soluble polar molecules or lipid soluble drugs?
water soluble polar molecules
86
What is the general process of drug clearance by the kidney?
1. Glomerular filtration
2. Active Tubular secretion
3. passive tubular secretion
87
What is glomerular filtration
Free drug passes through the capillary into the bowman space
88
What is the glomerular filtration rate?
125 mL/min
89
If renal disease is present what decreases?
GFR
90
Does lipid solubility of drug and the pH of the medium affect the glomerular filtration process?
no
91
Does GFR and drug-protein binding affect glomerular filtration process?
yes
92
Proximal Tubular secretion
for drugs not transferred into glomerular filtrate
drugs leave glomeruli through efferent arteries
secretion of organic cationic drugs and organic bases primarily happens by energy-requiring active transport systems
93
Distal tubular reabsorption
as a drug moves towards this its concentration incr
uncharged drugs diffuse out the nephric lumen and go back into systemic circulation n
can manipulate urine pH to minimize this
94
To minimize distal tubular reabsorption what should be done for an acidic drug? A basic drug?
for acidic drugs alkaline the urine
for basic drugs acidify the urine
95
When drug concentration in the filtrate is greater than in the tubular lumen…
hydrophobic drugs diffuse out
96
Are polar/ionized conjugate able to diffuse out of the kidney lumen?
no
97
Biliary Excretion
transporters in liver cells transport amphipathic lipid soluble drugs into the bile which is then eliminated in feces
98
Enterohepatic Recycling
some drugs that are secreted into the bile can be reabsorbed by the intestinal tract and renter the circulation
99
passive diffusion
concentration gradient across a membrane
[high] the gut lumen -> [low] the blood
no energy/carrier
not saturable
majority of drugs absorbed this way
water soluble drugs: aqueous channels/pores
lipid-soluble drugs: dissolve in lipid bilateral membranes and cross the biological membranes
100
facilitated diffusion
concentration gradient across a membrane
does not require energy
[high] -> [low]
requires carriers
- conformational changes
- can be saturated
- could be inhibited by compounds competing for the carrier
101
Active transport
against a concentration gradient across a membrane
[low] -> [high]
requires energy
requires carriers
- can be saturated
- selective
- may be inhibited by co-transported substances competing for the carrier
102
endocytosis
large drug molecules engulfed by the cell membrane and transported into the cell through a vesicle
103
P-glycoprotein
transmembrane transporter protein
transports drugs from tissues to blood by pumping drugs out of cell
if highly expressed it reduces drug absorption
associated with multidrug resistance
