The Ultimate Test Flashcards
What does ADME stand for?
Absorption
Distribution
Metabolism
Excretion
What is up-regulation?
Receptor numbers are increased in response to a chronically low concentration of the agonist to optimise sensitivity
What is down-regulation?
Receptor numbers are decreased in response to a chronically high concentration of the agonist to optimise sensitivity
What are the two types of ligand?
Agonist and antagonist
What is an agonist?
A ligand with both affinity and efficacy
What is an antagonist?
A ligand with affinity but not efficacy (blocks the receptor but does not activate a response)
Name three different examples of signal transduction
Direct opening of an ion-channel
Direct activation of an enzyme
Indirect activation of an enzyme
What makes indirect activation of an enzyme different from direct activation of an enzyme?
Indirect activation involves a G-protein
Give three examples of the importance of calcium signalling
Muscle contraction, secretion, metabolism, neuronal excitability, cell proliferation
What is calcium?
Calcium is a second messenger and is neither produced nor destroyed - it is only stored and moved between compartments
Give two examples of calcium channel blockers
Nifedipine and verapamil (modulate muscle contraction)
What is pharmaceutics?
The process of turning an NCE into a medication to be used safely and effectively by patients
What does NCE stand for?
New Chemical Entity
What is a medicine?
A drug delivery system that allows the administration of drugs into the body in a safe, efficient, accurate, reproducible and convenient way
Name three administration routes
Oral, Rectal, Topical, Parenteral, Respiratory, Nasal, Ocular, Vaginal/Urethral
What is a drug?
A molecule that interacts with a biological system to produce a biological response
What does endogenous mean?
Made in the body
Give an example of a biologic
Antibodies
Proteins
What is drug safety dependent on?
The therapeutic index of that specific drug
Give an example of a biomacromolecule
Ion channel
Enzyme
Receptor
What does COX stand for?
Cyclo-oxygenase
What is the substrate of COX?
Arachadonic acid
Where are B2 adrenoreceptors located?
Bronchial smooth muscle
What do adrenaline and noradrenaline do?
Dilate the airways
What is salbutamol?
A B2 adrenoreceptor agonist
Name the five different types of intermolecular bonding
Hydrogen bonding, Van der Waals, pi-pi bonding, electrostatic, dipole
What is the buccal cavity?
The mouth (teeth, tongue, salivary glands)
What is the first organ of the digestive system?
The buccal cavity
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
What type of buccal cavity tissues are keratinised/nonpolar?
Gingival and palatal
What type of buccal cavity tissues are nonkeratinised/polar?
Buccal and sublingual
What route of buccal delivery has the quickest onset time and why?
Sublingual - it is the closest to the bloodstream
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.
What is the MAIN advantage of buccal administration?
It avoids first pass metabolism
Give two examples of solid buccal dosage forms
Buccal tablets, bioadhesive wafers, lozenges, bioadhesive micro/nanoparticles
Give two examples of semisolid buccal dosage forms
Medicated chewing gums, buccal films/patches, adhesive gel/ointments
Give two examples of liquid buccal dosage forms
Mouthwash, mouth fresheners, mouth spray
What is bioadhesion?
Adhesion to a biological surface
What is mucoadhesion?
Adhesion to a mucosal surface
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
What polymer is better for mucoadhesion?
(Anionic, cationic or uncharged)
Anionic
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
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
What is the definition of a solution?
A mixture of two or more components that form a single, molecularly homogeneous phase
What is the definition of dissolution?
The process by which a solution is formed - solid dissolving in a solvent
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
Why are solutions important for drug delivery?
Generally, only drugs in solution can be absorbed into systemic circulation
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
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
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)
Describe the post-absorptive state
Glucose levels decrease so there is an increase in:
1. Glucagon
2. Gluconeogenesis
3. Glucose sparing
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.
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.
What part of the stomach gets relaxed by the presence of fat and what is the consequence?
The fundus - lowers intragastric pressure
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
What makes up the Enteric Nervous System?
The myenteric and submucosal plexus
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
What is the CNS?
The Central Nervous System - comprised of the brain and spinal cord
What is the PNS?
The Peripheral Nervous System - connects the CNS to limbs and organs
What is the ANS?
The Autonomic Nervous System - the division of the PNS influencing the function of organs
What is the ENS?
The Enteric Nervous System - the intrinsic nervous system of the GI tract
What connects the CNS and ENS?
