The Ultimate Test Flashcards
(264 cards)
1
Q
What does ADME stand for?
A
Absorption
Distribution
Metabolism
Excretion
2
Q
What is up-regulation?
A
Receptor numbers are increased in response to a chronically low concentration of the agonist to optimise sensitivity
3
Q
What is down-regulation?
A
Receptor numbers are decreased in response to a chronically high concentration of the agonist to optimise sensitivity
4
Q
What are the two types of ligand?
A
Agonist and antagonist
5
Q
What is an agonist?
A
A ligand with both affinity and efficacy
6
Q
What is an antagonist?
A
A ligand with affinity but not efficacy (blocks the receptor but does not activate a response)
7
Q
Name three different examples of signal transduction
A
Direct opening of an ion-channel
Direct activation of an enzyme
Indirect activation of an enzyme
8
Q
What makes indirect activation of an enzyme different from direct activation of an enzyme?
A
Indirect activation involves a G-protein
9
Q
Give three examples of the importance of calcium signalling
A
Muscle contraction, secretion, metabolism, neuronal excitability, cell proliferation
10
Q
What is calcium?
A
Calcium is a second messenger and is neither produced nor destroyed - it is only stored and moved between compartments
11
Q
Give two examples of calcium channel blockers
A
Nifedipine and verapamil (modulate muscle contraction)
12
Q
What is pharmaceutics?
A
The process of turning an NCE into a medication to be used safely and effectively by patients
13
Q
What does NCE stand for?
A
New Chemical Entity
14
Q
What is a medicine?
A
A drug delivery system that allows the administration of drugs into the body in a safe, efficient, accurate, reproducible and convenient way
15
Q
Name three administration routes
A
Oral, Rectal, Topical, Parenteral, Respiratory, Nasal, Ocular, Vaginal/Urethral
16
Q
What is a drug?
A
A molecule that interacts with a biological system to produce a biological response
17
Q
What does endogenous mean?
A
Made in the body
18
Q
Give an example of a biologic
A
Antibodies
Proteins
19
Q
What is drug safety dependent on?
A
The therapeutic index of that specific drug
20
Q
Give an example of a biomacromolecule
A
Ion channel
Enzyme
Receptor
21
Q
What does COX stand for?
A
Cyclo-oxygenase
22
Q
What is the substrate of COX?
A
Arachadonic acid
23
Q
Where are B2 adrenoreceptors located?
A
Bronchial smooth muscle
24
Q
What do adrenaline and noradrenaline do?
A
Dilate the airways
25
What is salbutamol?
A B2 adrenoreceptor agonist
26
Name the five different types of intermolecular bonding
Hydrogen bonding, Van der Waals, pi-pi bonding, electrostatic, dipole
27
What is the buccal cavity?
The mouth (teeth, tongue, salivary glands)
28
What is the first organ of the digestive system?
The buccal cavity
29
Name the four different tissues present in the buccal cavity and their thickness in mm
Gingival - 0.2
Palatal - 0.25
Buccal - 0.55
Sublingual - 0.15
30
What type of buccal cavity tissues are keratinised/nonpolar?
Gingival and palatal
31
What type of buccal cavity tissues are nonkeratinised/polar?
Buccal and sublingual
32
What route of buccal delivery has the quickest onset time and why?
Sublingual - it is the closest to the bloodstream
33
What is first pass metabolism?
When the drug is absorbed into the bloodstream and gets passed through the liver before reaching systemic circulation. It then gets metabolised in the liver.
34
What is the MAIN advantage of buccal administration?
It avoids first pass metabolism
35
Give two examples of solid buccal dosage forms
Buccal tablets, bioadhesive wafers, lozenges, bioadhesive micro/nanoparticles
36
Give two examples of semisolid buccal dosage forms
Medicated chewing gums, buccal films/patches, adhesive gel/ointments
37
Give two examples of liquid buccal dosage forms
Mouthwash, mouth fresheners, mouth spray
38
What is bioadhesion?
