Parkinsons Disease

Neurodegenerative Disorder The main nuclei involved is the Substantia nigra o It sends signals in the form of dopamine o Controls normal movements of the body

YOU NEED DOPAMINE FOR NORMAL MOVEMENT!!!! PARKINSONS PTS WILL NOT HAVE ADEQUATE DOPAMINE LEVELS!!!! Dopamine is the INHIBITORY neurotransmitter Acetylcholine is the EXCITATORY neurotransmitter Parkinsons pts have not enough dopamine and too much acetylcholine Degeneration of dopaminergic neurons in the substantia nigra of the midbrain There is an imbalance between dopamine and acetylcholine in the basal ganglia o Dopamine is the neurotransmitter essential for normal functioning of extrapyramidal motor system. It controls posture, support, and voluntary motion Parkinsons Disease Acetylcholine is unopposed Excessive stimulation of GABA o Since there is too much acetylcholine which is excitatory, the body will compensate by making more GABA which is inhibitory o Now there is a lot of GABA and the thalamus realizes there is too much GABA and slows it back down o Now we are back to too much acetylcholine and not enough dopamine AND GABA MOVEMENT DISORDERS is the big problem with Parkinsons! Symptoms Dyskinesias o Tremors at rest o Rigidity o Postural instability o Bradykinesia slow movement o Akinesia without movement o Psychological disturbances Goal No cure goal is to approve the ability to perform ADLs Drugs are looking to improve bradykinesia, gait disturbance, and postural instability o Its trying to make the tremor and rigidity less disabling Two Options for Drug Therapy Dopaminergic agents have multiple mechanisms of action (these ones will raise dopamine levels)

Anticholinergic agents block muscarinic receptors in the striatum (these ones will block excess of acetylcholine)

Dopaminergic Agents Dopamine Replacement o Levodopa Dopamine Agonists o Bromocriptine, Pergolide, Pramipexole, Ropinirole Catecholamine O-methyl Transferase Inhibitors (COMT Inhibitors) o Entacopone Dopamine Releaser o Amantadine MAO-B Inhibitor o Selegiline Name of Agent Levodopa Dopamine Replacement Therapeutics Used for advanced Parkinsons -Will have good control of symptoms for 2 yrs GRADUAL LOSS pt is starting to lose the drugs effects right before its time for their next dose not holding them the entire time. Symptoms start returning which means Pharmacokinet ics ABRUPT LOSS ON/OFF PHENOMENO N: Episodes of the ability to be mobile (on) and an unpredictabl e period of immobility (off). --Occurs at any time --Off periods can be minutes or hours --Usually see intensity and frequency of OFF periods as time goes on Dosage -Full therapeutic response may take a few months! -PO, give lowest dose as possible -ABSORBED RAPIDLY ONCE IT REACHES THE SMALL INTESTINE!! !! -HIGH PROTEIN FOODS DECREASE THERAPEUT IC Side Effects --Postural hypotension & dysrhythmias CHECK BP & HR!!!! --DYSKINESIAS IN FIRST YEAR!!! Tics, head bobbing.. if symptoms get worse in the first year, lower the dose --PSYCHOSIS IS A HUGE SIDE EFFECT!! Will start with nightmares and hallucinations DECREASE DOSAGE to fix this Interactions --VITAMIN B6 teach pts not to eat foods that have B6 in them --MAO INHIBITORS must have a TWO WEEK WASHOUT PERIOD before giving Levodopa --ANTICHOLINERGIC DRUGS ARE A GOOD INTERACTION it enhances the response Considerations Every Parkinson pt will get this eventually Between years 2-5 they will regress and by year 5 they are back to where they were before they started any meds -As Parkinsons progresses, youll see more OFF periods -<2% of each dose enters the brain -Raise BP to counteract postural hypotension by increasing salt and water intake -DRUG HOLIDAY people will always

they are subtherapuet ic what to do to fix this: ---Shorten dosing interval ---Add a drug to prolong Levodopas life ---Give a direct acting dopamine agonist

ON/OFF periods are unpredictabl e & not related to dosing or meds!

EFFECTS!!! CAN TRIGGER AN OFF PERIOD!!!! -FOOD IS A BIG PROBLEM WITH LEVODOPA! IT DELAYS ABSORPTIO N BY DELAYING GASTRIC EMPTYING!! !

