All Pharmacology Flashcards

Question

Explain the mechanism of action of Noradrenaline.

Answer 1

Norepinephrine is a precurser of epinephrine secreted by the adrenal medulla. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. Norepinephrine functions as a peripheral vasoconstrictor by acting on both alpha-1 and a-2 adrenergic receptors. It is also an inotropic stimulator of the heart and dilator of coronary arteries as a result of it's activity at the beta-adrenergic receptors.

Answer 2

Verapamil is a Class IV anti-arrythmia agent (a calcium channel blocker). Verapamil inhibits voltage-dependent calcium channels. In the heart it blocks the L-type calcium channels causing a reduction in ionotropy and chronotropy, reducing heart rate and blood pressure. There are two enantiomers of Verapamil. The R-enantiomer is more effective at reducing blood pressure compared to the S-enantiomer. However, the S-enantiomer is 20 times more potent than the R-enantiomer at prolonging the PR interval in treating arrhythmias. Verapamil is still used (not commonly) but it can only be given via IV. Diltiazem more common as a non-dihydropyridine Calcium Channel Blocker, but this is not available via IV (although it is in the USA).

Answer 3

Chlorpromazine is a phenothiazine based antipsychotic. Chlorpromazine is an antagonist on dopaminergic-receptors (subtypes D1, D2, D3 and D4), serotonergic-receptors (5-HT1 and 5-HT2), histaminergic-receptors (H1-receptors), alpha1/alpha2-receptors and muscarinic (cholinergic) M1/M2-receptors. Chlorpromazine's antipsychotic actions are due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup Chlorpromazine is now used less due to longterm side effects. Prochlorperazine is preferentially used. It is from the same class of drug.

Answer 4

Domperidone inhibits the dopamine receptor (D2 and D3) in the chemoreceptor trigger zone, located just outside the blood brain barrier. Domperidone also acts as a gastrointestinal emptying (delayed) adjunct and peristaltic stimulant.

Answer 5

Metoclopramide is a dopamine receptor antagonist. Therefore it raises the threshold of activity in the chemoreceptor trigger zone and decreases the input from afferent visceral nerves. In addition high doses of metoclopramide can antagonize 5-hydroxytryptamine (5-HT) receptors in the peripheral nervous system. Metoclopramide can also inhibit gastric smooth muscle relaxation produced by dopamine, therefore increasing cholinergic response of the gastrointestinal smooth muscle. Furthermore it can decrease reflux into the oesophagus by increasing the resting pressure of the lower oesophageal sphincter and improves acid clearance from the oesophagus by increasing amplitude of oesophageal peristaltic contractions.

Answer 6

Perhpenazine is a phenothiazine. Perphenazine is 10 to 15 times as potent as chlorpromazine. Perphenazine inhibits the dopamine D1 and dopamine D2 receptors. The mechanism of the anti-emetic effect is due predominantly to blockage of the dopamine D2 neurotransmitter receptors in the chemoreceptor trigger zone and vomiting centre. Perphenazine also binds the alpha andrenergic receptor that activate a phosphatidylinositol-calcium second messenger system. Perphenazine is a piperazinyl phenothiazine, and has a greater behavioural potency than other phenothiazine derivatives.

Answer 7

Vomiting is a protective mechanism for removing irritant/harmful substances from the upper GI tract. It is controlled by the vomiting centre in the medulla region of the brain, which includes the chemotrigger zone (CTZ). The vomiting centre possesses neurons rich in muscarinic cholinergic and histamine containing synapses. The histamine receptors are especially important in transmission of vomiting signals from the vestibular apparatus, induced by motion sickness to CTZ and then the vomiting centre. Competitive antagonists at histamine H1 receptors may be divided into sedating or non-sedating agents.

Answer 8

Cyclizine is antiemetic agent used in the prevention and treatment of nausea, associated with motion sickness. Additionally, it has been used in the management of vertigo in diseases affecting the vestibular apparatus. Its mechanism of action is not understood, but it possesses anticholinergic, antihistaminic, central nervous system depressant, and local anaesthetic effects.

Answer 9

Cinnarizine inhibits dopamine D2 receptors, histamine H1 receptors, muscarinic acetylcholine receptors, and also vascular smooth muscle contraction via by blockage of L-type and T-type voltage gated calcium channels.

Answer 10

Promethazine is a H1-antagonist with anticholinergic, sedative, and antiemetic effects and some local anaesthetic properties.

Answer 11

Hyoscine is a muscarinic antagonist. Scopolamine is a muscarinic antagonist that blocks the muscarinic acetylcholine receptors. It is used to prevent motion sickness. It is thought Ach plays an important role in communication between the vestibular system and the vomiting centre. Therefore by blocking this communication there is a reduction in the activity of the vomiting centre and a reduction in nausea. However, as Scopolamine also may work directly on the vomiting centre its precise mechanism of action is unclear. Scopolamine works best before the onset of motion sickness.

Answer 12

Ondansetron is a selective serotonin 5-HT3 receptor antagonist with low affinity for dopamine receptors. The serotonin 5-HT3 receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the CTZ. The antiemetic activity of the drug is via inhibition of 5-HT3 receptors present both centrally (CTZ) and peripherally (GI tract). This inhibition of 5-HT3 receptors in turn inhibits the visceral afferent stimulation of the vomiting center, and serotonin activity in the CTZ. The drug of choice for the 5-HT3 pathway is now **Granisetron** rather than Ondansetron

Answer 13

The analgesic, antipyretic, and anti-inflammatory effects of acetylsalicylic acid are due to actions by both the acetyl and the salicylate portions of the intact molecule as well as by the active salicylate metabolite. Acetylsalicylic acid directly and irreversibly inhibits the activity of both types of cyclooxygenase (COX-1 and COX-2) to decrease the formation of precursors of prostaglandins and thromboxanes from arachidonic acid. Acetylsalicylic acid's antirheumatic actions are a result of its analgesic and anti-inflammatory mechanisms. Irreversible inhibition of COX prevents the formation of the aggregating agent thromboxane A2 in platelets. Platelets cannot produce more COX enzyme and thus, the effects of aspirin persist for the life of the exposed platelets (7-10 days).

Answer 14

Ibuprofen is a reversible inhibitor of the COX enzyme. Its pharmacological effects are believed to be due to inhibition cylooxygenase-2 (COX-2) which decreases the synthesis of prostaglandins involved in mediating inflammation, pain, fever and swelling. The antipyretic effects may be due to action on the hypothalamus, resulting in an increased peripheral blood flow, vasodilation, and subsequent heat dissipation.

Answer 15

The mechanism of action of naproxen, like that of other NSAIDs, is believed to be associated with the inhibition of cyclooxygenase activity. Naproxen has analgesic and antipyretic properties.

