Farmakologický stav1
SPECIFICITIES OF PHARMACOTHERAPY IN PATIENTS OF SENIOR AGE
MUDr. Jana Nováková, Ph. D.
Department of Pharmacology
Faculty of Medicine, Masaryk University in Brno
Why change prescription in geriatric medicine?
How to change prescription in geriatric medicine?
Drugs potentially unsuitable at senior age
Drug mistakes in geriatric medicine
Specific characteristics of old-age morbidity I
Organs lose their functional reserve
Lower adaptation to changes of both internal and external environment
Easy decompensation of organ functions and organism as a whole
Health state assessment is difficult – discrepancy between objective and
subjective condition
Polymorbidity (concomitant diseases – unrelated; chain of causes:
Immobilisation → phlebotrombosis → pulmonary embolism → pressure
sores, urinary incontinence → sepsis)
Microsymptomatology – asymptomatology
no fever, leucocytosis, silent myocardial ischemia
Mono(oligo)symptomatology
tachyfibrilation (thyreotoxicosis)
➢ Non-specific symptoms
fatigue, dysorexia, weight loss
Secondary affection syndromes
symptoms in other than the affected organ – the lowest reserve (brain –
delirious state, kidneys)
Catenating of symptoms (cascade reaction)
Atypical drug reactions
Specific characteristics of old-age morbidity II
Geriatric patient requires a complex approach + individualization of therapy
Age associated changes
Polymorbidity
Drug – drug, drug – disease interactions
Chronic pharmacotherapy – changes in efficacy and safety
with time, revision of medication every 6 months
Course and results of treatment –
– increased variability
Safety of treatment
Complications of pharmacotherapy at old age
Chronic diseases
Disability
Increase in post-medication reaction
Polypharmacy
Potentially inappropriate medicaments for elderly
patients
Non-compliance
Change in pharmacokinetics
Change in pharmacodynamics
Most frequent AEs in elderly patients
Cardiovascular system – orthostatic hypotension,
arrythmia, syncopes, falls
Gastrointestinal system - diarrhea, constipation,
sickness, vomiting
Central nervous system - sedation, delirium,
confusion, depression, extrapyramidal symptoms
Compliance decreases with old age
Up to 60% of seniors do not take medications
according to their doctor′s recommendation
Pharmacological compliance decreases with the
number of drugs used and limited self-sufficiency
(impaired eyesight, memory, ability, thinking)
Social compliance - loneliness, isolation, poverty
10 most frequently taken drugs in seniors
(International study Shelter 2009 - 2011)
1. Laxatives 42%
2. Drugs for acid-related disorders 41%
3. Antiaggregatory drugs 38%
4. Benzodiazepines 36%
5. Antidepressants 36%
6. Diuretic stimulants 35%
7. Analgesics 34%
8. Antipsychotics 26%
9. ACE inhibitors 23%
10.β-blockers 23%
Polypharmacy
Concurrent use of multiple drugs in a risky
combination or in excess (clinically unnecessary)
Usually 4 and more drugs
Increases with age and polymorbidity
Polypharmacy
̶ Drug reactions often qualify a state considered to be a
manifestations of ageing:
imbalance somnolence
giddiness tiredness
falls asomnia
nervousness malaise
incontinence depression
confusion
Some may be indicative of a psychiatric treatment
→ with psychotropic drugs
Inappropriate prescription (most frequent mistakes)
- Insufficient treatment (underprescribing)
Doctors do not prescribe drugs with demonstrable
benefits (statins, antidepressants, ACEi)
- Redundant treatment with no indication
(overprescribing)
Hypnotics, benzodiazepines, peripheral
vascular dilators, nootropics
- "Imperative drugging"
A drug is prescribed for every single disease
- Prescription with a risk of interactions
- Prescription of high-risk profile medications
Drugs that are counter-indicated for comorbidities
(β-blockers + COPD)
PHARMACOKINETICS at old age
Influenced by age-related changes