--SWEAT AND URINE WILL BECOME DARK! -THIS MED REACTIVATES MALIGNANT MELANOMA!!

come to the hospital bc stopping the med immobilizes the pt stopping med for 10 days helps them get more benefit for longer time & you can use lesser amount of the drug when you restart it -Pt still needs protein so you need to spread it out throughout the day

Name of Agent Levodopa PLUS Carbidopa (Sinemet) Dopamine Replacement

Therapeutics Carbidopa has no therapeutic effect on its own INCREASED AVAILABILITY OF DOPAMINE IN CNS

Pharmacokinet ics Inhibits decarboxylat ion (or breaking down of) Levodopa enough for it to get to the brain --GOES FROM <2% GOING TO THE BRAIN TO 10%!!!!!!!!!!

Dosage

Side Effects LESS POSTURAL HYPOTENSION & ARRHYTHMIA!! LESS N/V!! LESS CONCERN ABOUT VITAMIN B6 INTERACTION!!

Interactions

Considerations

Dopamine Agonists Once Parkinsons advances, you would give Levodopa (dopamine replacement) but would not give it after initial diagnosis YOU WOULD GIVE A DOPAMINE AGONIST AS INITIAL TREATMENT!

NEW SIDE EFFECT IS NOW DAYTIME SLEEPINESS!! Directly activates dopamine receptors in the striatum Lower incidences of dyskinesias Two Forms: o Ergot comes from a plant o Nonergot Newer Less side effects Selective for dopamine receptors

Name of Agent Pramipexole (Mirapex) Dopamine Agonist NONERGOT

Therapeutics Used alone in early stages, combined with Levodopa in later stages

Pharmacokinet ics

Dosage MAXIMAL BENEFITS TAKE SEVERAL WEEKS TO DEVELOP!!! Still quicker than Levodopa

Side Effects

Interactions

Considerations Ropinirole (Requip) main competitor (also Nonergot)

Name of Agent Bomocriptin e (Parlodel) Dopamine Agonist ERGOT

Therapeutics Used alone in early stages, combined with Levodopa in later stages

Pharmacokinet ics

Dosage MAXIMAL BENEFITS TAKE SEVERAL WEEKS TO DEVELOP!!! Still quicker than Levodopa

Side Effects Limited psychological reactions

Interactions

Considerations This has more side effects because its from the older generation of drugs!!

Catecholamine-O-methyl transferase (COMT) Inhibitors Inhibits metabolism of Levodopa in the periphery No therapeutic effect on its own

Name of Agent Entacapone (Comtan) Catecholamin e-O-methyl transferase (COMT) Inhibitors Selegiline (Eldepryl, Carbex) MAO-B Inhibitors Amantadine (Symmetrel) Dopamine Releaser

Therapeutics PROLONGS THE HALF LIFE OF LEVODOPA IN THE BLOOD!!!!! 3 or 4 line drug to treat Parkinsons It MAY slow down progression Causes patient to make their own Dopamine OR to block reuptake of Dopamine
rd th

Pharmacokinet ics ON TIMES ARE EXTENDED AND OFF TIMES ARE DELAYED!!! Blocks COMT Irreversible inhibition of MAO enzyme

Dosage LONG HALF LIFE OF LEVODOPA, LESS GRADUAL LOSS SYMPTOMS

Side Effects INCREASE LEVODOPA LEVELS!!!

Interactions

Considerations

Conflicting data on the effects/benefits why it was moved to 3rd or 4th line treatment!!! 2-3 day response time but diminishes between 36 months -Confusion, light-headed, anxiety -Blurred vision, dry mouth, constipation -LIVEDO RETICULARIS is mottled looking skin!!! Side Effects Peripheral effects dry mouth, blurred vision, photophobia, urinary retention, constipation and tachycardia Interactions Withdraw drugs slowly do not discontinue abruptly may intensify Parkinsons symptoms!!!!! WORKS QUICKLY BUT BURNS OUT JUST AS QUICKLY!! -Side effects USUALLY goes away when drug is stopped NOT ALWAYS!! Considerations START LOW AND GO SLOW when it comes to anticholinergics !!!!

Name of Agent Artane and Cogentin Centrally Acting AntiCholinergic

Therapeutics Reduces tremor and rigidity but NOT BRADYKINESI A!!!

Pharmacokinet ics Second line drugs

Dosage

DRUGS FOR EPILEPSY

Epilepsy is a group of disorders characterized by excessive excitability of neurons Seizures are a generalized term for any epileptic event Convulsion is an abnormal motor phenomenon Seizures and convulsions are symptoms, so we are going to manage the symptoms

Seizures Not every seizure means they have epilepsy trauma to the head, congenital defects, hypoxia at birth, and cancer can cause them Biggest cause of seizures in adults is cancer If pt has a seizure, remove anything they can injure themselves on, dont put anything in their mouth, and time the seizure

