Pharmacology-Drugs of Abuse Flashcards Preview

Multisystems II > Pharmacology-Drugs of Abuse > Flashcards

Flashcards in Pharmacology-Drugs of Abuse Deck (59)
Loading flashcards...
1
Q

A 20 year old man with a heavy history of heroin use presents to the ED with an 8 hour history of nausea, vomiting, diarrhea, muscle aches and anxiety. He reports that he is trying to quit and had his last hit 24 hours ago. Physical exam reveals a fidgety man with elevated temp, HR, BP, and extreme sensitivity to touch (painful). How might you start to manage his symptoms?

A

High dose methadone to suppress withdraw symptoms. This can be done because of opiate cross-dependence. He should then be enrolled in a 28 day detox program with decreasing doses of methadone (note that as you decrease the dose, he will feel very uncomfortable). Physical addiction will be gone by 7 days, psychologic addiction may continue for much longer.

2
Q

Relapse rate for heroin abuse

A

80.00%

3
Q

When you take opiates, what effect do they have when they bind to their receptor?

A

Opiate binds u-opoid receptor -> Gai/o subunit activated -> hyperpolarization (disinhibits DA release) and inhibition of Ca entry (reduced NT release)

4
Q

When you take cannabinoids, what effect do they have when they bind to their receptor?

A

Cannabinoids bind CB receptor -> Gai/o subunit activated -> hyperpolarization (disinhibits DA release) and inhibition of Ca entry (reduced NT release). Note that there are many more cannabinoid receptors than opioid receptors.

5
Q

When you take LSD or mescaline, what effect do they have when they bind to their receptor?

A

LSD/mescaline are partial agonists at 5HT2 receptors -> activates Gq subunit -> increases IP3 -> Depolarization of neurons -> hallucinations.

6
Q

When you take caffeine, what effect does it have when it binds to its receptor?

A

Caffeine antagonizes adenosine-1 receptor -> A1R inhibits Gi/o, A2R activates Gs -> adenosine is displaced from receptors and you get less tired.

7
Q

What effect does nicotine have once it is bound to receptors?

A

Nicotine binds nACH receptor (alpha4-beta2) -> cation conductance is increased -> depolarization of neurons facilitates DA release

8
Q

What effect do benzodiazepines have once bound to their receptors?

A

Benzodiazepine binds GABA-a receptor -> potentiates GABA -> hyperpolarization and DA release -> Sedation, euphoria

9
Q

What effect does alcohol have when it binds to its receptor?

A

Alcohol binds GABA-a -> increases GABA release -> hyperpolarization -> sedation. It also binds NMDA receptors and inhibits glutamate release -> DA release -> Euphoria.

10
Q

What effect do ketamine and PCP have when they bind to their receptors?

A

They block the NMDA receptor release of glutamate -> DA release -> Disorientation, hallucinations, euphoria

11
Q

What are the effects of huffing?

A

Disorientation and mild euphoria.

12
Q

How does cocaine cause a euphoric high?

A

Blocks DAT, NET and SERT -> prevents reuptake of DA, NE and 5HT -> Euphoria from excess DA, NE and 5HT

13
Q

How do amphetamines cause a euphoric high and neurotoxicity?

A

Blocks VMAT -> displaces DA, NE and 5HT -> Euphoria from displacement of DA, NE and 5HT. Note that this depletes neuronal stores of these monamines.

14
Q

How does MDMA cause euphoria and neurotoxicity?

A

Blocks SERT -> Displaces 5HT -> Euphoria. Note that this depletes neuronal stores of 5HT.

15
Q

Stimulants of drug abuse.

A

Cocaine, amphetamines, MDMA, bath salts (weak amphetamines) and nicotine

16
Q

What are the physiologic changes that occur with chronic stimulant abuse?

A

Excess release of NE, DA and 5HT causes down regulation of their respective receptors because the receptors are being over activated. Neuronal stores also become depleted of the monamines. This results in decreased stimulatory effects (less NE = less focus), depression (DA & 5HT are mood elevating), anxiety, hunger and weight gain.

17
Q

What are the DA, NE and 5HT pathways?

A

*

18
Q

A patient presents to the ED with tachycardia, arrhythmia, HTN, MI, hyperthermia and intracranial hemorrhage. What will differentiate this as a cocaine overdose vs. an amphetamine overdose?

