1
Q
- it is the passage of administered drug to reach the systemic circulation
- it is the first process in pharmacokinetics
A
ABSORPTION
2
Q
it is improtant in predicting drug asborption
A
ROUTE OF ADMINISTRATION
3
Q
According to Shargel, ____ occurs when drug reaches the systemic circulation, or sometimes when it reaches the portal vein blood stream
A
ABSORPTION
4
Q
DRUG ABSORPTION occurs when it reaches the ____ and ____ and leaves the ____ and crosses the ____
A
systemic circulation (blood)
portal vein blood stream
lumen and crosses the apical membrane
5
Q
MEMBRANES that the cell may cross to enter
A
Intracellular membranes
Nuclear membrane
Endoplasmic reticulum
6
Q
a semi-permeable structure composed primarily of LIPIDS and proteins
A
CELL MEMBRANE
7
Q
these CANNOT cross cell membranes easily
A
protein, protein-bound, macromolecules
8
Q
these drugs traverse cell membranes MORE EASILY than ionic or water-soluble drugs
A
NONPOLAR LIPID-SOLUBLE drugs
9
Q
____ molecular weight DIFFUSES across a cell membrane MORE EASILY
A
low mw
10
Q
drugs may be transported across the barrier by;
2
A
Transcellular transport
Paracellular transport
11
Q
- transport through membrane porters or channels
- this takes place INSIDE the cell
A
INTRACELLULAR TRANSPORT
12
Q
- transport through TIGHT JUNCTIONS
- this happens BETWEEN cells
A
PARACELLULAR TRANSPORT
13
Q
a part of the intestine that FACES the CELL/LUMEN
A
APICAL MEMBRANE
14
Q
a part of the intestine that faces the NEIGHBORING CELLS
A
BASOLATERAL MEMBRANE
15
Q
TRANSCELLULAR TRANSPORT
- MOST drugs undergo transport by ____ within the cytoplasm or interstitial fluid
A
SIMPLE DIFFUSION
16
Q
TRANSCELLULAR TRANSPORT
MOVEMENT in DIFFUSION
A
HIGH to low concentration
SOLUTE/DRUG moves
17
Q
what is the goal of simple diffusion
A
to balance the concentration
18
Q
TRANSCELLULAR TRANSPORT
what LAW does DIFFUSION follows
A
FICK’S LAW
19
Q
TRANSCELLULAR TRANSPORT
SIMPLE PASSIVE DIFFUSION:
* according to Fick’s Law, diffusion is ____ to the concentration gradient
A
PROPORTIONAL
20
Q
TRANSCELLULAR TRANSPORT
what EQUATION does diffusion follows
A
NOYES-WHITNEY
21
Q
TRANSCELLULAR TRANSPORT
SIMPLE PASSIVE DIFFUSION:
* PASSIVE drug transport across cell membranes involves ____ between aqueous and lipid phases as well as diffusion within the repsective phases
A
PARTITIONING OF SOLUTE
22
Q
TRANSCELLULAR TRANSPORT
SIMPLE PASSIVE DIFFUSION:
* SOLUTE separate according to ____ (divide as more hydrophilic and more lipophilic)
A
AFFINITIES
23
Q
TRANSCELLULAR TRANSPORT
SIMPLE PASSIVE DIFFUSION:
* more HYDROPHILIC molecules will DIFFUSE through ____ which are FEWER inside the membrane
A
AQUEOUS PORES
24
Q
TRANSCELLULAR TRANSPORT
SIMPLE PASSIVE DIFFUSION:
* what is the RATE of DIFFUSION of more HYDROPHILIC molecules
A
SLOWER
25
# **TRANSCELLULAR TRANSPORT**
SIMPLE PASSIVE DIFFUSION:
* ____ molecules can cross **FASTER** since the entire membrane is made up of **lipids**
LIPOPHILIC
26
# **TRANSCELLULAR TRANSPORT**
SIMPLE PASSIVE DIFFUSION:
* **MORE lipophilic** drugs are ____ than **LESS lipophilic** drugs
MORE ABSORBED
27
# **TRANSCELLULAR TRANSPORT**
SIMPLE PASSIVE DIFFUSION:
* the **rate of diffusion** is DEPENDENT on the ____
oil:water partition coefficient
28
this **describes LIPOPHILICITY**
* **HIGH** partition coefficient, **HIGH** lipophilicity
oil:water partition coefficient
k = oil/water
29
# **TRANSCELLULAR TRANSPORT**
SIMPLE PASSIVE DIFFUSION:
* **PC** that is **GREATER than 1** is ____, thus can diffuse **readily** across the lipid barrier
MORE LIPOPHILIC
30
# **TRANSCELLULAR TRANSPORT**
SIMPLE PASSIVE DIFFUSION:
* **LOW PC** means ____, thus diffusion is **slower**
MORE HYDROPILIC
31
# **TRANSCELLULAR TRANSPORT**
SIMPLE PASSIVE DIFFUSION:
* molecules that can cross membrane **RAPIDLY** and **EFFICIENTLY**
SMALL, NONIONIC, LIPOPHILIC
32
# **TRANSCELLULAR TRANSPORT**
CHARACTERISTICS:
* **carrier**, **specificity**, **competitive inhibition**, **saturation of transport**, **poisoning of carrier**
CARRIER-MEDIATED TRANSPORT
33
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED:
* transporter that can **INCREASE** drug absorption
INFLUX / UPTAKE transporter
34
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED:
* transporter which can **DECREASE** drub absorption