Types of Seizures Partial only one hemisphere, NO LOSS OF CONSCIOUSNESS Complex only one hemisphere, impaired consciousness Generalized both hemispheres, IMMEDIATE LOSS OF CONSCIOUSNESS o Tonic-clonic (grand mal) seizure o Absence seizures no movement, eyes are open but have a staring look like no one is home when looking at the child o Atonic seizures o Myclonic seizures o Status Epilepticus medical emergency, pt cant break the seizure on their own, pt loses airway and cardiac disturbances start o Febrile seizures commonly seen in kids can have one or can get them every time they get a fever

3 Mechanisms of Action to Treat Seizures Suppression of Na influx sodium channel blockers suppress sodium influx to prolong action potential to calm down excitable neuron Suppression of Ca influx calcium channel blockers suppress calcium influx to prolong action potential to calm down excitable neuron Potentiation of GABA this is an inhibitory neuron so it can calm things down also Goal No cure for seizures, it is a symptom so we are treating the symptom Reduce seizures so pt can live a normal life Balance between side effects and seizure control

Treatment Must match the drug to the seizure certain seizure meds will only treat a certain type of seizure Antiepileptic drugs should be withdrawn over a period of 6 weeks If taking two drugs, withdraw them at one time Steroids, beta blockers, and anti-epileptic drugs CAN NEVER BE ABRUPTLY STOPPED!! Name of Agent Phenytoin (Dilantin) AntiTherapeutics ALL SEIZURES EXCEPT ABSENCE! Pharmacokinet ics Inhibits Na+ channels delaying the onset of action Dosage PO, IV, suspension Doses individualized Side Effects Mild CNS effects w/ therapeutic levels (10-20) Interactions Hepatic drugmetabolizing enzymes effects of Considerations DILUTE DILANTIN W/ NSS WHEN GIVING IV. NOT COMPATIBLE

epileptic / Sodium Channel Blocker

potentials. Prophylactic tx to prevent pt from having seizures Certain dysrhythmias as an alternate to lidocaine.

Adhere strictly as small can cause seizures, toxicity or failure of RX. High incidence of phlebitis w/ IV Dilute in NSS. Destroys veins-crystal formations AVOID IV DILANTIN @ ALL COSTS! CAUTION-not compatible w/ dextrose! Will form precipitates.

Toxic levels >20 causes ataxia, nystagmus, diplopia, sedation! Gingival hyperplasia (overgrowth of gums)manage w/ oral care, surgery. Rash IV infusion can cause hypotension and dysrhythmias infuse s l o w l y, diluted and pt on a cardiac monitor!

oral BCP, warfarin, glucocorticoids. RX that plasma phenytoin levels tagamet, INH, diazepam, valproic acid. RX that plasma phenytoin carbamazapine, phenobarbital CNS depressants have an additive effect & should be avoided.

W/ DEXTROSE! ASSESS HR AND BP BEFORE AND AFTER GIVING! TERATOGENIC!

Name of Agent Fosphenytoi n (Cerebyx) Antiepileptic / Sodium Channel Blocker

Therapeutics Treat all seizures except absence

Pharmacokinet ics PRODRUG form in the body immediately converted to phenytoin in blood stream.

Dosage IV admin immediate conversion to phenytoin. less irritating you can push this drug faster which will help pt faster!

Side Effects Neutral pH makes it less irritating to veins, faster infusion.

Interactions NO CV EFFECTS WITH THIS ONE COMPARED TO PHENYTOIN

Considerations $$$-Hospitals dont carry

Carbamazep ine (Tegretol) Antiepileptic / Sodium Channel Blocker

TX of epilepsy NOT effective tx for absence, myoclonic or atonic seizures. Bipolar d/o Trigeminal & glossopharyng eal neuralgias.

Inhibits Na+ channels. Absorption is delayed and variable.

ABSORPTION IS DELAYED AND VARIABLE PO Low doses give large portion of dose at bedtime to minimize effects! Give with food but not with other suspensions potentially delays absorption. SAFER THAN PHENYTOIN wider therapeutic range (50150)

Hematologic effects, teratogenic effects how it differs from phenytoin** CNS effectsvisual disturbances, ataxia, vertigo tolerance to CNS ses develops w/ use.

HIGHLY TERATOGENIC! GRAPEFRUIT JUICE- Inhibits metabolism toxicity! Phenytoin & Phenobarbitol accelerate metabolism

ELIMINATED THROUGH HEPATIC METABOLISM! MONITOR CBC FOR LEUKOPENIA, ANEMIA, AND THROMBOCYTOPENIA FROM HEMATOLOGIC EFFECTS! FLUSH TUBE BEFORE GIVING ANOTHER MED THROUGH SAME TUBE!!!

