Karteikarten
Week 6
Karten in diesem Stapel (41)
- 1Define absorption (pharmacological POV)Movement of a drug from its site of administration into the plasma
- 2Define distribution (pharmacological POV)Reversible transfer of a drug from 1 location to another within the body
- 3What does passive diffusion involve passage through?Cells:
-involves diffusion through membrane lipids
Intracellular pores:
-found in some blood vessels
-for diffusion of small water-soluble molecules - 4In what forms do drugs exist in the body?Exist in equilibrium between ionised and unionised forms
Only the unionised form is sufficiently lipid-soluble to diffuse across membranes
Drugs accumulate in areas where ionisation is favoured - 5What is the chemical nature of drugs?-Many are weak acids or weak bases
-pKa values are in physiological pH range
-Degree of ionisation depends on local pH - 6What does the Henderson-Hasselbalch equation show? What does the pKa value show?It describes properties of ionisable groups
It is a quantitative expression of the strength of an acid/base - 7Where do weak acids accumulate?They are well absorbed from acidic environments and accumulate in basic environments
- 8Where do weak bases accumulate?Well absorbed from basic environments and accumulate in acidic environments
- 9What is ion trapping?It results in basic drugs being secreted into the stomach where the pH is acidic and acidic drugs being excreted in urine when alkaline
- 10How does the degree of ionisation change for acidic/basic drugs as pH increases?Acidic- increases
Basic- decreases - 11What group do acidc/basic drugs contain?Acidic- carboxylate
Basic- nitrogen - 12Define bio-availabilityThe fraction of the total dose administered that reaches the plasma
- 13What chemical properties affect drug administration?-Chemical nature
-Molecular weight
-Solubility
-Partition coefficient - 14What physiological variables affect drug administration?-Gastric motility
-pH at the absorption site
-Area of absorbing surface
-Blood flow
-Presystemic elimination
-Ingestion with or without food - 15What factors affect absorption of drugs in the GI tract?-Dispersal/solubility of drugs in gut contents (dependent on formulation)
-Stability of the drug (against digestive enzymes)
-Lipid solubility of the drug
-Time available for absorption (eg. day/night)
-Other GI tract problems like diarrhoea/vomiting
-Interaction with food
*Drug can irritate GI tract!!! - 16What pharmaceutical interventions influence absorption?-Particle size
-Dry power inhaler
-Enteric coated drugs
-Slow/delayed release preparations
-Osmotic mini-pumps - 17What factors affect transdermal absorption?-Lipid solubility
-Formulation
-Skin thickness (depends on age, area, damage)
-Hydration
-Blood flow - 18What does distribution of drugs in the body depend on?-Blood flow
-Ability of drug to pass through diffusion barriers
-Tissue binding - 19Where is insulin made and what does it do?-Produce in B cells in pancreas
-Reduces blood glucose levels
-Regulates glucose uptake by cells
-Secretion is regulated by AA, glucagon, fatty acids and somatostatin - 20How does glucose cause insulin to be released?1) Glucose enters B cells and is metabolised
2) [ATP]i increases
3) Activity of ATP-sensitive K+ channel (Katp) decreases. The channels are closed
4) Decrease in K+ efflux (--> depolarisation)
5) Ca2+ channels are open and insulin is secreted - 21How would you describe insulin release? How does this change for a patient with Type 2 diabetes?It is biphasic.
The 1st phase is normally fast as there is fast vesicle release of pre-made insulin
The 2nd phase is slower as insulin needs to be produced, packaged and released.
The patient has no 1st phase. 2nd phase occurs as normal (no problem with longer term response) - 22Describe the insulin receptor: -where is it found? -structure?Insulin binds to receptors on the liver, muscle and fat.