Adhesion to a biological surface
39
What is mucoadhesion?
Adhesion to a mucosal surface
40
What qualities should a good buccal "glue" have?
Strong enough to hold the formulation
Removable when treatment is complete
Safe for oral application
Permits drug diffusion
41
What polymer is better for mucoadhesion?
| (Anionic, cationic or uncharged)
Anionic
42
Give three advantages to buccal delivery systems
Good patient compliance
Avoids first pass metabolism
Convenient and painless administration
Versatility in design of local or systemic action
Predictable drug concentration in blood
Facility to modulate the selection of excipients
43
Give three disadvantages of buccal delivery systems
Need for taste-masking
Eating, drinking, smoking can affect drug absorption and efficacy
Accidental swallowing
Potential gum irritation
44
What is the definition of a solution?
A mixture of two or more components that form a single, molecularly homogeneous phase
45
What is the definition of dissolution?
The process by which a solution is formed - solid dissolving in a solvent
46
What is the solubility of a substance?
The amount of substance that will go into solution when equilibrium is reached between the solute in solution and excess substance
47
Why are solutions important for drug delivery?
Generally, only drugs in solution can be absorbed into systemic circulation
48
What do the parameters in the Noyes-Whitney equation stand for?
| (dm/dt, A, D, Cs, C, h)
dm/dt = the rate of dissolution
A = effective surface area of the undissolved drug particles
D = diffusion coefficient
Cs= saturated solubility
C = concentration in the bulk
h = thickness of diffusion layer
49
What is hunger and satiety regulated by?
| (neuronal, hormonal and mechanical)
Plasma glucose levels
Hormones
Stretch receptors in GI tract
Stress, body temperature, food palatability
50
Describe the well-fed/absorptive state
Glucose levels increase, insulin secretion stimulated so glucose decreases and there is an increase in storage fuels and proteins (glycogen synthesis)
51
Describe the post-absorptive state
Glucose levels decrease so there is an increase in:
1. Glucagon
2. Gluconeogenesis
3. Glucose sparing
52
Describe the hunger signals and the location of the brain involved
There is a decrease in glucose, fat and protein along with an increase in ghrelin. This is signalled to the lateral hypothalamus which causes hunger.
53
Describe the satiety signals and the location of the brain involved
These is an increase in glucose, fat, protein and leptin. There are also signals produced by the stretch receptors in the GI tract. This is sent to the medial hypothalamus to cease hunger.
54
What part of the stomach gets relaxed by the presence of fat and what is the consequence?
The fundus - lowers intragastric pressure
55
Give three effects of fat content on gastric emptying
Lowers intragastric pressure
Prolongs the feeling of fullness
Influences intake at next meal
Prolongs elevation of pH in the stomach
56
What makes up the Enteric Nervous System?
The myenteric and submucosal plexus
57
Give the order (out - in) of the following GI tract wall parts: myenteric plexus, mucosa, submucosal plexus, circular muscle, serosa, longitudinal muscle, lumen
Serosa, longitudinal muscle, myenteric plexus, circular muscle, submucosal plexus, mucosa, lumen
58
What is the CNS?
The Central Nervous System - comprised of the brain and spinal cord
59
What is the PNS?
The Peripheral Nervous System - connects the CNS to limbs and organs
60
What is the ANS?
The Autonomic Nervous System - the division of the PNS influencing the function of organs
61
What is the ENS?
The Enteric Nervous System - the intrinsic nervous system of the GI tract
62
What connects the CNS and ENS?
The vagus nerve - largest parasympathetic nerve and the X cranial nerve
63
What is the primary route used by gut bacteria to transmit information to the brain?
The vagus nerve
64
What does serotonin control?
Mood control, depression, aggression
65
What is the code for serotonin?
| (Number - Letter Letter)
(5-HT)
66
What are the two different types of neurons?