Valproic Acid (Depakote) Anti-epileptic

Treats ALL seizures, including absence! Tx bipolarmood stabilizer and migraines

-All three -Suppression of Na+ influx -Suppression of Ca+ influx -Potentiation of GABA

Hepatotoxicity and Pancreatitis rare but serious. N&V Preg. Cat D Teratogenic!

phenobarb metabolism Displaces phenytoin may result in toxicity!

Perfect pharmacokinetics absorbed readily, metabolized in liver, excreted in urine

Name of Agent Phenobarbit ol Barbituate

Therapeutics TX partial or tonic clonic seizures.

Pharmacokinet ics Suppresses seizures by potentiating the effects of GABA!

Dosage PO, IM, IV

Side Effects -Drowsiness -Physical dependence -Congenital defects in fetus TOXICITY Nystagmus &

Interactions NO ALCOHOL!! TOO MUCH CNS DEPRESSION! NO PREGNANCY!!

Considerations

ataxia generalized CNS depression death!! NO ANTIDOTE FOR TOXICITYSUPPORTIVE CARE. Lamotrigine (lamictal) Anti-epileptic TX of epilepsy (adjunct tx for partial and tonicclonic seizures) Bipolar d/o Used as adjunctive therapy in partial seizures. Bipolar, neuropathic pain, leg cramps and migraines Levetiracet Used for tx of am (Keppra) partial and tonic-clonic seizures. Unknown mechanism of action No drug interactions Does not interact with other drugs; few side effects; newer agent use not well established. SERIOUS Aseptic meningitis Stevens Johnson Syndrome Newer agent, limited uses.

Gabapentin (Neurontin)

ENHANCES THE RELEASE OF GABA!

Drowsiness, otherwise generally well tolerated.

Not given as much for seizures but more for bipolar, neuropathic pain, leg cramps, and migraines

You can give Phenytoin only during pregnancy only if the benefit outweighs the risk, but use the lowest dose possible Status Epilepticus must stop seizure or pt will die Status epilepticus is defined as a Seizure lasting longer than 30minutes Goals of therapy Terminate seizure, support patient airway, intubation. Pad bed rails, keep pt safe Suction @ HOB!

IV line Administer benzos ATIVAN/LORAZEPAM to STOP AN ACTIVE SEIZURE! The only rx that WILL stop an active seizure! Follow benzo administration with Dilantin or cerebyx as a prophylactic measure to prevent more seizures form occurring.

Cholinesterase Inhibitors
Myesthenia Gravis is an auto-immune disorder where the body is attacking itself Progressive and profound muscle weakness antibodies are attacking nicotinic receptors! Symptoms ptosis (drooping eyes), difficulty swallowing, may progress to difficulty breathing Eventually they will need to be on a ventilator or they will die Therapeutics Will increase muscle strength Pharmacokinet ics Cholinestera se breaks down Acetylcholine , so this will prevent Ach from being inactivated which means there is more available at muscarinic receptors & at the neuromuscul ar junction Dosage Dose is titrated based on pts response Side Effects SX of undermedication weakness, trouble swallowing, breathing, speaking, ptosis =MYASTHENIC CRISIS SX of overmedication secretions everywhere! Excess saliva, SOB=CHOLINERG IC CRISIS Interactions Considerations Acetylcholine levels will go up!!!!

Name of Agent Neostigmin e (Prostigmin ) Cholinesteras e Inhibitors

Myasthenic crisis occurs when clients are inadequately medicated Neostigmine Cholinergic crisis caused by an overdose of a cholinesterase inhibitor TX w/ Atropine Diagnosis is made by edrophonium (Tensilon) If symptoms improve after Tensilon administration = myasthenic crisis If symptoms intensify after Tensilon administration = cholinergic crisis give atropine Respiratory support, suction equipment must be readily available

Drugs for Muscle Spasm and Spasticity

Muscle Spasm Sudden involuntary contraction of muscles Can be from epilepsy, hypocalcemia, trauma, and acute/chronic pain Spasticity Heightened muscle tone, spasm and loss of dexterity From SCI, MS, cerebral palsy **Know the diff b/w SPASM AND SPASTICITY!** Spasms are sudden involuntary contractions! Non-Pharmacological Measures Immobilize the affected muscle Cold compresses Whirlpool baths Physical therapy Treat the cause Name of Agent Cyclobenza prine (Flexeril) Centrally Therapeutics Treats local spasm from muscle injury Pharmacokinet ics Mechanism is unknown Dosage Oral Side Effects CNS depressiondrowsiness, sedation; hepatic toxicity, anticholinergic Interactions Can cause physical dependence w/d over a 2 week period to Considerations Methocarbamol and diazepam (are also centrally acting muscle relaxants) can be given IV or IM

Acting Muscle Relaxants Diazepam (Valium) BENZO Centrally Acting Muscle Relaxants Used as a muscle relaxant ACUTELY and is also an ANTISPASMO DIC -Also used in status epilepticus MS and traumatic lesions of the spinal cord, & CP. NOT effective in spasticity of Parkinsons or Huntingtons chorea IV CENTRAL ACTING!

effectsdry mouth, blurred vision, urinary retention, constipation. MANY ADDICTED PTS OUT THERE! THIS CAUSES PHYSICAL DEPENDENCE! CNS DEPRESSANT!

avoid w/d sx.

