Drug Names

Question 1

Name two drugs removed from the market due to drug-drug interactions:

Answer 1

1. Sorivudine- anti-viral, inhibition of 5-fluorouracil metabolism.
2. Terfenidine- anti-histamine, when coadministered with ketoconazole (and grapefruit juice), leading to cardiotoxicity.

Question 2

What 1960s drug contributed to the formation of regulatory authorities of drugs?

Answer 2

Thalidomide- given the pregnant women to help with sleep and depression, but ended up causing bird abnormalities.

Question 3

Name three drugs which were discovered from development of herbal/traditional remedies:

Answer 3

1. Morphine from opium poppy.
2. Digoxin/digitoxin from foxgloves.
3. Salicyclic acid (aspirin) from willow bark.

Question 4

Name two drugs which were discovered by the empirical approach, using models felt to be predictive of activity and screening a large number of compounds:

Answer 4

1. Anti-cancer drugs.

2. Cyclosporin (immunosupressant).

Question 5

Name two drugs which were discovered by the rational drug design, understanding the cellular/molecular basis of diseases (e.g. receptors), using computer technology to get the 3D structure of the receptor to design agonist drug:

Answer 5

1. Propanolol- beta-blocker.

2. Cimetidine- H2-antagonist.

Question 6

Name two drugs which are prodrugs, analogs or metabolites of existing drugs:

Answer 6

1. Aspirin (salicyclic acid).

2. Paracetamol (phenacetin).

Question 7

Name three drugs discovered by serendipity (chance):

Answer 7

1. Penicillin.
2. Valproate (anti- epilleptic).
3. Sildenafil (Viagra).

Question 8

Describe how drugs may be discovered from genomics- information on genes to identify drug targets:

Answer 8

Gene therapy, siRNA.

Question 9

Describe some of the NSAID adverse reactions:

Answer 9

Occur due to chronic COX inhibition. This is important because some prostaglandins are cytoprotective and so initial lesion results in overt damage.

NSAID may induce lesions by interacting with phosphotidyl choline and reduce the ability of gastric mucosa to protect itself from e.g. HCl.

Question 10

Describe some of the paracetamol adverse reactions:

Answer 10

Toxicity is due to saturation of detoxification pathways.

There is some dose dependency and predictability. Toxic metabolite is a quinoneimine that can react with sulfhydryl groups in critical cellular proteins.

Loss of intracellular calcium regulation disrupts mitochondrial function and leads to necrotic cell death.

Question 11

How does 6-Mercaptopurine relate to adverse drug reactions and toxicity, and gene predisposition?

Answer 11

Undergoes S-methylation catalysed by the enzyme TPMT. 89% of individuals have high TMPT activity, 11% have intermediate. ~1 in 300 patients are at high risk of potentially fatal haemopoietic toxicity due to accumulation of thioguanine nucleotides in haematopoietic tissues. Suitable therapy can be achieved by using 10-15 fold reduction in dose.

Question 12

Name a drug which undergoes a lack of detoxification, leading to secondary effects.

Answer 12

Perhexiline, an anti-angina drug that has cationic, amphiphilic properties. If it is not metabolised by CYP2D6, it will accumulate in lysosomes, resulting in hepatoxicity and neuropathy.

Question 13

Describe adverse reactions to penicillin:

Answer 13

Nausea, vomiting, epigastrci distress, diarrhoea, and black, hairy tongue.

Haemolytic anaemia, leucopoenia, thrombocytopenia, neuropathy, and nephropathy and infrequent reactions and are usually associated with high doses of parental penicillin.

Hypersensitivity reactions include:
Skin eruptions (ranging from maculopapular to exfoliative dermatitis).
Urticaria.
Reactions resembling serum sickness, including chills, fever, oedema, arthralgia, and prostration.
Laryngeal oedema.
Anaphylaxis.

Question 14

Describe the pharmacological interactions with ethanol (alcohol):

Answer 14

Ethanol can act at GABAa receptors. Drinking alcohol with sedatives, hypnotics and some anti-histamines can result in additive or synergistic effects. Outcome is too much sedation or come and death.

Question 15

Describe the pharmacokinetic interactions of Warfarin with cimetidine:

Answer 15

Has a narrow therapeutic index, so patients are stabilised on a dose. Cimetidine inhibits warfarin metabolism: Blood concentrations of warfarin are increased to toxic levels.