EFFLUX transporter
| should be INHIBITED to increase absorption of drug
35
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED:
* **transporter proteins**
PUMPS
CHANNELS
TRANSPORTERS
36
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | TRANSPORTER PROTEINS:
* **Sodium-Potassium** pump (NaP) INHIBITOR
* used for **heart failure**
DIGOXIN
37
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | TRANSPORT PROTEINS:
* what is the effect of the **inhibition** of **sodium-potassium pump** by **digoxin**
POSITIVE INOTROPY
| inotropy = force of contraction of heart (improves)
38
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | TRANSPORT PROTEINS:
* what **type** of receptors are the **G protein-Gated Ion Channel**
TYPE 2
39
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | TRANSPORT PROTEINS:
* transports **1 substance** in **ONE direction**
UNIPORT
40
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | TRANSPORT PROTEINS:
* transports **TWO different substances** in the **SAME direction**
SYMPORT
41
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | TRANSPORT PROTEINS:
* transports **TWO different substances** in **OPPOSITE directions**
ANTIPORT
42
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | TRANSPORTER:
* an **EFFLUX** transporter
* causes **effluxing** of the drug **out** and causing **resistance** which **decreases** absorption
* **PGP/MDR1** is one of the many proteins known as an example. it is important in **pum[ing drugs out of cells** and causing **treatment resistance** in some cells
MULTI-DRUG RESISTANCE ASSOCIATED PROTEIN
43
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | MUTLI-DRUG RESISTANCE:
* transporter protein embedded in the **lipid bilayer** of cell membranes in tandem with **a-helical transmembrane regions or domains**
* **ATP-DEPENDENT** pumps = **requires energy**
* often found in conjunction with **CYP450 3A4**
* determines pharmacokinetic disposition of **cyclosporin**, **nifedipine**, and **digoxin**
P-GLYCOPROTEINS (PGP)
44
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | MULTI-DRUG RESISTANCE:
* **P-glycoproteins** are in tandem with ____
a-helical transmembrane regions or domains
45
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | MULTI-DRUG RESISTANCE:
* PGP is often found in **conjunction** with ____
CYP450 3A4
46
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | MULTI-DRUG RESISTANCE:
* PGP **energy requirement**
ATP dependent - requires energy
47
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | MULTI-DRUG RESISTANCE:
* PGP determines the **pharmacokinetic disposition** of these drugs
| 3
cyclosporin
nifedipine
digxoin
48
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED:
* involves transport **AGAINS** concentration gradient
* movement: **LOW to high** concentration
* movement of **molecules** across membranes
* **energy-REQUIRING**
* carrier may be **SELECTIVE**
* carrier system may be **SATURATED** at high concentration which could **SLOW/STOP** the process
* the process may be **COMPETITIVE**
ACTIVE TRANSPORT
49
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | ACTIVE TRANSPORT:
* movement of **concentration**
LOW to high
50
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | ACTIVE TRANSPORT:
* the **SATURATION** is described by
MICHAELIS-MENTEN
51
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | ACTIVE TRANSPORT:
* these drugs are an example in which they **compete** for the **same carrier** in the **renal tubules**
PENICILLIN and PROBENECID
52
* used for **GOUT**, a **uricosuric** agent
* enhances **excretion** of uric acid
* it affects also the **excretion** of **Penicillin** (inhibits) which causes the Penicillin's **concentration** to be **increased**
PROBENECID
53
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | ACTIVE TRANSPORT:
* substances that are **transported** through this mechanism
| 5
ions
vitamins
sugars
amino acids
5-fluorouracil
54
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | ACTIVE TRANPORT:
* an **AMINO ACID transporter** that is a **a2 AGONIST**
METHYLDOPA
55
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | ACTIVE TRANSPORT:
* an **AMINO ACID transporter** that is a **GABA B AGONIST**
BACLOFEN
56
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | ACTIVE TRANSPORT:
* an **OLIGOPEPTIDE transported** with a **BCS class IV**
CAPTOPRIL
57
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED:
* transport mechanism for molecules with **LOW LIPID SOLUBILITY**
* it is a diffusion that requires a **carrier** ONLY to facilitate the diffusion
* movement is **ALONG** the concentration gradient
* **NO ENERGY** required
* **Specificity of substrate** for its carrier
FACILITATED DIFFUSION
58
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | FACILITATED DIFFUSION:
* **transport mechanism** for molecules with ____
LOW LIPID SOLUBILTIY
59
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | FACILITATED DIFFUSION:
* **movement** and **energy requirement**
ALONG the conc gradient
NO ENERGY required
60
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED:
* the process of **ENGULFING** particles or dissolve materials by a cell
* **DOES NOT** require a drug to be in aqueous solution to be absorbed
* also referred to as **TRANSCYTOSIS**
VESICULAR TRANSPORT
61
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | VESICULAR:
* ____ require a drug to be in **aqueous solution** to be absorbed
DOES NOT
62
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | VESICULAR:
* also referred to as ____
TRANSCYTOSIS
63
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | VESICULAR:
* a drug example
SABIN POLIO VACCINE
64
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | VESICULAR:
* cell **EATING**
* engulfment of **LARGER** particles or **MACROMOLECULES**, generally by **macrophages**
PHAGOCYTOSIS
65
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | VESICULAR:
* cell **DRINKING**: engulfment of **SMALL** molecules or **fluid volumes**
PINOCYTOSIS
66
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | VESICULAR:
* moving macromolecules **INTO** the cell
ENDOCYTOSIS
67
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | VESICULAR:
* moving macromolecules **OUT** of a cell
EXOCYTOSIS
68
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | VESICULAR:
* an example of **exocytosis**
INSULIN
69
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED:
* form **electrochemical neutral complexes** and these neutral complexes are then absorbed by **passive diffusion**
* cation (+) + anion (-) = neutral complex
ION PAIR TRANSPORT
70
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | ION PAIR:
* a **β-blocker** that forms ion pair with **OLEIC ACID**
PROPRANOLOL
71
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | ION PAIR:
* a drug for **malaria** that forms ion pair with **HEXYLSALICYLATE**
QUININE
72
# **TRANSCELLULAR TRANSPORT**
CARRIER-MEDIATED | ION PAIR:
* forms ion pair with **DISTEROYLPHOSPHATIDGLYCEROL** (DSPG)
AMPHOTERICIN B
73
# **PARACELLULAR TRANSPORT**
* drug passes through **WATER FILLED PORES**
* **ONLY** paracellular transport mechanism
* PORE SIZE: **7-10A**, MW **<150-400**
* PORE LINING is **charged** (drugs with opposite charge may **pass through**)
* movement is by **SOLVENT DRAG**
* movement is **ALONG** the concentration gradient
CONVECTIVE TRANSPORT / BULK FLOW / PORE TRANSPORT
74
# **PARACELLULAR TRANSPORT**
CONVECTIVE / BULK / PORE:
* drug passes through ____
WATER FILLED PORES
75
# **PARACELLULAR TRANSPORT**
CONVECTIVE / BULK / PORE:
* **pore size**
7-10A, MW <150-400
76
# **PARACELLULAR TRANSPORT**
CONVECTIVE / BULK / PORE:
* **pore lining**
CHARGED
(opposite charge may pass through)
77
# **PARACELLULAR TRANSPORT**
CONVECTIVE / BULK / PORE:
* movement is by ____
SOLVENT DRAG
78
# **PARACELLULAR TRANSPORT**
CONVECTIVE / BULK / PORE:
* movement is ____ the **concentration gradient**
ALONG
79
# **PARACELLULAR TRANSPORT**
CONVECTIVE / BULK / PORE:
* **examples**
| 3
WATER
SUGAR
UREA
80
what is the **crystalline shape** of **UREA**
TETRAGONAL
81
**PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
1. GI motility / Gastric emptying
2. Blood flow
3. Presence of food in the GIT
82
* Saliva (**pH ~7**) contains **ptyalin** (amylase) and **mucin**
* absorption possible for lipid-soluble drugs (***nitroglycerin***, ***fentanyl***)
* **ODTs** disintegrate here but **absorption** mainly occurs in GI tract
ORAL CAVITY
83
ORAL CAVITY:
* **pH** of SALIVA
apprx 7
84
ORAL CAVITY:
* SALIVA contains ____ and ____