Afferent and efferent
67
What is an afferent neuron?
A sensory receptor neuron - carry nerve impulses from receptors or sense organs to the brain
68
What is an efferent neuron?
A motor or effector neuron - carry nerve impulses from CNS to effectors like muscles and glands
69
What is another name for the Myenteric plexus?
Auerbach's plexus
70
What is another name for the Submucosal plexus?
Meissner's plexus
71
What type of neuron is the Myenteric plexus?
Efferent
72
What type of neuron is the Submucosal plexus?
Afferent
73
What does the Myenteric plexus influence?
Muscle activity
74
What does the Submucosal plexus receive signals from?
The epithelium and stretch receptors
75
What makes up the PNS?
Sympathetic and Parasympathetic nerves
76
What links the nerve plexuses to the CNS?
Afferent fibres (activated by stretch and chemical stimulation)
77
What links the nerve plexuses to the ANS?
Efferent neurons
78
What muscle controls segmentation?
The circular muscle
79
What is segmentation used for?
To mix food
80
What muscle controls peristalsis?
The longitudinal muscle
81
What is peristalsis used for?
To propel food through the GI tract
82
How long is the ideal gut transit time?
12 - 48 hours
83
What are the two downsides of gut transit time being too quick?
Diarrhoea
Poor absorption of nutrients
84
What are the two downsides of gut transit time being too slow?
Constipation
Poor gut health
85
Name two types of drugs that can cause constipation as a side effect
Antacids
Anticholinergics
Antihypertensives
86
What do antacids do?
Neutralise stomach acid
87
What do anticholinergics do?
Reduce muscle spasms
88
What to antihypertensives do?
Reduce blood pressure
89
What are the three opioid receptor subtypes?
Mu, kappa, gamma
90
How many pairs of salivary glands are there?
THREEEEEEEEEEEEEEEEEEEEEEE
91
How much saliva is secreted in a day?
1500ml
92
What are the three main components of saliva?
Mucus, amylase, lysozyme
93
What is mucus used for in saliva?
To lubricate food
94
What are the names of the salivary glands and where are they found?
Parotid - roof of mouth at back
Submandibular - under tongue at back
Sublingual - under tongue at front
95
Where is saliva made?
Salivary ducts
96
What is produced by the acinar cells in the salivary ducts?
Isotonic fluid (electrolytes and water)
97
What does the final composition of saliva depend on?
Flow rate through duct and neuronal input
98
What nervous system regulates saliva secretion?
ANS
99
What gland(s) secrete watery saliva and amylase?
Parotid and submandibular
100
What gland(s) secrete thick saliva and mucus?
Sublingual
101
What is the scientific name for swallowing?
Deglutition
102
What are the two stages of deglutition?
The voluntary stage and the pharyngeal stage
103
What does the oesophagus connect?
The laryngopharynx to the stomach
104
Describe the muscularis layer of the oesophagus (in thirds)
First third is striated muscle, middle third is a combination of striated and smooth muscle, last third is smooth muscle
105
What is the average surface area of the oral mucosa?
200cm2
106
By what mechanism do drugs get through the oral mucosa?
Passive diffusion
107
What the three main oral problems?
Dry mouth, oral ulcers, oral thrush
108
Give three examples of dental hygiene advice
Brush teeth twice a day
Drink plenty water
Regular check-ups
Reduce or give up smoking
Reduce intake of dehydrating and caffeinated drinks
109
What is the sphincter that controls entry into the stomach from the oesophagus?
The lower oesophageal sphincter
110
Name the three parts of the stomach
Fundus, antrum, body
111
Name the sphincter separating the stomach and the duodenum
The pyloric sphincter
112
What is the pH of the stomach?
2
113
What is chyme?
Food once the digestive process has begun
114
Digestion of what begins in the stomach?
Protein and fat
115
What are the two types of digestion in the stomach?