Question 16

Describe the pharmacokinetic interactions of Terfenadine with ketoconazole:

Answer 16

Metabolised to CYP to fexofenadine. Fatal interaction with ketoconazole, an inhibitor of CYP34A which increased plasma concentrations and revealed secondary pharmacology.

Interference with cardiac slow rectifier K+ channel, prolonging QT interval and quinidine-like effects on the heart.

Question 17

Describe the pharmacokinetic interactions of alcohol with paracetamol:

Answer 17

Ethanol induces the enzymes that bioactivates paracetamol. Chronic alcoholics may produce more of the toxic metabolite and have greater risk of hepatotoxicity.

Question 18

Describe the adverse effects and toxicitiy of Baycol/Lipobay, a statin:

Answer 18

Baycol (cerivastatin) lowers cholesterol, and is associated with the very rare symtoms of rhabdomyolysis, fatal cases have been reported with this brand than for other brands of statins.

Most frequently when used at higher doses, when used in elderly patients and particularly when used in combination with gemfibrozil, another lipid lowering drugs.

Question 19

How is ipecac used to decrease absorption of poisons?

Answer 19

Vomiting agent, consits of cephaeline, which stimulates the central vomiting centre and emetine, which activates sensory receptors in the proximal small intestine. Only useful over a short timeframe. Contraindicated for substances that could cause further injury during emesis e.g. caustic substances and hydrocarbons. Will affect the absorption of other antidotes (e.g. acetyl cystein and activated charcoal).

Question 20

How is activated charcoal used to deccrease absorption of poisons?

Answer 20

Drug may adsorb onto the charcoal and thereby prevent absorption in the first place. It may create a concentration gradient across the mesenteric vasculature, such that the drug or metabolite is eliminated faster. Useful for some drugs that undergo substantial enterohepatic recirculation, or small volume of distribution or low protein binding and are highly absorbed by charcoal. Dose usually 1-2g/kg orally or naso-gastric tube.

Question 21

How may iron and deferoxamine be used to neutralise the poisonous chemical?

Answer 21

Ingestion of a large amount of iron overwhelms gastrointestinal regulatory mechanisms resulting in massive iron absroption. When serum iron levels exceed the capacity of the binding protein, transferrin, sever toxicity may occur secondary to deposition of iron in soft tissues. Free iron causes toxicity by directly injuring the intestinal mucosa and generating oxygen free radicals.

Deferoxamine mesylate is an anti-dote for iron poisoning, which chelates the free iron to form feroxamine but it does not remove from proteins such as transferrin, ferritin, haemoglobin and cytochromes. Feroxamine is excreted unchanged in the urine.

Question 22

How may paracetamol and N-acetyl cystein be used to neutralise the chemical?

Answer 22

N-acetly cystein is an antidote for paracetamol overdose. NAC acts as a precursor for glutathione synthesis and so boosts the resynthesis of this vital intracellular agent and thus prevents liver damage.

Question 23

How can salicylate and urinary alkalisation be used to enhance elimination?

Answer 23

Aspirin is readily hydrolysed to salicylate, which stimulates the medullary respiratory centre, producing hyperventilation, respiratory alkalosis and eventually metabolic acidosis. Uncouples oxidative phosphorylation increasing gluconeogenesis and lipid metabolism, produces tinnitus, nausia, vomiting, ataxia, coma and hyperthermia.

Sodium bicarbonate can be used to raise the urinary pH>7.5, weak acids with pKa<7 that undergoes significant urinary excretion become trapped in the kidney tubular fluid.

Can also be used for phenobarbital, chlorpropamide and 2,4-dichlorophenoxyacetic acid (herbicide). Used in conjunction with activated charcoal.

Question 24

Describe pharmacodynamic intervention of heroin and naloxone:

Answer 24

Overdoses of heroin frequent when used in conjunction with alcohol, benzodiazepines, cannabis, amphetamine etc. or when a purer form is used. Many routes of administration.

Heroins typical nacrotic effects because it is converted to morphine, associated with coma, seizures and delayed encephalopathy in overdose. Letahl dose is hard to define.

Naloxone, antagonist at the mu, kappa and delta opiod recpetors, it may be necessary to administer by i.m., s.c., endotracheal or intralingual routes.

