Neuro - Complications Of Drug Abuse

Front 1

Substance dependence includes...(2)

Back 1

Physical dependence (withdrawal sx with/without a craving)

Psychic dependence - Craving without physical sx or signs..

And note that addiction is psychic dependence with or without physical dependence. Synonymous with substance dependence.

Front 2

Reward circuit

Back 2

Involves VTA (dopaminergic neurons)
MFB (GABAergic)
NA
medial PFC
Amygdala
Ventral pallidum (VP)

Front 3

Where do cocaine and amphetamines self-administer?

Back 3

NA and VP
(not the VTA)

Front 4

Where do opioids and nicotine self-administer?

Back 4

VTA

Front 5

Dopamine antagonists

Back 5

Can block reward effects of cocaine and amphetamine

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Serotonin antagonists

Back 6

Block reward effect of opiates.

Front 7

Sensitization

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Undesired side effects appear at progressively lower doses.

Front 8

Causes of withdrawal sx

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Increased hepatic metabolism
Up/down reg of various receptors and ligands.

Levels of phosphorylation of second messengers inside various populations of neurons.

Front 9

Opioid mechanism of action

Back 9

Binds to mu, delta, kappa receptors (in hypothal, brainstem, spinal cord)

Front 10

Endogenous peptides bind where?

Back 10

Mu receptors

Front 11

Beta-endorphins bind where?

Back 11

Delta receptors

Front 12

Leu- and met-enkephalin and dynorphin bind where?

Back 12

Kappa receptors

Front 13

Mu receptors cause...

Back 13

ANalgesia, euphoria and reinforcement.

Analgesia is via descending pathways from midbrain to spinal cord with a large limbic/emotional component.

Front 14

Delta/Kappa receptors have a role in...

Back 14

hippocampal learning and memory

(note - opioids inhibit these two)

Front 15

Opioid effects

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Less sensitivity to pain (but at low dose there can be more sensitivity to minor pain)

Sedation, euphoria, pupil constriction, diaphoresis, dry mouth, itching, resp suppression.

Can cause social withdrawal and inactivity.

Front 16

Opioid overdosage

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Hypotension (tx with fluids)

Resp suppression (art vent)

Non-cardiac pulm edema

Front 17

Opioid OD tx (pharm)

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Naloxone - opioid antag - will put pt in acute withdrawal. Needs to be given repetitively bc short half life.

Acute non-cardiac pulm edema is a rare complication.

Naloxone and flumazenil often used to tx opiate and benzodiazepine intoxication.
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Long term - Saline injection, methadone, buprenorphine.
Naltrexone can be used to block the high from opiates, but are not too effective.

Front 18

Withdrawal from opiates

Back 18

within hours.
irratibility, anxiety, yawning.
Pupillary dilation, lacrimation, diaphoresis, N/V, erection/orgasm.

Rarely fatal.

Acute tx - supportive care, fluids, autonomic stabiliization with alpga blockers (clonidine and guanfacine).

Methadone and buprenorphine can prevent withdrawal sx.

Front 19

Opioid complications (non-neuro)

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Cardiac arrythmias (possible from quinine used to dilute heroin)

Nephropathy (autoimmune)

Pulm edema

Immunosupp. (bc endog opioids regulate T-cell function)

Infections.

Front 20

Opioid Neuro Complications

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Cord compression from vertebral osteomyelitis and spinal epidural abscess.

Endocarditis with aneurysm/stroke.

Stroke due to hypotension/vasculitis

Heroin myelopathy (spinal cord)

Front 21

Chasing the dragon

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Inhaling heroin vapors - can result in severe leukoencephalopathy. Coenzyme Q can help (so it is probably a mitochondrial dysfunction)

Front 22

Amphetamine mechanism of action

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Block degradation of DA and uptake into storage so more in synapse.

Ritalin - blocks re-uptake of DA into presyn. neuron.

Front 23

Reasons for amphetamine sensitization

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Changes in receptors at various levels resulting in dyskinesia (less vol movement) and tolerance regarding anorectic (eating less) and cv effects

Front 24

Effects of amphetamines

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Increases HR and BP
Insomnia, restlessness, HA, appetite supp.
Improves focus and [].
Controls narcolepsy.
Antidepressant.

Front 25

MDMA

Back 25

An amphetamine look-alike.

Front 26

Amphetamine OD

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Wild excitement, diaphoresis, pupil dilation, HTN, tachycardia.

Oral and inhaled produces longer euphoria.

Hallucinations, hyperthermia, muscle necrosis, pulm edema, sz.

Front 27

Amphetamine OD tx

Back 27

Fluids, diuresis to promote renal excretion.

Labetalol for alpha and beta blocking to slow HR and dilate vessels.

Heavy sedation with benzos.

Front 28

Amphetamine withdrawal effects

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Depression, fatigue, rebound hunger, somnolence with more REM sleep (rebound), suicidal depression.

