Pharmacology Flashcards
What are the 3 key neurons involved in parkinsonism?
dopaminergic, GABAergic, cholinergic
How does the distribution of levodopa in both the presence and absence of a dopamine decarboxylase inhibitor change?
increased distribution with a dopamine decarboxylase inhibitor
What are the 5 dopamine receptor agonists used for movement disorders?
Levodopa Apomorphine Bromocriptine Pramipexole Ropinirole
What are the 2 MAO inhibitors used for movement disorders?
Selegiline
Rasagiline
What are the 2 COM-T inhibitors used for movement disorders? (catechol-0-methyltransferase)
Tolcapone
Entacapone
What are the 5 anticholinergic drugs used for movement disorders?
Benztropine Trihexyphenidyl Biperiden Orphenadrine Procyclidine
Which drug is used to treat ALS?
Riluzole
Which drugs are used to treat huntington dz?
Reserpine, tetrabenazine
Examples of neurodegenerative disorders that manifest as abnormalities in the control of movement including _________ dz and ___________dz. Other a neurodegenerative disorders result in impaired memory or cognitive ability (__________dz) and muscular weakness (____).
Parkinson Dz; Huntington Dz
Alzheimer Dz, ALS
A tremor of a part during maintenance of sustained posture (e.g., the outstretched upper limb when holding a cup)
postural tremor
A tremor of a part during movement (e.g., the outstretched upper limb when lifting a cup)
essential/intention tremor
A tremor consisting of slow, regular movements of the hands and sometimes the lower limbs, neck, face, or jaw; it typically stops upon voluntary movement of the part and is intensified by stimuli such as cold, fatigue, and strong emotions; may be at rest
parkinsonian tremor
The occurrence of a variety of continual, rapid, highly complex, jerky, dyskinetic movements that look well coordinated but are actually involuntary
chorea
-An involuntary, compulsive, rapid, repetitive, stereotyped movement or vocalization, experienced as irresistible although it can be suppressed for some length of time
-exacerbated by stress and diminished during sleep or engrossing activities
-may be psychogenic or neurogenic in origin and are classified as either simple
(e.g., eye blinking, shoulder shrugging, coughing, grunting, snorting, or barking) or
complex (e.g., facial gestures, grooming motions, coprolalia, echolalia, or echokinesis)
Tics
Pt presents with…Dx?
- Bradykinesia (slowness and poverty of movement)
- Muscular Rigidity
- Resting tremor (abates during voluntary movement)
- Impairment of postural balance leading to disturbances of gait and failling
Parkinson disease
What is the pathological hallmark of PD?
loss of the pigmented, dopaminergic neurons of the substantia nigra, with the appearance of intracellular inclusions known as Lewy bodies
Under normal conditions, dopaminergic neurons originating in the substantia nigra _____ the GABAergic output from the striatum while cholinergic neurons exert an __________ effect on GABAergic neurons
inhibit
excitatory
In PD, loss of dopaminergic neurons results in __________ of GABAergic neurons and disturbed movement
disinhibition
Based on the pathophysiology of PD, pts may be treated with which two classes of drugs?
dopamine agonists
anticholinergic agents
Levodopa is used to treat PD and is an immediate metabolic precursor to ________.
dopamine
What is the MOA of levodopa?
agonist of dopamine R (D2)
Levodopa by itself is rapidly absorbed from the small intestine with a peak plasma conc b/t 1-2 hours after oral dose; only 1-3% of the drug enters the bran unaltered. What can we do to combat this?
Add carbidopa
Why do we coadminister carbidopa with levodopa? What are the effects?
carbidopa=dopamine decarboxylase inhibitor that doesn’t cross the BBB
results in reduced peripheral metabolism of levodopa, increased plasma levels, increased half-life, and increased levodopa available for entry into the brain
Coadministration of levodopa and carbidopa may _______ (increase/reduce) the daily requirements of levodopa by 75%.
reduce
less drug and more to brain
T/F: Even though levodopa is effective, long-term tx may experience declining efficacy and response fluctuations. Therefore, the best results occur during first few years of treatment (use once necessary or in severe cases).
True!
Levodopa given without a peripheral decarboxylate inhibitor cause ______, _______, and ______ in 80% of pts.
anorexia, nausea, vomiting
Vomiting in levodopa can be attributed to dopamine activation of ____________ _____ ____
chemoreceptor trigger zone
What are the cardiovascular risks associated with levodopa?
cardiac arrhythmias (incr. catecholamines)
postural hypotension at first
HTN with nonselective MOA inhib
T/F: 80% of levodopa pts experience dyskinesias of the face and distal extremities
True!
Are there behavioral effects of levodopa?