Naloxone has a shorter half life than heroin, so replase may occur. May also precipitate heroin withdrawal.

Question 25

Describe how wafarin and vitamin K may be used to replace acitivity:

Answer 25

Warfarin is used in the prophylaxis and treatment of venous thrombosis and pulmonary embolism, inhibits vitamin K dependent coagulation factors, results in a sequential depression of 'factors' activity. Vitamin K reductase and vitamin K epoxide reductase are blocked. Vitamin K therapy may be required for long time until prothrombin (coagulation) returns to normal.

Question 26

Describe organophosphates toxicity:

Answer 26

Used extensively in agriculture, industrail and terrorism. Has nicotinic effects, CNS effects and muscarinic effects. Organophosphate inhibits acetylcholinesterase, so it cannot be readily hydrolysed and depletes cholinergic acitivity.

Question 27

How may pralidoxime be used to regenerate the target affected by organophosphates?

Answer 27

Pralidoxime can remove the phosphate group from the cholinesterase enzyme to regenerate catalytic activity, effects at nicotinic greater than muscarinic. Effect is great at erythrocytic esterase is given soon after toxicity. Reactivation of plasma cholinestease activity is minimal.

Question 28

List two types of anti-inflammatory steorids:

Answer 28

Steroids- e.g. endogenous steroids include cortisol, progesterone, which act via intracellular receptors to regulate gene transcription. Glucocorticoids- e.g. adrenal steroids, have immunosupressive effects.

Question 29

Describe the pro-inflammatory effects of glucocorticoids:

Answer 29

Pro-inflammatory genes are downregulated: Pro-inflammatory cytokines, COX-2, phospholipase A2 (PLA2), cell-adhesion molecules, endothelins, inducible nitric oxide synthase (iNOS). Genes that are up-regulated by gluccocorticoids: Il-10/Il-4 (anti-inflammatory cytokines), lipocortins/annexins (PLA2 inhibitor).

Question 30

What are the three types of GC preparations:

Answer 30

Oral- e.g. prednistone, methyl prednisone, predinsolone, dexamethasone. Inhalable- e.g. fluticasone, beclomathasone. Topical- e.g. prednisone, prednisolone, dexamethasone.

Question 31

How do NSAIDs relate to prostaglandins?

Answer 31

Non-steroidal anti-inflammatory drugs, not narcotic drugs. Inhibit prostaglandin (PHG2) biosynthesis via COX enzymes. Taken to reduce pain (analgesic), swelling, inflammation and fever (anti-pyretic). Can have significant side-effects, rarely fatal.

Question 32

List four common NSAIDs and what they are used for:

Answer 32

Aspirin, ibuprofen, diclofenac and naproxen. They are commonly used for post-operatively, head-ache, migraine, pyrexia (fever), menstruation pain, tooth ache.

Question 33

How do NSAIDs work?

Answer 33

They inhibit block the enzymatic acitivity of cyclooxygenase (COX).

Question 34

Describe the pathways of prostanoid biosynthesis:

Answer 34

Glycerophospholipids and converted into arachindonic acid by phospholipases. COX-1 and COX-2 are inhibited aspirin ibuprofin.

Question 35

Describe the effects of aspirin on inflammation:

Answer 35

This is acetylsalicyclic acid and irreversibly inhibits COX-1. Effective inhibitor of PG-mediated pain. Also inhibits TXA2 release by platelets (anti-thrombotic).

Question 36

What are some side effects of aspirin:

Answer 36

Associated with significant GI-side effects. Caution if prone to GI ulceration or gastritis.

Question 37

Describe the effects of paracetamol on inflammation:

Answer 37

Good anti-pyretic and anagesic, ineffective anti-inflammatory indications. Mechanism is that it reduced prostaglandin sysnthesis and is a relatively weak inhibitors of COX.

Question 38

What are some side effects of paracetamol?

Answer 38

Metabolised in the liver to a toxic metabolite which can cause serious liver damage. Has a low therapeutic index, so 10x adult dose can be fatal.

Question 39

Describe some of the general adverse effects of NSAIDS:

Answer 39

Gastric upset, ulcers, GI bleeded, renal complications/impairment, increased clotting time, not for use following heart surgey, asthmatics can have an allergic type response to NSAIDs that may be fatal, hepatic toxicity, skin rashes, early pregnancy loss, fertility complications. There are all largely associated with COX-1 inhibition.