Answer 16

Proton pump inhibitors target gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell. This inhibition block transport of H+ ions into the stomach lumen and therefore increases the pH of the stomach contents. Inhibits gastric acid secretion and is indicated in the treatment of gastroesophageal reflux disease (GERD), and H. pylori eradication to reduce the risk of duodenal ulcer recurrence. Esomeprazole belongs to a new class of antisecretory compounds, the substituted benzimidazoles that do not exhibit anticholinergic or H2 histamine antagonistic properties, but that target specifically the H+/K+ ATPase in the gastric parietal cell. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus.

Answer 17

Proton pump inhibitors target gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell. This inhibition block transport of H+ ions into the stomach lumen and therefore increases the pH of the stomach contents. The anti-secretory effect of omeprazole occurs within one hour of oral dosing with a maximal effect within two hours. However the effect is long lasting with an approximate 50% inhibition of acid secretion and duration of inhibition lasting upto 72 hours. This is due to prolonged irreversible binding to the parietal H+/K+ ATPase enzyme. When the drug has been discontinued, secretory activity will return to baseline over 3-5 days. Systemic effects of omeprazole in the CNS, cardiovascular and respiratory systems have not been found to date.

Answer 18

**Histamine H2 antagonists: Ranitidine** is a competitive inhibitor of histamine on parietal cells in the stomach, decreasing acid production. It is an example of an inverse agonists rather than a true receptor antagonists. Rantidine reduces stomach acid by blocking histamine binding. Reduce the effect of other substances that promote acid secretion (such as gastrin and acetylcholine) on parietal cells. These drugs are used in the treatment of dyspepsia, however their use has waned since the advent of the more effective proton pump inhibitors.

Answer 19

Antacids can neutralize gastric acid and reduce acid delivery to the duodenum. They might be useful for treatment against peptic ulcers (although PPIs are much more likely to be used). There are different mechanisms by which they could aide healing of peptic ulcers, 1) Aluminum hydroxide binds growth factors, possibly serving to deliver growth factors to injured mucosa. 2) Antacids promote angiogenesis in injured mucosa 3) Antacids bind bile acids and also inhibit peptic activity. 4) Heavy metals suppress, but generally do not eradicate, H. pylori.

Answer 20

Misoprostol is used for the treatment and prevention of stomach ulcers induced by NSAIDs. Misoprostol inhibits gastric acid secretion by binding to the prostaglandin receptor on the parietal cell. This receptor inhibits the activity of adenylate cyclase, reducing cAMP levels, and the downstream protein kinase activity. This reduces the availability of the proton pump at the surface reducing acid secretion. In addition Misoprostol can also 1) Increased secretion of bicarbonate. 2) Reduce the volume and pepsin content of the gastric secretions. 3) Prevent harmful agents from disrupting the tight junctions between the epithelial cells which stops the subsequent back diffusion of H+ ions into the gastric mucosa. 4) Increase the thickness of mucus layer. 5) Enhanced mucosal blood flow as a result of direct vasodilatation. 6) Stabilization of tissue lysozymes/vascular endothelium. 7) Improvement of mucosal regeneration capacity 8) Replacement of prostaglandins that have been depleted.

Answer 21

Amoxicillin is a beta-lactam antibiotic. Amoxicillin is active against a wide range of Gram-positive, and a limited range of Gram-negative organisms. Amoxicillin binds to penicillin-binding protein 1A (PBP-1A) located inside the bacterial cell well. This inactivation of PBP-1A prevents the cross-linking of two linear peptidoglycan strands, inhibiting bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins. Amoxicillin is susceptible to degradation by β-lactamase-producing bacteria, and so may be given with clavulanic acid to increase its susceptibility. Amoxicillin can be combined with clavulanic acid, a β-lactamase inhibitor, to overcome bacterial antibiotic resistance mediated through β-lactamase production.

Answer 22

Clarithromycin is a macrolide antibiotic. Clarithromycin activity includes many (Staphylococcus aureus, S. pneumoniae, and S. pyogenes) aerobic (Gram-negative and gram positive) bacteria (Haemophilus influenzae, H. parainfluenzae, and Moraxella catarrhalis), many anaerobic bacteria, and some mycobacteria. Clarithromycin penetrates the bacteria cell wall and reversibly binds to domain V of the 23S ribosomal RNA of the 50S subunit of the bacterial ribosome, blocking translocation of aminoacyl transfer-RNA and polypeptide synthesis. Clarithromycin also inhibits the hepatic microsomal CYP3A4 isoenzyme and P-glycoprotein, an energy-dependent drug efflux pump.

Answer 23

A nitroimidazole antibacterial and antiprotozoal. Metronidazole, is used against protozoa such as Trichomonas vaginalis, amebiasis, and giardiasis. Metronidazole is extremely effective against anaerobic bacterial infections and is also used to treat Crohn's disease, antibiotic-associated diarrhea, and rosacea. Metronidazole is a prodrug. Unionized metronidazole is taken up by anaerobic bacteria, and is then reduced to its active form. This reduced metronidazole then covalently binds to DNA, disrupting its helical structure, inhibiting bacterial nucleic acid synthesis and resulting in bacterial cell death.

Answer 24

Thalidomide is an immunomodulatory agent can also have anti-angiogenic effects. Its mechanism of action is not well understood, but it is thought that its immune modulation is due to changes in the concentration of TNFa, whilst it can also affect VEGF leading to its effects on the blood vessels. It has teratogenic effects on humans.

Answer 25

Orlistat is a lipase inhibitor. Orlistat is a reversible inhibitor of gastric and pancreatic lipases. The inactivated enzymes cannot hydrolyze triglycerides into absorbable free fatty acids and monoglycerides. Therefore as fat absorption is reduced this can have a positive effect on weight control. At the recommended therapeutic dose, orlistat inhibits dietary fat absorption by approximately 30%. As some vitamins are fat soluble, there absorption can be affected and as such orlistat should be taken with fatty meals, and a multivitamin tablet containing these vitamins (D E K and beta-carotene).

Answer 26

It is a HMG-CoA reductase inhibitor. Atorvastatin, is a selective, competitive HMG-CoA reductase inhibitor. HMG-CoA reductase converts HMG-CoA to mevalonate in the cholesterol biosynthesis pathway. This results in a subsequent decrease in hepatic cholesterol levels, stimulating upregulation of hepatic LDL-C receptors, and therefore increasing hepatic uptake of LDL-C. As a consequence serum LDL-C concentrations are reduced. The total cholesterol to HDL-C ratio is a strong predictor of coronary artery disease and high ratios are associated with higher risk of disease. Therefore, atorvastatin by reducing total cholesterol it reduces the risk of cardiovascular morbidity and mortality. Atorvastatin has a long half-life and hepatic selectivity, which gives it greater LDL-lowering potency than other HMG-CoA reductase inhibitors.

