Clinical Pharmacology Questions pps (15/30)

1. Clinical Pharmacology Questionspps (15/30)

2. Define: • Pharmacokinetics (1) • What the body does to the drugs • Pharmacodynamics (1) • What the drug does to the body

3. Give three ways in which you would improve patient compliance (3) Keep regimen simple Provide patient education Avoid side effects

4. Define: • Bioavailability (3) • The proportion of administered drug which reaches systemic circulation and available for distribution to site of action • S/R (1) • Slow release • E/C (1) • Enteric coating

5. Name the 4 factors involved in the pharmacokinetic process (4) “A D M E” Absorption Distribution Metabolism Excretion

6. Name three factors that can affect the rate of absorption in the GI tract (3) Gastrointestinal motility Food Malabsorptive state (cealiac disease)

7. What are the 2 biochemical pathways of metabolism in the liver (4)? • Phase 1 Reactions • increase polarity of drug (unmask functional groups) • controlled my microsomal mixed function oxidase system (NADPH, CYP450 + O2) • Phase 2 Reactions • conjugation of drug to promote excretion (more hydrophillic) • glucuronyl, acetyl, methyl

8. What 4 factors affect metabolism by the liver (4)? • Age • elderly + neonates have reduced function • Drug Interactions • EtOH, rifampacin, carbamazepine increase CYP450 • cimetidine, azoles, macrolides decrease CYP450 • Genetic Polymorphisms • CYP2D6 = codeine to morphine (underactive i.e. poor effect) • Liver Disease • decreases metabolism • increased bioavailability as decreases 1stPM and decreased protein binding (hypoalbuminaemia)

9. What is first pass metabolism (1) and where does it occur (3)? “extent of metabolism occurring before the drug enters the systemic circulation – oral route only” Occurs in the… gut lumen gut wall liver

10. How can first pass metabolism be avoided (5)? give drug to avoid porto-hepatic system: mucosal – sublinual, buccal rectal, vaginal inhalation transdermal IV IM

11. Describe the molecular action of insulin release (6) glucose uptake by GLUT2 glucose  ATP ATP causes ATP-senstive K+ channels to close depolarisation of the membrane voltage-gated Ca2+ channels open increase in i[Ca2+] PIP2  PLC  IP3 + DAG Insulin vesicles fuse to membrane and release

13. State 5 broad actions of insulin (5) • Carbohydrate metabolism • increased glycogenesis • increased glucose uptake • decreased gluconeogenesis • decreases lipolysis • increases fatty acid and TG synthesis • increases protein synthesis • decreases protein degredation • Increased cellular uptake of K+

14. What are the types of diabetes (6)? • Type 1 Insulin Dependent • B-cell destruction • Type 2 Non-Insulin Dependent • insulin resistance • Gestational Diabetes • insulin resistance • Genetic: MODY • genetic defect in insulin production • Drug-Induced • cortisol, steroids • Disease-Induced • Cushing’s pheochromocytoma

15. State some long term complications associated with diabetes (6) • Blindness (diabetic retinopathy) • Kidney failure (diabetic nephropathy) • Nerve damage (diabetic neuropathy) • diabetic foot • Atherosclerosis • CHD/Stroke • Hypoglycaemia and DKA • Coma and death • Infection

16. What treatments are available for type I diabetes sufferers? (4) What are the types of insulin available (4)? • short acting –human insulin or analgue (novorapid) • intermediate acting –isophane insulin • long acting - glargine • premixed – fast + inter/long acting Lifestyle Insulin Diet, exercise Islet transplantation

17. Name three types of diabetic emergency and their general treatments (6) Ketoacidosis Hypoglycaemia Lactic acidosis IV fluids (saline) Insulin (DKA) + K+ replacement Treat the cause (glucose for hypo)

18. What is the main treatment given in type II diabetes? Metformin Generally what strategy should be used in a diabetes consultation / examination? (8) Alphabet strategy: Advice Blood pressure Cholesterol Diabetes control Eye examination Feet examination Guardian drugs Heart risk score

