N3380 Therapeutic CNS Stimulants and Drugs of Abuse Exam2

BBB

-only permits lipid soluble drugs "Big Booty Bitches in da club bc fat booty"

-other drugs must have a (transport) system to enter

-if can cross the BBB then placenta also

Tolerance

Decreased response w prolonged use

Physical dependence

Abrupt discontinuation will precipitate withdrawal

-ETOH withdrawal can cause seizures = DEATH

Amphetamine (Adderall) (prototype)

-CNS stimulant

-Increase Dopamine and Norepinephrine (central and peripheral) by reversing the transporter "DAT/NET" and inhibiting the storage "VMAT".

-Used in ADHD and Narcolepsy

(mixture of L and R enantiomer)

-Drug interactions- MAOI=HTN crisis; 3wk prevention gap, DONT combine stimulants

Dextroamphetamine (Dextro=right)

-CNS stimulant

-Increase Dopamine and Norepinephrine (central and peripheral) by reversing the transporter "DAT/NET" and inhibiting the storage "VMAT".

-Used in ADHD and Narcolepsy

MORE POTENT bc R crosses BBB

-Drug interactions- MAOI=HTN crisis; 3wk prevention gap, DONT combine stimulants

Lisdexamfetamine

-CNS stimulant

-Increase Dopamine and Norepinephrine (central and peripheral) by reversing the transporter "DAT/NET" and inhibiting the storage "VMAT".

-Used in ADHD and Narcolepsy

(Pro-Drug-Vyvanse "less abusable must be given PO")

SPECIAL NAME BC SPECIAL USE (phonetically same)

-Drug interactions- MAOI=HTN crisis; 3wk prevention gap, DONT combine stimulants

Levoamphetamine (Levo=left)

-CNS stimulant

-Increase Dopamine and Norepinephrine (central and peripheral) by reversing the transporter "DAT/NET" and inhibiting the storage "VMAT".

-Used in ADHA and Narcolepsy

*LESS POTENT bc L can NOT cross BBB)

-Drug interactions- MAOI=HTN crisis; 3wk prevention gap, DONT combine stimulants

Methylphenidate (Ritalin, Concerta) (prototype)

-CNS stimulant

-Increase Dopamine and Norepinephrine (central and peripheral) by reversing the transporter "DAT/NET" and inhibiting the storage "VMAT". (same as AMPHETAMINES but w different chemical structure)

-FIRST LINE in ADHD and Narcolepsy

-50:50 mixture half ACTIVE isomer=Dexmethylphenidate and half LESSACTIVE isomer=L-methylphenidate.

-dex=R (crosses BBB) so more potent

-Drug interactions- MAOI=HTN crisis; 3wk prevention gap, DONT combine stimulants

Dexmethylphenidate (Focalin)

-CNS stimulant

-Increase Dopamine and Norepinephrine (central and peripheral) by reversing the transporter "DAT/NET" and inhibiting the storage "VMAT". (same as AMPHETAMINES but w different chemical structure)

-FIRST LINE in ADHD and Narcolepsy

-100% Dexmethylphenidate MORE POTENT out of the amphetamine-like-agents

-Drug interactions- MAOI=HTN crisis; 3wk prevention gap, DONT combine stimulants.

Atomoxetine (prototype)

-NON-stimulant (not as severe as amphetamines)

-Increase Norepinephrine by selectively inhibition reuptake (only Norepinephrine)

-SECOND LINE therapy if stimulants fail in ADHD/Narcolepsy

-Drug interactions- MAOI=HTN crisis; 3wk prevention gap, DONT combine stimulants

****MONITOR FOR SUICIDAL IDEATIONS****

Caffeine (prototype)

-CNS Stimulant

-CLASS- Methylxanthine

-Competitively blocks Adenosine receptor w/o agonizing it; normally binds with unenergized ATP (just adenosine no phosphate) by doing so prevents signal from adenosine to tire the body resulting in wakefulness. Also inhibits phosphodiesterase causing bronchial dealation and increased activity of Norepinephrine and Dopamine.

-Recommended daily amount=400mg

-Adverse effects: Tolerance, Tachycardia, Convulsions

CAREFUL w stimulant combination

Theophylline

-CNS Stimulant

-CLASS- Methylxanthine

-Competitively blocks Adenosine receptor w/o agonizing it; normally binds with unenergized ATP (just adenosine no phosphate) by doing so prevents signal from adenosine to tire the body resulting in wakefulness. Also inhibits phosphodiesterase causing bronchial dealation and increased activity of Norepinephrine and Dopamine.