Answer 27

Bezafibrate is an antilipemic agent. Bezafibrate is an antilipemic agent that lowers cholesterol and triglycerides via activation of triglyceride lipases (lipoprotein lipase and hepatic lipoprotein lipase) and reduction of cholesterol biosynthesis. These lipases are involved in the catabolism of triglyceride-rich lipoproteins. Therefore elevated VLDL and LDL are reduced leading to formation of increased concentrations of HDL precursors leading to an increase in HDL-levels. Elevated fibrinogen is an important risk-factor, in the development of atheroma due to its role in blood flow and viscosity, and in thrombus development and lysability. Bezafibrate can cause a significant decrease in elevated plasma fibrinogen levels.

Answer 28

Hydroxocobalamin is a synthetic form of vitamin B12 (a coenzyme). Hydroxocobalamin is a precursor of two cofactors or vitamins (Vitamin B12 and Methylcobalamin). Vitamin B12 acts as a coenzyme for various metabolic functions, including fat and carbohydrate metabolism and protein synthesis. As such it is important in growth, cell proliferation as well as myelin synthesis. Therefore deficiency of vitamin B12 can cause neurological lesions. Methylcobalamin, however is required for the metabolism of folic acid, deficiency of which leads to reduced DNA synthesis.

Answer 29

Ferrous Sulfate (FeII) is taken in order to replace body iron and therefore maintain red blood cell production. If the patient is lacking iron, this can lead to iron-deficiency anaemia.

Answer 30

Folic acid is found in mushrooms, spinach, and green leaves. Folic acid, is converted to tetrahydrofolic acid and methyltetrahydrofolate by dihydrofolate reductase. Tetrahydrofolic acid and methyltetrahydrofolate are transported across cells by receptor-mediated endocytosis, as they are required to maintain normal erythropoiesis, synthesize purine and thymidylate nucleic acids, interconvert amino acids, methylate tRNA, and generate and use formate. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia.

Answer 31

It is an antagonist of purine metabolism. Azathioprine acts to inhibit purine synthesis, and therefore inhibit DNA and RNA synthesis leading to an inhibition of cell proliferation. It is used to treat auto-immune diseases, and also transplant recipients. Its mechanism of action is probably incorporation of thiopurine analogues into the DNA structure, causing chain termination and cytotoxicity. Its most severe side effect is bone marrow suppression, and it should not be given in conjunction with purine analogues such as allopurinol. The enzyme thiopurine S-methyltransferase (TPMT) deactivates 6-mercaptopurine. Genetic polymorphisms of TPMT can lead to excessive drug toxicity, thus assay of serum TPMT may be useful to prevent this complication. Blood tests and monitoring for signs of myelosuppression are essential in long-term treatment with azathioprine.

Answer 32

Cyclosporin is an immunosupressive agent (a cyclophillin binder). Cyclosporin is used as an immunosuppressive agent, used for the prophylaxis of graft rejection in organ and tissue transplantation. It binds to cyclophilin, which causes the inhibition of calcineurin, which is responsible for activating the transcription of IL-2. This causes a reversible inhibition of immunocompetent lymphocytes, in the G0 or G1 phase of the cell cycle. T-lymphocytes are preferentially inhibited, with the T1-helper lymphocyte is the main target, although it may also inhibit the T1-suppressor cell.

Answer 33

Clopidogrel is an anti platelet therapy agent. It is a prodrug, and requires metabolism by CYP450 enzymes to produce the active metabolite. Its mode of action is the irreversible blocking of the P2Y12 receptor, and thereby blocking the binding site of ADP. ADP is both a direct platelet agonist, and is also secreted by the platelet and acts as a secondary agonist that is critical to complete platelet activation. As a consequence the activation of the GPIIb/IIIa receptor is reduced leading to a reduction in fibrinogen binding and thrombus formation. Therefore within those patients with an elevated risk of arterial thrombus risk, clopidigrel acts to reduce the risk of a significant thrombotic effect.

Answer 34

Heparin is an anticoagulant agent. Heparin is a commonly used anticoagulant with antithrombotic properties. Small amounts of heparin in combination with antithrombin III, a heparin cofactor, can inhibit thrombosis by inactivating Factor Xa and thrombin (Factor IIa). Once active thrombosis has developed, larger amounts of heparin can inhibit further coagulation by inactivating thrombin and preventing the conversion of fibrinogen to fibrin. Heparin also prevents the formation of a stable fibrin clot by inhibiting the activation of the fibrin stabilizing factor. Heparin prolongs several coagulation tests, for example activated partial prothrombin time (aPTT).

Answer 35

Lepirudin is an anti-thrombin agent. Lepirudin is a recombinant form of hirudin.

Answer 36

It is a glucocorticoid receptor agonist. Prednisone, is a heavily prescribed corticosteriod. It is derived from cortisone, and metabolised in the liver to its active form, prednisolone. Prednisolone can cross the cell membrane and can bind to the cortisone receptor. This leads to changes in DNA transcription reducing the production of inflammatory proteins. One specific example is the reduction in the activity of phospholipase A2, leading to the reduced production of arachidonic acid. It can also affect the cell membrane altering ion permeability, and also can affect neurohormone production

Answer 37

Tetanus vaccine is given in childhood. However booster vaccination are beneficial to ensure the patient will resist tetanus infection. The vaccine contains inactive vaccine, which induces a weaker immune response, and as such there is a need for a booster injection. An inactive vaccine contains virus/bacterial particles which are grown in the lab, but that have been killed using either heat or formaldehyde. In active vaccines can be subdivided into whole virus, split virus or subunit virus vaccinations. In this case the booster should be given every ten years, although can be given within 2 days or the patient’s injury.

Answer 38

Epinephrine, also known as Adrenaline, is a hormone produced from the adrenal medulla. Its mode of action is stimulation of alpha, beta-1 and beta-2 adrenergic receptors. Its effects on a-adrenergic receptors lead to reductions in vasodilation and increased vascular permeability that occurs during anaphylaxis. Its actions on b-adrenergic receptors cause bronchial smooth muscle relaxation, and help to alleviate bronchospasm.

Answer 39

It is a H1 histamine receptor inverse agonist. Chlorphenamine binds to hitamine H1 receptor, blocking its activity. Chlorphenamine competes with histamine for binding to the H1 receptor. This leads to temporary relief of the effects of histamine, such as sneezing, watery and itchy eyes, and runny nose due to hay fever.