The vagus nerve - largest parasympathetic nerve and the X cranial nerve
What is the primary route used by gut bacteria to transmit information to the brain?
The vagus nerve
What does serotonin control?
Mood control, depression, aggression
What is the code for serotonin?
(Number - Letter Letter)
(5-HT)
What are the two different types of neurons?
Afferent and efferent
What is an afferent neuron?
A sensory receptor neuron - carry nerve impulses from receptors or sense organs to the brain
What is an efferent neuron?
A motor or effector neuron - carry nerve impulses from CNS to effectors like muscles and glands
What is another name for the Myenteric plexus?
Auerbach’s plexus
What is another name for the Submucosal plexus?
Meissner’s plexus
What type of neuron is the Myenteric plexus?
Efferent
What type of neuron is the Submucosal plexus?
Afferent
What does the Myenteric plexus influence?
Muscle activity
What does the Submucosal plexus receive signals from?
The epithelium and stretch receptors
What makes up the PNS?
Sympathetic and Parasympathetic nerves
What links the nerve plexuses to the CNS?
Afferent fibres (activated by stretch and chemical stimulation)
What links the nerve plexuses to the ANS?
Efferent neurons
What muscle controls segmentation?
The circular muscle
What is segmentation used for?
To mix food
What muscle controls peristalsis?
The longitudinal muscle
What is peristalsis used for?
To propel food through the GI tract
How long is the ideal gut transit time?
12 - 48 hours
What are the two downsides of gut transit time being too quick?
Diarrhoea
Poor absorption of nutrients
What are the two downsides of gut transit time being too slow?
Constipation
Poor gut health
Name two types of drugs that can cause constipation as a side effect
Antacids
Anticholinergics
Antihypertensives
What do antacids do?
Neutralise stomach acid
What do anticholinergics do?
Reduce muscle spasms
What to antihypertensives do?
Reduce blood pressure
What are the three opioid receptor subtypes?
Mu, kappa, gamma
How many pairs of salivary glands are there?
THREEEEEEEEEEEEEEEEEEEEEEE
How much saliva is secreted in a day?
1500ml
What are the three main components of saliva?
Mucus, amylase, lysozyme
What is mucus used for in saliva?
To lubricate food
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
Where is saliva made?
Salivary ducts
What is produced by the acinar cells in the salivary ducts?
Isotonic fluid (electrolytes and water)
What does the final composition of saliva depend on?
Flow rate through duct and neuronal input
What nervous system regulates saliva secretion?
ANS
What gland(s) secrete watery saliva and amylase?
Parotid and submandibular
What gland(s) secrete thick saliva and mucus?
Sublingual
What is the scientific name for swallowing?
Deglutition
What are the two stages of deglutition?
The voluntary stage and the pharyngeal stage
What does the oesophagus connect?
The laryngopharynx to the stomach
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
What is the average surface area of the oral mucosa?
200cm2
By what mechanism do drugs get through the oral mucosa?
Passive diffusion
What the three main oral problems?
Dry mouth, oral ulcers, oral thrush
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
What is the sphincter that controls entry into the stomach from the oesophagus?
The lower oesophageal sphincter
Name the three parts of the stomach
Fundus, antrum, body
Name the sphincter separating the stomach and the duodenum
The pyloric sphincter
What is the pH of the stomach?
2
What is chyme?
Food once the digestive process has begun
Digestion of what begins in the stomach?
Protein and fat
What are the two types of digestion in the stomach?
Mechanical (stomach movements)
Chemical (pepsin)
Where in the stomach is the mechanical digestion strongest?
Antrum
What are the three secretory cells present in the gastric glands?
Goblet (neck) cells
Peptic (chief) cells
Oxyntic (parietal) cells
What do goblet cells secrete?
Mucus
What do peptic cells secrete?
Pepsinogen
What do oxyntic cells secret?
HCl and intrinsic factor
Which of the three secretory cells are zymogenic?
Peptic cells
What is a zymogenic cell?
One that secretes the inactive form of the enzyme
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
What are the three additional cells found in the gastric glands?
D cells
Enterochromaffin (mast-like) cells
G cells
What do D cells secrete?
Somatostatin
What do G cells secrete?
Gastrin
What do enterochromaffin like cells secrete?
Histamine
What is intrinsic factor used for?
The absorption of vitamin B12
What does pepsin do?
