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1 NMIH 206 NOTES TOPIC PAGE NUMBER PHARMACOKINETICS 2-15 INFECTIONS & VACCINATIONS ANTICOAGULANT & CLOTTING TIMES CARDIAC DRUGS: ANGININE & LANOXIN ANAESTHETICS NUTRITION HYPOLIPIDAEMIC AGENTS VITAMINS & MINERALS ANTI-HYPERTENSIVE AGENTS STEROIDS NON-STEROIDS HERBAL MEDICINES ANTI-INFECTIVE AGENTS DRUGS OF THE WEEK Page 1 of 5
2 Pharmacokinetics Iatrogenic Disease Result from medical (or nursing) interventions 3% of all hospital admissions are primarily due to medication reactions 30% have 2 nd medication reaction while in hospital 6-15% Australian patients on medical wards suffer some sort of reaction from medicines in hospitals Average patient receives 6-10 medicines Adverse reaction rate 7-10% < 130,000 Australians a year admitted to hospital after severe drug reaction 800,000 take time of work/medical help 1.6M suffer adverse reactions to medications 50% moderate-severe reactions 7.6% hospital admission 70% experience side effects 11% experience an allergic reaction Pharmacokinetics Study of the way medicines are handled in the body - Absorption - Distribution - Effects - Metabolism - Excretion Absorption after Oral Drug Administration Most medicines taken orally convenience Tablet, capsule, mixture Little to no absorption via mucous membrane Swallowed Majority pass unabsorbed into small intestine Dissolution continues in the alkaline intestinal fluid enter portal circulation pass through liver entering the systemic circulation reaching their site of action Sub-lingual absorption very few medications bypass the portal circulation (blood vessels surrounding the small intestine drain into the gepatic portal vein that passes through the liver) glyceryl trinitrate s l rapid absorption to treat angina pain 98% metabolised to an inaction form by a single pass through the liver Cannot be given p.o Page 2 of 5
3 Anticonvulsants - Current PBS Antiepileptics 1. Phenytoin (Dilantin) 2. Carbamzepine (Tegretol, Teril) 3. Sodium valproate (Epilim, Valpro, Valprease) 4. Clanzepam (Rivotril, Paxam) Tiagabine Gabapentin Levetiracetam Lamotigine Primidone Sultthiame Lascosamine Zonisamide Vigabatrin Topiramate Phenobarbitone Oxcarbazepine Ethosuximde Pregabalin Acetazolamide Page 3 of 5
4 Phenytoin Hydantoins Used for generalized tonic-clonic seizures with minimal sedation & hypnosis Trade name is Dilantin Absorption: Slowly absorbed from GIT Maximum serum level 8 hours after po Plasma protein binding: 90% plasma prtein bound Readily displaced by aspirin Serum Concentration: Therapeutic range micromol/l Narrow therapeutic ratio Stable blood level 7 days after daily fixed doses Metabolism: Metabolised by the liver Needs 6 monthly LFTs Half-life: At low doses t 1/2 is 24 hours Slight increase in dosage the liver enzyme metabolizing pathway is saturated & toxic serum level result Dosage: mg, 1-2 x daily Paediatric suspension Page 4 of 5
5 Hypolipidaemic Agents Hyperlipdaemia Metabolic disorder of serum lipids Elevated serum cholesterol & triglycerides Important physiological functions e.g. hormones (oestrogen, testosterone), bile salts, lipid bilayer of cell membranes Excess promotes atherosclerosis Causes CAD & ^ mortality Sources of cholesterol Exogenous diet saturated fats Endogenous liver synthesis from other dietary sources Cholesterol & triglycerides water insoluble transported in blood by carrier proteins Called lipoproteins Lipoproteins Based on density HDL little cholesterol transports back to liver good cholesterol VLDL lots of triglycerides not too bad 50% transformed to: LDL Lots of cholesterol transports to cells where it is deposited bad cholesterol CV mortality & morbidity Directly related to total serum cholesterol & LDL-C levels Inversely related to HDL-C level Want to reduce total-c & LDL-C & increase HDL-C Want high HDL/LDL ratio Hyperlipdaemia promoted by diabetes, nephrotic syndrome Lipid Profile Total serum cholesterol = LDL + HDL + Triglycerides Total Cholesterol LDL HDL o High > 6.20 mmol/l o Target: <3.5 mmol/l o <1mmol/L ^ risk of CHD o Deseriable <5.18 mmol/l (NHF 5.5) o 1% ^ in CHD for each 1% ^ in LDL o mmol/l decrease risk of CHD o Borderline high mmol/l o 2-3% decrease CHD for each 1% ^ in HDL o Desirable <5.18 mmol/l (nhf 5.5) o Target <4.0 mmol/l Page 5 of 5
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