Mechanical (stomach movements)
Chemical (pepsin)
116
Where in the stomach is the mechanical digestion strongest?
Antrum
117
What are the three secretory cells present in the gastric glands?
Goblet (neck) cells
Peptic (chief) cells
Oxyntic (parietal) cells
118
What do goblet cells secrete?
Mucus
119
What do peptic cells secrete?
Pepsinogen
120
What do oxyntic cells secret?
HCl and intrinsic factor
121
Which of the three secretory cells are zymogenic?
Peptic cells
122
What is a zymogenic cell?
One that secretes the inactive form of the enzyme
123
Describe the distribution of parietal cells in the stomach
Parietal cells are mainly found in the body, with few in the fundus and none in the antrum
124
What are the three additional cells found in the gastric glands?
D cells
Enterochromaffin (mast-like) cells
G cells
125
What do D cells secrete?
Somatostatin
126
What do G cells secrete?
Gastrin
127
What do enterochromaffin like cells secrete?
Histamine
128
What is intrinsic factor used for?
The absorption of vitamin B12
129
What does pepsin do?
Breakdown protein
130
What triggers the change from pepsinogen to pepsin?
HCl
131
Why doesn't the stomach digest itself?
1. Tight junctions between mucosal epithelial cells prevent leakage of gastric juice onto underlying tissue
2. Mucus secreted by epithelial/goblet cells has higher pH so provides localised neutralisation and physical barrier to acid
3. Prostaglandins increase mucosal thickness and stimulates bicarbonate production
132
Name the three stages of gastric secretion and whether they increase or decrease secretion
1. Cephalic Phase - increase
2. Gastric Phase - increase
3. Intestinal Phase - decrease
133
What regulates the Cephalic Phase?
The brain (medulla oblongata)
134
What secretions are stimulated in the Cephalic Phase?
HCl, pepsin and gastrin (which further stimulates the secretion of HCl and pepsin)
135
What stimulates the Gastric Phase?
Stomach distension caused by the presence of food
136
Where is gastrin produced?
In the antrum of the stomach
137
What secretions are stimulated in the Gastric Phase?
HCl, pepsin and gastrin
138
What stimulates the Intestinal Phase?
The presence of acid in the duodenum
139
Describe the three ways that the Intestinal Phase inhibits gastric secretion
1. Neuronal impulses to the medulla to decrease the parasympathetic stimulation of gastric glands
2. Local reflexes in the gut wall
3. The release of three local hormones
140
Name the three local hormones secreted in the intestinal phase
Secretin, gastric inhibitory peptide and cholecystokinin
141
When does the inhibition of HCl secretion begin?
Once the food has left the stomach
142
What is the enterogastric reflex?
The neuronal inhibition of HCl secretion mediated by the medulla oblongata
143
What HCl hormonal inhibitors are there?
Secretin, CCK, GIP, gastrone, glucagon and vasoactive intestinal peptide (VIP)
144
What is diarrhoea?
The frequent passing of water stools (more than 3 times a day)
145
How long does acute diarrhoea last for?
5-10 days
146
How long does chronic diarrhoea last for?
Longer than 2 weeks
147
Why is the removal of fluid prevented in diarrhoea?
The large intestine is inflamed
148
Give three symptoms of diarrhoea
Flatulence
Weakness
Electrolyte imbalance
Fluid loss
Nausea, vomiting, fever
Headache, loss of appetite
149
Give a cause of acute diarrhoea
Bacterial or viral infection
Food poisoning
Certain drugs
150
Give a cause of chronic constipation
Symptom of a serious condition (Crohn's, IBS...)
Laxatives
Poor diet
151
What can be used to treat diarrhoea?
Often goes away after a few days without treatment
Drink plenty of fluids
Rehydration sachets
Loperamide
Eat as soon as you can - food high in carbs
Painkillers for fever or headache
152
What do rehydration drinks do?
