Units 1-8 principles Flashcards
Drugs either work via … or …
Receptors: agonist; antagonist
Enzymes: ACEi
When do pharmacodynamic interactions happen
2 drugs work via different pathways to have the same effect
Principles of pharmacokinetics (ADME)
Absorption
Distribution
Metabolism
Elimination
Lipophilic drugs are distributed
Around the whole body
Hydrophilic drugs
Stay in the plasma
The most important enzyme involved in metabolism
P450 system
The two phases of metabolising drugs from lipophilic to hydrophilic in the liver
Phase I - oxidation/reduction/hydrolysis
Phase II - conjugation with glucuronide/sulphate
Inducers of P450 system
Carbamazepine Phenytoin Rifampicin Chronic alcohol intake Barbecued meat St John’s Wort
Inhibitors of P450 system
Erythromycin Ciprofloxacin Miconazole Sodium valproate Grapefruit juice Cranberry juice
Which type of drugs are excreted unchanged
Hydrophilic
Drugs that are metabolised into active metabolites and may accumulate in liver failure
Opioids
Therapeutic window
Range in which the drug is clinically effective without causing toxic side effects
Drug half-life
Time taken for plasma concentration of a drug to decrease to 50% of its original value
A steady state of a drug is reached after how many half-lives
4
Why is a loading dose necessary for drugs with a long half-life
Drugs with long half-lives take longer to reach steady state
4 cases of drug monitoring
- cannot predict how much drug px requires
- narrow therapeutic window
- if symptoms are due to side effects
- concern that px is not taken the drug
Examples of monitored drugs
Digoxin Lithium Carbamazepine Phenytoin Theophylline Certain IV antimicrobials
Pros oral
Convenience
Cons oral
- nauseated px
- NBM/swallowing problems
- first pass metabolism
- compliance
- time to reach steady state
Pros rectal, sublingual & buccal
- avoids first pass metabolism
- good for nauseated/NBM
- no need for IV access
- topical tx
Cons rectal, sublingual & buccal
Local irritation
Pros IV
- fast
- reliable
- bolus or infusion
Cons IV
- requires IV access
- drugs reactions common
- avoid in IVDUs
Pros IM
- fast
- reliable
- no IV access needed
Cons IM
- painful
- not if clotting problems
Pros subcutaneous
- avoids first pass metabolism
- no IV access needed
- relatively painless
- px can self-inject
Cons subcutaneous
- local irritation
- px acceptability
- needle-phobias
Pros topical
- avoids first pass
- px acceptability
- avoid systemic side effects
Cons topical
- local irritation
- require adequate technique/appropriate dosing
Consider this safety aspect when prescribing
ALLERGY
Compliance
Extent to which px behaviour matches prescriber’s recommendations
Adherence
Extent to which px behaviour matches agreed recommendations form prescriber
Concordance
Consultation process in which doctor and patient agree therapeutic decisions that incorporate their perspective views
Five divisions of side effects
Predictable Bizarre Chronic Delayed End of treatment effects
When does prescribing cascade happen
Medication given to counteract the side-effects of another medication
Safety wise, attention should be paid with what 4 drugs in particular
Insulin
Opiates
Warfarin
DOACs
4 potential fates of drugs in terms of first metabolism (absorption)
- not metabolised before entering general circulation
- substantially metabolised but that can be overcome by prescribing large amounts
- completely metabolised before entering circulation (GTN)
- become active after 1st pass
A hydrophilic drug such as digoxin is prescribed in the same quantities in a 90kg or a 65kg. How so without accounting for the extra weight?
Extra weight is fat
Int ems of drug safety, what are the characteristics of drugs that make you worry in terms of P450 interactions
- narrow therapeutic window
- old-fashioned drugs
Why should you initially start slow and then increase the dose of carbamazepine and phenytoin
They induce their own metabolism
Drugs the patient is on that should make you alert regarding interactions
Warfarin Theophylline Carbamazepine Phenytoin OCP
4 general considerations when prescribing a new medication
Allergy
Comorbidities & drug interaction
Pregnancy/breastfeeding
Hepatic/renal failure
Alternative classification of drug administration
Enteral: GI tract eg oral/rectal
Parenteral: non-GI eg IV/IM/subcutaneous
Topical
Patient-centred factors for non-compliance
Age
Psycho-social factors
Ethnicity
Patient-prescriber relationship
Therapy-centred factors for non-compliance
Route of administration
Duration of treatment
Complexity of regime
Side effects
Five types of side effects of drugs
Type A: predictable, common & rarely fatal
Type B: unpredictable, rare, fatal (can be), should document
Type C: chronic, taking meds for too long
Type D: delayed, uncommon, after completing tx
Type E: end-of-tx, if stopped abruptly
2 Abx please look for them for P450 interaction
Ciprofloxacin
Clarythromycin