Answer 40

Diclofenac is a COX inhibitor. Diclofenac is a NSAID. As such it has analgesic due to the inhibition of both COX-1 and COX2 enzymes. In addition it has anti-pyretic properties due to effects on the hypothalamus leading to peripheral dilation, increased cutaneous blood flow, and subsequent heat dissipation. Examples of conditions in which Diclofenac is prescribed are pain, dysmenorrhea, and ocular inflammation.

Answer 41

Hydrocortisone is a glucocoritcoid nuclear receptor agonist. Hydrocortisone binds to the cortisol receptor forming a receptor-ligand complex, which translocates to the nucleus, binds to glucocorticoid response elements (GRE) in the promoter region of the target genes, causing the increase in their expression. Corticosteroids are thought to cause the expression of lipocortins, which inhibit phospholipase A2, thereby reducing arachidonic acid synthesis and production of inflammatory mediators. Additionally the immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding.

Answer 42

Alendronic acid is a nitrogen-containing, second generation biphosphate. Alendronate, strengthens bone and as such is used to treatcorticosteroid-induced osteoporosis and Paget's disease, and to prevent osteoporosis in postmenopausal women. Nitrogen containing bisphosphonates inhibit farnesyl pyrophosphate (FPP) synthase by acting as analogues of isoprenoid diphosphate lipids. Inhibition of this enzyme in osteoclasts prevents the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins, such as Rac and Rho. This causes a reduction in osteoclast activity reducing bone resorption and turnover. Furthermore osteoclast survival is also affected, further increasing the ability of the bone to be rebuilt. Therefore, in postmenopausal women, it reduces the elevated rate of bone turnover, causing a net gain in bone mass.

Answer 43

Bioactive vitamin D is a steroid hormone required for regulating body levels of Ca2+ and phosphorus, and in mineralization of bone. Vitamin D3 is activated by 25-hydroxylation catalysed by the 25-hydroxylase in the liver. The active form of vitamin D3 (calcitriol) binds to the vitamin D receptor, forms a complex with another intracellular receptor, the retinoid-X receptor, that then function as transcription factors to generally activate gene expression. Calcitriol increases the serum Ca2+ concentrations by: 1) Increasing GI absorption of phosphorus and Ca2+, 2) Increasing osteoclastic resorption, and 3) Increasing distal renal tubular reabsorption of Ca2+. Promote intestinal absorption of calcium through binding to the vitamin D receptor in the mucosal cytoplasm of the intestine. Subsequently, Ca2+ is absorbed through formation of a Ca2+-binding protein.

Answer 44

They are hormones produced by the thyroid gland. Calcitonin is produced by the thyroid gland, and is important for the control of calcium concentration within the blood. It antagonises the action of parathyroid hormone. In order to have an effect, calcitonin acts as an agonist and binds to the calcitonin receptor (found primarily in osteoclasts). The calcitonin receptor is an example of a GPCR. This activates the cAMP and calcium signalling pathways, leading to the enhance production of vitamin D producing enzymes (25-hydroxyvitamine D-24-hydroxylase), greater calcium retention and enhanced bone density. This leads to a net increase in bone mass and a reduction in plasma calcium levels. In addition to affecting osteoclasts, in also stimulates bone building by osteoblasts. Calcitonin also promotes the renal excretion of calcium, phosphate, sodium, magnesium, and potassium ions by decreasing tubular reabsorption, and so increases jejunal secretion of water, sodium, potassium, and chloride ions.

Answer 45

Hormone replacement therapy is most likely to be associated with the replacement of the hormones diminishing during the menopause. There are different types of HRT, with oestrogen or progesterone alone therapies, or a oestrogen and progesterone combination therapy. The therapy therefore restores the levels of these hormones, and so removes the symptoms associated with the menopause. There has been debate over the effects of this therapy in regards to it having a detrimental effect in the patients, by increasing the chances of suffering from either cancer (breast and ovarian), and cardiovascular events.

Answer 46

Raloxifene is a selective estrogen receptor modulator. Raloxifene, produces estrogen-like effects on bone and lipid metabolism, while antagonizing the effects of estrogen on breast and uterine tissue. Raloxifene in the bone, binds to the estrogen receptors, resulting in reduced bone resorption and increased bone mineral density in postmenopausal women, slowing the rate of bone loss. This is achieved via activation of transforming growth factor-β3, which is a bone matrix protein with antiosteoclastic properties. In addition Raloxifene can inhibit the proliferation of preosteoclastic cells. Raloxifene also antagonizes the effects of estrogen on mammary and uterine tissue. Here Raloxifene prevents the transcriptional activation of genes containing the estrogen response element. The precise mechanism by which Raloxifene has these dual effects is not fully understood, but there are two possibilities Raloxifene’s tissue-specific estrogen agonist or antagonist activity is dependent on the structural differences between the raloxifene-estrogen receptor complex and the estrogen-estrogen receptor complex. The presence of at least 2 estrogen receptors (ERα, ERβ) may determine the tissue specificity of Raloxifene.

Answer 47

Codeine is an opiate receptor agonist. Codeine is an opiate agonist in the CNS. Codeine's analgesic activity is, most likely, due to its conversion to morphine. Therefore its mechanism of action is via mediation of opiate receptors are coupled with G-protein receptors, which activate adenylate cyclase and the production of cAMP. Opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of the nociceptive neurotransmitters substance P, GABA, dopamine, acetylcholine and noradrenaline and the hormones vasopressin, somatostatin, insulin and glucagon is inhibited. Opioids also close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist). This results in hyperpolarization and reduced neuronal excitability.

Answer 48

Pethidine is a synthetic opiate agonist. Meperidine is a synthetic opiate agonist recommended for relief of moderate to severe acute pain. The onset of action is more rapid than morphine, but has a shorter duration of action. Meperidine is a kappa-opiate receptor agonist with local anesthetic effects. Meperidine has greater affinity for the kappa-receptor than morphine. Opiate receptors are coupled with G-protein receptors, which activate adenylate cyclase and the production of cAMP. Opioids decrease intracellular cAMP by inhibiting adenylate cyclase. Subsequently, the release of the nociceptive neurotransmitters substance P, GABA, dopamine, acetylcholine and noradrenaline and the hormones vasopressin, somatostatin, insulin and glucagon is inhibited. Furthermore opioids can close N-type voltage-operated calcium channels (OP2-receptor agonist) and open calcium-dependent inwardly rectifying potassium channels (OP3 and OP1 receptor agonist) resulting in reduced neuronal excitability.