ptyalin and mucin
85
ORAL CAVITY:
* absorption for ____ drugs are possible
* give examples
LIPID SOLUBLE DRUGS
Nitroglycerin, Fentanyl
86
* **pH 5-6**, LITTLE to NO drug dissolution/absorption
* tablets/capsules may **lodge** and **irritate mucosa**
* **LOWER SPHINCTER** prevents reflux
ESOPHAGUS
87
ESOPHAGUS:
* **pH**
5-6
88
ESOPHAGUS:
* this **prevents reflux**
* should have **high pressure** to be **closed**
LOWER SPHINCTER
89
* pH **fasting**: **2-6**
* pH **with food**: **1.5-2**
* **BASIC DRUG** solubilize **rapdily**
* intense mixing = **antral milling**
* SOME fat-soluble, acid-stable drugs (ethanol) are **absorbed**
* **GATRIC EMPTYING** strongly influences absorption rate
* **HIGH pH** can **disrupt** enteric-coated formulations
STOMACH
90
STOMACH:
* pH **fasting**
2-6
91
STOMACH:
* pH **with food**
1.5-2
92
STOMACH:
* ____ solubilize **RAPIDLY**
BASIC DRUGS
93
STOMACH:
* **intense mixing**
antral milling
94
STOMACH:
* ____ pH can **disrupt ENTERIC-COATED** formulations
HIGH
95
* it is the **FIRST REGION** of the **small intestine**
* **pH 6-6.5** (bicarbonate neutralizes acid chyme)
* MAJOR SITE of **passive drug absorption** (large surface area, high blood flow)
* many **prodrugs** are hydrolyzed here
* provides a large surface area due to the presence of **villi** and **microvilli**
* has **abundant blood supply**
DUODENUM
96
DUODENUM:
* **pH**
6-6.5
97
DUODENUM:
* **major site** of ____
passive drug absorption
98
DUODENUM:
* has a **large surface area** due to the presence of ____ and ____
VILLI and MICROVILLI
99
DUODENUM:
* many ____ are **hydrolyzed** here
PRODRUGS
100
DUODENUM:
* these **aid** in **solubility**
pancreatic enzyme + bile
101
* continues **protein/carboydrate digestion**
* preferred site for **drug absorption STUDIES** due to relatively **fewer contractions**
JEJUNUM
102
* **pH ~7-8**; bicarbonate dissolves acidic drugs
* **Bile salts** solubilize fats/hydrophobic drugs; important for **LIPID-SOLUBLE drug absorption**
* separated from colon by **ileocecal valve**
ILEUM,
103
ILEUM:
* **pH**
approx 7-8
104
ILEUM:
* **solubilize** fats / hydrophobic drugs
BILE SALTS
105
ILEUM:
* **bile salts** are also important for
LIPID-SOLUBLE drug absorption
106
ILEUM:
* is **separated** from colon by ____
ileocecal valve
107
* **pH ~7**
* drug **absorption** depends on **placement** and **vein drainage**
RECTUM
108
* **pH 505-7**; LIMITED absorption (small surface area, viscous contents)
* suitable for **SUSTAINED-RELEASE** drugs (***theophylline***, ***metoprolol***)
* contains **MICROFLORA** which metabolizes drugs (***L-dopa***, ***lactulose***)
* **pH-sensitive coating** deliver drugs (***mesalamine*** for **Crohn's**)
COLON
109
COLON:
* **pH**
5.5-7
110
COLON:
* suitable for ____ drugs
* give examples
SUSTAINED-RELEASE drugs
***theophylline***, ***metoprolol***
111
COLON:
* contains **MICROFLORA** which metabolizes what drugs
***Levodopa***, ***lactulose***
112
COLON:
* **pH-sensitive** coating drugs
MESALAMINE for Crohn's disease
113
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
* tends to move the drug through the **alimentary canal** (stomach to the large bowel)
* **Normal peristaltic movements** mix the contents of the duodenum bringing the drug particles into **intimate contact** with the **intestinal mucosal cells**
* movement of the drug within the GI tract depends also on the GI contents (**fed or fasted state**)
GASTROINTESTINAL MOTILITY
114
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
GASTROINTESTINAL MOTILITY:
* the **time** that the contents **STAYED** in a **specific region**
* the drug must have a **sufficient time** at the absorption site for optimum absorption
TRANSIT TIME (RESIDENCE TIME)
115
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
GASTROINTESTINAL MOTILITY | **FASTED STATE**:
* **phase I** contraction and duration
NO contraction
30-60 minutes
116
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
GASTROINTESTINAL MOTILITY:
* how many **phases** are there in the **FASTED state**
4 phases
117
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
GASTROINTESTINAL MOTILITY | **FASTED STATE**:
* **phase II** contraction and duration
has contractions due to BILE SECRETION
20-40mins
118
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
