downers

Question 1

definition of downers

Answer 1

generally hypnotics (drowsiness) and sedatives

depressants lower the level of arousal.

Question 2

inorganic bromides

Answer 2

KBr was recommended for epilepsy due to its reputation for diminshing libido.

a sedative that likely acts by replacing CNS chloride resulting in neuronal depression. widely used in 19th century and available otc until 1975

Question 3

Chloral hydrate

Answer 3

a sedative with an unclear MMoA - does act as a cardiac K+ channel inhibitor

reduces alcohol metabolism and induces rapid loss of consciousness - used as date rape drug

historically was widely consumed and frequently used in asylums

Question 4

Paraldehyde

Answer 4

a cyclic trimer of acetaldehyde that was used to calm alcohol withdrawal from 1880s-

limited risk of abuse

Question 5

Barbiturates

Answer 5

formed from barbituric acid - e.g., barbitone (1903). 2500 variants discovered.

50 marketed for sleep, anxiety, and anticonvulsants

sodium thiopental is a short acting barbiturate used in pet euthanasia and lethal injection - unconsciousness in 30s

induce CYP450s and cause severe physical and psychological dependence.

Acts primarily through GABAA PAM.

Question 6

Benzos

Answer 6

Hypnotics and sedatives discovered by accident in 1957

flunitrazepam (rohypnol) “roofies” is BZD. withdrawn from most European countries in 2010s

Long term use is often linked to consumption of other drugs. acute withdrawal is associated with anxiety, increased HR and BP, shaking, insomnia, and seizures (possible death).

Acts at GABAA as a PAM. binds to BZD site at the interface of gamma and alpha subunits. GABAA difficult to investigate due to the 19 genes that can form, in theory, almost 500,000 receptor types.

Question 7

GABA analogues

Answer 7

e.g., GBL, GHB, gabapentin, pregabalin

GHB (GBL a prodrug) has similar effects to alcohol. very steep dose dependent effects.

gabapentin and pregabalin also act at alpha2delta ion channels to cause neuronal depression. Neither actually exert their psychotropic effects through GABA.

Question 8

Alcohol

Answer 8

Causes rapid effects.

Major factor in 25% of males admitted to uk hospitals.

Severe withdrawals with delusions, tremor, seizures and death. 15-50% mortality.

unclear full MMoA

Question 9

Overview of downers statistics of use and deaths

Answer 9

3% have lifetime use of tranquillisers.

BZD deaths most common in older adults (30-69) 40-49 most common.

about 500 annual deaths in the last few years from BZD. steep increase in pregabalin deaths since 2010s. almost 500 annually. almost 10,000 annual deaths from alcohol last few years