A

Cocaine: SEIZURES, coma and death. Amphetamine: PSYCHOSIS, paranoia, aggression, skin lesions, tooth/gum disease. Other than these aspects, they both stimulate the sympathetic nervous system and have similar presentations.

19
Q

Symptoms of cocaine and amphetamine withdraw?

A

Dysphoria, depression, hunger and drug craving. Note that cocaine withdraw is typically more mild and amphetamine withdraw may include drowsiness and irritability.

20
Q

A patient presents to the ED with an elevated HR, BP and level of alertness. He is dehydrated and having mild hallucinations. What symptoms might he have if he overdosed on MDMA?

A

Marked hyperthermia leading to myonecrosis, renal and CV failure. MI, stroke, seizures can occur. 5HT depletion can lead to memory impairment. MDMA is an amphetamine, but hallucinations are more mild than that of normal amphetamines.

21
Q

Why is it easy for the user to control how much nicotine is absorbed?

A

Lipophilic droplets are inhaled in the lungs and it rapidly crosses the alveolar membrane and diffuses into the blood where it can travel to the NAc and VTA to initiate DA release.

22
Q

What would you look for on a drug test if you wanted to know that someone was a smoker?

A

Cotinine.

23
Q

Who overdoses on nicotine? What symptoms do they experience?

A

Tobacco workers. They get green tobacco sickness from elevated nicotine levels in the air. They get sick from overstimulation of the sympathetic nervous system (increased BP, HR and MI). People who smoke often have elevated levels of carboxyhemoglobin and risk for cancer.

24
Q

Hallucinogens of abuse

A

Marijuana (THC), LSD, mescaline, psilocybin, MDMA, scopalamine (anti-cholinergic), phencyclidine (PCP), ketamine and salvinorum A (kappa opioid agonist).

25
Q

Classic features of smoking a single marijuana cigarette?

A

Tachycardia (NE increase), dry mouth, hunger and peripheral vasodilation. Central effects: euphoria, altered perception of time, visual/auditory stimuli, garrulousness (talking a lot), relaxation/sedation and psychomotor impairment.

26
Q

What symptoms might someone present with if they have eating marijuana cookies with high levels of marijuana?

A

Confusion, delusion, hallucination and euphoria turns to anxiety, panic and paranoia.

27
Q

Receptors that mediate the effects of THC?

A

CB1 (psychoactive effects in nervous system) and CB2 (immune cells). Binding activates Gi and Go -> inhibits adenylate cyclase -> K+ channels open and Ca conductance is reduces

28
Q

Where are there a high concentration of CB1 receptors affected by THC?

A

Hippocampus, cortex, NAc and striatum

29
Q

Endogenous lipid regulators of CB receptors

A

Lipid substances: anandamide (AEA) and arachidonyl-glycerol (2AG). It is thought that these facilitate loss of memory (use in PTSD?) by retrograde signaling to the hippocampus and cerebellum, regulate appetite, potentiate analgesia.

30
Q

CB2 actions of THC

A

Immunosuppression

31
Q

Therapeutic uses of THC

A

Radiation-induced nausea and vomiting in cancer chemotherapy. Enhance appetite in wasting patients. Reduce intra-ocular pressure in glaucoma.

32
Q

Side effect of a CB1 antagonist (rimonabant)?

A

Increased depression and suicide, endogenous cannabinoids may be involved in avoiding depression.

33
Q

Chronic effects of smoking marijuana.

A

Respiratory problems, immunosuppression, decrease in gonadotropins (inhibits spermatogenesis and disrupts placenta), amotivational syndrome (memory loss and impaired mental performance)

34
Q

Pharmacologically related drugs to LSD

A

Mescaline (cactus) and psilocybin (shrooms)

35
Q

Effects of lysergic acid diethylamide (LSD)

A

Somatic: dizziness, mydriasis, tremor. Perception: blurry vision, altered awareness of shape and color, micropsia, macropsia, hallucinations. Mood swings, dysphoria, panic, fear (a “bad” trip), detachment.

36
Q

Is LSD addictive?

A

No, their lifestyle is typically not disruptive and use is not compulsive.

37
Q

How could you block the effects of LSD if someone is having a really bad trip?

A

5-HT2 antagonists

38
Q

Do people develop tolerance to LSD?

