Week 6 Reading: Prescription Drugs; the US Opioid Crisis

Question 1

Diversion : two problems that can occur with prescription drugs

Answer 1

• People who receive medication on prescription and take too much or become dependant

-People who use them without medical direction

Question 2

Most common prescription drugs that are diverted and misused

Answer 2

Benzodiazepines, painkillers like codeine, morphine and oxycodone and stimulants like Ritalin.

Question 3

Fentanyl

Answer 3

• Rising deaths due to fentanyl

-50 x more potent than heroin.

-Often fentanyl is mixed with other drugs, provided to users without knowledge (i.e. don’t know it’s fentanyl so take their usual dose), or provided in way too high doses.

Question 4

US opioid crisis number of death stats

Answer 4

• In 2018 there was more deaths due to opioid overdose than from road traffic accidents and more than the amount of US combatants killed in action in the Vietnam war.

Question 5

Two reasons for the ‘perfect storm in the US’ (opioid crisis):

Answer 5

• The attempt by the UN to reduce heroin misuse by limiting production of opium poppy –> cartels turn to fentanyl (one third of price to synthesize). It’s very profitable as a drug.
• Massive rise in prescription opioids such as oxycontin in the last fifteen years –> begun the opioid problem that has now morphed into the massive use of illicit opioids.

Question 6

Information provide by doctors contributing to the opioid crisis

Answer 6

There was not much information available about the addictive nature of opioids with many doctors pushing the narrative to patients that if you were taking opioids for pain relief you would not get addicted. Also limited other alternatives e.g. physiotherapy and behavioural therapy.

Question 7

Acute versus chronic pain:

Answer 7

• Acute pain : body telling you something that might be damaging. Lasts a short period and goes away when the damage is removed or when you body is healed itself.
• Chronic pain : persistent pain often lasts after the body has healed, when it isn’t a useful sensation although it sometimes is caused by a long-term health problem.

Question 8

Pharmaceutical companies fueled the problem

Answer 8

• Encouraged doctors to overprescribe to the point where some of them became pill mills.
• Very real consequences for people: powerful opioids became accessible and this lead to addictions + accidental overdose.

Question 9

PDMPs (prescription drug monitoring program)

Answer 9

-tried to combat the trend:

• Identified physicians with a high rate of prescribing
• Tried to implement inventions to stop doctor shopping i.e. patients going round different doctors to get multiple scripts (can go of state though to avoid these restrictions).

Question 10

Government influence in trying to shut down the opioid crisis:

Answer 10

• Guidelines for limiting prescriptions
• Some states sued pharmaceutical companies —> Some doctors became scared of prescribing: which worsened the situation for people already dependant on opioids who had to turn to the black markets to relieve withdrawal symptoms (who provided fentanyl instead of oxycontin) –> death
• Now naloxone (rapidly reverses effects of opioid overdose) for first responders are readily available and for members of community e.g. family members of drug users.
• Safe injection spaces and fentanyl testing kits have not been authorized.

Question 11

What is needed to help those addicted to opioids for pain purposes

Answer 11

A proper program on how to control pain without prescription is required. But there should never be a sudden cut off in supply once someone is addicted to opioids –> need gradual weaning off and substitution of less toxic opioid painkillers e.g. buprenorphine and/ or non-medication treatments for pain.

Question 12

What are benzodiazepines?

Answer 12

• First appeared in the 1960s

-Treat a range of physical and mental health problems.

Common benzodiazepines:
- Librium (1960)
- Diazepam (1963) approved for use under trade name Valium
- Ativan
- Xanax
- Rohypnol
- Mogadon

Question 13

How do benzodiazepines work?

Answer 13

• Act by increasing the effects of whatever GABA is present. GABA has the effect of calming the brain –> with this comes the risk of overdose: could switch off essential functions including breathing.

Question 14

Barbiturates + how they compare to benzos

Answer 14

-Were the first wave of drugs shown to be useful for anxiety and were replaced by benzodiazepines.
(semi dangerous and used in suicides e.g. Marilyn Monroe)

-Benzodiazepines are different to alcohol + barbiturates in that they can’t exceed the effects of the GABA that naturally occur in the brain –> less likely to overdose.

