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Connecting Pharmacology with Therapeutics Clive Roberts.

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Presentation on theme: "Connecting Pharmacology with Therapeutics Clive Roberts."— Presentation transcript:

1 Connecting Pharmacology with Therapeutics Clive Roberts

2 Become wise!





7 What can be predicted from a drugs pharmacological profile Pharmacological actions Some adverse effects Some contraindications Some drug interactions Acute toxicity risk Mode of administration possibilities

8 What can NOT be predicted? Therapeutic effect Appropriate usage in comparison with other drugs Some adverse effects Some drug interactions


10 What does the pharmacological profile consist of Pharmacodynamic data Pharmacokinetic data Physicochemical properties Potential to induce or inhibit hepatic enzymes Acute toxicity information The therapeutic ratio Usage history Cost

11 Pharmacodynamic information What receptors does it block or stimulate Or what ionic channels or enzymes etc does it affect What is the hypersensitivity risk What unrelated toxicity occurs, how serious and how often What happens in acute overdose

12 Pharmacokinetic information How is it cleared from the blood – liver/kidney/lung etc First order / zero order process If liver, how high is the clearance rate What is the bioavailability If low is it due to pre-systemic hepatic clearance or poor absorption





17 Pharmacokinetic info. continued How is the drug distributed in the body What is the volume of distribution What is the extent of plasma protein binding What is the plasma half life




21 Patient groups at risk Liver disease Renal disease Heart disease Lung disease Elderly Those taking other drugs Pregnancy

22 So lets take the example of Phenytoin




26 ?? Digoxin





31 Mrs Y.Y. Born 1912 Admitted late Feb with general deterioration in health, nausea, anorexia, constipation At her EPH there had been an outbreak of D+V 4 weeks previous. She had never really got better. Dehydrated, hypotensive, pale, slow reg pulse

32 Drugs – perindopril, digoxin, frusemide, aspirin, Isosorbide mononitrate Urea 31, creatinine 223 ECG ……………


34 Digoxin level 3.5 What went wrong?

35 What is it about the patient with hepatic failure that puts them at risk Pharmacokinetic disturbance - –Decreased clearance of some drugs –Increased bioavailability of some drugs –Altered distribution volume –Decreased protein binding CNS sensitivity Electrolyte abnormality

36 What is it about the patient with hepatic failure that puts them at risk - continued Fluid retention Risk of bleeding – generally and specifically in gut Metabolic disturbance Encephalopathy risk

37 And the renal patient ? Pharmacokinetic disturbance –Mainly affecting drug clearance –Also protein binding Increased sensitivity Poor tolerance of adverse effects Decreased effectiveness of some drugs

38 Drugs in the elderly Multiple indications leads to polypharmacy Pharmacokinetic disturbance of metabolism, excretion, protein binding and drug distribution Increased sensitivity to the actions of drugs on CVS, CNS, GIT Poor tolerance of adverse effect

39 Drug interaction Pharmacodynamic mechanisms usually easy to predict Pharmacokinetic mechanisms – need to know / look up.

40 Le Fin

41 Profile of new drug for reflux oesophagitis Phenothiazine drug with powerful antigastric secretory action at low doses. Acts on both h2 receptors and the proton pump Also blocks muscarinic receptors throughout the body Inhibits some hepatic enzymes Causes a rise in transaminases in some patients Limited experience in overdose

42 Profile of new drug for reflux oesophagitis High hepatic clearance with extraction ratio of 65% Widely distributed in tissues Plasma half life of 48 h

43 What might you predict about the adverse effects? Who might be at greatest risk? What drug interactions might occur? What about self harm doses?


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