-Adverse effects: Tolerance, Tachycardia, Convulsions

CAREFUL w stimulant combination

Methamphetamine (Speed, Glass, Ice)

-CNS Stimulant

-Increases Norepinephrine and Dopamine release by same reversal of storage and transporter causing wakefulness, elevated mood and physical/mental capacity.

-Adverse effects: Reduced appetite, Aging, Tooth decay, Tolerance, Sympathetic stimulation.

-FACE, MITES, MOUTH

INTENSE psychological dependence

3,4-Methylenedioxymethamphetamine (MDMA) (Ecstasy, Mollie, Adam, Disco biscuit, Hug drug, Lovers speed)

-CNS Stimulant

-Increase Dopamine and Norepinephrine (central and peripheral) by reversing the transporter "DAT/NET" and inhibiting the storage "VMAT", Also contains "Mescaline" (from peyote cactus) which causes HALLUSANAGENIC effects.

low dose= psychologic effects/high dose=amphetamine effects

damage to serotonin receptors

seizures

Cocaine (blow, coke, crack)

-CNS Stimulant

-Blocks the reuptake of Norepinephrine, Dopamine, and Serotonin, ALSO

Blocks Na+ channels which causes neuro-transmissions to halt leading to loss of sensation

-EFFECTS: local anesthetic, Vasoconstriction "rebound congestion=lack of o2 to cells and necrosis i.e. holes in nose", Cardiac stim, Agitation.

S/S of Stimulant OD

-Agitation, Tremor, Dysrhythmias, Stroke, Hallucinations, Paranoia, Convulsions

-Mydriasis "dilated pupils"

-Rhinorrhea

-Excitability

-Talkative

-Social isolation

-Mood swings

Management of Stimulant Toxicity

Treatment is different based off s/s

-Hallucinations: Anti-psychotics (Chlorpromazine)

-HTN: Alpha adrenergic blocker (phentolamine)

-Agitation/Seizures: Benzos

Nicotine

-CNS Stimulant "exceptions"

-Nicotinic receptors are in both SNS and PNS so there are symptoms of both being activated i.e. SNS= Cardiac/Vasoconstriction stim. PNS=increased gastric acid production and peristalsis.

-EFFECTS: Teratogenic, Premature birth, SUID, Cancer, Stained teeth/nails, premature aging, Cardiovascular and lung disease.

-Physical dependence and Abstinence syndrome

Varenicline (Chantix)

-Nicotine-free

-Partially agonizes nicotinic receptors

-used to wean off nicotine

Bupropion (Zyban)

-Nicotine-free

-Norepinephrine and Dopamine-reuptake inhibitor "gives a lesser feeling of no nicotine stimulation"

NicoDerm (patch)

-Nicotine-containing

CAN OVERDOSE

-use as intended

-Careful of absorption altering skin conditions

-signs of OD vary

Nicorette (gun/lozenge)

-Nicotine-containing

CAN OVERDOSE

-use as intended

-signs of OD varies

Nicotrol (spray/inhaler)

-Nicotine-containing

CAN OVERDOSE

-use as intended

-signs of OD varies

give the hit feeling and helps w motion of smoking

Alcohol (ETOH)

-CNS Depressant (MOST COMMOLY ABUSED)

-Enhances GABA (lights out) and inhibiting Glutamate (lights on) Also, stimulates 5-HT "serotonin" receptors which is what partially causes Emesis from inebriation.

-Metabolized in liver at 1drink/hr, can become Tolerant, also is altered by food in stomach.

-20% absorption in stomach and 80% in small intestine.

-Some SUGGESTED positive effects

-AVERSE effects: hepatotoxicity, cancer, heart damage, vitamin deficiencies, neuro deficiencies, psych disorders, respiratory depression, erosive gastritis, pancreatitis, teratogenic.

-DRUG interactions: CNS depressants, NSAIDS, Tylenol. Disulfiram, Anti-HTN drugs

-WITHDRAWL management- anxiety, depression, fatigue, irritable, diaphoresis, clammy skin. SEVERE: fever, hallucinations, SEIZURE=DEATH.