Replace lost electrolytes but do not treat diarrhoea
153
How do antidiarrhoeals work?
They slow gut transit time which increases water and electrolyte absorption
154
Give warning symptoms of diarrhoea
Mucus or dark blood in stools
Dehydration - dry mouth, lethargy, headache
Diarrhoea lasting longer than 5 days
Vomiting for more than a day
High fever
Recent change in bowel habit or travel abroad
155
What is constipation?
The passage of hard stools less frequently than the patient's regular pattern
Inability to completely empty the bowel
156
Give three symptoms of constipation
Change in stool frequency
Unusually hard, lumpy or small stools
Stomach ache and cramps
Feeling bloated, nauseous, loss of appetite
Chronic problems - haemorrhoids, faecal impaction
157
Give some causes of constipation
Poor diet - lack of fibre and/or fluids
Lack of mobility
Medication (antidepressants, antiepileptics, iron)
Pregnancy
Medical conditions (diabetes, Parkinson's, underactive thyroid)
158
Give lifestyle advice for the treatment of constipation
Increase dietary fibre
Increase fluid intake
Increase daily exercise
159
Name the three types of laxative
Osmotic
Bulk-forming
Stimulant
160
Give examples of stimulant laxatives
Senna and bisacodyl
161
Explain how stimulant laxatives work
| What they do, onset time and side effects
Increase intestinal motility
8-12 hours so usually night time administration
Abdominal cramps, fluid loss, electrolyte imbalance
162
Explain how bulk-forming laxatives work
| What they do, onset time and side effects
Stimulate peristalsis in a similar way to fibre
24-36 hours
Flatulence and abdominal bloating
163
Give examples of bulk-forming laxatives
Bran
Ispaghula husk (fybogel)
164
Give examples of osmotic laxatives
Lactulose
Magnesium salts
Macrogols
165
Explain how osmotic laxatives work
| What they do, onset time and side effects
Retain fluid in the bowel by osmosis so its important to drink plenty of fluids
Up to 3 days
Flatulence, abdominal pain, colic
166
Give warning symptoms of constipation
Constipation alternating with diarrhoea
Mucus or dark bloods in stools
Weight loss
Abuse of laxatives
Vomiting
Fever
Angina
167
What are haemorrhoids?
Abnormal swelling or enlargement of the anal vascular cushions
168
Give three symptoms of haemorrhoids
Bright red blood on the stool
Pruritis - due to chronic mucus discharge
Soiling due to incontinence
Rectal fullness or an anal lump
169
Give some causes of haemorrhoids
Excessive straining (from constipation)
Increasing age
Raised intraabdominal pressure (pregnancy, chronic cough, ascites)
Less common - pelvic/abdominal masses, family history, cardiac failure, portal hypertension
170
What can be used to treat haemorrhoids?
Treat the constipation (bulk-forming to stimulate cushions)
Creams, ointments, suppositories (for symptoms)
Local anaesthetic, astringent, barrier cream
Short term treatment (5-7 days)
171
Give warning symptoms of haemorrhoids
Dark blood in stools (could be caused by malignancy, inflammatory bowel disease, diverticular disease)
Other anorectal symptoms wrongly attributed to haemorrhoids - anal fissure, absess, perianal fistula
172
What are the 3 steps in the solution process?
1) A drug molecule is "removed" from its crystal
2) A cavity (from the molecule) is created in the solvent
3) The drug molecule inserts into this cavity
173
What is a saturated solution?
A solution containing a drug at the limit of its solubility at any given temperature and pressure
174
What happens if the solubility limit is exceeded?
Solid particles of solute may be present
175
Give the 4 factors that affect solubility
Temperature
Molecular structure of the drug (shape, surface area, hydrophobicity, degree of ionisation)
Nature of the solvent (pH, cosolvents, solubilising agents)
Crystal characteristics
176
Give the 2 important molecular properties of a solvent
Polarity (like dissolves like)
Surface area
177
What do antibiotics partition into?
