drug targets within the body1. With regard to drug targets within the body, which is the best answer? a. Carriers: regulate protein concentrations & bioactive products b. Enzymes: move nutrients & waste in and out of cells c. Ion channels: move small ions, eg sodium and potassium, in and out of cells d. Receptors: recognise only drugs to change cellular response2. An agonist is different from an antagonist with regard to the following, which is the best answer? a. It has affinity b. It has efficacy c. It can?t mimic the response of an endogenous ligand d. It does not bind to a drug target3. With regard to an antagonist, which of the following is false? a. It can be competitive or non-competitive, irreversible or reversible b. It has affinity c. It can shift the dose-response curve of an agonist to the right d. It has efficacy4. The four receptor superfamilies fall into categories on the basis of structure. Which superfamily has a DNA binding domain as a structural feature? a. Ligand gated ion channel b. G-protein coupled c. Kinase linked d. Nuclear5. A pharmaceutical company has designed a new drug. Which of the following methods is correctly matched to pharmacodynamics information it provides about the drug? a. Organ bath / site of drug action b. Ligand binding / affinity of drug for receptor c. Autoradiography / structure-activity relationship d. In vivo animal model / receptor density4. Enzymes involved in Phase I reactions include:(i)__________________________________________________________________________ (ii)_________________________________________________________________________ (iii)_________________________________________________________________________ (iv)_______________________________________________________________________6. Common enzymes involved in Phase II reactions include: (i) _________________________________________________ (ii) _________________________________________________ (iii) ________________________________________________You can use either the notes or the simulation at http://www.icp.org.nz/icp_t3.html for the following question7. If a drug has one the following Volume of Distribution, which body compartment(s) would you expect it to be distributed into? Vd=5L______________________________________________________________________ Vd=15L_____________________________________________________________________ Vd=150L____________________________________________________________________You can use either the notes or the simulation at http://www.icp.org.nz/icp_t2.html for the following question8. A patient is administered a drug which is predominantly cleared through the liver, if the patient has their liver function reduced by 50%, what kind of adjustment (if any) to the drug dosagemust be made to ensure the drug reaches a therapeutic concentration in their body?________________________________________________1. What are the physiological consequences of activating the main two components of the autonomic nervous system on a) gastrointestinal motility & secretion b) heart function and c) airway function d) lung e) adrenal medulla? In each case include the target organ transmitters involved and the types of receptors involved. i) Parasympathetic system:ii) Sympathetic system:2. Using a representative diagram, illustrate the anatomical differences between parasympathetic and sympathetic nerve fibres in terms of their origin, relays and termination to a) blood vessels, b) heart and c) adrenal medulla.3. What are the main neurotransmitters & receptor types involved in neurotransmission at the following sites? Use your textbook to help you answer this question.Type of Nerve Terminal Neurotransmitter Receptors Involved preganglionic sympathetic fibrespreganglionic parasympathetic fibrespostganglionic sympathetic fibres at vascular smooth musclepostganglionic parasympathetic fibres at cardiac muscle4. Outline the main differences between the metabolism of acetylcholine and noradrenaline at the nerve terminal. Name one drug that can influence the metabolism of each and how it works. 1. Using a diagram, outline the principle differences between cyclo-oxygenase (COX) inhibition by non selective and COX-2 selective drugs. [3 marks] 1. Describe how gastric acid is produced and discuss the mechanisms of action and major side effects of THREE major classes of drugs used to treat gastric/duodenal ulcers. [10 marks]1. What is the main challenge to modern antibiotic therapy? Give some examples of the origin of this challenge and how it might be overcome.2. What is the difference between a bacteriostatic drug and a bactericidal drug? Give an example of each.3. With a brief sketch illustrate the different parts of the HIV virus life cycle which can he interrupted by drug therapy.5. What mode of therapy is common to anti-viral therapy and anti-cancer therapy?6. Why are microtubules important in cancer? Illustrate this with the mode of action of one anticancer drug?7. What is the new therapy for Chronic Myeloid Leukemia? Explain how this represents a new approach to cancer therapy.8. There are multiple steps in the bacterial translation process that can be attacked by antibiotics, gives 4 examples and an antibiotic that works at each step.1. Which of the following statements about gamma-aminobutyric acid (GABA) is CORRECT? a. it is a major excitatory neurotransmitter in the central nervous system b. it is formed from aspartate by the enzyme glutamic acid decarboxylase c. it activates GABAB receptors which are found mainly at postsynaptic site d. it activates GABAA receptors which leads to Cl- influx2. Which of the following statements about dopamine is CORRECT? a. it is present at high concentrations within the regions of the limbic system b. its reduction within the nigrostriatal pathway is associated with schizophernia c. it can only have excitatory effect within the central nervous system d. its hyperactivity in the nigrostriatal pathway is associated with Parkinson?s disease3. Which of the following statements about drugs that act as selective inhibitors of monoamine oxidase type A (MAO-A) is CORRECT?a) they increase 5-HT receptor activity in the central nervous system b) their pharmacological