Drug Study CSB601 Lecture Notes 1-13 PDF

lOMoARcPSD|48481542 DRUG- Study-CSB601 - Lecture notes 1-13 Introduction to Clinical Therapeutics for health (Queensland University of Technology) Scan to open on Studocu Studocu is not sponsored or endorsed by any co...

lOMoARcPSD|48481542 DRUG- Study-CSB601 - Lecture notes 1-13 Introduction to Clinical Therapeutics for health (Queensland University of Technology) Scan to open on Studocu Studocu is not sponsored or endorsed by any college or university Downloaded by Danie Danie ([email protected])  lOMoARcPSD|48481542 CSB601 PHARMACOKINETICS - Study the effect the body has on drugs - Absorption – movement of drug into blood stream o blood flows from the gut to the liver via the hepatic portal system o from the liver back through the venous circulation and into the right side of the heart o from the pulmonary arteries through the lungs and back through the left side of the heart o then flows through arterial circulation o oral – move through digestive system and absorbed by gut then throughout rest of system o IV – doesn’t have such a long journey to reach circulatory system therefore quicker rise in drug concentration o inhalation – only has to go to heart and straight into arterial circulation therefore larger Cmax and Tmax - Distribution o body has 4 major compartments – collections of fluid and numerous minor  major = blood (plasma), fat, extracellular and intracellular fluid  minor – CSF (cerebral spinal fluid) peritoneum, synomial fluid and foetus o when drug placed into compartment ie IV it binds with associating molecules, increasing the storage capacity in the compartment  there is an equilibrium between the bound drug and unbound  unbound drug within a compartment Is then able to move into another compartment  when drug moves into a new compartment, some of it is sequestered by binding molecules within new compartment – continues until balance between each compartment and a balance of bound and unbound drug within each compartment o balance between each compartment is determined by a number of factors  equilibrium constants – dependent on  permeability of barriers between compartments  the pH balance within compartments  binding capacity within the compartment  others ie – fat solubility of drug o Volume of distribution (Vd): Downloaded by Danie Danie ([email protected])  lOMoARcPSD|48481542  Property of the drug which shows how much of the drug needs to be within the body to get a certain concentration into the plasma (blood) Total amount of drug ∈the body Vd= Concentration of drug∈the plasma - Metabolism o Often takes place in liver – also lungs, gut and kidneys o drug given orally may be metabolised by the liver before reaching systemic circulation – first past metabolism o biochemistry of drug metabolism  Cytochrome P450 (CYP) – abundant in the liver, different types metabolise different drugs through variety of ways :  Oxidation – oxygen binding  Hydrolysis  Aspirin – hydrolysis – salicylic acid – acted upon by UDP-GT – product easily excreted by the kidneys  Hydroxylation  Turn drug carrying hydrogen into a drug carrying hydroxyl group. Creates target for much larger molecule to be attached – series of process that produce a polar drug therefore it becomes water soluble and easily excreted by the kidneys - Excretion o The irreversible removal of drugs from the body o Two main ways  Hepatobiliary system – liver excretes a drug or drug metabolite into the faeces  Kidneys – drug filtered into the nephron of the kidney – once in the nephron, flows through into the collecting ducts and out of the body into the urine o Certain amount of drug in the plasma (Cp) and a certain about of drug in the urine (Cu) certain rate at which the urine with be produced (Vu) Cu×Vu - Clearance= Cp o order of kinetics  higher concentration of drug in the plasma the fast the drug will be excreted  speed at which the drug is being illuminated slows down as plasma concentration drops  half life is constant  = first order kinetics o if more drug added to body it won’t change the rate of excretion as there is no extra enzyme to absorb the drug = rate of excretion is independent of concentration in blood plasma Downloaded by Danie Danie ([email protected])  lOMoARcPSD|48481542 o = zero order kinetics – more easily overdosed because rate of excretion doesn’t increase as concentration does o once enzyme is no longer saturated the drug follows first order kinetics o Drug elimination  Bile, saliva, sweat, tears, faeces, milk, exhaled air, urine o Length of time for total elimination = 5 half-lives because 5 halves is 96.875% 100% - 50% - 75% - 87.5% - 93.75% - 96.875% PHARMACODYNAMICS - Study of the effects of the drugs on the body and the mechanism of action Cmax - maximum concentration(help predict medical benefit and side effects) Tmax - maximum time Half life - time it takes to remove half of the current concentration of drug - Same of a drug regardless of a route Area under the curve is the total exposure to a drug that the body receives Downloaded by Danie Danie ([email protected])  lOMoARcPSD|48481542 DRUGS CLASSES ACE inhibitors MOA: - Relax blood vessels and lower blood pressure – prevent enzyme from producing angiotensin II (which narrows blood vessels and increased BP) - Prevents sodium water reabsorption - Produces vasodilation by inhibiting formation of angiotensin II Metabolism: - Most eliminated by the kidneys (hepatic metabolism) and to a lesser extent through the liver Indication: - Used primarily for treatment of hypertension and congestive heart failure - Diabetic nephropathy – type 1 - Prevention of progressive renal failure - Post myocardial infarction Contraindications: - Pregnancy – lactation – insufficient info - Renal impairment – may increase potassium in blood and worsen - Geriatric – care when using monitor potassium - Potassium increasing drugs/NSAIDs/diuretics/anaesthetics Major Side Effects: - Hypotension, cough, hyperkalaemia, headache, dizziness, fatigue, nausea and renal impairment Examples: - Benazepril, captopril, enalapril (usually end in pril) Nitrates MOA: - Provide exogenous source of nitric oxide – mediates vasodilator effects - Reduce venous return and preload to the heart – reducing myocardial oxygen requirement Metabolism: - Metabolised in the stomach and excreted through urine Indication: - Prevention and treatment of angina Contraindications: - Pregnancy – lactation and limited data - Hypovolaemia, raised intracranial pressure, anaemia, numerous cardiovascular conditions - NOT with sildenafil/tadalafil – can cause profound hypotension and MI - Surgery remove patches before Major side-effects: - Headache, flushing, palpitations, orthostatic hypotension, fainting, peripheral oedema Downloaded by Danie Danie ([email protected])  lOMoARcPSD|48481542 Examples: - Short acting - glyceryl trinitrate - Long acting – more chronic angina Aldosterone antagonists MOA: - Inhibit sodium absorption in the distal tubule of the nephron in kidney by antagonising aldosterone - Increase sodium and water excretion and decrease potassium excretions Metabolism: - Excreted in urine then bile - Indication: - Heart failure, hyperkalaemia Contraindications: - Pregnancy – avoid - Hepatic impairment - Renal if CrCl