Breakdown protein
What triggers the change from pepsinogen to pepsin?
HCl
Why doesn’t the stomach digest itself?
- Tight junctions between mucosal epithelial cells prevent leakage of gastric juice onto underlying tissue
- Mucus secreted by epithelial/goblet cells has higher pH so provides localised neutralisation and physical barrier to acid
- Prostaglandins increase mucosal thickness and stimulates bicarbonate production
Name the three stages of gastric secretion and whether they increase or decrease secretion
- Cephalic Phase - increase
- Gastric Phase - increase
- Intestinal Phase - decrease
What regulates the Cephalic Phase?
The brain (medulla oblongata)
What secretions are stimulated in the Cephalic Phase?
HCl, pepsin and gastrin (which further stimulates the secretion of HCl and pepsin)
What stimulates the Gastric Phase?
Stomach distension caused by the presence of food
Where is gastrin produced?
In the antrum of the stomach
What secretions are stimulated in the Gastric Phase?
HCl, pepsin and gastrin
What stimulates the Intestinal Phase?
The presence of acid in the duodenum
Describe the three ways that the Intestinal Phase inhibits gastric secretion
- Neuronal impulses to the medulla to decrease the parasympathetic stimulation of gastric glands
- Local reflexes in the gut wall
- The release of three local hormones
Name the three local hormones secreted in the intestinal phase
Secretin, gastric inhibitory peptide and cholecystokinin
When does the inhibition of HCl secretion begin?
Once the food has left the stomach
What is the enterogastric reflex?
The neuronal inhibition of HCl secretion mediated by the medulla oblongata
What HCl hormonal inhibitors are there?
Secretin, CCK, GIP, gastrone, glucagon and vasoactive intestinal peptide (VIP)
What is diarrhoea?
The frequent passing of water stools (more than 3 times a day)
How long does acute diarrhoea last for?
5-10 days
How long does chronic diarrhoea last for?
Longer than 2 weeks
Why is the removal of fluid prevented in diarrhoea?
The large intestine is inflamed
Give three symptoms of diarrhoea
Flatulence
Weakness
Electrolyte imbalance
Fluid loss
Nausea, vomiting, fever
Headache, loss of appetite
Give a cause of acute diarrhoea
Bacterial or viral infection
Food poisoning
Certain drugs
Give a cause of chronic constipation
Symptom of a serious condition (Crohn’s, IBS…)
Laxatives
Poor diet
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
What do rehydration drinks do?
Replace lost electrolytes but do not treat diarrhoea
How do antidiarrhoeals work?
They slow gut transit time which increases water and electrolyte absorption
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
What is constipation?
The passage of hard stools less frequently than the patient’s regular pattern
Inability to completely empty the bowel
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
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)
Give lifestyle advice for the treatment of constipation
Increase dietary fibre
Increase fluid intake
Increase daily exercise
Name the three types of laxative
Osmotic
Bulk-forming
Stimulant
Give examples of stimulant laxatives
Senna and bisacodyl
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
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
Give examples of bulk-forming laxatives
Bran
Ispaghula husk (fybogel)
Give examples of osmotic laxatives
Lactulose
Magnesium salts
Macrogols
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
Give warning symptoms of constipation
Constipation alternating with diarrhoea
Mucus or dark bloods in stools
Weight loss
Abuse of laxatives
Vomiting
Fever
Angina
What are haemorrhoids?
Abnormal swelling or enlargement of the anal vascular cushions
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
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
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)
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
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
What is a saturated solution?
A solution containing a drug at the limit of its solubility at any given temperature and pressure
What happens if the solubility limit is exceeded?
Solid particles of solute may be present
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
Give the 2 important molecular properties of a solvent
Polarity (like dissolves like)
Surface area
What do antibiotics partition into?
Micro-organisms
Can drugs partition into plastics?
Yes
What is logP and what does it measure?
The partition coefficient and it measures the lipophilicty/hydrophilicity of unionised molecules
What are the types of solids?
Ionic solids
Molecular solids
Molecular salts
What is polymorphism?
Molecules arrange themselves in different ways in the crystal (the ability of a structure to adopt more than one 3D structure)
What are the names of the 2 polymorph forms?
Crystalline form
Amorphous form
What is gastric motility?
The contraction and relaxation of the layers of muscle in the stomach wall to mix and propel contents
What coordinates gastric motility?