Yes! changes in mood and personality such as depression, anxiety, agitation, insomnia, etc
(tx with atypical antipsychotic agents)
TQ: whats the difference between levodopa wearing off vs. on-off phenomena?
wearing off=depends on timing of the dose
on-off=NOT related to dose timing, off period=marked akinesia with on-periods of improved mobility w/ dyskinesia
TQ: What may provide temporary benefit to pts with severe levodopa off-periods?
subcutaneous injection of apomorphine!
Which 2 patient groups are contraindicated for levodopa?
- MAO inhibitors
- psychotic pts
The other dopamine agonists act on two different dopamine receptors (D2 and D3). Match the drug to its receptor:
Bromocriptine
Pramipexole
Ropinirole
Bromocriptine: D2 agonist
Pramipexole: D3 agonist
Ropinirole: D2 agonist
Pramiprexole is used for both PD and _____ _____ _______.
restless leg syndrome
What are the adverse effects of the dopamine receptor agonists Bromocriptine, Pramipexole, Ropinirole?
- GI: anorexia, N/V, constipation, dyspepsia, reflux
- Cardiovascular: postural hypotension , digital vasospasm (bromocriptine), peripheral edema and arrhythmias
- Dyskinesias
- mental disturbances: confusion, hallucinations, delusions
- headache, nasal congestion
What are the contraindications to using dopamine receptor antagonists? (3)
What additional contraindication is specific for bromocriptine?
- psychotic illness
- MI
- peptic ulcers
-bromocryptine contraindicated in pts with peripheral vascular dz due to vasoconstricting effects
What are the two monoamine oxidase (MAO) inhibitors?
Selegiline
Rasagiline
There are two forms of MAO. What are they and which is involved with inhibiting levodopa metabolism via Selegiline and Rasagiline?
MAO-A: norepi and serotonin
MAO-B: phenylethylamine and benzylamine
(Dopamine and tryptamine metab via both MAO-A and B)
The two MAO inhibitors target MAO-B (and MAO-A (selegiline) at high doses)
Why must we avoid the combined administration of levodopa and a nonselective MAO inhibitor?
may lead to a hypertensive crisis due to peripheral accumulation of norepi
(MAO B and A breakdown catecholamines but A is selective for Norepi/serotonin which can lead to an accumulation of norepi…also bad if pt is on an SSRI b/c can cause serotonin syndrome)
What are the two catechol-o-methyltransferse (COMT) inhibitors? What are their MOA?
Tolcapone and entacapone prolong the activity of levodopa by inhibiting its peripheral metabolism, which decreases clearance and increases bioavailability
Which COMT inhibitor would you avoid in pts with liver dz? why?
Tolcapone! may cause and increase in liver enzymes and death by acute hepatic failure
Which dopamine agonist stimulates the postsynaptic dopamine D2 receptors and is injected for quick, temporary relief of off-periods of akinesia in pts on dopaminergic therapy?
Apomorphine
What antiviral agent can help treat parkinsons via unknown causes?
Amantadine
What is the main adverse effect of Amantadine? What some other adverse effects?
livedo reticularis (purplish mottled discoloration of the skin, usually on the legs)
restlessness, depression, irritability, insomnia, headache, hypotension, heart failure etc
Which patients should you be cautious of when giving Amantadine?
pts with a history of seizures or heart failure
Which central acting anticholinergic drugs are available to treat PD? (5)
Benzotropine trihexyphenidyl biperiden orphenadrine procyclidine
What is the MOA of anticholinergic drugs?
centrally acting mAchR antagonists help correct the balance between dopamine and Ach
What are some adverse effects of anticholinergic drugs such as benzotropine?
peripheral anticholinergic effects (sedation, mental confusion, constipation, urinary retention, dry mouth, dry eyes)
Huntington dz is characterized by progressive chorea and dementia beginning in adulthood due to the overactivity of ___________ pathways
dopaminergic
Drugs that impair dopaminergic neurotransmission alleviate chorea, such as _______ and ________.
reserpine and tetrabenzine
What is the MOA of reserpine and tetrabenzine in the treatment of huntingtons?
Reserpine (irreversible) and Tetrabenzine (reversible) are agents that block the vesicular monoamine transporter and deplete cerebral dopamine stores
What is the only drug that has any impact on survival in ALS?
Riluzole
What is the MOA of riluzole in treating ALS? (3)
- inhibits glutamate release
- blocks post-synaptic glutamate R -inhibits VG-Na channels
What are the major AE of riluzole?
nausea and weakness
What are the first line treatments for restless leg syndrome? (2)
Pramipexole and Ropinirole
Which drug would you gibe a patient with wilson disease (increased copper in the blood)? What is it MOA?
Penicillamine
chelating agent that forms a complex with copper
What do all drugs of abuse begin with?
Elective use
What are the three stages of elective abuse?