A

Yes, cross-tolerance also develops with dimethyl tryptamine, mescaline and psilocybin but not with THC, antimuscarinics or PCP.

39
Q

Effects of phencyclidine

A

PCP antagonizes the NMDA receptor and prevents release of glutamate and Ca conductance. This results in intoxication, ANALGESIA, hyper salivation, sweating, HTN, aggression, paranoia, psychosis and convulsions.

40
Q

Treatment of a patient with acute symptoms from phencyclidine use?

A

Diazepam (for convulsions), hydralazine (for HTN) and haloperidol (for psychosis)

41
Q

Chronic effects of phencyclidine abuse

A

Difficulty with organized thinking, memory and speech impairment.

42
Q

How is ethanol metabolized? What drug can inhibit it?

A

1st to acetaldehyde by alcohol dehydrogenase. 2nd to acetic acid by aldehyde dehydrogenase. The minor pathway involves CYP2E1. Fomepizole inhibits alcohol dehydrogenase.

43
Q

Why is binge drinking so prone to cause alcohol toxicity?

A

Alcohol dehydrogenase is zero order and can become saturated very quickly.

44
Q

Effects of ethanol on the liver

A

Accumulation of triglycerides and fatty liver disease due to increased NADH:NAD ratio, increased rate of fatty acid synthesis (increased NADH), decreases oxidation of fatty acids (decreased NAD), increased plasma FFAs (increased sympathetic activity) and reduced release of triglycerides from the liver.

45
Q

Why can alcohol cause dyspepsia and ulcers?

A

Stimulation of gastric acid secretion

46
Q

Why are alcoholics at risk for cardiac arrhythmias and heat loss?

A

Increased sympathetic tone and epinephrine release.

47
Q

Why do alcoholics have to pee so much?

A

Suppression of the hypothalamus results in inhibition of ADH release and causes a diuresis.

48
Q

At what blood alcohol level do people begin to experience impaired gait, ataxia, slurred speech, analgesia, confusion, disinhibition and sedation?

A

1-2 mg/mL (1 mg/mL = 0.1%). The legal limit is 0.8 mg/mL.

49
Q

At what BAC do people begin to have emesis, severe sedation and respiratory depression? When do they progress to coma and death from respiratory depression?

A

2-4 mg/mL. Coma and death from respiratory depression comes around 4-5 mg/mL.

50
Q

What happens if an alcoholic decides to drink methanol instead of ethanol?

A

Methanol -> formaldehyde. Formaldehyde -> formic acid. These are toxic, can cause blindness and you must give ethanol or fomepizole to saturate alcohol dehydrogenase to prevent formation of the toxic intermediates of methanol metabolism.

51
Q

Antioxidant in wine? What else about alcohol may be beneficial for prevention of CVD?

A

Resveritrol, increases HDL.

52
Q

Alcohol withdraw symptoms

A

Tremors, hyper-reflexia, sweating, cramps, vomiting, hallucinations, DELIRIUM TREMENS (day 3-4), hyperthermia and seizures

53
Q

Partial paralysis of eye movements, nystagmus, ataxia and disorientation from alcohol abuse

A

Wernicke’s encephalopathy (thiamine deficiency)

54
Q

Memory loss, confusion, confabulation from alcohol abuse

A

Korsakoff’s psychosis

55
Q

Why can people have acute liver failure if they drink alcohol with tylenol?

A

Alcohol induces CYP2E1, increasing the rate of production of toxic NAPQI from tylenol

56
Q

Treatment of alcohol withdraw syndrome

A

Diazepam (seizures), fluids, electrolytes and vitamins

57
Q

A patient is undergoing alcohol withdraw counseling and decides to sneak a drink. Shortly thereafter he has vasodilation, nausea, vomiting, hypotension, scope, hepatitis, jaundice, fatigue, fever and abdominal pain. What may have caused this?

A

Disulfiram: this is an alcohol dehydrogenase inhibitor that increases acetaldehyde levels and is used as aversion therapy.

58
Q

What drug can be used to reduce the effects of ethanol, decrease relapse and antagonize opioid receptors?

A

Naltrexone.

59
Q

What drug can be used to reduce neuronal hyper excitability during alcohol abstinence and reduce cravings?

A

Acamprosate: GABA analogue that activates GABAa receptors and weakly antagonizes NMDA receptors.