DC s l o w l y!

Physical and psychological dependence Withdraw over a 2 week period

Baclofen (Lioresal) Centrally Acting Spasmolytics

Mimics GABA on spinal neurons. Suppresses hyperactive reflexes

Used in people who have been maxed out on their oral opiates or centrally acting spasmolytics GIVEN INTRATHECA LLY!

CNS depressant Anti-cholinergic effects Toxicitycoma, respiratory depression, vent support.

Use caution in pt w/ seizure d/o deteriorates seizure control even if pt never had a seizure before!

Intrathecallyinjection into the CSF for patients unresponsive to or unable to tolerate PO therapy.

Dantrolene (Dantrium) Peripherally Acting Spasmolytics

Drug of choice for Malignant Hyperthermia Effective in tx upper motor neuron disorders, management of spasticity from MS, SCI, CP, Stroke

works in the peripheral nervous system where innvervates muscles. excitation & contraction coupling & reduce muscle strength by interfering

Muscle Weakness Serious Hepatotoxicity

Contraindicate d when spasticity is used to maintain an upright posture & balance as in cerebral palsy bc dantrolene works

Withdraw over a 2 week period

with intracellular Ca++ movement

peripherally directly @ the muscle!

CNS STIMULANTS/ ADHD

CNS STIMULANTS
Increase CNS activity Neuronal inhibitionblocking NT that are inhibitory Neuronal excitationdirectly excite the neurons Indications for CNS stimulant use o ADHD o Narcolepsy o CNS stimulants do not TX depression!

Name of Agent Amphetamines

Therapeutics ADHD Narcolepsy wakefulness and alertness, fatigue, mood, augment self confidence Talkative, peripheral increased motor activity, appetite, respirations, pain perception NE release HR, BP, dysrhythmia s (in high doses) Tolerance develops with regular userequire a higher dose of drug to get the same effect ADHD Narcolepsy

Pharmacokine tics Promote/incr ease the release of NE and dopamine (**dopamine blocks GABA)

Dosage

Side Effects CNS Stimulation insomnia, increased wakefulness, excessively talkative Weight loss CV Effects dysrhythmias, chest pain, HTN Psychosisw/ higher doses Acute toxicity Dizzy, confused, paranoid delusions, hallucinations, palpitations, HTN convulsions, coma, death Remove source of medication Treatment Alpha-adrenergic blocker, chlorpromazine (to manage psychosis),benzo s to tx seizure activity

Interactions

Considerations Abuse/physical dependence Physical dependencebody becomes dependent and when drug is removed pt will have physical sx abstinence syndrome s/s are opposite the effects of the drug Psychological dependenceintense cravings for euphoria amphetamines give Schedule II Abrupt withdraw after prolonged use exhaustion, depression, prolonged sleep, excessive eating craving for more amphetamines

Methylphenida tes

Short duration BID, TID 35 hours Intermediate durationBID/QID 4

Schedule II-high abuse potential

Dexmethylphe nidate

ADHD

Methylxanthin es CAFFEINE

Structurally different from methylpheni date CNS-increased wakefulness, nervous, tremors Heartincreases HR, dysrhythmias in high dose Blood vesselsPeripheral vasodilation CNS vasconstriction in brain used to TX HA! Bronchi dilate bronchi THEOPHYLLINE! Kidney diuretic Reproductionduring early pregnancy can cause birth defects; miscarriage. Not recommended for pregos. ADHDnon stimulant Selectivey inhibits the reuptake of NE.

8hours Long duration Daily 14 hours Half the dose of methylphen idate

Schedule II

Modafinil (Provigil)tx of narcolepsy Cocaine-Local anestheticvasconstrictive properties

Strattera (atomoxetine)

Takes a few days for initial response rapidly and completely absorbed w/ PO.