Question 40

Name some second generation COX-2 inhibitors, and explain their advantages:

Answer 40

Celecoxib and rofecoxib. Reduced GI irritation and ulcer rate, with similar efficacy to non-selective NSAIDs, useful for long term use in treatment of chronic conditions, also exhibit good short-term pain relief profile.

Question 41

Describe the unexpected adverse effects of COX-2 selective inhibitors:

Answer 41

Celecoxib associated with acute cardiovascular events. Rofecoxib increases the risk of thrombolytic events, may relate to inhibition of COX-2 derived prostacyclin, increase BP and some renal impairment.

Question 42

Name two attempts to treat malaria using natural substances:

Answer 42

Qinghaosu plant and cinchona bark.

Question 43

Describe the use of quinine as an anti-malarial:

Answer 43

This is the main alkaloid in the bark of the cinchona tree (quinidine also found, but not used because it causes long QT syndrome). This is active against erythrocytic stages of the parasites, and its mode of action may involve binding to DNA, stopping synthesis of nucleic acids, inhibition of haem digestion.

Question 44

Describe chloroquinine, and synthetic anti-malarial:

Answer 44

Based on the quinine structure, accumulates in the food vacuole of the parasite, interferes with haem digestion, effective against blood stages and is relatively safe. Resistance is a problem.

Question 45

Describe amodiaquine and synthetic malarials:

Answer 45

Effective against blood stages, even in some choloroquine-resistant strains of P.falciparum. Has an unacceptable risk of toxicity towards granulocytes and the liver.

Question 46

Describe primaquine and synthetic malarials:

Answer 46

Active against liver stages of P.vivax. Mechanism of action may involve oxidative stress in the parasite. Effective against other stages of the life cycle, but it is too toxic.

Question 47

Describe mefloquine and synthetic malarians:

Answer 47

Minor side effects (nausea, dizziness, difficulty sleeping) do not last long and do not require stopping the drug. Not recommended for use if a known allergy to melfoquine, a history of epilepsy, severe psychiatric disorders, or cardiac conduction abnormalities.

Question 48

Describe pyronaridine and synthetic malarias:

Answer 48

Pyronaridine, potential replacement for choloroquine. Requires new routes for synthesis.

Question 49

Describe proguanil and synthetic malarias:

Answer 49

It is a prodrug that requires metabolic activation to cycloguanil. Effective against erythrocytic and liver stages of P. falciparum. Inhibits dihydrofolate reductase and hence DNA synthesis. Used as a prophylactic, but is too slow for a cure.

Question 50

Describe sulfonamides/sulfone and synthetic malarias:

Answer 50

Sulfones (Dapsone) and sulfonamides (Sylfasoxine) inhibit dihydropteroate synthase, involved in folate and hence pyrimidine and DNA synthesis. They act too slowly on their own, but act synergistically with proguanil and pyrimethamine because they act different parts of the same pathway, always used in combination therapy.

Question 51

Describe artemisinin derivatives and synthetic malarias:

Answer 51

Artemisinin derivatives are highly effective, rapid, have limited toxicity, CHEAP. However, inappropriate use may lead to the development of resistance and untoward toxicity.

Question 52

Describe artemisinin combination therapy (ACT):

Answer 52

Can be used with lumefantrine, amodiaquine, mefloquine, sulfadoxine/pryrimethamine and artemether.

Question 53

Describe the risk factor artsunates:

Answer 53

Counterfeit artesunate has been found in SEA, caused deaths. May result in appropriate dose levels and the emergence of resistance.

Question 54

What are the types of antibiotics with examples, and what do they do?

Answer 54

Bacteriostatic- prevent or inhibit bacterial replication/division, but do not actually kill. Stop or slow growth so the immune system eventually kills the bacteria. Sulphonamides (trimethoprim), tetracyclines, chloraphenicol, macrolides (erythromycin). Bactericidal- these actually kill bacteria. Penicillins, cephalosporins (B-lactams), aminoglycosides and quinolones.

Question 55

Describe the mechanism of action of inhibition of protein synthesis by B-lactams (anti-biotics):

Answer 55

Several majar classes of antibiotics act prinicipally by inhibiting bacterial protein synthesis, act on the bacterial ribosome (70S) to inhibit bacterial protein synthesis with little effect on mammalian cell protein synthesis. This is because the bacterial ribosome differs in several ways from the eukaryotic ribsome (80S) i.e. example of selective toxicity.