19. What effect does metformin have on the body? (2) Increased peripheral insulin action Increased glucose uptake What other drug is metformin usually taken in combination with? (1) Insulin

20. What three side effects can metformin have? GI symptoms B12 malabsorption Lactic acidosis What is the mechanism of action for sulphonylureas? Increased insulin release via KATP channel blocking What do sulphonylureas need in the body to work properly? Working B-cells i.e. won’t work in type 1 DM

21. State three adverse effects of sulphonylureas (3) Hypoglycaemia Weight gain Reactions Why is insulin said to have a biphasic response (2) Early spike Late plateau

22. What is the mechanism of action of thiazolidinediones (1)? Reduced insulin resistance Name three side effects Weight gain Oedema Hypoglycaemia

23. List some adverse effects of insulin (4) Weight gain Hypoglycaemia Retinopathy Reactions Lipoatrophy Insulin resistance Infection at site of injection

24. Give an example of... • Gram positive cocci • Staphlococcusaureus • Streptoccuspneumoniae • Gram negative cocci • Neisseria meningitides • Neisseria gonorrhoeae • Gram positive baccili • Bacillus cereus • Clostridium difficile • Gram negative bacili • Haemophilusinfluenzae • Campylobacter jejuni

25. In what 3 main ways do antibiotics work ? Inhibit DNA synthesis Inhibit protein synthesis Inhibit cell wall synthesis

26. Give 3 classes of antibiotics that inhibit DNA synthesis with examples (6)? • Sulphonamides • Trimethoprim • Quinolones • Ciprofloxacin • Nitroimidazoles • Metronidazole

27. Give 3 classes of antibiotics that inhibit protein synthesis with examples (6)? • Tetracyclins • doxycyclin • Macrolides • erythromycin • Aminoglycosides • Gentamycin

28. Give 4 classes of antibiotics that inhibit bacterial cell wall synthesis with examples (8)? • Penicillins • amoxycillin • Carbapenems • meropenam • Cephlosporins • Ceftriaxone • Glycopeptides • Vancomycin

29. What two drugs make up co-amoxiclav (2)? Amoxicillin Clavulanic acid What is the mechanism behind penicillin resistance (2)? increase in Beta-Lactamase breaks down beta-lactam ring

30. State some long term complications of asthma (4) • Hypertrophy of airways muscle • Hyperplasia of mucous secreting cells • Angiogenesis • Subepithelial fibrosis Define Asthma (3) • Reversible, inflammatory, obstructive disease of lungs

31. COPD Give two examples • Emphysema • Chronic bronchitis What can cause it? • Chronic irritation (smoking) What is the cell that is mostly involved with COPD? • Neutrophils

32. Give three symptoms of COPD • Dyspnoea • Chronic cough • Production of sputum Why is there an increased risk of infection in COPD (2)? • destruction of mucociliary escalator • cannot remove pathogens

33. How is COPD treated (5)? Early – Lifestyle (prevent irritant) Physiotherapy B2-adrenoreceptor agonists Corticosteroids Late – combined therapy with oxygen

34. What principle cell is involved in inflammation of allergic asthma (1)? Eosinophils

35. What are the 4 main treatments of asthma + give an example of each (8)? • B2-adrenoreceptor agonist • Salbutamol, terbutaline • Glucocorticoids • Prednisolone(oral), budesonide (inhaled) • Anti-cholinergics • Ipratropium bromide • Methylxanthine / PDE inhibitors • Theophylline, aminophylline / roflumilast

36. What are the other possible drug treatments for asthma (4)? • O2 • Leukotrine receptor antagonists • monteleukast • IgEmAb • omalizumab • Mast cell stabiliser • sodium cromoglycate • Mucolytics • carbocysteine