1) Experimental
2) Social (cigarette break, bars)
3) Sporadic Abuse
What can elective drug abuse turn into it?
nonelective abuse (compulsive abuse)
Which 2 drugs quickly turn from elective to nonelective
cocaine and meth
- Intensity of the response decreases
- Duration of response decreases
- usually both occur
Tolerance
user ups dose and frequency
Metabolic tolerance (dispositional, pharmacologic)
metabolize drug faster and to greater extent
Cellular tolerance (adaptive, pharmacodynamic)
level to cause euphoria increases
-affected cells adapt to presence of drug (down regulation)
(increase dose, frequency, or both)
T/F: If you are tolerant to one drug you are tolerant to many like it
TRUE
T/F: Tolerance disappears with stoppage
TRUE
risk of overdose
Heroin tolerance includes? (3)
Analgesia, Euphoria, Respiratory depression
little tolerance to constipation and miosis
Repeated use causes a state such that sudden withdrawal produces effects (often opposite of drug) is called…
what are some features?
Physical dependence Features • Repeated/frequent use • Withdrawal time • Intensity • Negative reinforcer • Not with all drugs
which intense drugs have a short duration and rapid onset?
alcohol heroin
what are 2 less intense, slower onset, and longer duration drugs?
chlordiazepoxid (helps with alcohol withdrawal)
methadone (long acting heroin)
Compulsion requiring continuous or periodic use for pleasure or to avoid discomfort is called…
what are some features?
Psychological depedence
Features • May be most powerful reinforcing factor in drug seeking/taking behavior • Most universal characteristic • Influenced by setting • Biological basis • More harmful than physical dependence
What is the drug abuse addiction triad?
Tolerance
Physical dependence
Psychological dependence
_______ is a chronic Brain Disorder ‐ chronic
disease
Addiction
What is the most powerful reinforcing factor in drug
seeking/taking behavior?
Psychological dependence
What are the 2 main causes of AIDS?
needle sharing and sex
What are in the upper category of drug abuse?(2)
nicotine, stimulants
What are in the downers category of drug abuse? (2)
depressants, narcotics
Which category of drug abuse is all arounders?
hallucinogens
What do we see in sedative-hypnotics, such as alcohol
- CNS
- Tolerance, Psychological, Physical Dependence
- Eye signs: Glazed look, nystagmus, corneal reflex, droopy lids
- Acute use – do not function well
- Overdose – BDZ antidote, others none. Support
- Withdrawal – life threatening
Sedative-hypnotics
What are some examples of sedative/hypnotics?
- alcohol
- barbiturates (reds, yellows, blues…)
- benzodiazepines
- gasoline, glue, freon, spray paint, shoe polish, dust remover (Huffing)
T/F: Alcohol withdrawal is life threatening
TRUTH
secobarbital, pentobarbital, amobarbital are barbiturates (sedative hypnotics) and are______-acting and ______ abused.
short acting, highly abused
Phenobarbital (sedative hypnotic) is a _____-acting and _____-abused
long-acting, less-abused (not at all)
Which benzodiazepine is a “very dry martini”?
diazepam
Which benzodiazepine is the date rate drug?
rohypnol (C1 drug)
alprazolam vs. clonazepam
clonazepam is slower acting and slower onset (less likely to be abused)
high abuse of alprazolam
colorless, odorless, few drops in drink–>unconscious
Date rape drug (GHB)
What drug class do the following fall into?
- Morphine (heroin): “pure” white, “Mexican” brown, smack, horse
- Codeine ‐ cough syrup abuse
- OxyContin (Hillbilly Heroin): international internet sales
- Hydrocodone: increased abuse, now a CII (Vicodin)
- Dilaudid: drug store heroin, Mr. Brownstone
- Fentanyl: China white (Acetylfentanyl), 3x as potent as heroin
Narcotics
How can we abuse-proof oxycontin?
What are the risks assoc?
hard coating, harder to crush to snort or inject
causes shift to heroin
(Black box warning implemented as well)
Which narcotic is widely abused on the streets?
heroin
How are we fighting back against abuse? (2)
states and cities sue big pharmaceuticals similar to old tobacco suits
monitoring programs
What are some reasons medical personnel abuse narcotics? (4)
- access
- “immune because I am in control”
- cope with long hours, hard work
- “just this one time”
What are the common narcotics abused by medical personnel? (3)
Anesthesiologists-fentanyl
morphine
merperidine
What are highly effected by tolerance to narcotics?
What is minimally effected (2)?
- analgesia
- euphoria
- mental clouding
- respiratory depression
- N/V
minimal: miosis constipation
What are the events that lead up to coma and death of narcotic/heroin use?
- Euphoria
- Psychological dependence
- Physical dependence
- Tolerance
- Miosis
- Respiratory depression
- Coma
- Death
Narcotics vs. sedative-hypnotics in regards to….
acute use?
overdose treatment?
withdrawal?