Question 56

Describe the mechanism of action of inhibition of bacterial cell wall synthesis by anti-biotics:

Answer 56

Bacterial cell walls consist of a complex polymeric material called peptidoglucan, containing both sugars and amino acid cross-links. B-lactam antibiotics inhibit the transpeptidase enzymes involved in crosslinking during the formation of the cell wall.

Question 57

Describe the mechanism of action of inhibition of DNA synthesis by anti-biotics (anti-folates):

Answer 57

Bacteria and human cells require folic acid as a cofactor for nucleic acid synthesis. Bacterial synthesise their folic acid starting with PABA from the diet. Sulphonamides are analogues of PAVA and compete with PABA to inhibit folic acid synthesis.

Question 58

Describe the action of trimethoprim and sulphonamide:

Answer 58

Trimethoprim inhibits DHFR, the next enzyme along the folate synthetic pathway. Sulphonamide + trimethoprim= cotrimoxazole. Less chance of resitance.

Question 59

Describe the action of inhibition of DNA synthesis by quionolones, such as fluoroquinolone:

Answer 59

Inhibit the bacterial enzyme DNa gyrase (topoisomerase II) which changes the 3D structure of DNA, necessary for its replication.

Question 60

Describe the effect of tetracyclin on bactrial uptake and drug efflux?

Answer 60

This has a lack of failitated uptake, so has reduced bacterial uptake and enhanced efflux of drug.

Question 61

What is the effect of B-lactamase on penicillin?

Answer 61

It produces and enzyme which inactivates the drug and causes destruction of penicllin.

Question 62

How can B-lactamase resistance be overcome?

Answer 62

With a B-lactamase inhibitor, such as clavulanic acid which is a potent inhibtior.

Question 63

Why are amoxycillin and clavulanic acid used together as augmentin?

Answer 63

To overcome resitance to B-lactams.

Question 64

Describe why vancomycin may be used:

Answer 64

As a last resort against hospital-acquired superbugs such as MRSA.

Question 65

Describe an example of nucleoside reverse transcriptase inhibitors:

Answer 65

Zidovudine, originally developed as an anti-cancer agent. It is an effetctive anti-retroviral, particularly in combination with other drugs, but subject to rapid resistance. It is selective for viral reverse transcriptase and does not affect mammalian DNA polymerase.

Question 66

Name some adverse effects of zidovudine:

Answer 66

Associated with haematological toxicity, pancreatitis, liver damage and severe anaemia.

Question 67

Describe the mechanism of action of zidovudine:

Answer 67

It is a prodrug which enters the cell and is triple phosphorylated by various cellular nucleoside kinases before it can react with the viral reverse transcriptase to halt DNA synthesis.

Question 68

Name an example of a non-nucleoside reverse transcriptase inhibitors:

Answer 68

Nevirapine, which has serious adverse effects including life-threatening skin reactions and liver damage. Used by themselves, resistance develops quickly. Useful as part of anti-HIV combination therapy (HAART).

Question 69

Name an example of a protease inhibitors:

Answer 69

Saquinavir. Blocks the processing of viral proteins, and thus the viron assembly. They bind to the active site of the protease inhibiting its function and leaving proteins uncleaved and inactive. Used mostly in combination therapy. Side effects are nausea, vomiting and diarrhoea.

Question 70

Name a first fusion inhibitor:

Answer 70

Enfuvirtide, which inhibits the entry of HIV into the host CD4 lymphocytes. Can have flu like symptoms, GI effects, mood alterations, headaches and dizziness, hypersensitivity reactions.

Question 71

How can cytokine therapy be used as an anti-HIV therapy?

Answer 71

IFN-a, glycoprotein, augments the host immune system and target cell by killing lymphocutes and inhibits viral replication in infected cells. Various recombinant forms of interferons are approved to treat viral hepatitis. Needs to be admisitered subcutaneously at least 3times/week in the treatment of chronic hepatitis C.

Question 72

List some adverse effects of interferon-a:

Answer 72

Fatigue, depression, flu-like symptoms, nausea, diarrhoea and appetite loss.