Bc of depression, long-term tx with antidepressants are useful.

Front 29

Medical complications of amphetamines

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Infections

Hepatocellular toxicity

MI bc of HTN and vasospasm.

Vasculitis (incl aortic dissection, ischemic colitis, renal failure).

Front 30

Amphetamine neuro complications

Back 30

Tolerance to euphoria, anorexia and hyperthermia...but SENSITIZATION to psychosis and movement disorders (can last years).

Paranoia, hallucinations.
(the psychosis is like + sx of schizophrenics)

Stroke (hemorrhage due to acute HTN and also ischemic brain lesions from necrotizing vasculitis).

Front 31

Alkaloid cocaine

Back 31

Free base or crack.

Can be smoked and will give a very rapid high.

Front 32

Cocaine mech of action

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Block reuptake of DA, NE, 5HT.

Reward from midbrain PFC and limbic cortex. (DA activity)

Glutamate rec. involved in response to cocaine and in animal models blockers of the receptor can block effects of cocaine.

GABA receptors downreg by cocaine which also increases excitation.

Front 33

Intended effects at low doses of cocaine

Back 33

Local anesthetic. (more of a vasoconstrictor than lidocaine)

Euphoria, garrulousness, excitement.

Might promote long term potentiation in hippocampus just like amphetamine or Ritalin.

Tachypnea, HTN, HA, hallucinations, psychosis, "crack dancing" (tics and chorea).

Front 34

Cocaine OD tx

Back 34

HTN (labetalol, hydralazine, nitroprusside)

Pulm edema (ventilator, diuretics, morphine)

Acidosis (bicarb)

Rhabdomyolysis (fluids)

Atrial arryth (verapimil)

Sz (benzos or phenobarbital)

Acute agitation (benzos)

Front 35

Withdrawal of cocaine and long term tx

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Depression, restlessness, fatigue, paranoia.

Many cocaine users may already be treating underlying depression.

No good pharm bc there are no good agonists that block cocaines effects.

Front 36

Medical complications of cocaine

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Chest pain, MI, cardiomyopathy, aortic dissection, limb/organ ischemia.

Rhabdomyolysis, interstitial nephritis, hepatotoxicity.

Infections from injections.

Destruction of nose/palate.

Front 37

Cocaine neuro complications

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Acute ischemic stroke (from vasospasm). Vasospasm is from subarachnoid hemorrhage from hypertension and aneurysm rupture.

Chronic vasculitis from multiple infarcts.

Intra-cerebral hemorrhage.

Depression. Cognitive impairment.

SCZ sx get worse.

Acute psychosis.

Cerebral atrophy and less perfusion in frontal lobes.

Pregnancy complications.

Front 38

Cannabis mech of action

Back 38

Delta-9-tetrahydrocannabinol is the active ing.

Enandaminde (binds CB1 and 2) is the endogenous ligand. Affects the hippocampus, basal ganglia and brainstem.

Effects G-proteins (direct or through cAMP)

Net effect - decreased neuronal firing by changes in K+ or Ca++ currents.

Front 39

Cannabis effects

Back 39

Tachycardia, hypertension, urinary freq, conjunctival itching.

Anxiety then euphoria.

Cognitive function in decreased.

May relieve MS sx.

Anti-emetic.

Front 40

Cannabis toxicity

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Hallucination, depersonalization, altered perception of time. Can result in stupor, hypotension, coma (no one dies from OD)

Front 41

Withdrawal effects of cannabis

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Irritability, tremor, yawning, nausea, diaphoresis.

Front 42

Toxicity of cannabis

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Inc risk of MI if pre-existing heart disease is there.

Impaired pulm func and increased cancer risk.

Anti-adrogenic effects (men)

Cognitive impairment and less motivation

Worsens SCZ

Front 43

Alcohol mech of action

Back 43

Disrupts lipid membranes (not clinically relevant)

Interacts with glutamate receptors and is an antagonist (so less excitation)

GABA agonist

Also affects 5HT, dopamine, opioids.

Front 44

Alchohol metabolism

Back 44

Metab to acetaldehyde via alcohol dehydrogenase.

Acetaldehyde metab to acetate via aldehyde dehydrogenase. Acetate then enters tricarboxylic acid cycle.

Asians - less aldehyde dehydrogenase, so they get red and tachycardic. They are less susc. to alcoholism.

Front 45

Alcohol intox

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Can progress to stupor and coma.

Pathologic intoxication - Sudden rage, aggression, destructive behavior. Followed by sleep and amnesia.

Front 46

Alcoholic coma

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Kills via resp depression. Tx is supportive. Artificial vent. is necessary. Dialysis can be used.

Front 47

Tx for methanoll or ethylene glycol poisoining

Back 47

Give ethanol bc its metabolites are less harmful.

Front 48

Alcohol withdrawal

Back 48

Early - hangover (HA, irritability, N/V, anorexia, tremor.