Micro-organisms
178
Can drugs partition into plastics?
Yes
179
What is logP and what does it measure?
The partition coefficient and it measures the lipophilicty/hydrophilicity of unionised molecules
180
What are the types of solids?
Ionic solids
Molecular solids
Molecular salts
181
What is polymorphism?
Molecules arrange themselves in different ways in the crystal (the ability of a structure to adopt more than one 3D structure)
182
What are the names of the 2 polymorph forms?
Crystalline form
Amorphous form
183
What is gastric motility?
The contraction and relaxation of the layers of muscle in the stomach wall to mix and propel contents
184
What coordinates gastric motility?
The myenteric plexus
185
Where does the myenteric plexus receive input from?
ANS
186
What is the effect of parasympathetic stimulation on motility?
Increases motility
187
What is the effect of sympathetic stimulation on motility?
Decreases motility
188
What does gastric pepsin do?
Initiates digestion of proteins in the stomach
189
How does pepsin digest proteins?
Hydrolyses proteins to polypeptides and amino acids which stimulate acid production
190
When is pepsin activated and inactivated?
Inactivated above pH=6 but can be reactivated upon reacidification
191
What is the function of salivary amylase and at what pH?
Begins the digestion of carbohydrates in the mouth (pH=6) so is far less active in the acidic environment in the stomach
192
What determines the force of contraction and amount of gastric emptying?
Neuronal and hormonal input to the antral smooth muscle
193
What influences the rate of gastric emptying?
The physical and chemical nature of stomach/intestine contents:
- Distension of stomach increases antral contraction
- Increased gastrin levels increases antral contraction
194
What 3 things does stomach emptying involve?
- constriction of lower oesophageal sphincter
- contraction of gastric muscularis
- relaxation of pyloric sphincter
195
What is the enterogastric reflex and what causes it?
The inhibition of gastric emptying by the distension of the duodenum, presence of fat or increased [HCl]. Prevents too much chyme entering the duodenum all at once and aids digestion/absorption
196
Name some factors that influence gastric emptying
Meal size, fat content, composition of food, posture, volume, temperature, pregnancy, conditions (migraine, gastric ulcer, pernicious anaemia), other factors (drugs - alcohol, anticholinergics)
197
What gets absorbed in the stomach?
Limited absorption of water, electrolytes, alcohol and SOME drugs
198
Where does main absorption start and why?
The small intestine because chyme is acted upon by products of the pancreas, liver and gallbladder
199
What are gastric ulcers?
Erosion of mucosal layer leading to inflammation and damage to underlying tissue
200
What are causes of gastric ulcers?
H Pylori, NSAID use, other factors may contribute (smoking, caffeine, alcohol and stress)
201
How are gastric ulcers managed?
- Explanation and reassurance
- Dietary control
- Drug therapy - control acid production
- Eradication of H Pylori - antibiotics
202
What is the exocrine function of the pancreas (99% of cells)?
Secretes enzyme rich fluid into duodenum to break down all categories of digestible food
203
What is the endocrine function of the pancreas (1% of cells)?
Release of hormones into bloodstream that affect carbohydrate metabolism (insulin - B cell, glucagon - a cell, somatostatin - g cell)
204
Describe the structure of the pancreas
Lobules containing acinar cells which secrete enzymes and fluid into duct system. Pancreatic duct fuses with bile duct on entry to the duodenum
205
Describe the aqueous component of pancreatic juice
- 200-800ml secreted a day
- Rich in bicarbonate (pH~8)
- Helps to neutralise acidic chyme as it enters the duodenum
- Secretion stimulated by secretin
206
Describe the enzymatic component of pancreatic juice
Proteolytic enzymes
- trypsin, chymotrypsin, carboxypeptidases
- secreted in inactive form, activated in duodenum by enterokinase
Pancreatic amylase
- majority of starch digestion - secreted in active form
Lipolytic enzymes (fat digestion)
- lipase - secreted in active form
- colipase, cholesterol esterase, phospholipase A2 - activated by trypsin n duodenum
207
What is pancreatitis, how is it caused and how is it treated?