The myenteric plexus
Where does the myenteric plexus receive input from?
ANS
What is the effect of parasympathetic stimulation on motility?
Increases motility
What is the effect of sympathetic stimulation on motility?
Decreases motility
What does gastric pepsin do?
Initiates digestion of proteins in the stomach
How does pepsin digest proteins?
Hydrolyses proteins to polypeptides and amino acids which stimulate acid production
When is pepsin activated and inactivated?
Inactivated above pH=6 but can be reactivated upon reacidification
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
What determines the force of contraction and amount of gastric emptying?
Neuronal and hormonal input to the antral smooth muscle
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
What 3 things does stomach emptying involve?
- constriction of lower oesophageal sphincter
- contraction of gastric muscularis
- relaxation of pyloric sphincter
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
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)
What gets absorbed in the stomach?
Limited absorption of water, electrolytes, alcohol and SOME drugs
Where does main absorption start and why?
The small intestine because chyme is acted upon by products of the pancreas, liver and gallbladder
What are gastric ulcers?
Erosion of mucosal layer leading to inflammation and damage to underlying tissue
What are causes of gastric ulcers?
H Pylori, NSAID use, other factors may contribute (smoking, caffeine, alcohol and stress)
How are gastric ulcers managed?
- Explanation and reassurance
- Dietary control
- Drug therapy - control acid production
- Eradication of H Pylori - antibiotics
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
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)
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
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
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
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
How much of the body’s total blood supply is held by the liver?
~13%
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
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
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)
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
What are the 2 characteristics of bile?
- excretory product of liver metabolism
- a digestive secretion
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
What produces the bile components?
Hepatocytes
What is secreted by epithelial cells lining the bile ducts?
Bicarbonate ions
What affects secretion from the liver?
Vagal stimulation and secretin increase secretion
What is the function of the gallbladder?
Stores and concentrates bile by extracting water and ions
When and how does bile enter the gallbladder?
Via the cystic duct when the small intestine is empty
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
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)
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
What is bioavailability?
The amount of drug that enters systemic circulation and is available at the site of action
What are the 4 factors affecting the concentration of drugs in solution in GI fluids?
Complexation
Adsorption
Chemical stability
Micellar solubilisation
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
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)
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
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
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
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
What is Ka?
The dissociation constant
What does Ka measure?
How strong or weak an acid or base is relative to water
Why is pKa used?
Because Ka tends to be small
What is pKa?
The pH at which 50% of the acid or base is dissociated
Does pKa depend on concentration?
At a given temperature, the pKa value is a thermodynamic constant and does NOT depend on concentration
What does pKa have an influence on?
lipophilicity, solubility, permeability, pharmacokinetic characteristicsH
How do we estimate pKa?
Functional groups
What is logD?
The distribution coefficient
What is logD dependent on?
pH
What is higher, logP or logD?
logP
What 3 factors does passive transport rely on?
Concentration gradient, diffusion, molecule size
What are the three types of transport?
passive transport, facilitated diffusion, active transport
What is the effect of a carbohydrate meal on pH?
little change to acidity
What is the effect of a protein meal on pH?
elevates pH (like a fat meal)
What is the effect of a liquid mixed meal on pH?
elevates but returns to base levels
What are the three parts of the small intestine?
Duodenum
Jejunum
Ileum
What are the three parts of the large intestine?
Caecum
Colon
Rectum
Describe the mucosa of the small intestine
Pits lined with glandular epithelium
Intestinal glands secrete enzymes
What enzymes do the intestinal glands of the small intestine secrete?
Maltase and sucrose - sugar breakdown
endo and exopeptidases - protein breakdown
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
What do the mucosa and submucosa of the small intestine secrete in common?
Ions, water and mucus for lubrication and protection from enzymes
What appears on the epithelia of the small intestine but nowhere else?
Microvilli
What are villi for?
Increased surface area for transport of nutrients
What 4 things does each villus contain?
Arteriole, venule, capillary bed, lacteal (lymph system)
What is the pH of the small intestine?
7 - 8
What triggers the secretion of intestinal juices?
Reflex from presence of chyme, secretin, CCK
What causes digestion in the small intestine?
pancreatic juice, bile, intestinal juice
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
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
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
Where the most absorption occur?
Small intestine
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
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)
Describe the basic absorption of fructose
Enter and leave epithelium by facilitated diffusion via glucose transporters (GLUTs)