GASTROINTESTINAL MOTILIY | **FASTED STATE**:
* **phase III** contraction and duration
STRONGER contractions due to MUCUS DISCHARE
10-20mins
119
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
GASTROINTESTINAL MOTILITY | **FASTED STATE**:
* **phase IV** contraction and duration
contractions are starting to DIE DOWN
0-5mins
120
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
GASTROINTESTINAL MOTILITY | **FED STATE**:
* **contractions**
CONSTANT contraction but not that strong
121
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
the **time** it takes for the stomach to **EMPTY ITS CONTENTS** into the small intestine
GASTRIC EMPTYING TIME
122
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
GASTRIC EMPTYING:
* **Normal GET**
2-3 hours
123
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
GASTRIC EMPTYING:
* **HIGH GET**, ____ absorption
SLOWER
124
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
GASTRIC EMPTYING:
* **LOW GET**, ____ absorption
FASTER
125
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
GASTRIC EMTPYING:
* **HIGH GER**, ____ absorption
FASTER
126
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
GASTRIC EMPTYING:
* **LOW GER**, ____ absorption
SLOWER
127
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
GASTRIC EMPTYING:
* a **phenomenon** that DESCRIBES GET
Kitchen-sink phenomenon
128
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
GASTRIC EMPTYING:
* **DELAY** in gastric emptying will ____ the **rate** and **extent** of drug **absorption**
SLOW
129
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
GASTRIC EMTPYING:
* **DELAY** in gastic emptying can ____ the **onset time** for the drug
PROLONG
130
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
TYPES AND VOLUME OF MEAL:
* the ____ the **starting volume**, the ____ the **initial rate** of emptying
LARGER, GREATER
131
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
TYPES AND VOLUME OF MEAL:
* **FASTING** state **small intestine transit time**
4-8 hours
132
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
TYPES AND VOLUME OF MEAL:
* **FED** state **small intestine transit time**
8-12 hours
133
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
TYPES AND VOLUME OF MEAL:
* these drugs bioavailability are **best** if taken during **fasetd stated** and with **high water volume**
aspirin
erythromycin
134
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
TYPES AND VOLUME OF MEAL:
* these generally **decreases** the rate of gastric emptying = **slower** absorption
FATS
(fatty acids, triglycerides)
135
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
TYPES AND VOLUME OF MEAL:
* rate of gastric emptying is dependent on **osmotic pressure**
carbohydrates and proteins
136
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
TRANSIT TIMES IN HEALTHY HUMANS AFTER STANDARD MEAL:
* **50%** of **STOMACH CONTENTS** emptied
2.5 - 3 hours
137
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
TRANSIT TIMES IN HEALTHY HUMANS:
* **TOTAL emptying** of the **STOMACH**
4 - 5 hours
138
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
TRANSIT TIMES IN HEALTHY HUMANS:
* **50%** emptying of the **SMALL INTESTINE**
2.5 - 3 hours
139
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
TRANSIT TIMES IN HEALTHY HUMANS:
* Transit through the **COLON**
30 - 40 hours
140
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
* is dependent upon **concentration** of **SALTS** and **NONELECTROLYTES**
OSMOTIC PRESSURE
141
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
OSMOTIC PRESSURE:
* at **LOWER** salt concentration, **osmotic pressure** ____ but the **rate of emptying** _____
osmotic pressure DECREASES
rate of emptying INCREASES
142
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
OSMOTIC PRESSURE:
* at **HIGHER** salt concentration, **osmotic pressure** ____ but the **rate of emptyinh** ____
osmotic pressure INCREASES
rate of emptying DECREASES
143
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
* **Solutions** or **suspensions** of small particles empty **MORE RAPIDLY** than chunks of material that must be reduced in size prior to gastric emptyinh
PHYSICAL STATE OF GASTRIC CONTENTS
144
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