Answer 49

Lidocaine is an anaesthetic agent (a sodium channel blocker). Lidocaine is an anaesthetic agent used for local or regional anaesthesia. Lidocaine alters signal conduction in neurons by blocking the signal propagation fast voltage gated sodium channels in the neuronal cell membrane. With sufficient blockage the membrane of the postsynaptic neuron will not depolarize and will thus fail to transmit an action potential. This creates the anaesthetic effect by both preventing the initiation of the pain signal, and the prevention of the propagation of that signal to the brain. In addition Lidocaine is a class Ib drug that blocks voltage-sensitive sodium channels during phase 0 of the cardiac action potential, thus slowing and depressing impulse conduction. Lidocaine dissociates rapidly from the channel and almost completely between action potentials. In tissue that is depolarised, or firing at a high frequency, dissociation between pulses is decreased, promoting channel blockade and depression of conduction. Lidocaine is used to treat ventricular tachyarrhythmias associated with Myocardial infarction. Lidocaine depresses Ventricular excitability and increases the stimulation threshold of the ventricle during diastole. The sinoatrial node is, however, unaffected.

Answer 50

Tramadol is a multi target analgesic. Tramadol is a centrally-acting analgesic. It is metabolised to O-desmethyl metabolite (M1). Both the parent molecule and the metabolite are OP3-receptor agonists. Its mechanims of action is not clear but it is thought Tramadol works by -opioid receptors and weak inhibition of reuptake of norepinephrine and serotonin in the CNS

Answer 51

Arnica Montana is a homeopathic therapy. Arnica montana is a well-known homeopathic remedy. It has been used for several trials to demonstrate the effect of homeopathic remedies on bruising and trauma, possibly due to the levels of manganese.

Answer 52

Dobutamine is a B-adrenergic agonist. Dobutamine is a direct-acting **inotropic** agent. Its mechansim of action is mediated via stimulation of b1-adrenergic receptors, with little effect on b2 or a adrenergic receptors. This leads to increase myocardial contractility and stroke volume, resulting in increased cardiac output.

Answer 53

Isoprenaline is a B-adrenergic agonist. Isoproterenol is a relatively selective b2-adrenergic bronchodilator used for the treatment of bronchospasm associated with COPD. The mechanism of action of Isoproterenol are in part due to stimulation intracellular adenyl cyclase, elevatation of cAMP levels, and therefore the relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells.

Answer 54

Salbutamol has two isomers. The R-isomer, levalbuterol, is responsible for bronchodilation while the S-isomer increases bronchial reactivity. Salbutamol’s mechanism of action is that it stimulates b2-adrenergic receptors, leading to adenyl cyclase activation, increases in cAMP concentration, and therefore activation of cAMP-dependent protein kinase A. PKA modulates myosin phosphorylation and lowers intracellular calcium concentrations causing smooth muscle relaxation and bronchodilation. In addition to bronchodilation, salbutamol inhibits the release of bronchoconstricting agents from mast cells, inhibits microvascular leakage, and enhances mucociliary clearance.

Answer 55

Salmeterol is a B2-adrenergic agonist. Salmeterol is a long acting b2-adrenoceptor agonist (LABA). Salmeterol's long, lipophilic side chain binds to exosites near b2-receptors in the lungs and bronchiolar smooth muscle allowing the active portion of the molecule to remain at the receptor site, continually binding and releasing. When used regularly inhaled salmeterol decreases the number and severity of asthma attacks. However, it is not for use for relieving an asthma attack that has already started. Salmeterol’s duration of action lasts approximately 12 hours in comparison to 4-6 hours of salbutamol. Inhaled salmeterol causes bronchodilatation by relaxing the smooth muscle in the airway as per Salbutamol. Salmeterol is similar in action to formoterol, however formoterol has a faster onset of action and is more potent.

Answer 56

Noradrenaline is an alpha-adrenergic agonist. Norepinephrine is a precurser of epinephrine secreted by the adrenal medulla. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. Norepinephrine functions as a peripheral vasoconstrictor by acting on both a1 and a1-adrenergic receptors. It is also an inotropic stimulator of the heart and dilator of coronary arteries as a result of it's activity at the b-adrenergic receptors.

Answer 57

Phenoxybenzamine is an alpha-adrenergic antagonist. Phenoxybenzamine is used to treat hypertension and sweating associated with pheochromocytoma. Its mechanism of action is that Phenoxybenzamine blocks the a-adrenergic receptors which leads to muscle relaxation, and blood vessel dilatation. This widening of the blood vessels results in a lowering of blood pressure. It has no effect on the parasympathetic system.

Answer 58

Doxazosin is an alpha-adrenergic blocking agent. Doxazosin is a selective inhibitor of the a1-adrenoceptors and therefore is used to treat hypertension. Doxazosin inhibits the postsynaptic a1-adrenoceptors on vascular smooth muscle, blocking the vasoconstrictor effect of circulating and locally released catecholamines (epinephrine and norepinephrine). This drug has replaced Prazosin.

Answer 59

Pilocarpine is a muscarinic cholinergic receptor agonist. Pilocarpine is a slowly hydrolyzed muscarinic agonist used in the treatment of glaucoma. Its mechanism of action is the stimulation of muscarinic receptors leading to contraction of the iris sphincter muscle and ciliary muscle.

Answer 60

Atracurium is a competative cholinergic receptor antagonist. Atracurium is a nondepolarizing skeletal muscle relaxant. Its mode of action is it antagonizes the neurotransmitter action of acetylcholine by binding competitively with cholinergic receptor sites on the motor end-plate. This leads to muscle relaxation. The duration of neuromuscular block is between 1/3 to ½ of d-tubocurarine, metocurine, and pancuronium at initially equipotent doses. Repeated administration of maintenance doses of Atracurium has no cumulative effect on the duration of neuromuscular block if recovery is allowed to begin prior to repeat dosing. Moreover, the time needed to recover from repeat doses does not change with additional doses. Repeat doses can therefore be administered at relatively regular intervals with predictable results. The action of Atracium is reversed by acetylcholinesterase inhibitors such as neostigmine, edrophonium, and pyridostigmine.

Answer 61

Botulinum A toxin is an acetylcholine release inhibitor. Botulinum toxin is produced by Clostridium botulinum, a gram-positive anaerobic bacterium. The clinical syndrome of botulism can occur following ingestion of contaminated food, or from a wound infection. The toxing has 7 types (A, B, C [C1, C2], D, E, F, and G), which are antigenically and serologically distinct but structurally similar. Human botulism is caused mainly by types A, B, E, and (rarely) F. The mechanism of action of Botulinum toxin is by binding presynaptically to high-affinity recognition sites on the cholinergic nerve terminals. This causes a decrease in the release of acetylcholine, causing a neuromuscular blocking effect. Recovery occurs through proximal axonal sprouting and muscle re-innervation by formation of a new neuromuscular junction.