Pancreatic enzymes are activated within the pancreas, causing them to attack the organ itself. Acute becomes chronic when pancreatic tissue is destroyed and scarring develops.
Causes - gallstones, alcohol abuse, idiopathic
Treatment - pain and infection management, electrolyte therapy, surgery in sever cases
208
How much of the body's total blood supply is held by the liver?
~13%
209
What are the functions of the liver?
- Processing digested food from the intestine
- Manufacture of bile
- Storage - converts extra monosaccharides to glycogen, stores iron vitamins and other essential chemicals
- Metabolism - breaks down stored glycogen, fat or protein to glucose (hormonal control), metabolises drugs and breaks down poisons, bacterial activity of Kupffer cells
210
Describe the structure of the liver
- Hepatic cells arranged in radial pattern around central vein
- Hepatocytes make up functional units called lobules which form the two main lobes of the liver
211
What is the double blood supply to the liver?
- Oxygenated from hepatic artery (to let the liver function)
- De-oxygenated, nutrient rich from portal vein (for the liver to act on)
212
What are the 3 functions of hepatic cells?
- Extract oxygen and most nutrients
- detoxify or store poisons and drugs
- secrete products (NOT BILE) into hepatic vein
213
What are the 2 characteristics of bile?
- excretory product of liver metabolism
- a digestive secretion
214
What are the 3 components of bile and their functions?
- Bile salts emulsify fat into small droplets
- Bile cholesterol made soluble by bile salts
- Bile pigments (bilirubin) are absorbed from blood
215
What produces the bile components?
Hepatocytes
216
What is secreted by epithelial cells lining the bile ducts?
Bicarbonate ions
217
What affects secretion from the liver?
Vagal stimulation and secretin increase secretion
218
What is the function of the gallbladder?
Stores and concentrates bile by extracting water and ions
219
When and how does bile enter the gallbladder?
Via the cystic duct when the small intestine is empty
220
When does bile get ejected into duodenum?
Protein or fat-rich chyme enters duodenum which causes CCK release which causes the gallbladder to contract and the sphincter of oddi to relax
221
What are gallstones and how are they treated?
Crystalline deposits that accumulate when there is too much cholesterol and not enough bile salts. Can be dissolved or removed if extreme (cholecystectomy)
222
What is jaundice?
Stones block the common bile duct which increases the level of bilirubin n the blood plasma and causes the discolouration of skin
223
What is bioavailability?
The amount of drug that enters systemic circulation and is available at the site of action
224
What are the 4 factors affecting the concentration of drugs in solution in GI fluids?
Complexation
Adsorption
Chemical stability
Micellar solubilisation
225
How does complexation affect the concentration of drugs in solution?
Mucin present in GI fluids forms complexes with some drugs and reduces absorption and bioavailability
226
How does adsorption affect the concentration of drugs in solution?
The co-administration of drugs and medicines containing solid adsorbents (eg antidiarrhoeals) may result in the adsorbents interfering in the absorption of drugs (eg kaolin or charcoal can adsorb drugs which reduces their absorption)
227
How does chemical stability affect the concentration of drugs in solution and how does instability happen?
Drugs that breakdown in the GI fluids will have reduced absorption and bioavailability. Instability can be caused by stomach pH (acidic hydrolysis) and enzyme degradation
228
How does micellar solubilisation affect the concentration of drugs in solution?
Can increase the solubility of drugs in the GI tract. The ability of bile salts to solubilise drugs depends mainly on the lipophilicity of the drug
229
What are the 3 steps involved in drug absorption from the GI tract?