Age-related changes in drug pharmacokinetics and their clinical consequences - ABSORPTION
Decreased splanchnic and periphery perfusion,
Decreased GIT motility,
Absorption area decay (atrophy of mucosa and
villi)
Increase in ventricle pH
Prolonged absorption after p.o. /i.m. administration
Delayed reactions to medications
Age-related changes in drug pharmacokinetics and their clinical consequences - DISTRIBUTION
1. Decrease in total body water
2. Increase in body fat
3. Hypoalbuminemia
1. Increase in plasmatic levels for hydrosoluble medicines (↓ Vd)
2. Risk of cumulation of liposoluble medicines – toxicity,
prolonged elimination
3. Increase in free fraction of medicines with albumin linking
(frequent malnutrition)
Age-related changes in drug pharmacokinetics and their clinical consequences - METABOLISM
Decrease in weight and liver perfusion
Decrease in CYP3A4 function
Decrease in glucuronidase in very old persons
Slight slow-down in biotransformation
Increased risk of AE of drugs – drug
interactions in polypharmacy
Age-related changes in drug pharmacokinetics and their clinical consequences – ELIMINATION
Decreased renal blood flow
Decreased glomerular filtration – physiological
characteristic of old age
Decreased tubular secretion
Decreased excretion of drugs that are eliminated by
kidneys
Prolonged T1/2 (amiodarone, digoxin, fluoxetine,
alprazolam)
Danger of toxicity
PHARMACODYNAMICS at old age
Deterioration of homeostatic mechanisms
Changes cause an increased risk of adverse and unexpected reactions
Changes at receptor levels cause changes in tissue receptivity
Frequent clinical problems of seniors in relation to changes accompanying ageing:
Drugs with a negative impact I
Orthostatic hypotension (centrally effective antihypertensives, diuretics, β-blockers, tricycl.
antidepressants, benzodiazepines)
Postural instability (same drugs as with ort. hypotension)
Extrapyramidal symptoms, dyskinesia (metoclopramide, classic antipsychotics, haloperidol)
Decrease in cognitive functions, behavioural disorders, delirium (centr. sympatholytics,
tricyclic antidepressants, barbiturates, benzodiaz., analgesics-anodynes, antiparkinsonian
agents, antihistaminics, H2-blockers, theofyline, digoxin, indometacin)
Constipation, subileus (anodynes, tricycl. antidepressnats, antihistaminics, spasmolytics)
Urinary incontinence (diuretics – loop, anticholinergics)
Increased risk of hypothermia (sedatives, hypnotics, antipsychotics, vasodilatants,
myorelaxants)
Risk of hyponatremia, susceptibility to dehydration (chlorpropamid, diuresics, SSRI)
Susceptibility to erectile dysfunction, gynaecomastia (α1-sympatholytics, sedatives, urin.
tract spasmolytics, spironolaktone, digoxin)
Frequent clinical problems of seniors in relation to changes accompanying ageing:
Drugs with a negative impact II
Increased risk of bleeding (increased sensitivity to warfarin, heparin)
Increased sensitivity to digoxine – AE already at therapeutical
concentrations
Frequent clinical problems of seniors in relation to changes accompanying ageing:
Drugs with a negative impact III
Mark H. Beers, 54, Expert on Drugs Given to Elderly, Dies Feb 28, 2009
Beers' List
— Potentially Inappropriate
Medications for the Elderly
It is not about counterindications at administration, however utmost care is
required!!!
Fick DM, Cooper JW, Wade WE, Waller JL, Maclean JR, Beers MH.
Updating the Beers criteria for potentially inappropriate medication use in older adults:
results of a US consensus panel of experts. Arch Intern Med. 2003;163:2716-2724
New Beers' criteria (modified) 2012, 2015!!!
BEERS' LIST – for instance:
Medicament/drug
group
Note, risks
Tricyclic
antidepressants
Significant anticholinergic effect, risk of
sedation, orthostatic hypotension and
arrhythmias. SSRI are a safer alternative.
Barbiturates
(nowadays obsolete)
Significant sedation, habit-forming,
especially those with short-term effect
are inappropriate.
