Polypharmacy Flashcards
Define polypharmacy
Polypharmacy is the concurrent use of multiple medications by a patient.
Which group are at higher risk of polypharmacy
Chronic disease and increased age are factors that increase the risk of polypharmacy.
what are the risks of polypharmacy
Risks of polypharmacy include non-adherence, confusion, incorrect storage, drug-drug interactions, interfere with desired drug effect, drug-disease interactions, and negatively impacting other diseases/symptoms.
Drug-drug interactions can occur between
- Prescription drug-drug interactions
2.Prescription/OTC/herbal drug-drug interactions
- Prescription/illicit drug-drug interactions
- Illicit drug-drug interactions
Drug-alcohol interactions
Give examples of prescription drug-drug interactions include
tramadol and antidepressants, which can lead to hyperthermia and serotonin syndrome.
Pain and Depression are common comorbidities, infact people with depression are more likely to be sensitised to pain.
Antidepressants work by acting as ↑ Serotonin
- SSRI’s (selective serotonin reuptake inhibitors)
-SNRIs (selective noradrenaline reuptake inhibitors)
-TCAs (Tricyclic anti depressents)
-MAOIs (Monoamine oxidase inhibitors) (inhibit metabolism)
TRAMADOL can also at as a SSRI - too much serotonin post receptor activity can lead to- serotonin syndrome.
Seratonin syndrome side effects: Hyperthermia and Tacchycardia
STAT: Clinical practise research datalink: 4.6 million people in 2016 there was a annual death rate of 40% with coprescription of tramadol and antidepressants
Give examples of prescription-OTC drug-drug interactions
Prescription-OTC drug-drug interactions can occur between antihistamines and benzodiazepines, affecting peripheral and central histamine receptors.
Combination cold medicine often contains antihistamines. (Diphenhydramine) It’s known as a drowsy (sedating) antihistamine
Histamine is a neurotransmitter that governs 2 major but different functions:
- Peripheral Histamine Receptors regulate the immune Response -Central Histamine receptors regulate Consciousness
Benzodiazipines: anxiety (at higher doses sedatives)
Mode of action: Stabilise the GABA a receptor in an active conformation - increased affinity to the GABA A receptor. (Inc. influx of cl- ions which result in the hyperpolarisation of the membrane and hence increased inhibition)
The combination of both could lead to loss of consciousness, affect breathing and lead to death at higher doses.
Describe Prescription-herbal remedy interactions:
- St. John’s Wort and antidepressants,
DAT/SERT/NET Blockade & MAO inhibition— can lead to serotonin syndrome - taking valerian (sedative) and sedatives (BENZODIAZEPINES & ANTI-HISTAMINES)- lead to respiratory depression.
- Good interaction: melatonin and antipsychotics.
-melatonin taken for sleep
antipsychotics function by reducing dopaminergic drive - so pateints get parkinsons like symptoms and have associated movement symptoms
When melatonin taken with antipsychotics it Reduces tardive dyskinesia
Describe a Prescription-illicit drug interaction
Prescription-illicit drug interactions include methadone and heroin
Methadone is a opioid used for opioid substitution therapy - to wean addicts off opioids and reduce severe withdrawal symptoms and avoid relapse.
Illicit methadone is combined with heroin to reduce “come down’ and withdrawal symptoms - why? because Methadone has a much longer half life than Heroin.
But the combination of these two can lead to Overdose of opiods and increased risk of respiratory depression.
Describe another Prescription-illicit drug interactions
Gabapentinoids are Gabapentin & Pregabalin. - they don’t act on GABA receptors- they inhibit VGCC- inhibit neurotransmitter release
Drug users of Gabapentin and pregabalin and reports: * Enhances the ‘high’ - inc sedation, analgesia
* Less heroin/opioid required (cost effective)
National programme of substance abuse- pregabalin has a higher rate of deaths despite higher level gabapentin prescriptions.
why- Pregabalin has enhanced pharmacokinetics
-Enhanced bioavailability (93% vs 33-66%)
- Pregabalin absorption is much faster (1hr vs 3-4hrs)
-Gabapentin absorption is rate-limited * Enhanced affinity: 6 times more potent
Give example of Illicit drug-drug interactions
Psychostimulants mode of action:
-Amphetamines: pH gradient lost ↑NT in cytosol Reversal/endocytosis of transporter ↑NT in cytosol
-MDMA/Ecstasy undergoes competitive reuptake at the Dopamine, Noradrenaline and Serotonin transporters (DAT, NET and SERT). Blocks VMAT1/2, MDMA also interacts with TAAR1.
-COCAINE/khat : as a non-competitive blocker of DAT and NET
Combined Stimulants and Psychedelics –Serotonin Syndrome
2. Combined Heroin, Non-pharmaceutical fentanyls and Novel benzodiazepines—— respiratory depression
- Cocaine, synthetic cannabinoids and chronic cannabis—cardiotoxicity
Describe cocaine and alcohol interaction
Drug-alcohol interactions: cocaine and alcohol
Normally cocaine when taken alone is metabolised to:
Benzoylecgonine and Ecgonine methylester.
When alcohol is taken with cocaine- an additional metabolite is formed- Cocaethylene: CARDIOTOXIC
The risk of sudden death is 20 times greater for use of cocaine & alcohol than it is for cocaine alone.
How can Alcohol can increase the risk of death when combined with heroin/morphine.
Rats dosed with morphine or alcohol or saline and the respiratory rate was measured using a pleythsmograph chamber.
rats given a wax pellet or a wax pellet that released morphine for 6 days and then they were given a injection of a dose of morphine
results:
Morphine pellet - slight reduction in respiratory rate (developed tollerance)
No pellet- Significant reduction in respiratory rate
results with coadministration of alcohol and morphine
No Pellet : Ethanol does not potentiate or summate with morphine in naïve animals
Morphine alone- significantly reduced respiratory rate
Morphine + ethanol- significantly reduced respiratory rate
Morphine Pellet : Low dose ethanol reverses tolerance
Morphine alone- did not signficantly reduce respiratory rate (due to tolerance)
Morphine + ethanol- significantly reduced respiratory rate