Question 73

Describe cell cycle-specific agents as anti-cancer drugs, with examples:

Answer 73

Act during a certain phase of cell cycle, and G0 cells appear to be unaffected. Antimetabolites (methotrexate, 5-fluorouracil), antimicrotubules (vince alkaloids) and podophyllin alkaloids (etopside).

Question 74

Describe cell cycle-nonspecific agents, with examples:

Answer 74

Kill both dividing and G0 cells, although dividing cells are usually more sensitive. Alkylating agents (cyclophosphamide), antheracycline antibiotics (doxorubicin) and platinum drugs.

Question 75

Describe how alkylating agents may be used in anti-cancer therapy:

Answer 75

Act by transferring alkyl groups to cellular consituents such as DNA, RNA and proteins. Cyclophosphamide, platinum drugs.

Question 76

Describe how antimetabolites may be used in anti-cancer therapy:

Answer 76

Inhibit DNA synthesis similar structure to endogenous molecules (folates, purine and pyrmidines) required for nucleic acid synthesis. Methotrexate, 5-fluorouracil.

Question 77

Descibre how topoisomerase interactive drugs may be used in anti-cancer therapy:

Answer 77

Induce DNA damage by inhibiting topoisomerase action. Ectoposide.

Question 78

Describe how antimicrotubule drugs may be used in anti-cancer therapy:

Answer 78

Induce metaphase arrest by disrupting microtubules and mitotic spindle. Vincristine.

Question 79

Describe how hormonal agents may be used in anti-cancer therapy:

Answer 79

Tamoxifen- antioestrogen for breast cancer. | Antiandrogens- prostate cancer.

Question 80

Describe how targeted therapies may be used in anti-cancer therapy:

Answer 80

Target specific molecules involved in cancer progression. Transtuzumab (herceptin) for Her-2 positive positive breast cancer.

Question 81

Name a drug type used to reduce heart rate:

Answer 81

B1 adrenergic antagonists.

Question 82

Name two drugs used to widen blood vessels:

Answer 82

Doxazosin- antagonise the actions of vasoconstrictors (e.g. a1 adrenoreceptor blockers). Nifedipine- Ca2+ channel blockers.

Question 83

Name two drugs used to reduce blood volume, and their drug class:

Answer 83

These are diuretics which increase naturesis to help the kidneys eliminate excess salt and water from the blood. Furosemide, bendoflumethiazide.

Question 84

Name a drug class used to reduce the thickness of blood:

Answer 84

Anticoagulants.

Question 85

Name two drug types which can prevent a further loss of compliance:

Answer 85

Statins and ACE inhibitors.

Question 86

Describe how prazosin is used as an anti-hypertensive:

Answer 86

alpha1 antagonist, induces vasodilation.

Question 87

Describe how captopril is used as an anti-hypertensive:

Answer 87

beta-1 antagonist, decrease the rate and force of contraction thus cardiac output, decreasing renin production.

Question 88

Describe how nifedipine is used as an anti-hypertensive:

Answer 88

Ca2+ channel blocker, induces vasodilation.

Question 89

Describe how frusemide is used as an anti-hypertensive:

Answer 89

Loop diuretic (inhibits Na reansorption), which influences blood volume.

Question 90

What drugs are recommended as anti-hypertensives for people who have raised or normal plasma renin:

Answer 90

ACE inhibitors or AT1 antagonists.

Question 91

What drugs are recommended as anti-hypertensives for people who are elderly who are likely to have low plasma renin.

Answer 91

ACE inhibitor/diuretic or ACE inhibitor/Ca2+ channel blocker combination.

Question 92

Which drugs are least tolerated as hypertensives?

Answer 92

B-blockers are less well tolerated than ACE inhibitors or AT1 antagonists.

Question 93

In what case might Methyldopa be used as an anti-hypertensive:

Answer 93

During pregnancy as ACE inhibitors, sartans and B-blockers contraindicated during pregnancy.

Question 94

Describe why humulin may be given to people?

Answer 94

If they have insulin-dependent diabetes as it is better tolerated than animal insulins, and less risk of diseases through animal products.

Question 95

Describe the use of humalog in insulin therapy:

Answer 95

Very fast acting. Lowers blood sugars 45-90 minutes. Stops acting after 3-4 hours.