CHEMICALS:
* for **ACIDS**, rate of gastric emptying is DEPENDENT upon
concentration and molecular weight of the acid
145
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
CHEMICALS:
* for **ACIDS**, ____ molecular weight acids are **MORE EFFECTIVE** = HIGHER rate of emptying
LOWER
146
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
CHEMICALS:
* for **ALKALI**, rate of gastric emptying **increases** at ____ concentrations
LOW (1%)
| decrease at HIGH conc (5%)
147
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
DOSAGE FORM:
* **stay LONGER** in the stomach
* DOES NOT reach the duodenum **rapidly**, **delaying** drug release and systemic absorption
ENTERIC-COATED tabs
148
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
DOSAGE FORMS:
* drugs that **DECREASE** gastric emptying
Anticholinergics (Atropine - prototype)
Narcotic-analgesics
Ethanol
| all can cause CONSTIPATION
149
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
DOSAGE FORM:
* drugs that can **INCREASE** gastric emptying
METOCLOPRAMIDE
a dopamine 2 antagonist
150
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
BODY POSITION:
* patient lying on the ____ side **REDUCES** the rate of GE but has **better digestion**
LEFT SIDE
151
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
VISCOSITY:
* ____ solutions **INCREASES** GER
LESS VISCOUS
152
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
EMOTIONAL STATES:
* in **aggresive** or **stressful emotional states**, stomach contractions and GER ____
INCREASES
153
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
EMOTIONAL STATES:
* in **depression**, stomach contractions and GER ____
DECREASES
154
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
____ **REDUCES** GER
BILE SALTS
155
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
**Vigorous exercises** can ____ GER
REDUCE / DECREASE
156
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
DISEASE STATES:
* **diabetis** with **local pyloric lesions** and **HYPOthyroidism**, the GER is ____
REDUCED / DECREASED
157
# **FACTORS INFLUENCING GASTROINTESTINAL MOTILITY**
DISEASE STATES:
* in **HYPERthyroidism** the GER is ____
INCREASED
158
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
* important in **carrying** the absorbed drug to the systemic circulation
BLOOD PERFUSION OF THE GIT
159
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
BLOOD PERFUSION OF THE GIT:
* substances absorbed from the stomach and small intestine are **carried by the** ____ to the **vena cava** via the **hepatic portal vein**
MESENTERIC BLOOD FLOW
160
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
BLOOD PERFUSION OF THE GIT:
* ____ circulation **receives** about **28%** of the **cardiac output**
SPLANCHNIC (mesenteric)
161
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
BLOOD PERFUSION OF THE GIT:
* **Splanchnic** circulation is ____ **AFTER MEALS**
INCREASED
162
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
BLOOD PERFUSION OF THE GIT:
* **Splanchnic** circulation is ____ **AFTER PHYSICAL WORK**
DECREASED
163
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
BLOOD PERFUSION OF THE GIT:
* contents are more on **immunity** NOT blood
* **bypasses the first-pass effect**; hepatic portal vein is avoided
* important for absorption of **dietary lipids**, **lipophilic drugs**
LYMPHATIC CIRCULATION
164
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
BLOOD PERFUSION OF THE GIT | LYMPHATIC:
* drugs that were prepared in **CHYLOMICRONS** to **improve oral absorption**
BLEOMYCIN or ACLARUBICIN
165
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
BLOOD PERFUSION IN THE GIT | LYMPHATIC:
* **example** of drugs
Bleomycin or Aclarubicin
Halofantrine
Vitmain D3
Ontazolast
Temarotene
Testosterone derivatives
166
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
PRESENCE OF FOOD | **EMPTY STOMACH**
* Acid-labile
* need rapid onset
* prone to food binding or chelation
* eneteric-coated or delayed-release
167
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
PRESENCE OF FOOD | **EMPTY STOMACH**
* **acid-labile drugs**
erythromycin
pen G
168
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
PRESENCE OF FOOD | **EMPTY STOMACH**:
* drugs that need **rapid onsett**
aspirin
levodopa
169