action is mainly restricted within the periphery c) they are used to treat patients suffering from Schizophrenia d) they decrease the presynaptic cellular levels of dopaminePart B: Short Answer Questions 1. Describe briefly the mechanisms of action and major side effects of TWO Drug classes that affect central 5-hydroxytryptamine systems. (3 marks)2. Describe the pharmacodynamic targets for amphetamines and their adverse effects. (3 marks)1. Describe the use of drugs in the treatment of schizophrenia, focusing on the mechanisms of action and main side effects of TWO major classes of antipsychotic drugs. (10 marks)2. What are the THREE main criteria that define whether a person is dependent on a drug/substance? a. b. c. 3) How do opioids work to provide analgesia?Q2. What sort of steps are involved in developing new drugs?Q3. Compare and contrast combinatorial chemistry and rational drug designQ4. What approaches were used in the design of the drug Zanamavir? Did it work?Q5. With a quick sketch, illustrate the success rate of potential drugs at each step of the drug discovery process Q6. With a quick sketch illustrate the proportion of modern pharmaceuticals that come from natural or synthetic routes.Q8 We often use a natural product as a basis from a pharmaceutical therapy, why is this? Give one illustration of a natural compound that has been modified to give a therapeutic (and why it was modified)1. G-protein coupled receptors depend on 2nd messengers to elicit their effects on cell function. Name 3 of these messengers and explain their role in this process. [3 marks] 3. What are the key factors that influence drug absorption across biological membranes? [3 marks] 4. List two important organ structures that are innervated via ?2 adrenoceptors. In addition, briefly describe the functional (physiological) role that ?2 adrenoceptor activation plays in those organs related to homeostasis (e.g. fight or flight response). [3 marks]7. Describe briefly why drugs that block histamine (H2) or muscarinic (M1) receptors are used to treat duodenal or gastric ulcers. [3 marks] 10. Describe briefly why we use drugs that affect brain 5-HT levels or 5-HT receptors to treat major brain disorders. [3 marks]11. What is the active ingredient of Khat and what is its relevance to western drug use? [3 marks]12. Using brief notes compare and contrast the mechanisms of resistance to anticancer drugs and antiviral drugs. [3 marks]13. Compare and contrast the use of complementary therapies by asthmatics and people with depression. [3 marks]3. Some anti-viral drugs and some anti-cancer drugs share a common mechanism. Explain what this mechanism is, why it is important to both viral and cancer chemotherapy and give one example of such a therapy. If possible, also name a drug that has been used as both anti-viral and anti-cancer therapy. [10marks]4. Aspirin is one of the most commonly used non-steroidal anti-inflammatory drugs (NSAID) for many different pain conditions as well as fever. Aspirin can also cause duodenal or gastric ulcer, platelet disorders and renal function impairment. Explain why these side effects occur and suggest an alternative NSAID with reduced side effects. [10marks]5. With a simple illustration, draw the autonomic innervation which projects to the adrenal medulla and heart. Include relevant transmitters and receptors in your answer. [6 marks] 10. Compare and contrast the use of complementary therapies by pregnant women and healthy people. [3 marks] 12. Non-steroidal anti-inflammatory drugs (NSAID) are used for many different pain conditions as well as fever. Some of these drugs cause platelet disorders and gastric ulcer. Explain why these side effects occur. [3 marks] 3. Describe the pharmacodynamic effects of amphetamines, their mechanisms of action, and explain how this relates to their chemical structure. [10marks]4. Describe why drug effects within the central nervous system are far more complex than on the autonomic nervous system by focussing on antidepressant and antipsychotic drugs. Explain mechanisms of action and main side effects of these drugs. [10marks]5. Compare and contrast rational drug design and combinatorial chemistry as methods of drug discovery. [10marks]6. Production of gastric acid is finely regulated both by neurons and by hormones. Describe effects of drugs that act as an agonist at histamine (H2) and muscarinic (M1) receptors on gastric acid production. Can these drugs be used to treat duodenal or gastric ulcers? Explain your answer. [10marks]2010 5. Describe the dynamics of acetylcholine production, storage, release and inactivation at the synapse. Use a diagram to assist your answer if you wish. Also, name one type of drug that can prevent acetylcholine mediating its effect there. [3 marks] 2. What major therapeutic challenge is common to both anti-bacterial and anti-viral therapy? [10marks]3. A pharmaceutical company has developed a new drug ?Whimsolidine?. Following in vitro and in vivo experiments they have the following information about the drug?s action: (i) organ bath: drug at low concentrations causes a significant contraction response. (ii) autoradiography: drug binds to receptors in the brain, stomach, liver, and kidney. (iii) dosing in rats: drug response following oral administration was observed on day 1 but diminished on day 2-5 of dosing and most of the drug was excreted in the urine as metabolites. (iv) dosing in rats with liver disease: drug accumulated in the plasma causing severe toxicity after heightened response.Referring to the above information, discuss the pharmacological properties of the drug including: type of drug (agonist/antagonist), site of action, pharmacokinetics (absorption and clearance organ), changes in dosing required with continued administration, and patient groups who should not take the drug due to toxicity. [10marks]4. Compare and contrast natural versus synthetic drugs. Include in your answer a discussion of the differences in concepts between natural products used as pure drugs and herbal medicines. What problems may arise with the use of herbal preparations as medicines?:
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