37. What are the mechanisms of action of B2 agonists (5)? • Gs-> adenylatecyclase -> cAMP -> PKA -> • inactivates MLCK (needed for myosin phosphy) • activates K+ channels = membrane depolarises • decreases intracellular Ca2+ levels • increase mucocillary clearance • decrease neutrophil function • decreases cholinergic transmission

38. State the mechanism of action for... • Glucocorticoids • expression of anti-inflammatory genes: IL-10, IL-1 antagonist • decreases pro-inflammatory genes: NF-Kb, AP-1, IL-1, IL-2 • Methylxanthines • Stops cAMP being degraded = muscle relaxation • Anti-cholinergic • blocks M3 receptors = stops parasympathetic constriction • USUALLY: M3 (Gq) -> PLC -> PIP2 + DAG -> PKC + Ca2+

39. Why would a patient with acute asthma be given IV hydrocortisone (2)? To prevent late-stage asthma attack (4-72 hours later) IV as unlikely to be able to swallow tablet or inhale

40. What are the side effects of B2 agonists (6)? • Muscle tremor • Cramps • palpitations/tachycardia • hyperkalaemia • insomnia • headache • dry mouth • anxiety • flushing • myocardial ischaemia (steel syndrome)

41. Give 6 side effects of corticosteroids on different body systems (6) • MSK: atrophy, osteoporosis, myopathy • Metabolic:weight gain, adrenal supression, hypokalaemia • CV: hypertension, oedema • Immune:candidiasis (poor immune function) • GIT: peptic ulcers, pancreatitis, oesophagitis • Neuro: psychosis

42. How do methylxanthines work synergistically with B2-agonists? B2agonists increase cAMP = bronchodilation. cAMPis broken down by phosphodiesterases. Methylxanthines block the action of the phosphodiesterase therefore, enhancing the levels of cAMP

43. State some side effects of anticholinergics (9) Nausea Constipation Dry mouth and cough Pharyngitis URTI’s Bitter taste Supraventricular tachycardia Atrial fibrillation Urinary retention

44. State three side effects of over-use of theophyllines Seizures Cardiac arrhythmia's Nausea

45. What are the ANS actions of the GIT + what neurotransmitters are released (4)? • Parasympathetic (Ach and 5-HT) • increase GI motility • increase secretions • Sympathetic (NA) • decrease GI motility • decrease GI secretions

46. Give 2 types of anti-emetic and explain how they work (4)? • 5-HT antagonist • ondansetron • D2 antagonist • metoclopramide both drugs inhibit 5-HT or D2 receptors in emesis centre of medulla  decrease vagal tone

47. What 5 types of drugs can be given for constipation with examples (10)? • Purgatives/Motility Stimulants • metoclopramide, domperidone • stimulate myenteric plexus = increase GI motility • Bulk laxative • methylcellulose • Increase volume of non-absorbable residue = stimulating peristalsis • Osmotic laxative • Lactulose • Increases water content • Faecal softener • arachis oil + docusate • Alter faecal consistency • Stimulant laxative • senna (anthracene) • Increases secretions and motility

48. Describe the MOA of lactulose (5)? broken down into fructose + galactose fermentation produces lactic and acetic acid both poorly absorbed, causing an osmosis increasing water content of the bowel increased volume (water and gas from fermentation) stretches bowel, triggering peristalsis increased water content softens stools, making them easier to pass

49. What 2 drugs would be first choice and why (3)? • bulk laxative and faecal softners • very few side effects What lifestyle modifications would you advise (2)? • increased fibre e.g. fruit and veg • increase bulk e.g. bran • drink more water What are the side effects to laxative use (5)? • explosive diarrhoea • cramps+ gas • electrolyte loss • dehydration • cathartic colon • chronic malapsorption, steatorrhoea+ decreased Na/K levels

50. State the four reasons a patient may develop diarrhoea (4)? Secretory – cholera toxin Osmotic pull – Mg2+, lactose in chyme Inflammatory – salmonella, IBD Increased motility – drug-induced