-TREATMENT: benzos, beta blockers, clonidine (A2 agonist), carbamazepine

-ABSTENCE: DISULFIRAM (ANTABUSE)- makes small amount of ETOH miserable

**(Zofran has been used to cause less reward/reinforcement from blocking 5-ht receptor stimulation to help alcoholics wean off drinking)

Nitrous Oxide (whippits, huffing) (prototype)

-CNS Depressant

-NMDA antagonist (like ketamine), GABA agonist ex.

-Effects: slurred speech, loss of coordination, euphoria, dizziness

*last few min

Toluene

-CNS Depressant

-NMDA antagonist (like ketamine), GABA agonist ex.

-Effects: slurred speech, loss of coordination, euphoria, dizziness

*last few min

Morphine (prototype)

-CNS Depressant

-CLASS- Opioid

-Dulls pain perception and stimulate euphoria by agonizing opioid receptors

Myosis, Out-of-it "sedation", Respiratory depression, Pneumonia, Hypotension, Infrequency, Nausea, Emesis

-Can build a tolerance and have diminished effects

-Physical dependance/Abstinence syndrome, rarely fatal- ACUTE-yawning, diaphoresis, rhinorrhea, n/v/d, cramps, ostealgia's/ myalgias

CHRONIC-insomnia, irritable, Hyperactive bowels

Heroine (illegal)

-CNS Depressant

-CLASS- Opioid

-Dulls pain perception and stimulate euphoria by agonizing opioid receptors

Fentanyl

-CNS Depressant

-CLASS- Opioid

-Dulls pain perception and stimulate euphoria by agonizing opioid receptors

Alfentanil

-CNS Depressant

-CLASS- Opioid

-Dulls pain perception and stimulate euphoria by agonizing opioid receptors

Sufentail

-CNS Depressant

-CLASS- Opioid

-Dulls pain perception and stimulate euphoria by agonizing opioid receptors

Remifentanil

-CNS Depressant

-CLASS- Opioid

-Dulls pain perception and stimulate euphoria by agonizing opioid receptors

Meperidine

-CNS Depressant

-CLASS- Opioid

-Dulls pain perception and stimulate euphoria by agonizing opioid receptors

Methadone

-CNS Depressant

-CLASS- Opioid

-Dulls pain perception and stimulate euphoria by agonizing opioid receptors

Hydromorphone

-CNS Depressant

-CLASS- Opioid

-Dulls pain perception and stimulate euphoria by agonizing opioid receptors

Oxymorphone

-CNS Depressant

-CLASS- Opioid

-Dulls pain perception and stimulate euphoria by agonizing opioid receptors

Oxycodone

-CNS Depressant

-CLASS- Opioid

-Dulls pain perception and stimulate euphoria by agonizing opioid receptors

Hydrocodone

-CNS Depressant

-CLASS- Opioid

-Dulls pain perception and stimulate euphoria by agonizing opioid receptors

Codeine

-CNS Depressant

-CLASS- Opioid

-Dulls pain perception and stimulate euphoria by agonizing opioid receptors

s/s of OPIOD use disorder

-Physical: malnourished, track-marks "scarring and blown veins; check well hidden areas for scarring", stuporous state.

-Behavioral: change in personality, isolation/secretive, stealing.

-Advanced warnings: missing shoelace/belts="makeshift tourniquet's", Drug paraphernalia, Missing spoons/bottle caps.

Managing Opioid use Disorder

-ACUTE-NALOXONE (narcan)

-TREATMNET-

METHADONE- FULLY agonizes (long time)

BUPRENORPHINE (Suboxone)- mixed (some agonist/antagonist)

NALTREXONE- Full antagonist cant get the high at all

*Narcan can be given to all OD s/s just to be safe

*2mg of fentanyl is all that's req to kill human

Flunitrazepam

-CNS Depressant

-Enhances action of GABA receptors (lights out)

-has sedative and amnesia effect

*COMMON date-rape DOC

GHB (gamma hydroxybutyric acid)

-CNS Depressant

-Enhances action of GABA receptors (lights out)

-has sedative and amnesia effect

*COMMON date-rape DOC

Marijuana ( cannabis, Mary jane, pot, weed, grass)

-CNS depressant-like drug

- Agonizes the cannabinoid 1 (CB1, body/CNS) and cannabinoid 2 (CB2, immune system) receptors of endocannabinoid system.

-Tetrahydrocannabinol (THC) causes euphoria

-Adverse effects: panic attacks, confusion, paranoia. INHILATION= lung cancer, COPD. CHRONIC= Hyperemesis syndrome.