Some adults cant tolerate CNS stimulant b/c of CV effectsHTN. and they can tolerate Strattera GI effectsappetite suppression-wt loss, growth retardation in children

MAO inhibitors cause a HTN crisis SSRIsincrease levels of Strattera

Metabolized bt the liver No data on long term effectsnot as effective as amphetamines need more controlled trials

Drugs of Abuse
Addiction

Tolerance body adjusts to drug, requiring a higher dose to achieve desired effect Cross-tolerance one substance for another; heroinwill have tolerance to morphine, etc. Psychologic dependence intense urges/craving for drug Physical dependence-body develops dependence and when w/d physical sx occur Cross-dependence- satisfy physical need to have drug. Withdrawal syndrome abstinence syndrome, s/s when pt has physical dependence and removes drug. Can be dangerous unpleasant. Substance Abuse vs Substance Dependence (addiction) SA continued use despite missing days @ work, social issues w/ family/friends, high risk behaviors SD- physical dependence and tolerance Contributing Factors Reinforcing properties makes pt feel good, going to want to do it again. Reward circuit in the brain. Physical dependence Psychologic dependence Social dependence Drug availability! Vulnerability genetic component, impulsive behaviors Neurobiology of Addiction Molecular changes in the brain Reward circuit Reinforces behaviors essential for survival Drugs can activate the reward circuit system the user has a tendency to repeat behaviors that activated the system Principles of addiction Treatable GOAL is complete cessation moderation vs total abstinence Addiction is chronic and we must anticipate relapsing TX must be multifaceted and comprehensive Controlled Substance Act DEArequires written record of all controlled substances Schedule I-V I high potential for abuse no medically approved use II-V assigned based on abuse potential and potential for dependence Regulations by DEA on prescribing scheduled drugs Alcohol Pharmacology CNS effects general depression of CNS function

Alcohol activates the brains reward circuit Alcohol interacts with 2 proteins affecting receptors GABA is an inhibitory CNS depressant 5HT3 subset of serotonin receptors which is how it activates the reward circuit in the brain Low doses Affects higher brain areas cortical areas Thought processes/learned behaviors are altered, inhibitions released, sociability replaces self-restraint, motor function affected Higher doses Primitive areas affected Impaired consciousness, respiratory depression. Chronic Effects Disorders caused by thiamine deficiency poor diet, suppression of thiamine absorption. Wernickes Encephalopathy Directly r/t thiamine deficiency! Confusion, nystagmus, abnormal ocular movements Reversible with thiamineIV Korsakoffs psychosis Also r/t thiamine deficiency Polyneuropathy, inability to convert short term memory to long term memory, confabulation Not reversible! PERMANENT Effect on Sleep Alters sleep cycles total sleeping time quality of sleep Intensifies snoring/exacerbates sleep apnea

CV Effects Moderate dilates cutaneous blood vessels Feel warm but promotes heat loss! Risk for hypothermia! Chronic and excessive use Damage to myocardium HTN Beneficial effects w/ moderate consumption 1-2 drinks/day CAD, MI, stroke and heart failure raises HDL platelet aggregation

TPAtissue plasminogen dissolves clots Suppresses inflammatory component of atheroscelerosis Respiratory Depression with large amounts of alcohol ingestion Liver Acute consumption reversible accumulation of fat and protein Major cause of fatal cirrhosis Stomach Erosive gastritis Kidney -- Diuretic inhibits release of ADHbreak the seal dehydration Pancreas -- 2nd most common cause of pancreatitis Sexual function -- Releases inhibitions and Decreases physiologic capacity Increased risk of Breast CA Effects in pregnancy Fetal alcohol spectrum syndrome Mild to moderate mental retardation Slow growth rate Craniofacial abnormalities Limb abnormalities Still birth Spontaneous AB Low birth weight Mental retardation Infants need withdrawal therapy Lactation May affect infants feeding & behavior Pharmacokinetics Absorption Stomach 20% Small intestine 80% Affected by food and gastric emptying time Distribution Widely distributed Crosses blood brain barrier easily Crosses placenta; breast milk Metabolism Liver and stomach Constant ratemetabolism doesnt speed up if drink more One drink per hour Induces hepatic drug metabolizing enzymes increase rate of its own metabolism and other drugs Tolerance

Still @ high risk for respiratory depression Cross tolerance to General Anesthetics, barbituates and other general CNS depressants (benzos) tolerance to alcohol will have tolerance to these agents requiring a higher dose No cross tolerance to opioids!

