Drug abuse 2 Flashcards
MDMA (3,4-methylenedioxymethamphetamine)
- Designer drug “Ecstasy”; “Adam”; “XTC”, “E”
- Amphetamine derivative
- Popular club / rave drug especially in Europe
MDMA (3,4-methylenedioxymethamphetamine): MOA
• Indirect serotonergic agonist
o ↑ release of 5-HT; Blocks reuptake of 5-HT
MDMA (3,4-methylenedioxymethamphetamine): actions
Actions: • Can have prolonged effect up to 1 week • Sympathomimetic and psychotomimetic • Increased euphoria, emphathy • Enhances pleasure, Heightens sexuality, Expands consciousness, positive change in self-image
MDMA Tox
• Narrow margin of safety • Cardiac arrhythmias • Hyperthermia • Convulsions • Rhabdomyolysis • Renal failure • Fatalities may occur • Chronic use may cause hepatic damage Psychiatric effects: • Psychosis • Depression (after long term use)
Cocaine
- Derived from Erythroxylon coca plant
* Very effective pleasure enhancer
Cocaine: Mechanism
Blocks reuptake of NE, DA, 5-HT
Binds transporter and reduces capacity to transport NE, DA, 5-HT
Blocks Na+ channel
Slows/blocks nerve conduction
Acts as a local anesthetic by altering the recovery of the neuronal Na+ channels
Increases the concentration of the excitatory amino acids glutamate and aspartate
in the brain, particularly in the nucleus accumbens
Cocaine: CNS
stimulation
Cortex and brainstem are targets of cocaine
↑ mental awareness, euphoria
Feeling of well- being, increased self confidence
Can produce hallucinations, delusions, paranoia
Reduction of fatigue
With regular use, feelings of restlessness, irritability, anxiety, sleeplessness, mood
swings
Prolongation of DA effects in limbic system → Euphoria
Chronic cocaine intake → DA depletion → Triggers craving for cocaine
Cocaine: Sympathetic
Potentiates action of NE
“Fight or flight” syndrome
Tachycardia, hypertension, papillary dilation, peripheral vasoconstriction
Cocaine: Withdrawal
l Fatigue, Depression, Sleep disturbances, Increased appetite
Cocaine: Metabolites
benzoylecgonine - spontaneous hydrolysis ~50%
Ecgonine - plasma / liver pseudocholinesterase 40-50% for cocaine use
Norcocaine - Liver P450 induced n-demythylation ~5%
Cocaethylene Formed only in presence of alcohol via a transesterification ~17% Crosses BBB Active metabolite, blocking reuptake As potent as cocaine
Cocaine Tox (OD)
• Delirium, violent behavior
• Pulse may be weak, irregular rapid
• Tonic-clonic seizures can be induced
• Malignant encephalopathy
• Cardiac failure: rapid elevation of blood
pressure which can lead to stroke, irregular
heartbeat, cardiac arrest
Cocaine Treatment
Agitation • Benzodiazepine (diazepam / lorazepam) Hypertension • Benzodiazepine (sedation) • Phentolamine • NO BETA BLOCKERS
MI • Aspirin • Nitroglycerin • Phentolamine • NO BETA BLOCKERS • Bromocriptine used during withdrawal to reduce craving of drug
– DA receptor agonist; effectiveness not firm
Cocaine Prolonged use
• Addiction and Physical dependency common • Continued use may result in adverse conditions: – Malnutrition – Weight loss – Sexual problems – Mental confusion – Anxiety
Cocaine Babies
- Hyperactivity
- Tension
- Muscle stiffness
- Poor reflexes
- Delayed motor development
How pure is your cocaine?
Found in 78% of seizures in 2011.
• Anthelminthic drug used by vets in Mexico
• Has some MAOI and COMT inhibitory action
• “more bang for your Buck” believed to be a player in the death of DJ
AM.
