Drug Regimes Flashcards
Name 4 factors which help to determine dosage regimen for drugs
- Activity/toxicity - therapeutic window, side effects
- Pharmacokinetics - dose, onset, loading dose, maintenance dose
- Clinical factors - state and compliance of patient
- Other factors e.g. route of administration, drug interactions
Define dosage
The giving of medicine in prescribed amounts over time
Name 4 considerations when deciding dosage of a drug
- Potency of the drug
- Absorption - route, proteins aiding movement
- Bioavailability and first-pass metabolism
- Distribution - staying in circulation or need to enter tissues
Define “first pass metabolism” and why is it an important factor
Definition - The degree of metabolic breakdown of an orally administered drug that occurs in the intestine or liver before it reaches the systemic circulation
Importance - as it can reduce total exposure of the body to the drug
What 3 factors can affect onset of action of a drug
- Route of administration - if oral then is affected by poly pharmacy, gut contents, splanchnic blood flow
- Chemical structure and formation - is pH effects release rate
- Clinical situations - change in pH, states of shock, tissue perfusion
Define “loading dose”
A large initial dose of a substance or series of such doses given to rapidly achieve a therapeutic concentration in the body.
How is the loading dose determined
By the volume of distribution of the drug
What does increasing the frequency of administration do to the plasma concentration of drug
Reduces the peaks and troughs of drug conc in plasma
What is the difference between normal kinetics and saturation kinetics
Normal = Plasma concentrations (at Css) increase proportionally with the dose
Saturation = If dose is increased, then disproportionate increase in steady-state concentrations
Which plasma proteins binds mainly to basic drugs
B-globulin
Which plasma protein binds mainly to acidic drugs
Plasma albumin
What does extensive protein binding do to rate of drug elimination
Slows it down
Which form of a drug is active in the body
Free/unbound drugs
Name the factors relating to the drug which affect drug absorption
Lipid soluble drugs - high absorption
Large molecules - low absorption
Small particle size - high absorption
High degree of ionisation - lower absorption
Name the factors relating to the body which affect drug absorption
High surface area of absorptive surface - increases
pH affects the level of ionisation
GI motility - slow motility increases absorption
Integrity of absorptive surface
Diseases
Name the factors relating to the body which affect drug distribution
Increases with high body fat content for lipid-soluble drug
Increases with high body water content for water-soluble drugs
Low for drugs highly bound to plasma proteins
Name the factors relating to the drug which affect drug distribution
High for lipid-soluble drugs
High for weak base drugs
Low for water-soluble drugs
Low for weak acid drugs
Name the factors relating to the drug which affect drug metabolism clearance
Lipid soluble drugs - high
Water soluble drugs - low
Drug-drug interactions - inhibition reduces clearance, induction increases clearance
Name the factors relating to the body which affect drug metabolism clearance
Quantity of drug-metabolising enzymes
Enzyme polymorphisms
Decreasing blood flow to metabolising organs - decreases clearance
Low binding to plasma proteins - increases clearance
Diseases
Name the factors relating to the body which affect drug excretion clearance
Quantity of drug transporters
Decreasing blood flow to excreting organ - decreases
Decreased GFR in the kidney - decreases clearance
Low binding to plasma proteins increases clearance
Diseases
Name the factors relating to the drug which affect drug excretion clearance
High for water-soluble drugs
High for ionisable drugs
Low for lipid-soluble drugs
Inhibitory drug–drug interactions
How is the absorption of a drug altered in the neonate and what is the outcome
Absorption is variable due to:
- altered gastric emptying
- irregular peristalsis
- increased permeability of the mucosa
- rapid topical absorption due to immature percutaneous barrier
Outcome => variable bioavailability
How is the distribution of a drug altered in the neonate and what is the outcome
Increased distribution for non-lipid drugs due to:
- Greater water content in the neonate
- Decreased plasma protein binding
Decreased distribution for lipid drugs due to:
- Lower adipose content in the neonate, therefore less fat uptake
Outcome => affects plasma level, dose and doing frequency
How is the metabolism of a drug altered in the neonate and what is the outcome
Neonates have reduced hepatic function
- Very species specific
- Foals can biotransform drugs within a few days
- Other species can take 3-6 weeks
Outcome => possible lower metabolic clearance
How is the excretion of a drug altered in the neonate and what is the outcome
GFR is normal
Drug tubular secretion in the nephron takes longer on neonate
- Weak acidic or basic drugs can take 3-4 weeks
Outcome => possible lower excretion clearance
Why is there a risk of undesired CNS penetration in the neonate
The blood-brain barrier is not full complete
How is the absorption of a drug altered in the geriatric and what is the outcome
Absorption is reduced
Gastric pH is increased - alters drug ionisation
Fewer microvilli
Less mixing and dissolution
Delayed disintegration of tablets
Outcome => reduced bioavailability, lower Cmax and later Tax
How is the distribution of a drug altered in the geriatric and what is the outcome
Body mass decreases
Less water content
Increased adipose tissue
Increased volume of distribution for lipid-soluble drugs => increased half-life
Decreased Vd for water-soluble drugs => decreased half-life
Outcome => affects plasma level, dose and dose frequency
How is the metabolism of a drug altered in the geriatric and what is the outcome
Effects on metabolism are minimal
Decreased plasma albumin - less binding can lead to more free drug for metabolism
Outcome => little change
How is the excretion of a drug altered in the geriatric and what is the outcome
Decreased renal elimination
Decreased renal mass, GFR and tubular secretion
Outcome => lower excretion clearance
For the geriatric, how to alter dose regimen for renal excreted drugs
Reduce dose or dosing frequency
Use a drug that is metabolised by the liver instead
For the geriatric, how to alter the dose regimen for lipid-soluble drugs
Reduce dose or dosing frequency
For the geriatric, how to alter dose regimen for water-soluble drugs
Rarely need to change the dose
How are the pharmacokinetics of a drug altered with chronic cardiovascular disease
Decreased mentation - increased effects of sedatives
Decreased blood flow - lower clearance for highly cleared drugs e.g. anaesthetics
How are the pharmacokinetics of a drug altered with liver disease
Content and activity of phase I and II reactions are decreased
Little effect on metabolism until 80% loss
Most antimicrobials are well tolerated
How are the pharmacokinetics of a drug altered with respiratory disease
Altered serum pH and protein binding
Mainly an issue for IV anaesthetics
How are the pharmacokinetics of a drug altered with renal disease
Gradual loss of urine concentrating ability and ability to acidify
Altered drug distribution patterns
Change in acid-base balance
Uraemia: chronic acidosis, reduced albumin binding of a drug, less hepatic metabolism
How to change the dosing regimen for a patient with renal disease
Avoid renally cleared drugs
Adjust dose down for changes in GFR
How to change the dosing regimen for a patient with hepatic disease
Rarely an issue
Reduce dose if necessary
Use a drug that is renally cleared instead
How to change the dosing regimen for a patient with chronic cardiovascular disease
Avoid drugs with high clearance
Reduce dose
How to change the dosing regimen for a patient with respiratory disease
Adjust dose down for IV anaesthetics
What types of drugs have a high therapeutic index
NSAIDS - aspirin, tylenol, ibuprofen
Sedatives - benzodiazepines
Most antibiotics
Beta blockers
What types of drugs have a low therapeutic index
Neuroleptics - phenobarbital
Lithium
Some antibiotics - gentamicin
Digoxin
Immunosuppressives
Why do we do therapeutic monitoring
Detect changes in pharmacokinetics
Optimize dose/therapeutic response
Monitor compliance
Avert toxicity