Question 96

Describe the use of humalin in insulin therapy:

Answer 96

Fast acting/ regular. Lower blood sugars 2-5 hours. Stops acting after 5-8 hours.

Question 97

Describe the use of NPH/Lente in insulin therapy:

Answer 97

Intermediate acting. Lower blood sugars 6-12 hours. Stops acting after 20-24 hours.

Question 98

Describe the use of ultalente in insulin therapy:

Answer 98

Long acting. Prolongs entry of insulin into blood stream for 4-6 hours. Stops acting after 28 hours.

Question 99

Describe the use of glargine in insulin therapy:

Answer 99

Ultra-long lasting. | Work at relatively constant rate for 24 hours.

Question 100

Describe how oral hypoglycemic agents may be used in non-insulin dependent diabetes treatment (sulfonyureas):

Answer 100

Sulfonylueas such as tolbutamide, used to increase insulin release by blocking KAPT channels, causing depolarisation of the B-cells and increased insulin release. Also shown to increase insulin sensitivity and stimulate glucose uptake into muscle and fat cells.

Question 101

Describe how oral hypoglycemic agents may be used in non-insulin dependent diabetes treatment (Meglitinides):

Answer 101

Meglitinides have the same mechanism of action as sulfonyureas, but bind at a different KATP binding site, and work on the pancreas to promote insulin secretion.

Question 102

Describe how oral hypoglycemic agents may be used in non-insulin dependent diabetes treatment (biguanides):

Answer 102

Biguanides e.g. metformin reduce hepatic glucose production and activate AMP-activated kinase, which has an important role in insulin signalling in the liver. Increase glucose uptake and utilisation in skeletal muscle (reduce insulin resistance). used alone or in combination with sulfonylurea drugs.

Question 103

Describe statins, and give four examples:

Answer 103

Class of drug used to prevent coronary heart disease by improving the lipid profile of patients at risk. They are reversible inhibitors of HMG-CoA reductase. Atorvastatin, simvastatin, pravastatin and rosuvastatin.

Question 104

Describe the mechanism of action of statins:

Answer 104

HMG-CoA reductase inhibition, leads to decreased mevalonate biosynthesis, causing decreased cholesterol synthesis, increased LDL uptake (primary mode of action) and non lipid-mediated mechanisms (indirect actions).These may include alterested post-translational modifications of proteins and altered localisation and activity of proteins. Alternative unrelated mechanisms may have independent actions to cause anti-inflammatory effects and reduced bone resorption.

Question 105

Describe how atorvastatin works:

Answer 105

Lipophilic, crosses by passive diffusion and mroe effective/potent lipid-lowering drug of the first generation of statins.

Question 106

Describe how simvastatin works:

Answer 106

Lipophilic, crosses by passive diffusion, prodrug that is metabolised in the liver to the active B-hydroxy fatty acid form.

Question 107

Describe how pravastatin works:

Answer 107

Hydrophilic, actively pumped into the hepatocyte, loer risk of myopathies and fewer significant drug interactions (not CYP450 substrate). Longer half-life but lower protein binding profile.

Question 108

Describe the significant drug interactions which may occur with statins:

Answer 108

CYP inhibitors (e.g. cyclosporin, ketoconazole, erythromycin, verapamil, protease inhibitors) can cause elevated levels and toxicity. Grapefruit juice can also be a CYP3A4 inhibitor. Coadministration with other lipid-lowering drugs such as fibrates and niacin can cause myopathy (fibrates inhibit statin-acid glucuronidation). CYP2D6 polymorphisms may also affect statin metabolism.

Question 109

List some of the adverse effects of statins:

Answer 109

``` Hepatotoxicity Myositis (rhabdomyolysis) Angio-oedema Dementia (reversible) Cancer (breast) Peripheral neuropathy Insomnia.headache/memory impairment Rash/flu symptoms GI disturbance Elevated liver ALT release (not usually associated with the signs of hepatitis) ```

Question 110

Describe some clinical uses of statins not related directly to lowering cholesterol:

Answer 110

Reduced rate of bone resorption preventing bone loss/osteoprorsis (reduced fracture incidence). Preventing Alzheimer's disease (reduced amyloid plaque formation). Anti-inflammatory agent. Lowering blood pressure. Reducing risk of deep vein thrombosis and stroke, and enhancing fibrinolysis. Reduced risk of cancer of the bowel.