Seizures peak btwn 24 and 48 hours. Tx with short-term benzos. Standard AEDs not helpful.

Delirium tremens

Front 49

Delirium tremens

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Peak is 96 hours after stopping drinking

Confusion, disorientation, hallucinations, restlessness, agitation.

Tachycardia, diaphoresis, mydriasis (dilatation).

Tx - ICU with fluids, vitamins, benzos.

Front 50

Wernicke-Korsakoff syndrome

Back 50

Ataxia, nystagmus and gaze palsy. Also tachycardia and orthostasis.

Due to thiamine def. - thiamine needed as cofactor in glycolysis and hexose-monophosphate shunt pathway. Deficiency worsened with glucose.
So give all alcoholics thiamine before glucose.

Necrotic lesions in thalamus, brainstem, mamillary bodies.

May be hereditary susceptibility due to trans-ketolase enzyme polymorphism.

Front 51

Alcohol-tobacco amblyopia

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Neuropathy optic atrophy, blurred vision, centrocecal scotmata. Improves with vitamins and diet.

(last outbreak in cuba)

Front 52

Beriberi

Back 52

With alcoholics.

Due to thiamine def and char by painful neuropathy and cardiomyopathy.

Front 53

Pellagra

Back 53

With alcoholics.

Due to nicotinic acid def and char by diarrhea, dermatitis, dementia, myelopathy.

Neuropathy may be associated with nutritional deficiencies.

Front 54

Alcoholic brain damage

Back 54

Cerebellar atrophy - abstinence doesn't lead to complete recovery.

Alcoholic dementia

Fetal alcohol syndrome - mildly retarded, uncoordinated, hyperactive.

Front 55

Alcohol induced hepatic encephalopathy

Back 55

Alcohol is most common cause of liver cirrhosis.

Clinical picture - drowsiness, delirium, coma, asterixis (wrist-flapping), tremor.

With cirrhosis, NH3 not conv. to urea so it is neurotoxic and alters glutamate activity.

Also more GABA activity. (So flumazenil--GABA antag--can help)

Tx - low protein diet, neomycin to reduce gut bacteria that make ammonia, and lactulose to deliberately cause diarrhea.

Front 56

Alcohol and stroke

Back 56

Incr risk of carotid and coronary vasc disease which increases risk of ischemic stroke.

Also more risk of hemorrhagic stroke.

Front 57

Tx of alcoholism

Back 57

Acute - Benzos

AA

Relapse rates are high.

Front 58

GHB

Back 58

Like a benzo. Used for date rape.

Front 59

Phenobarbitol and other barbs

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Prolong Cl channel opening in GABA receptor.

Pheno can be used for anticonvulsant.

Intox similar to alcohol.

Most people dont feel good taking it.

Withdrawal effects are strong.

No specific tx.

Front 60

Benzodiazepines

Back 60

Inc freq of cl channel opening on GABA

Used in sleeping pills, anxiolytics, control sz.

Toxicity and abuse potential is low compared to barbituates but withdrawal effects can be troublesome.

Front 61

Hallucinogens

Back 61

Common structure - Indole (serotonin)-like or alkyl amine (amphetamine)-like.

Active at 5-HT2 receptors and some stim dopamine.

Intense depression, paranoia, panic can be seen acutely (bad trip)

Flashbacks can be episodic or chronic.

Tx - SSRIs or benzos. NOT tricyclics or neuroleptics.

Front 62

Anticholinergics

Back 62

Pupillary dilation, dry mouth, drowsiness (binds both centrally and peripherally)

atropine and scopolamine are the actives.

Produce delirium, hallucination, sz, come, death.

Tx - supportive, activated charcoal, physostigmine [cholinergic agonist that inhib ach esterase])

Front 63

Examples of anticholinergics

Back 63

Mandrake AKA podophyllum peltatum - an emetic and laxative to treat warts.

Datura stramonium (Jimson weed)

anti-asthmatic properties.

Front 64

Phenylcyclidine

Back 64

Related to ketamine and dextromethorphan.

Blocks NMDA-type glutamate receptors. Inc. dopamine in the brain and binds sigma-type opiate receptors.

Effects - agitation, euphoria, psychosis, self-injury bc no pain felt, superhuman strength violence.

Tx - supportive, fluids, activ charcoal, diuretics, sedations with benzos.

Chronic use associated with SCZ sx that can be relieved by neuroleptics.

Front 65

Nitrous oxide

Back 65

Inhalant

Euphoria before anesthesia. Can prod func. B12 def. with neuropathy and myelopathy.

Front 66

Organic solvents

Back 66

Inhalant

Similar to alcohol. Relaxation and euphoria along with slurred speech and ataxia. Cerebellar damage and cognitive impairment.

Front 67

Nitrites

Back 67

Inhalant

Enhancing orgasm and producing a brief rush.
Immuno-suppression is a potential problem.