Answer 62

Cocaine is a local anaesthetic indicated for the introduction of local (topical) anaesthesia of accessible mucous membranes of the oral, laryngeal and nasal cavities. Cocaine produces anaesthesia by inhibiting excitation of nerve endings or by blocking conduction in peripheral nerves. This is achieved by reversibly binding to and inactivating sodium channels, which are necessary for the depolarization of nerve cell membranes and subsequent propagation of impulses along the course of the nerve. Cocaine is the only local anaesthetic with vasoconstrictive properties. This is a result of its blockade of norepinephrine reuptake in the autonomic nervous system. Cocaine binds differentially to the dopamine, serotonin, and norepinephrine transport proteins and directly prevents the re-uptake of dopamine, serotonin, and norepinephrine into pre-synaptic neurons. Its effect on dopamine levels is most responsible for the addictive property of cocaine.

Answer 63

Dexamphetamine is a noradrenaline releaser. The exact mechanism of action is not known. Amphetamines are agents with CNS stimulant activity. Peripheral actions include elevations of systolic and diastolic blood pressures and weak bronchodilator and respiratory stimulant action. The mechanism of action is unknown. Its possible mechanisms are - Stimulation of the release of norepinephrine from central adrenergic receptors. - At higher dosages, it causes dopamine release from the mesocorticolimbic system and the nigrostriatal systems by reversal of the monoamine transporters. - Act as a direct agonist on central 5-HT receptors - Inhibit monoamine oxidase (MAO). In the periphery cause the release of noradrenaline by acting on the adrenergic nerve terminals and alpha- and beta-receptors.

Answer 64

Dopamine is a dopamine receptor agonist. Dopamine is a precursor to norepinephrine in noradrenergic nerves and is also a neurotransmitter in the central nervous system. In the brain, dopamine act as as an agonist to the five dopamine receptor subtypes (D1, D2, D3, D4, D5). Dopamine has a agonist action on b-adrenoceptors and indirectly by causing release of norepinephrine from storage sites in sympathetic nerve endings producing positive chronotropic and inotropic effects on the myocardium, resulting in increased heart rate and cardiac contractility.

Answer 65

Fluoxetine is used to treat depression, bulimia nervosa, premenstrual dysphoric disorder, panic disorder and post-traumatic stress. Fluoxetine is metabolized to norfluoxetine. Its mechanism of action is the inhibition of the reuptake or serotonin at the serotonin reuptake pump of the neuronal membrane, enhancing the actions of serotonin on 5HT1A autoreceptors. SSRIs bind with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs.

Answer 66

Hemicholinium is a choline reuptake inhibitor.

Answer 67

Imipramine is a catecholamine uptake inhibitor. Imipramine is a tricyclic antidepressant. The mechanism of action of Imipramine is via inhibiting the sodium-dependent serotonin transporter and sodium-dependent norepinephrine transporter preventing or reducing the reuptake of norepinephrine and serotonin by nerve cells. The slowing of the uptake of these neurotransmitters is thought to contribute to relieving symptoms of depression. In addition imipramine causes down-regulation of cerebral cortical b-adrenergic receptors and sensitization of post-synaptic serotonergic receptors with chronic use. This leads to enhanced serotonergic transmission. It takes approximately 2 - 4 weeks for antidepressants effects to occur but can be up to 8 weeks.

Answer 68

Dopamine replacement therapy. Levodopa is a natural form of dihydroxyphenylalanine. It is therefore an immediate precursor of dopamine. It can be taken orally (alongside a dopamine decarboxylase to reduce metabolism at the gut wall) and can readily cross the blood brain barrier. Within the brain it is taken up by dopaminergic neurons and converted to dopamine. It is used to replace dopamine lost in Parkinson's disease.

Answer 69

Nicotine is a nicotinic acetylcholine agonist. Nicotine is a highly addictive stimulant drug. Nicotine inhalers and patches are used to treat smoking withdrawl syndrome. Its mechanism of action is that it is an agonist at nicotinic acetylcholine receptors on autonomic ganglia, the adrenal medulla, neuromuscular junctions and in the brain. In the brain, nicotine binds to nicotinic acetylcholine receptors on dopaminergic neurons in the cortico-limbic pathways, opening the channel and allowing conductance of sodium, calcium, and potassium. This leads to depolarization, activates voltage-gated calcium channels and the release of dopamine into the synapse. Dopamine binding to its receptors is responsible the euphoric and addictive properties of nicotine. In addition Nicotine also binds to nicotinic acetylcholine receptors on the chromaffin cells in the adrenal medulla. This binding opens the ion channel allowing influx of sodium, causing depolarization, activation of the voltage-gated calcium channels, triggering epinephrine release from intracellular vesicles into the bloodstream, causing vasoconstriction, increased blood pressure, increased heart rate, and increased blood sugar.

Answer 70

Phenelzine is a monoamine oxidase inhibitor. Phenelzine is an antidepressant. Its mechanism of action is not fully determined, but it is believed to irreversibly inhibit monoamine oxidase (MAO). There are two forms of MAO, (A+B). MAO-A is found in cells in the periphery, whilst MAO-B is found extracellularly and predominately in the brain. The two subtypes are different substrates, with MAO-A catalysing the breakdown of serotonin, norepinephrine, epinephrine, dopamine and tyramine, whilst MAO-B acts on phenylethylamine, norepinephrine, epinephrine, dopamine and tyramine. As Phenelzine inhibits MAO, it therefore increases the concentration of free amines, most specifically serotonin and norepinephrine. MAO A inhibition is thought to be more relevant to antidepressant activity as selective MAO B inhibitors (selegiline), have no antidepressant effects.

Answer 71

Pralidoxime is a cholinesterase reactivator. Pralidoxime is an antidote to organophosphate pesticides and chemicals. Organophosphates bind to the esteratic site of acetylcholinesterase, resulting in its reversible inactivation. Acetylcholinesterase inhibition causes acetylcholine accumulation in synapses, producing continuous stimulation of cholinergic fibers throughout the CNS. If given in 24 hours after organophosphate exposure, pralidoxime cleaves the phosphate-ester bond formed between the organophosphate and acetylcholinesterase, reactivating the acetylcholinesterase, allowing the breakdown of accumulated acetylcholine, and reestablishing the normal function of neuromuscular junctions. Because pralidoxime is less effective in relieving depression of the respiratory center, atropine is required concomitantly to block the effect of accumulated acetylcholine at this site.