Question 15

Natural benzodiazepines in the brain

Answer 15

Endozapines –> deficits = cause of anxiety disorders + insomnia?

Question 16

Benefits of benzodiazepines

Answer 16

-Commonly take for anxiety, can help relieve muscle spasm, treat convulsive disorders such as epilepsy, given before procedures to reduce anxiety.

• Heroin addicts take them to reduce the negative effects that occur as a heroin high wears off.

Question 17

Harms of benzodiazepines

Answer 17

• Side effects = light-headedness, heart [palpitations, headaches, mild impairment in memory (as GABA essential for this)
• Cognitive impairment will diminish once the individual comes off the medication.
• Can be used by people committing suicide i.e. taking in large doses depresses the respiratory system.

-Interactions between Heroin, benzodiazepines and alcohol can cause death via overdose.

Question 18

Physical dependence on benzodiazepines

Answer 18

• Common
• If used to them for a long time then stopping suddenly can cause severe withdrawal + convulsions (withdrawal is worse the longer you have been on them)
• With tapered doses people will still experience rapid heartbeat, insomnia, irritability, anxiety, wight loss and muscle cramps –> but withdrawals are not as severe as typically characterised addiction.
• 80% of benzodiazepine users who had taken them for an average of 17 years to help them sleep stopped without any trouble with a gradual reduction in dose and information about sleep hygiene (with doctors support transition off can be smooth).

Question 19

Tolerance phases for benzos

Answer 19

• Phase 1 = patient has abnormally low GABA function, feels anxious constantly
• Phase 2=doctor prescribes a benzodiazepine –> Brings GABA up to normal range (feel good) –> over time tolerance builds and GABA function decreases (still okay)
• Phase 3=doctor tapers dose
• Phase 4=coming off the drugs –> patient feels anxious (even more so when they first went to doctor). Once withdrawal passes they will probs feel better than before treatment.
• Phase 5=Outcome 1 –> GABA function and levels of anxiety are now in normal range (most optimum). Other outcomes with see Aa continued decrease in GABA functioning and heightened anxiety but their condition is still less severe than pre-treatment.

Question 20

Common SSRIs

Answer 20

citalopram, escitalopram, paroxetine, sertraline, fluoxetine.

Question 21

Benefits of SSRIs

Answer 21

• SSRI’s have less side effects than previous medications against depression e.g. tricyclic antidepressants and have almost no abuse potential.
• Almost impossible to die from overdose –> so suicide with them is not an option.
• SSRIs have almost no street value as can’t be taken for pleasure: animals won’t self-administer them i.e. not reinforcing.

Question 22

How do SSRI’s work?

Answer 22

Work by blocking reuptake of serotonin at nerve terminals –> serotonin levels in the brain slowly increase to rectify a deficit that we believe underpins depression in some people.

• Step up on benzodiazepines to treat anxiety as works on the serotonin system as opposed to GABA (down-regulation of GABA receptors cause withdrawal symptoms).

Question 23

Negatives of SSRIs

Answer 23

• Getting used to SSRI’s at first can take a great deal of motivation —> can increase insomnia, anxiety and restlessness –> overtime these effects wear off and the antidepressant function prevails (that’s the hope at least)

Question 24

So SSRIs increase the risk of suicide?

Answer 24

• Complicated relationship: confounding –> depressed people are more likely to commit suicide in the first place
• Energization effect = depressed people commit suicide after receiving treatment seeing their symptoms improvement because at lowest ebb they did not have the energy or ability to plan/ carry out a suicide plan.
• For the most part though using SSRIs drops suicide risk and this is reflected in the suicide rates of countries where they have become more widespread e.g. Hungary and the US.
• Reduces access to means for suicide in that the drugs themselves can’t be used to overdose.
• Some elevated risk in adolescents (but medications are rarely effective for this group anyway).
• Important that doctors educate patients on the shit first period of taking –> this will pass and the positive effects of taking SSRI’s will come out.

