Clinical Pharmacology Flashcards
Definition: Pharmacology
The study of drugs
Definition: Pharmacokinetics
Effects of the body on the drug over a period of time absorption distribution metabolism elimination
Definition: Pharmacodynamics
Effects of the drug on the body Here especially the effects of corticosteroids, local anaesthetics and adrenaline
Naming of drugs:
Chemical name Generic (approved) name e.g.Lidocaine Trade name e.g. Xylocaine [Astra]
Doses/concentrations - Absolute doses of drug
measured in milligrams (mg) of pure drug (as dry preparation) 1000mg=1g
Doses/concentrations - Volumes of solutions/suspensions
measured in millilitres (ml) 1000 ml = 1 l
Doses/concentrations - Concentrations of solutions/suspensions
described as the number of milligrams of drug contained in a specified volume of solution or suspension weight for volume: a 1% solution contains 1 gram of the drug in each 100ml of solution
Drug formulations
Solid - tablet, capsule Liquid form - medicine Solution - Drug is dissolved in liquid e.g.lidocaine Suspension - Drug is present as very small particles suspended in liquid - will settle - need to shake before use e.g.triamcinalone
Potency
Amount of drug given to achieve a given level of effect. e.g.bupivacaine is 4x as potent as lidocaine
Efficacy
The extent to which a drug can produce the maximum possible response when all receptors are occupied
Therapeutic ratio
Ratio between the toxic dose and the therapeutic dose of a drug The closer to 1 the more difficult to use
Affinidy
“fit” between drug and receptor
Absorption dependent on: 5
the drugs molecular size the drugs relative solubility in lipid and water the drugs ionisation/other properties acidity/alkalinity of environment cell membrane permeability
Lipid-solubility of a drug determines:
rate of absorption penetration into tissues duration of actions
Route of administration
Oral intramuscular subcutaneous intralesional intra-articular intravenous
Oral administration of drug:
Mostly in proximal small bowel Slowest/partial absorption affected by food, other drugs, lipid solubility, formulation “bioavailability” Some drugs are destroyed by acid, enzymes drugs enter portal circulation - may be metabolised in gut wall or liver with resulting reduced blood/tissue levels
Intravenous administration of drugs
Fastest route Direct access to bloodstream, gets to heart, lungs, brain quickly Rapid injection gives highest blood levels Biggest risk of adverse events - avoid by safety aspiration
Rate of absorption depends upon
diffusion through tissues local blood flow solubility of drug
Distribution 4*
DRUG => CIRCULATION => TISSUES Aided by
- diffusion-high to low concentration
- lipid-solubility
- filtration across semipermeable membranes
MAY BE BOUND TO PROTEINS IN BLOOD
- amount of protein may change in e.g. liver disease
CARRIER MOLECULES
- potential inter-action with other drugs e.g. warfarin
AFFECTED BY AGE/SEX/GENETIC MAKEUP OF PT
Intralesional administration of drug
Maximal ammount of drug to required location Potential for local soft tissue side effects Do get gradual absorption => systemic circulation
Intra muscular administration of drug
Next most rapid after intravenous
Subcutaneous administration of drugs
Poor/unpredictable absorption - lipotrophy
Metabolism
MAINLY IN LIVER (also plasma, lung, wall of intestine) -usually made less active -usually made more hydrophilic (less lipid soluble) to aid renal excretion ENZYME MEDIATED
- Phase 1 - usually oxidation (also reduction and hydrolysis)
- phase 2 - conjugation - addition of chemical group to reduce lipid solubility
AFFECTED BY -drugs (enzyme inducers/inhibitors) -age - tends to reduce with age -disease - especially hepatic impairment -genetic factors
Metabolism figure
Elimination - usually of drug metabolites
Renal
Renal - mainly for smaller molecules
- most common route
- usually simple filtration
- more reabsorption from tubules if lipid soluble
- some drugs actively excreted by tubules
- effects of age - decreased renal function (>65)
Elimination - usually of drug metabolites
Biliary
Biliary - mainly larger molecules
- Concentrated in bile => bowel
- may be reabsorbed - entero hepatic circulation
Elimination - usually of drug metabolites
Other routes
Other routes
- Lungs
- Tears
- Sweat
Absorption / Elimination balance
- equilibrium needed
- blood drug level = balance of absorption, metabolism + elimination
- if absorption = metabolism + elimination => steady blood level
- if absorption >..may be toxic
- if absorption
- Half life of drug: time taken for blood level of drug to fall 50%
- has implications for dosing frequency, beneficial and toxic effects.
Drug receptors
- these are usually situated on cell surfaces, but may be intracellular (e.g. steroids)
- drug receptors are usually proteins but may be “targets” -e.g. sodium ion channels with LA
- interaction of a drug with its receptor, produces a conformational change in the protein which then transmits a signal into the cell, usually via a self-amplifying cascade of biochemical events
- receptors tend to be highly specific for a particular drug, but this varies. Some drugs can stimulate more than one type of receptor, though may need higher or lower concentrations to do so - “selectivity”
- Agonists - activates receptor response. If all receptors are occupied, the maximal response is obtained
- Antagonists - block receptor response. If all receptors are occupied, no response can be obtained with the appropriate agonist
- Partial agonists - produce a less than maximum response, even when all receptors are occupied
- Down regulation - describes the situation where a reduction in receptor numbers and/or function is related to the continuing administration of a drug. This is one of the causes of “tolerance” to a drug. If it happens particularly rapidly, it is termed “tachyphylaxis”
Enzyme systems
- enzymes are catalysts which facilitate or speed up chemical reactions
- Drug may cause enzyme production
- drug may inhibit enzyme actions
Ion channels
Some drugs work by interacting with ion channels usually in excitable tissues
- local anaesthetics block sodium channels in neurones
- calsium channel blockers in cardiac muscle
Drug interactions
Pharmacokinetic interactions
- Absorption
- Distribution
- Metabolism
- Elimination
Pharmacodynamic interactions
- Conflicting effects on same body system
Adverse drug reactions
TYPE A
- predictable, dose related, easier to manage or avoid by dose adjustments e.g. NSAID => indigestion, steroid side effects
TYPE B
- Idiosyncratic, unpredictable, not dose related e.g. anaphylaxis with LA, penicillin etc.
