Clinical Pharmacology

Question 1

Definition: Pharmacology

Answer 1

The study of drugs

Question 2

Definition: Pharmacokinetics

Answer 2

Effects of the body on the drug over a period of time absorption distribution metabolism elimination

Question 3

Definition: Pharmacodynamics

Answer 3

Effects of the drug on the body Here especially the effects of corticosteroids, local anaesthetics and adrenaline

Question 4

Naming of drugs:

Answer 4

Chemical name Generic (approved) name e.g.Lidocaine Trade name e.g. Xylocaine [Astra]

Question 5

Doses/concentrations - Absolute doses of drug

Answer 5

measured in milligrams (mg) of pure drug (as dry preparation) 1000mg=1g

Question 6

Doses/concentrations - Volumes of solutions/suspensions

Answer 6

measured in millilitres (ml) 1000 ml = 1 l

Question 7

Doses/concentrations - Concentrations of solutions/suspensions

Answer 7

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

Question 8

Drug formulations

Answer 8

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

Question 9

Potency

Answer 9

Amount of drug given to achieve a given level of effect. e.g.bupivacaine is 4x as potent as lidocaine

Question 10

Efficacy

Answer 10

The extent to which a drug can produce the maximum possible response when all receptors are occupied

Question 11

Therapeutic ratio

Answer 11

Ratio between the toxic dose and the therapeutic dose of a drug The closer to 1 the more difficult to use

Question 12

Affinidy

Answer 12

“fit” between drug and receptor

Question 13

Absorption dependent on: 5

Answer 13

the drugs molecular size the drugs relative solubility in lipid and water the drugs ionisation/other properties acidity/alkalinity of environment cell membrane permeability

Question 14

Lipid-solubility of a drug determines:

Answer 14

rate of absorption penetration into tissues duration of actions

Question 15

Route of administration

Answer 15

Oral intramuscular subcutaneous intralesional intra-articular intravenous

Question 16

Oral administration of drug:

Answer 16

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

Question 17

Intravenous administration of drugs

Answer 17

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

Question 18

Rate of absorption depends upon

Answer 18

diffusion through tissues local blood flow solubility of drug

Question 19

Distribution 4*

Answer 19

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

Question 20

Intralesional administration of drug

Answer 20

Maximal ammount of drug to required location Potential for local soft tissue side effects Do get gradual absorption => systemic circulation

Question 21

Intra muscular administration of drug

Answer 21

Next most rapid after intravenous

Question 22

Subcutaneous administration of drugs

Answer 22

Poor/unpredictable absorption - lipotrophy

Question 23

Metabolism

Answer 23

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

Question 24

Metabolism figure

Answer 24

Question 25

Elimination - usually of drug metabolites

Renal

Answer 25

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)

Question 26

Elimination - usually of drug metabolites

Biliary

Answer 26

Biliary - mainly larger molecules

• Concentrated in bile => bowel
• may be reabsorbed - entero hepatic circulation

Question 27

Elimination - usually of drug metabolites

Other routes

Answer 27

Other routes

• Lungs
• Tears
• Sweat

Question 28

Absorption / Elimination balance

Answer 28

• 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.

Question 29

Drug receptors

Answer 29

• 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”

Question 30

Enzyme systems

Answer 30

• enzymes are catalysts which facilitate or speed up chemical reactions
• Drug may cause enzyme production
• drug may inhibit enzyme actions

Question 31

Ion channels

Answer 31

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

Question 32

Drug interactions

Answer 32

Pharmacokinetic interactions

• Absorption
• Distribution
• Metabolism
• Elimination

Pharmacodynamic interactions

• Conflicting effects on same body system

Question 33

Adverse drug reactions

Answer 33

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.