• can induce neutropenia and agranulocytosis
Crack
- Free base form of cocaine
- Rocks are smoked in crack pipe
- “Crack lips” due to hot pipe
- Cocaine frequently mixed with other drugs
Bath salts
• Ivory wave, White lightning, Charlie, Cloud 9
• Designer drugs available legally in some states
can be a combination of
– mephedrone, MDPV, and methylone
• Cathionones, similar in structure to amphetamine
Bath salts: Mechanism:
• similar transporter inhibition properties as the amphetamines though not as
potent.
Bath salts: Induce:
– Feelings of empathy (openness, love, closeness, sociability, well-being
– Stimulation / alertness
– Euphoria / mood lift / appreciation of music; and, awareness of senses.
Bath salts: Adverse Effect:
– Similar to amphetamine
– You will see on average 4 patients per month on your emergency medicine
rotation, probably more
• Clinically treat similar to methamphetamine
Khat
Catha edulis, is a flowering shrub native to East
Africa and the Arabian-Peninsula, Khat refers to
the shoots and leaves
• Most commonly abused amongst African immigrants
• Chewed and stored in cheek to release juices (much like chewing tobacco)
• Active chemical is cathinone (similar to bath salts)
• Structurally similar to amphetamine and about as potent
o Very similar effects to amphetamine with about a 90 min time of
action
o Side effects and withdrawal same as amphetamines
Nicotine
• Principal alkaloid of plants of genus Nicotiana • Lipid, soluble tertiary amine – Rapidly absorbed, distributed – Metabolite: cotinine – Tars in cigarette smoke accelerates metabolism of nicotine and other drugs
Cigarettes accelerate metabolism of certain drugs
Nicotine: Uses
Smoking cessation therapy
Nicotine nasal spray (Nicotrol NS)
Nicotine Inhaler (Nicotrol Inhaler)
E Cigarretes
Nicotine: MoA
• Activates cholinergic nicotinic receptors (CNS, PNS)
• Nicotine initially stimulates, then blocks the receptor
• Inhibits MAO → Activate DA neurotransmission →dependence?
• Stimulates release of NE and DA
• This promotes
– Mild euphoria
– ↑ arousal, concentration
– Improved memory
• Appetite suppression
Nicotine: Pharmacokinetics
• Absorption via oral mucosa of lung, GI mucosa, skin • Crosses placental membrane • Secreted in milk of lactating women • Metabolism in lung, liver – Cotinine major metabolite • Urinary excretion
Nicotine: Adverse Effects
- Irritability
- Tremors
- Intestinal cramps/diarrhea
- Increased heart rate
- Increased blood pressure
Nicotine Toxicity and withdrawl
Toxicity
• Central respiratory paralysis
• Severe hypotension caused by medullary paralysis
Withdrawal • Peak 1-2 days after quitting and then decreases over a period of weeks – Irritability – Anxiety – Restlessness, frustration – Difficulty concentrating – Headache – Insomnia
Caffeine: Clinical Uses
• Treatment of idiopathic apnea of prematurity (caffeine citrate)
Neonates.
• Emergency stimulant in acute circulatory failure; diuretic; treatment of
spinal puncture headaches (caffeine sodium benzoate) Adults.