Benzodiazepines
Risk of sedation, habit-forming, drugs
with a long half-life are inappropriate
(diazepam, flurazepam, chlordiazepoxid);
benzoadiazepine (oxazepam) with a
short-term effect is more suitable, or
nowadays these are not recommended at
all!
General PRINCIPLES of pharmacotherapy in geriatric medicine
Know the effects of changes caused by ageing on the effect of medicines
Try to contribute to optimization of compliance (adherence)
Know the drugs that are better to be avoided in geriatric medicine
Know the 7 fundamental principles of prescribing drugs in geriatric medicine
„Start low, go slow.“
„Start with a low dose and
increase it
slowly.“
Seven main principles of drug prescription in geriatric medicine
Remember a drug can cause a pathological symptomatology (disease)
Seek for establishing the diagnosis prior to prescription
Know the pharmacology of the prescribed drug well
Start „low" and proceed slowly; better still: start „low" and stay „low“
Be aware of other medications of the patient
Be careful about compliance
Regularly check the list of drugs taken
How to change prescription in geriatric medicine?
Adverse drug interactions
- Drug – drug interaction:
warfarin + sulfonamide (competition for a linkage to plasm. proteins)
alprazolam + zolpidem (drugs of the same group, potentiation of reaction)
anticholinergics + drugs with a high absorption capacity, antacids (slowed resorbence)
- Drug - disease interaction:
verapamil + impulse transfer disorder (heart rhythm disorder)
opiates, anticholinergics + dementia (delirium)
- Drug – food
grapefruit juice (CYP3A4 inhibitor)
herbaceous vegetables (vit. K – decreases the effect of warfarin)
chinolons + minerals (decreased absorption of chinolons)
Expert recommendations for geriatric pharmacotherapy
Expert consensus for the CR 2012
Recommended approach: Geriatric medicine for general practitioners 2010
Beers' criteria of 2003 (USA)
Laroche 2007 (France)
STOPP/START 2008 (Ireland) take into account (in)appropriateness of drugs at
simultaneous assessment of patient‘s chronic diseases
New Beers' criteria 2012
Potentially inappropriate medications at old age
PIMs – potentially inappropriate medications
- the term coined by Beers in 1991 (USA)
Indication unsupported with scientific evidence
Higher risk of post-drug reactions
Low cost effectiveness
A safer alternative is available in the market
= Drugs the potential risk in seniors over 65 overtops
expected benefit at long-term treatment, or the efficacy
of the medication is inadequate or inadequately verified
STOPP and START criteria
(Ireland 2008)
Listed according to physiological systems
STOPP criteria – e.g. cardiovascular system
digoxin – dosed 0.125 mg/day on a long-term basis in decreased kidney function ( Kr/S > 150 µmol/l and GF <
50ml/min)
loop diuretics with oedemas without signs of heart failure (unverified efficacy; suitable compression of
extremities
loop diuretics in monotherapy treating hypertension (safer and more efficient alternatives)
thiazide diuretics with gout (danger of causing an attack)
non-CS β-blockers with COPD (risk of bronchospasm)
diltiazem or verapamil with hearth failure NYHA III-IV (risk of retrogression)
Ca channel blockers with chronic constipation
ASA + warfarin without protection against GIT bleeding (H2 antagonists, proton pump inhibitors)
dipyridamol in secondary prevention of CVS in monotherapy
ASA dosed > 150 mg/day (unsubstantiated efficacy)
ASA with missing history or symptoms of IHD
warfarin unsubstantiated benefit of treatment longer than 6 months with uncomplicated deep vein thrombosis)
STOPP – patients with a history of falls
benzodiazepines
antipsychotic drugs
1st gen. antihistamine drugs
vasodilatants
opioids
STOPP – analgesics
Strong opioids (morphine, fentanyl)
Long-term use of opioids (longer than 3 months), if laxatives are not used
simultaneously, there is a risk of worsening cognitive deficite
(exception: paliative therapy, severe chronic pain)