It has 2 alpha subunits (extracellular) and 2 beta subunits (transmembrane)
Subunits are bound by disulfide bridges - 23What happens when insulin binds to an insulin receptor?1) Tyrosine kinase on the beta subunits is activated
2) The insulin receptor substrate protein is phosphorylated. It then acts as a second messenger
3) The enzyme is activated and gene transcription occurs
4) The Glut-4 transporter is expressed and increases glucose uptake
5) Glycogen synthesis increases - 24Describe characteristics of Type 1 diabetes mellitus-10% of all diabetics
-Occurs in the young
-Severe
-Caused by genetics/autoimmune response (B cell loss by antibodies)
-Pre-diabetic stage can last months to years - 25Treatments for Type 1 diabetes mellitus-Nicotinamide (repairs DNA)
-Diet (manage carbohydrate intake, avoid infrequent heavy meals)
-Insulin - 26How is insulin given to patients with Type 1 diabetes?-Is a peptide so has to be given parenterally (not orally)
-Made from recombinant human DNA
-Can be short (insulin lispro) /long acting (insulin glargine) depending on if insulin molecules form complexes with each other or other elements eg. zinc. - 27Complications of insulin therapy?-Hypoglycaemia
-Allergy to complexes
-Lipodystrophy (at site of injection) - 28Characteristics of Type 2 diabetes mellitus?-Often commonly caused by obesity, hypertension, hyperlipidaemia
- >25 yrs
-Less severe
-Caused by insulin resistance. There is no loss of B cells, but an increase in basal insulin in the blood (which is insufficient) - 29Treatment options for Type 2 diabetes?-Diet/excercise (often sufficient on its own)
-Drugs (incl. ACE inhibitors and statins)
-Only a third will need insulin - 30Describe the action of oral hypoglycaemic agents such as Metformin Side effects? Who can use it?-Deceases insulin resistance
-An AMP-activated protein kinase is activated, causing the rate of gluconeogenesis in the liver to fall
-Glucose uptake in muscle increases
-No hypoglycaemia (only lowers high glucose levels)
-No increase in appetite
-Lactic acidosis
-Can be used by obese patients
-As part of combination therapy - 31Examples of sulphonylureas (SU)?Tolbutamide
Glibenclamide
Gliclazide - 32Mechanism of SU?-Binds to SU receptor (part of Katp channel) ie. simulates ATP binding
-Channel closes
-Depolarisation occurs
-Increased insulin secretion
-Increased tissue sensitivity to insulin - 33How do SUR modulators such as Repaglinide work?-Binds to SUR
-Katp activity falls
-Has a shorter duraction of action
-More selective for Katp channels in B cells - 34Side effects of using SUR drugs?-Hypoglycaemia (esp. when combing SU with other drugs)
-Stimulates appetite (can't be used by obese)
-Contradicated for pregnant/breastfeeding (appears in milk/ crosses placenta) - 35How do Thiazolidinediones such as Pioglitazone work?-Binds to transcription factor to affect gene expression
-In adipose tissue, fatty acid uptake and lipogenesis increase
-There is a decrease in plasma fatty acids
-Leads to increase in glucose uptake and decrease in gluconeogenesis - 36Can Pioglitazone be used on its own? Side effects?No, can only be taken with a SU or metformin
-Not used much anymore as it is linked with liver toxicity, heart failure (due to hypovolemia in heart) and bladder cancer - 37What are incretins?GI hormones that increase insulin levels leading to a fall in blood glucose levels
- 38How do Gliptins work?-They inhibit gipeptidyl peptidase-4 (enzyme that breaks down incretins)
- 39How does Exenatide work?It is a GLP-1 agonist
-It slows down gastric emptying (used for obese)
-Used in combination
-Expensive - 40How does Acarbose work?- An alpha-glucosidase inhibitor
-Reduces carbohydrate absorption
-Used for the obese (alone/with metformin) - 41How do SGLT2 inhibitors work? Side effects?-Reduces glucose resorption in the proximal convoluted tubule of the kidney
-More glucose is excreted in the urine
-Peripheral vascular disease due to hypovolemia
-Ketoacidosis
Informationen
- Beschreibung
- Absorption and distribution of drugs
- Erstellt von
- Dolu Falowo
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