Answer 72

Sarin is an irreversible cholinesterase inhibitor. Nerve agents are extremely toxic and have a very rapid effect. The route of entry of the nerve agent is critical to both the speed and type of symptoms developed. Generally if the agent is absorbed via the respiratory system this induces the quickest response. Poisoning takes longer when the nerve agent enters the body through the skin, as although the Nerve agents are generally fat-soluble and can penetrate the the skin it takes time before the poison reaches the deeper blood vessels. Consequently, the first symptoms do not occur until 20-30 minutes after the initial exposure but the poisoning process may be rapid if the total dose of nerve agent is high. Nerve agents inhibit cholinesterases. Therefore this causes the acetylcholine concentration to increase causing potentiation of the effect of acetylcholine at cholinergic synapses. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system

Answer 73

Tropicamide is a muscarinic cholienrgic receptor antagonist. Tropicamide is used to treat mydriasis and cycloplegia. The mechanism of action is that it inhibits the muscarinic receptor M4. this inhibition leads to pupil dilation and relaxation of the lens.

Answer 74

Benzodiazepines generates the same active metabolite as chlordiazepoxide and clorazepate and binds nonspecifically to benzodiazepine receptors (BR). These receptors mediate sleep, affects muscle relaxation, anticonvulsant activity, motor coordination, and memory. The BRs are believed to be linked to the GABA-A receptors, and activation of the BRs lead to increasing the affinity of GABA for its receptor, enhancing its effects. Binding of GABA to its receptor opens the chloride channel, causing hyperpolarisation and preventing further cell excitation. Diazepam is still used selectively for anxiety and as a muscle relaxant .

Answer 75

Zopiclone is a GABAbZ agonist. Zopiclone is a nonbenzodiazepine hypnotic indicated for the short-term treatment of insomnia. Zopiclone’s mechanism of action is via by binding the α1, α2, α3 and α5 GABAA containing receptors as full agonists modulating the GABABZ receptor chloride channel macromolecular complex. This enhances the inhibitory actions of GABA to produce the hypnotic and anxiolytic effects of zopiclone.

Answer 76

Donepezil is structurally unrelated to other anticholinesterase agents. It is relatively specific for brain acetylcholinesterase, and its mode of action is the reversible inhibition of acetylcholinesterase, leading to an increase in aceylcholine at cholinergic synapses, enhancing cholinergic function. Donepezil is used to treat Dementia now, though has been used for Alzheimer’s disease.

Answer 77

Memantine is an NMDA receptor antagonist. Memantine, an amantadine derivative, is a NMDA receptor antagonist used in the treatment of Dementia. Its mode of action via binding to the NMDA receptor-operated cation channels. Prolonged increased levels of glutamate in the brain of demented patients counter the voltage-dependent block of NMDA receptors by Mg2+ ions and allow continuous influx of Ca2+ ions into cells, resulting in neuronal degeneration. Memantine binds more effectively than Mg2+ ions at the NMDA receptor, effectively blocking the prolonged influx of Ca2+ ions through the NMDA channel whilst preserving the transient physiological activation of the channels by higher concentrations of synaptically released glutamate. Thus memantine protects against chronically elevated concentrations of glutamate. Memantine also has antagonistic activity at the type 3 serotonergic (5-HT3) receptor with a potency that is similar to that at the NMDA receptor, and lower antagonistic activity at the nicotinic acetylcholine receptor.

Answer 78

Antacids are designed to make stomach acid less acidic. At the same time they can also aide heartburn and indigestion. The mechanism of action of gaviscon depends on the formulation. Its main role is to act as an antacid, and as such it neutralize or buffers existing stomach acid, raising stomach acid pH. However Gaviscon has no direct effect on stomach acid output. However double action Gaviscon can also prevent reflux and so reduce irritation of the esophagus.

Answer 79

It is a phenothiazine based antipsychotic. Chlorpromazine is an antagonist on dopaminergic-receptors (subtypes D1, D2, D3 and D4), serotonergic-receptors (5-HT1 and 5-HT2), histaminergic-receptors (H1-receptors), alpha1/alpha2-receptors and muscarinic (cholinergic) M1/M2-receptors. Chlorpromazine's antipsychotic actions are due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup

Answer 80

Haloperidol is a psychotropic agent, with sedative and antiemetic activity used to treat schizophrenia. Haloperidol’s mechanism of action is unknown. However it is thought to act via 1) Depressing the CNS at the subcortical level of the brain, midbrain, and brain stem reticular formation, via inhibition of the ascending reticular activating system of the brain stem (possibly through the caudate nucleus), thereby interrupting the impulse between the diencephalon and the cortex. 2) Antagonizing the actions of glutamic acid within the extrapyramidal system, 3) Inhibiting catecholamine receptors 4) Inhibiting the reuptake of various neurotransmitters in the midbrain 5) Directly affect the chemoreceptor trigger zone (CTZ) through the blocking of dopamine receptors.

Answer 81

Amitriptyline is a noradrenaline/5HT reuptake inhibitor. Amitriptyline, is a sedating antidepressant, and so can aide sleep patterns. Its mechanism of action is not clear, but it is believed that, its metabolite nortriptyline inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. This causes there to be a potentiation or prolonging of neuronal activity, since reuptake of norepinephrine and serotonin is important in termination of transmitting activity. As with other antidepressants, several weeks of therapy may be required in order to realize it’s full clinical benefit. It is not the first choice ant-depressant therapy available.

Answer 82

Citalopram is used to treat depression associated with mood disorders. The mechanism of action is via blocking the reuptake of serotonin at the serotonin reuptake pump of the neuronal membrane, with little effect on norepinephrine and dopamine reuptake. This enhances the actions of serotonin on 5HT1A autoreceptors. Citalopram does not inhibit monoamine oxidase. SSRIs bind with significantly less affinity to histamine, acetylcholine, and norepinephrine receptors than tricyclic antidepressant drugs.

Answer 83

Venlafaxine is a serotonin reuptake inhibitor. The exact mechanism of action of venlafaxine is unknown. However venlafaxine and its metabolite, O-desmethylvenlafaxine (ODV) potently inhibit serotonin and norepinephrine reuptake and weakly inhibit dopamine reuptake. This is associated with a potentiation of neurotransmitter activity in the CNS. Similar to SSRIs, Venlafaxine is not active at histaminergic, muscarinic, or a1-adrenergic receptors, nor does it inhibit monoamine oxidase (MAO) activity.

Answer 84

Methylphenidate is a noradrenaline/dopamine releaser. Methylphenidate is a CNS stimulant. Methylphenidate is used to treat attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), and narcolepsy. Methylphenidate mechanism of action is that it inhibits the sodium dependent dopamine transporter, and therefore blocks dopamine uptake in central adrenergic neurons. This causes increased sympathomimetic activity in the CNS. In addition Methylphenidate is also thought to block the reuptake of norepinephrine.