Interactions CNS depressantsadditive effect, sedation, resp depression, NSAIDs inhibit prostaglandins in the stomach etoh increases the risk for gastritis Acetaminophen Disulfiram antibuse flushing, nausea, more severe rxn cardiac collapse, even death! Commit to antibuse therapy and not use alcohol wait 12 hours inbetween last drink and disulfiram. Antihypertensivesnegates beneficial affects of antiHTN ALCOHOL WITHDRAWAL can be fatal mild and severe manifestations Mild sleep disturbances, weakness, nausea, mild tremors, anxiety Severe 12-72 hrs after last drink Last 5-7 days Cramps, vomiting hallucinations, intense tremors, seizures, Increased HR, HTN, tachycardia, increased BP, temp Delirium tremens severe persecutory hallucinations CV collapse and death Drugs for Facilitating Withdrawal Benzodiazepines high doses to tx sx of w/d Adjuncts to Benzodiazepines Carbamazipine for prevention of seizures Clonidine (catapres) manage the autonomic sx tremors, HTN associated w/ w/d. LONG TERM DETERENTS Disulfiram (Antabuse) Discourages drinking by causing severe reaction! Naltrexone (ReVia) Decreases craving, (made for opioid w/d but effective in decreasing cravings for alcohol)

Drug Abuse III OPIOIDS

Name of Agent Heroin Therapeutics Drug of choice Pharmacokine tics When Dosage Routes- IV, Side Effects Effects are Interactions Considerations

for street users

administered PO or SubQ cannot distinguish its effects from morphine and other opioids (once in the brain heroin is converted to morphinethe active form

smoking, nasal inhalation

immediate w/ an intense euphoria

Meperidine (Demerol)

Often a drug of choice for healthcare workers euphoria!

Effective PO administrati on so dont have to inject

Less pupillary constriction making it less obvious that person is using; minimal effects on smooth muscle function less constipation

Oxycodone

Highly abused

Tolerance
Tolerance to euphoria, respiratory depression and nausea requiring higher doses to achieve euphoria; using higher doses when tolerance develops and not have respiratory depression NO TOLERANCE TO CONSTIPATION AND MIOSIS! CROSS TOLERANCE TO other opioids but not CNS general depressants using one opioid can substitute w/ another. There is only cross tolerance b/w opioids not other drugs and opioids.

Physical dependence
Acute abstinence syndrome o Yawning, rhinorrhea and sweating -- followed by anorexia, irritability, tremor and gooseflesh o Peak effects include violent sneezing, weakness, NVD, abdominal cramps; muscle spasm and kicking movements o Lasting 710 days o Unpleasant but rarely dangerous o Mild w/d follows and may last for months w/ insomnia, irritability, fatigue, GI hyperactivity diarrhea, premature ejaculation

TX OF ACUTE TOXICITY o Triad of Sx pt presentation w/ an OD on opioids Pinpoint pupils Respiratory depression Coma o TX of acute toxicity w/ Naloxone (Narcan) Opioid antagonist Titrate carefully Short half life needs to be re-administered when Narcan wears off the opioid is still circulating and pt can go back into respiratory depression

DETOXIFICATION AGENTS Name of Agent Therapeutics Pharmacokine tics METHadone Easing Heroin w/d to prevent abstinence syndrome

Dosage PO opioid w/ long duration Once the pt is stabilized on methadone doses are titrated down

Side Effects

Interactions

Considerations The entire methadone substitution process and withdrawal takes about 10 days

Clonidine (catapres) Centrally acting alpha adrenergic agonist

For pt physically dependent on opioids, suppressing sx of abstinence. Most effective against s/s of NVD, HA

OPIOID CRAVING IS NOT DIMINISHED!

Drugs for Long term manangement of opioid addiction

Name of Agent Methadone Therapeutics Maintenance therapy and suppressive therapy Pharmacokine tics Dosage Suppressive therapy is done to prevent the reinforcing Side Effects Interactions Considerations Used to modify drug using behavior in pts who are not ready to withdrawal

Buprenorphine (Subutex) Agonist antagonist Opioid

Maintenance therapy and to facilitate detoxification

effects of opioid induced euphoria Low potential for abuse Suppresses craving for heroin

ABUSE OF GENERAL CNS DEPRESSANTS Name of Agent Barbiturates Subjective effects similar to effects of alcohol BENZODIAZEPI NES OD on benzos alone is rarely fataldeath is greatly increased when combining PO benzos w/ other CNS depressants! or administered IV. Antidote Flumazenil (Romazicon ) Therapeutics Pharmacokine tics Dosage Side Effects MILD SEDATION COMA AND DEATH Interactions Acute toxicity no antidote supportive therapy and removing the drug from the body Considerations No tolerance to respiratory depression but pt will have a tolerance to euphoria!