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
PRESENCE OF FOOD | **EMPTY STOMACH**:
* drugs that are prone to **food binding** or **chelation**
TETRACYCLINE + calcium/iron
170
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
PRESENCE OF FOOD | **WITH FOOD**
* Lipohpilic drugs
* Irritant drugs
* with POOR solubility in water
171
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
PRESENCE OF FOOD | **WITH FOOD**:
* **Lipophilic drugs** - BILE SECRETION helps dissolve them
| bile secretion is stimulated by fats
Griseofulvin
Carbamazepine
Propranolol
172
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
PRESENCE OF FOOD | **WITH FOOD**:
* **Irritant drugs** -- foods can protect stomach lining
NSAIDs
Corticosteroids
Potassium chloride
173
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
PRESENCE OF FOOD | **INTESTINAL pH & SOLUBILITY**:
* ____ **DECREASED** absorption with **MILK**
TETRACYCLINE
174
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
PRESENCE OF FOOD | **INTESTINAL pH & SOLUBILITY**:
* ____ **INCREASED** absorption with **HIGH FAT CONTENT**
GRISEOFULVIN
175
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
PRESENCE OF FOOD:
* **LOWERS** the pH causing **more rapid dissolution** and **better absorption** of **BASIC drugs** with LIMITED aqueous solubility
HCl acid secretion
176
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
PRESENCE OF FOOD:
* acts as **natural surfactants** of the body
* **INCREASES** the solubility of **fat-soluble** drugs through micelle form
BILE
177
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
PRESENCE OF FOOD:
* ____ in **gastric emptying**
DELAY
178
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
PRESENCE OF FOOD:
* ____ in the **splanchnic blood flow**
INCREASE
179
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
PRESENCE OF FOOD:
* ____ or ____ of the meal with the drug product or substance
physical or chemical interaction
180
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
PRESENCE OF FOOD:
* can also affect the **integrity** of ____
DOSAGE FORM
181
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
PRESENCE OF FOOD:
* can ____ the **release rate** of the drug
ALTER
182
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
PRESENCE OF FOOD | **MODIFIED/CONTROLLED-RELEASE**:
* bioavailability is **more rapid** when given to a subject in the **FED state**
THEO-24 CONTROLLED-RELEASE TAB
183
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
PRESENCE OF FOOD:
* absorption is **ENHANCED** with food or if taken closely after a **HEAVY MEAL**
CEFPODOXIME PROXETIL
184
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
PRESENCE OF FOOD:
* has **ENHANCED** absorption after meal
TICLOPIDINE
185
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
PRESENCE OF FOOD:
* systemic oral absorption is **GREATLY REDUCED**
* must be taken **at least one-half hour BEFORE first food**
ALENDORNATE SODIUM (FOSAMAX)
186
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
DRUG INTERACTIONS:
* **INCREASE** gastric pH can **decrease** the dissolution
Ketoconazole - Omperazole/Esomeprazole
187
# **PHYSIOLOGIC FACTORS AFFECTING DRUG ABSORPTION**
DRUG INTERACTIONS:
* **INCREASES** oral bioavailability of **Dextromethorphan** due to the inhibition of P-gp
* **inhibits CYP3A** activitiy = **INCREASE** oral bioavailability of **cyclosporin** or **saquinavir** by inhibiting **intestinal metabolism**
GRAPEFRUIT JUICE
188
P-GP **INHIBITORS**
Verapamil
Quininidine
Clarithromycin
Amiodarone
Grapefruit juice
Tariquidar
189
P-GP **INDUCERS**
Rifampin
St. John's Wort
190
* Attributed to variability in **stomach emptying**, **variable intestinal motility**, and **enterohepatic recycling**
* For a drug with **high water solubility**, **dissolution** of the drug **occurs in the stomach**, and **partial emptying** of the drug into the **duodenum** will result in the f**irst absorption peak**. A delay in stomach emptying results in a **second absorption peak** as the remainder of the dose is emptied into the duodenum.
DOUBLE PEAK PHENOMENON
191
drugs that undergoes **DOUBLE PEAK PHENOMENON**
Cimetidine and Acetaminophen
Ranitidine and Dipyridamole
BIOPHARM & PHARMACOKINETICS
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