• Adjuvant for analgesics
– Has some mild analgesic properties
• Do not interchange the caffeine citrate salt formulation with the
caffeine sodium benzoate formulation
Other Uses
• Most widely consumed stimulant in world
Caffeine: Source and MoA
• Methylxanthine • Source: coffee, tea, cola drinks, chocolate candy, cocoa, chewing gum • Mechanism of action – Translocation of extracellular calcium – ↑ cAMP, cGMP via inhibition of PDE – blockade of adenosine receptors
Caffeine as a Stimulant: • Effects
– ↓ fatigue – ↑mental alertness → via stimulation of cortex – ↑ anxiety – ↑ tremors – ↑spinal cord stimulation (2-5 g caffeine) – Lethal dose: cardiac arrhythmias (100 cups of coffee, 10 g)
Caffeine as a StimulantOther Effects
– Mild diuretic action
– At high doses: positive inotropic/chronotropic effects
on heart
– ↑secretion of gastric HCl
Moderate doses: insomnia, anxiety, agitation
– High doses: emesis, convulsions
Lysergic acid diethylamide (LSD)
• Agonist at 5-HT1 and 5-HT2 • Hallucinations with brilliant colors and mood alteration occurs • Adverse effects: hyperreflexia, nausea, muscle weakness; Increased BP, HR, mydriasis • Flashbacks (days to 1 yr) • Not considered a drug of abuse • Neuroleptic therapy with drugs such as Haloperidol block hallucinations
Ketamine and Phencyclidine (PCP, “Angel dust”)
Antagonizes glutamate action • Anticholinergic activity • Dissociative anesthesia (insensitivity to pain without loss of consciousness), (PCP, an analog of ketamine – Extremity numbness – Staggered gait – Slurred speech – Muscular rigidity – Blood pressure, heart rate increase – Nausea/vomiting – Violent behaviours/suicidal – Seizures
Hallucinogenic Mushrooms
• Street names: Shrooms,caps, divine flesh, magic mushrooms • Psilobycin, Psilocin • 20 min – 6 hr – Dilated pupils, confusion, vertigo – Exhilaration, laughter, hallucinations – Tachycardia, hypertension – Nausea, Vomiting • Treatment: Activated charcoal, diazepam
Use of hallucinogens in Religion
Native American Church: Practiced predominantly by Apache, Navajo and Plains Tribes.
• Involves the use of Peyote in ceremonies
– small, spineless cactus(Lophophora williamsii) found in the southwestern US and
northern Mexico.
– Contains a number of phenethylamine alkaloids, of which the principal one is mescaline
• Ingested as dried buttons, which are the round fleshy tops of the cactus. Or as a powder and
prepared as a tea.
• Mescaline produces effects similar to LSD, but is not as potent.
• Peyote may be used legally in the US by members of the Native American Church, it is
otherwise restricted under the US Controlled Substances Act.
Marijuana
- Δ9-tetrahydrocannabinol (THC) metabolized to 11-OH-Δ9-THC
- Euphoria followed by drowsiness/relaxation
- Receptors found in basal ganglia, hippocampus, cerebellum
- Impairs short-term memory and mental activity
- Visual hallucinations, delusions
- ↑Increased heart rate
- “munchies”
- Tolerance, withdrawal, addiction possible
- Highly lipophilic
Tetrahydrocannabinol (THC)
• Dronabinol:
– Used to treat severe nausea and pain caused by
some diseases such as AIDS and cancer as well as
an appetite stimulant “Medical Marijuana”
• Marijuana (dried plant material) vs. Hashish
(exuded resinous material from plant)-Hash
oil (liquid extract from plant material)
LIPOPHILIC
NBome
New Kid on the block, deaths reported in WV
• W.Va. man charged with wife’s drug death
• Dec. 06, 2013 @ 07:34 AM
The Associated Press
CHARLESTON, W.Va. (AP) — A West Virginia man has been charged with first-degree murder for
allegedly providing a synthetic hallucinogenic drug to his wife that led to her death.
According to the Charleston Gazette, a court affidavit reveals that 35-year-old Todd Anthony Honaker of
Left Hand believed he was buying LSD, but instead gave his wife an experimental drug. Honaker told
police his wife, Renee, took a dose of the drug and began convulsing. The Roane County woman died
March 1.
An autopsy determined that Honaker’s wife died from abusing a synthetic hallucinogen known as 25b- NBOMe.
• 5HT2A agonist
• Agitation and hallucinations
• Tachycardia and hypertension
• May require physical restraints and treatment with intravenous benzodiazepine.
• Prolonged periods of aggressive behavior.
Inhalants
Volatile Solvents
paint thinner
nail polish remover
spray paint
Aerosols
deodorant
hair products
cooking products
Gases
refrigerants
Nitrous Oxide
Nitrites
“poppers”