Question 25

Relapse versus recurrence as it relates to depression and SSRIs

Answer 25

• Relapse = first episode returns
• Recurrence = when a new episode of illness begins after full recovery.
• Over a 20 year period almost everyone who has had one episode of depression will have another one –> more frequent = more likely to happen again.
• Most powerful effect of SSRIs is preventing the recurrence of these disorders so long as the patient keeps taking the medication.

Question 26

Rebound versus overshoot in relation to SSRIs

Answer 26

• Rebound = when discontinuing the medication causes a deterioration in the condition being treated e.g. women become fertile after the stop taking the contraceptive pill.
• Over-shoot= deterioration is so greater that the patient’s condition is worse than before they started treatment. Could be lethal in cases like epilepsy.
• For SSRIs the longer you have been taking them the less likely rebound is compared to benzodiazepines where problems are more likely when come off if you have been taking them for longer periods.

Question 27

Discontinuation syndrome

Answer 27

-Results from stopping taking SSRIs. Syndrome characterised by Nausea, dizziness, lethargy, headache, influenza like feeling. Fully reversed by taking another dose. Peak at 2 to 5 fays then decay quickly over a few more days, occasionally lasts several weeks.

• Rare for someone not to be able to come off SSRIs at all.

Question 28

Painkillers : risk of abuse

Answer 28

-balance between the intensity of the drug and its availability e.g. a stronger painkiller than codeine would result in a greater tendency for addiction and abuse but they are less available in the first place so it’s unlikely to be an issue.

• When taking a painkiller for chronic pain as prescribed by a doctor it’s unusual to become addicted because the patient does not associate the drug with pleasure.

Question 29

Painkillers : differing approaches by countries

Answer 29

• Different countries have different approaches but it’s hard to find a balance between avoiding addiction and treating pain e.g. US is very liberal with prescriptions and have huge rates of addictions, the UK is very stingy and may have less of an addiction problem but more people in chronic pain suffering.

Question 30

Big Pharma

Answer 30

-Handful of pharmaceutical companies that produce most of the new medications.

-Concern about whether these medications are ineffective, unnecessarily or will have unpleasant side-effects.

Question 31

Regulations on the pharmaceutical industry

Answer 31

• The pharmaceutical industry today is one of the most regulated in the world and the process of getting drugs approved is rigorous.

Stages of approval:
- Company choose a target drug to investigate
- They run a toxicology test on animals to determine safety ratio , longer term effects and whether its addictive
- Move on to studies on healthy volunteer human subjects to establish correct dosage
- Clinical trials
- After two positive trails the company can apply for marketing authorization.

Question 32

Clinical trials:

Answer 32

• Transparent about process: very hard to get an ineffective/ harmful drug approved today
• Half patients are given the drug, half patients are placebo or existing treatment
• Double blind usually
• Outcomes collected by physicians but analysed by independent statisticians
• Danger that companies stop trying to generate new treatments because he approval process is so costly/ hard (particularly true for mental health disorders).

Question 33

Mental Health Epidemic

Answer 33

• Biggest health burden in Europe today –> costs more than heart disease, diabetes and cancer combined.
• Leading problem for men = alcoholism, Leading problem for women = depression.

Question 34

Gps effect on the mental health epidemic

Answer 34

• Gps have very little training about mental health issues –> has flow on effects e.g. people self-medicating and becoming addicted which places the healthcare system under even more strain (1/4 of male alcoholics are thought to have an undiagnosed anxiety disorder).
• Trusting therapeutic relationship is essential for treatment success –> acknowledge required that only the patient is a true expert in their own experience.

Question 35

Informed Consent

Answer 35

• Rather than allowing regulatory bodies or pharmaceutical companies to decide which drugs are made available to patients perhaps we could develop a new model for approving drugs based on informed consent.
• Work towards trajectory of personalised medicine : what might be beneficial to some might be harmful to others