1) partitioning of molecules between the GI fluid and GI membrane
2) diffusion of molecules across the membrane
3) partitioning of molecules between the GI membrane and the extracellular fluid prior to entering the bloodstream
230
What is the pH partition hypothesis?
Only the unionised form of the drug partitions into the membrane and the extent of ionisation is pH dependent
231
What is Ka?
The dissociation constant
232
What does Ka measure?
How strong or weak an acid or base is relative to water
233
Why is pKa used?
Because Ka tends to be small
234
What is pKa?
The pH at which 50% of the acid or base is dissociated
235
Does pKa depend on concentration?
At a given temperature, the pKa value is a thermodynamic constant and does NOT depend on concentration
236
What does pKa have an influence on?
lipophilicity, solubility, permeability, pharmacokinetic characteristicsH
237
How do we estimate pKa?
Functional groups
238
What is logD?
The distribution coefficient
239
What is logD dependent on?
pH
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What is higher, logP or logD?
logP
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What 3 factors does passive transport rely on?
Concentration gradient, diffusion, molecule size
242
What are the three types of transport?
passive transport, facilitated diffusion, active transport
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What is the effect of a carbohydrate meal on pH?
little change to acidity
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What is the effect of a protein meal on pH?
elevates pH (like a fat meal)
245
What is the effect of a liquid mixed meal on pH?
elevates but returns to base levels
246
What are the three parts of the small intestine?
Duodenum
Jejunum
Ileum
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What are the three parts of the large intestine?
Caecum
Colon
Rectum
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Describe the mucosa of the small intestine
Pits lined with glandular epithelium
Intestinal glands secrete enzymes
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What enzymes do the intestinal glands of the small intestine secrete?
Maltase and sucrose - sugar breakdown
endo and exopeptidases - protein breakdown
250
What does the submucosa of the small intestine contain and what does it secrete?
Brunner's glands which secrete alkaline mucus to protect intestinal wall and neutralise acidic chyme
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What do the mucosa and submucosa of the small intestine secrete in common?
Ions, water and mucus for lubrication and protection from enzymes
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What appears on the epithelia of the small intestine but nowhere else?
Microvilli
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What are villi for?
Increased surface area for transport of nutrients
254
What 4 things does each villus contain?
Arteriole, venule, capillary bed, lacteal (lymph system)
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What is the pH of the small intestine?
7 - 8
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What triggers the secretion of intestinal juices?
Reflex from presence of chyme, secretin, CCK
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What causes digestion in the small intestine?
pancreatic juice, bile, intestinal juice
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Describe the digestion of carbohydrates in the small intestine
- Starch converted to disaccharides by pancreatic amylase
- Disaccharides (maltose, sucrose) converted to monosaccharides (glucose, fructose) by glycosidase
- Monosaccharides absorbed
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Describe the digestion of proteins in the small intestine
-Polypeptides catabolised by pancreatic trypsin and chymotrypsin
- Peptidases complete digestion:
- carboxypeptidases act at carboxyl
- aminopeptidases act at amino end
- dipeptidases convert dipeptides to amino acids
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Describe the digestion of fats in the small intestine
- Fat globules in duodenum coated with bile salts to create an emulsion and disperse large fat globules into smaller ones, increasing SA
- Breakdown of triglycerides by water soluble pancreatic lipases producing monoglycerides and free fatty acids
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Where the most absorption occur?
Small intestine
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What is the difference between facilitated diffusion and active transport?
Facilitated diffusion requires a transporter protein but no energy input. Active transport requires a transporter protein coupled to ATP to go against the concentration gradient
263
Describe the basic absorption of glucose and galactose
Enter epithelium by co-transport with via sodium-glucose transporters. Leave epithelium and enter blood by facilitated diffusion via glucose transporters (GLUTs)
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Describe the basic absorption of fructose
Enter and leave epithelium by facilitated diffusion via glucose transporters (GLUTs)