Answer 85

Lithium is used in the treatment of bipolar disorder, as it counteracts both mania and depression. The active principle is the lithium ion Li+, which can displace K+, Na+ and even Ca2+, in several critical neuronal enzymes and neurotransmitter receptors. However, the exact mechanism of action is still unknown. Lithium's therapeutic action may be due to a number of effects, ranging from inhibition of enzymes such as glycogen synthase kinase 3, inositol phosphatases, or modulation of glutamate receptors.

Answer 86

Risperidone is a multitarget antipsychotic. Risperidone is an atypical antipsychotic therapy, used to treat delusional psychosis, bipolar disorder and psychotic depression. Its mechanism of action is inhibition of 1) Dopaminergic D2 receptors in the limbic system which alleviates symptoms of schizophrenia. 2) Serotonergic 5-HT2 receptors in the mesocortical tract. This causes an excess of dopamine and an increase in dopamine transmission and an elimination of core negative symptoms. Usefully dopamine receptors in the nigrostriatal pathway are not affected and therefore extrapyramidal effects are avoided. 3) Alpha (1), alpha (2) adrenergic receptors and histamine H1 receptors.

Answer 87

Clozapine is a psychotropic agent. Clozapine is indicated for the treatment of schizophrenia. It is a selective monoaminergic antagonist with high affinity for 5HT2, and D2 receptors. D2 antagonism relieves positive symptoms while 5-HT2A antagonism alleviates negative symptoms. However it has been shown to bind to a1 and a2 adrenergic, muscarinic M1-5 receptors and H1 histaminergic receptors, which may explain its therapeutic and side effect profile.

Answer 88

Phenelzine is a monoamine oxidase inhibitor. Phenelzine is an antidepressant. Its mechanism of action is not fully determined, but it is believed to irreversibly inhibit monoamine oxidase (MAO). There are two forms of MAO, (A+B). MAO-A is found in cells in the periphery, whilst MAO-B is found extracellularly and predominately in the brain. The two subtypes are different substrates, with MAO-A catalysing the breakdown of serotonin, norepinephrine, epinephrine, dopamine and tyramine, whilst MAO-B acts on phenylethylamine, norepinephrine, epinephrine, dopamine and tyramine. As Phenelzine inhibits MAO, it therefore increases the concentration of free amines, most specifically serotonin and norepinephrine. MAO A inhibition is thought to be more relevant to antidepressant activity as selective MAO B inhibitors (selegiline), have no antidepressant effects. As with other antidepressants, several weeks of therapy may be required in order to realize it’s full clinical benefit. It is not the first choice ant-depressant therapy available.

Answer 89

Thiopental is rapid onset short acting barbiturate. It is used to induce hypnosis and anesthesia, but not analgesia. Recovery after a small dose is rapid, however, repeated IV doses lead to prolonged anesthesia as fatty tissues act as a reservoir of Thiopental, which is then released over a prolonged period of time. The mechanism of action of Thiopental is that it binds the GABAA receptor, increasing the duration of time for which the Cl- ionopore is open. The effect of this is that the post-synaptic inhibitory effect of GABA in the thalamus is prolonged.

Answer 90

Insulin is an insulin kinase receptor agonist. It is an endogenous hormone, the body's main, endogenous hypoglycemic agent. It is released from pancreatic alpha cells in response to elevated blood sugar. Acts via the insulin receptor (IR) to control a vast range of processes in almost all metabolically active cells in the body. The main effects are the absorption of glucose into metabolising tissues and the subsequent promotion of glycolysis (converting glucose into useable energy ATP and storing of glucose for future use as glycogen (glycogenesis).

Answer 91

A glucose uptake stimulator. Metformin is highly effective at reducing blood sugar but the mechanisms remain incompletely elucidated. The main effect is to decrease conversion of glycogen to glucose (and subsequent release into blood) by inhibition of the enzyme glycogen phosphorylase. It also affects insulin sensitivity, thus increasing glucose uptake and utilisation in metabolising tissue.

Answer 92

Octreotide is a somatostatin analogue. It is an agonist of somatostatin receptors (SSTR) throughout the body. Affects a wide range of biochemical processes (thus long-side effect list!) but most potent at inhibiting INSULIN and GLUCAGON release.

Answer 93

Pancreatin is an exogenous enzyme mixture. It is a mixture of amylases, lipases and proteases designed to mimic the effects of pancreatic enzyme release. These enzymes are vital for normal digestion but do not directly affect blood glucose levels. Used more to restore general pancreatic function in type-1 diabetes.

Answer 94

Pioglitazone is a thiazodineodione drug. It is an agonist at peroxisome proliferator-activated receptor gamma nuclear receptor (PPAR-y). Reduces insulin resistance in metabolically active tissues (i.e. increases glucose absorption, storage and conversion into ATP) and prevents glucose release from the liver.

Answer 95

Acarbose is an alpha-glucosidase inhibitor. Alpha glucosidase is present in the gut and is essential for breaking down complex carbohydrates (i.e. starch) into glucose. Thus less glucose is released into the hepatic portal vein following a meal.

Answer 96

Glucagon-like peptide-1 receptor (GLP1R) agonists. GLP1 is released by intestinal endocrine cells following ingestion of food. Has a synergistic set of effects on binding to the receptor including promoting insulin resistance from pancreatic beta cells and reducing glucagon release from alpha cells.

Answer 97

Sitagliptin is an antagonist of the enzyme dipetidyl peptidase 4 (DPP-4). The enzyme is found throughout the body (where it is involved in immune responses) but in liver and kidney it is involved in the breakdown of GLP-1, thus preventing the GLP-1 mediated increase in insulin release following meal ingestion. Antagonising this effect with a gliptin drug would therefore boost insulin levels.

Answer 98

Sodium-glucose transport protein 2 (SGLT2) antagonists. SGLT2 is present in the kidney (proximal convoluted tubule) and is essential for reabsorption of glucose filtered through the glomeruli. Blockage of this transporter protein increases glucose excretion into urine and thus reduces blood glucose concentration.

Answer 99

Antagonists of sulphonylurea type-1 receptor (SUR-1) found in beta cells of the pancreas. The receptor is formed rom part of the quaternary protein structure of the ATP-modulated potassium channel kir6.2 Antagoism of this receptor prevents potassium ions from exiting the cell when intracellular ATP levels are low. As a result, potassium ions (K+) accumulate inside beta cells, this causes depolarisation fo the membrane potential (excitation) and promotes exocytosis. The main substance released in the manner from these cells is insulin. Note. Only acts as an agonist of Sur-1 receptors. Thus no cardiac side effects as myocytes have Sur-2a subtypes of sulphonylurea receptor. The drugs have other useful effects including prevention of beta cell apoptosis under heavy glucose load and prevention of fat accumulation in arteries (antiatherogenic effect).

All Pharmacology Flashcards

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