-Acute use: narcotics function well, sedative users dont
-Overdose:
naloxone (antidote to heroin), Benzos – flumazenil
Alcohol, barbs ‐ no antidote
-Withdrawal from narcotics: not life‐threatening
_______ ____ still require a prescription but now are provided by clinics. Now first responders are sometimes allowed to carry it with them (prefilled syringe). Overdose tx for narcotics
Naloxone kits
What are some long term drugs used to manage narcotic abuse?
-Methadone
-Naltrexone (u blocker)
-Buprenorphine (Several dosage forms)
-Buprenorphine + naloxone
Once daily sublingual
All of the following fall under what category of drugs?
- Cocaine (freebase,crack,rock)
- Methamphetamine (ice,crank,crystal)
- Ephedrine,pseudoephedrine
- Amphetamine (Adderall…)
- Methylphenidate (Ritalin)
- Caffeine
- Nicotine
Stimulants (uppers)
What is a popular stimulant that is abused that has a DEA restriction and is more addictive than meth?
Bath salts
What are the effects of stimulants?
- talkativeness
- paranoia
- restlessness and insomnia
- muscle tremors
- memory lapses and mental confusion
- hallucination
High plasma level=feeling of euphoria happens quickly but then rapidly falls. Leads to pattern of continued use….
Stimulants
What is a good sign of stimulant use?
Mydriasis
For stimulants...what do we see in regards to... acute use? chronic use? overdose? withdrawal?
Acute use: Function well, hyperactive
Chronic use: Paranoia, psychoses
Overdose: Convulsions, arrhythmias, incr body temperature
Withdrawl: Bromocriptine, TCAs
CNS fires–>seizures–>increased neuronal firing–>reuptake blockade–> ______ ______ _____
exaggerated sympathetic response (cardiovascular complications)
What are the symptoms of stimulant OD?
- psychomotor agitation (hypoxia, hypoglycemia, paranoia)
- seizures: benzos
- HTN: phentolamine,nitroprusside
- Cardiac: CCBS NOT BBs
What are the treatment of stimulant users?
- Get drug out of system (1 wk-drug/metabolites, 3 wks-4 mo restore NT)
- Build support system
- Restructure lives
What category do the following drugs fall under?
- Lysergic Acid Diethylamide ‐ LSD
- Methylenedioxyamphetamine ‐ XTC, MDA (Molly)
- Psilocybin
- Mushrooms ‐ shrooms
- Peyote ‐ Mescaline
- PCP, Angel Dust, Hog, Naked But
Hallucinogens
What are some risks of hallucinogens?
- Altered sense of consciousness -Psychological dependence
- Physical dependence: not a severe withdrawal
- Tolerance?
- Acute overdose
Ecstasy (MDA, MMDA) is a ____ hallucinogen and stimulant
mild
- Social drug
- Rave parties
- Dry mouth, grind teeth, elevated temperatures, obstructive sleep apnea)
- Cause of death‐ constriction of vessels in heart and brain, dehydration, hyperthermia, may cause hypercarbia
Ecstasy
- “Special K”
- Veterinary Medicine
- “Trail Mix” ‐ Ketamine + Ecstasy
- Used as date rape drug
Ketamine
- PCP
- Angel Dust
- Naked Butt
- Hog
Phencyclidine
Pt has bug eyed, walleye…suspect?
Phencylidine (PCP)
For phenclyclidine...what do we see in regards to... acute use? chronic use? overdose? withdrawal?
acute use: Hyperactivity, paranoia, analgesia, combativeness, hallucinations
chronic use: Psychosis
overdose: Haloperidol, other
lavage, acidifying agents
(no longer recommended)
Withdrawal: Close observation
Marijuana, hashish effects depends on the user and amount they use but can lead to 3 types of effects….
stimulant, depressant, hallucinogen
- Temporary alterations in brain function and behavior
- Some tolerance develops
- May intensify pre‐existing mental disorders
- No evidence to suggest it is a “stepping‐stone” to harder drugs
Marijuana
T/F: Prolonged use of marijuana does NOT produce permanent changes
TRUE
Marijuana use
-Does NOT lead to “amotivational syndrome”
-Temporary _______ in heart rate and blood
pressure
-Respiratory impairment including lung cancer (aggravates asthma)
-Suppression of sperm count, ovulation
-no birth defects / genetic damage
increase
What are some uses of marijuana?
- Nausea and vomiting (cancer chemotherapy)
- Wasting disease (AIDS,CA)…
Is medical marijuana legalized in some states? (medical clinics, licensed centers, recreational use)
YES
What effects do we see in marijuana users?
- Mental changes
- Psychological dependence
- Physical dependence
- Tolerance? (reverse?): saturated
- Acute overdose nonexistent
What is the differentiating eye sign for marijuana use?
red sclera
What is the final common pathway?
dopamine (pleasure center)