Withdrawal slowly

Alcohol Psychostimulants

Name of Agent COCAINE

Therapeutics Produces a euhporia

Pharmacokine tics Inhibits neuronal reuptake of dopamine increasing activation of dopamine receptors in the brains reward circuit

Dosage Cocaine HCL intranasally; IV Cocaine base crack Smoked

Side Effects MILD OD agitation, dizziness, tremor, blurred vision SEVERE ODhyperpyrexia, convulsions, ventricular dysrhythmias and hemorrhagic stroke Angina Anxiety, paranoid ideations and hallucinations Hallucinations, paranoid ideation; psychosis, vasoconstriction( increased BP and HR) Tolerance develops requiring higher doses Physical dependence is moderate Psychological dependence can be intense! Tachycardia, reddening of conjunctivae, orthostatic

Interactions

Considerations OD IS FREQUENT W/ chronic use nasal damage Use during prego is not recommended Physical dependence is unclearmay see more psychological dependence for the euphoric effects Detox, maintenance and abstinence are difficult!

Amphetamines

Arousal and mood elevation; sense of increased physical strength and mental capacity; increased self confidence; delayed intense and more pleasurable orgasm Therapeutic useantiemetic, appetite

PO, IV, smoked, snorted, rectally ice crystal meth

Marijuana and related preparations

Tolerance and dependence can occur w/ extremely high doses

stimulant, chronic pain management Euphoria, sedation, hallucinations, antimotivation al syndrome w/ chronic use

hypotension Respiratorychronic use asthma, lung CA Decrease in sperm production

restlessness, irritability.

Psychedelics

Name of Agent LSD

Therapeutics No therapeutic effects! Alterations in thinking, feeling, perception, sense of self and relationships w/ others Unpredictable effects sublime to terrifying Stimulant and psychedelic properties elevation of mood, increased sensory awareness and heightened sensitivity to music Low dose alcohol effects

Pharmacokine tics

Dosage PO, smoking, IV Effects can last 812 hours

Side Effects Panic rxns, flashbacks, fatalities from accidents and suicide

Interactions

Considerations

Ecstacy

Phencyclidine PCP

As dosage increase clinical picture become more variable and complex

Rhabdomyolosisb/d of muscle, increase in myoglobinrena l failure Dehydration/hyp onatremiadrink lots of fluids Neuro effects teeth grinding Increases HR and BP HYPERTHERMIA Hallucinations, CNS depression, and excitation and analgesia

TX of toxicity is supportive care no antidote

INHALANTS Anesthetics Volatile Nitrates Organic solvents Nicotene Low dose activates nicotinic receptors Absoprtion depends on system of delivery CVincreased HR and BP GINV decreases overtime ToleranceNV goes away Dependence

Toxicity management is supportive

Causes harm to the fetuspasses thru breastmilk avoid all preparations of nicotine

Pharmacologic Aids to Smoking Cessation Nicotine Replacement Therapy Nicotine Chewing gum Patches Inhalers Nasal Spray Bupropion (Zyban) not approved for smoking cessation Antidepressant drug Reduces the urge to smoke and reduces symptoms of withdrawal

DIETARY SUPPLEMENTS History and prevalence Complementary and alternative medicine

Natural does not mean harmless

Legislation National Center for Complementary & Alternative Medicine o Originally named Office of Alternative Medicine by National Institutes of Health (1992) Dietary Supplement & Health Education Act (DSHEA) 1994 o Define herbals as dietary supplements & provide regulatory framework for their sale Unlike FDA approved agents, DSHEA herbal supplements o Require NO proof of efficacy or safety o Presumed safe until proved hazardous o Quality may be questionable b/w manufacture o Removal when agents are proved unsafe by court order! ephedra FDA enforced o Current Good Manufacturing Practices (2007) Ensure product does not have contaminants, impurities Label must reflect purity, quality, strength Label must include active and inactive ingredients o Dietary Supplement and Nonprescription Drug Consumer Protection Act (2006) Manufacturers must report deaths, serious events, birth defects to FDA THE NURSING PROCESS ASSESSMENT o Medication history documenting allergies, prescription & over the counter (OTC) agents, herbal agents, vitamins & minerals Tobacco & ETOH use Drug interactions often unknown! o Developmental concerns Little information exists on herbal supplements with pregnant women, nursing mothers, infants & children
Name of Agent Garlic Therapeutics Antioxidant reduces carcinogens, activation and boosts the immune Pharmacokine tics Dosage Side Effects CV PROTECTIVE FACTORS lowers cholesterol, blocks platelet aggregation, Interactions INTERACTION S W? ANTICOAGULA NTS Considerations

Ginko Biloba

system Sx relief of memory loss, mental alertness, dementia; PAD relief

St. Johns Wort

Sx relief of mild to moderate depression

Works as an antioxidant and free radical scavenger, inhibits platelet aggregation, increases and improves cerebral blood flow and perfusion Active ingredients work similar to SSRIs and MAOIs

lowers BP Spontaneous bleeding, lowers seizure threshold

Pts w/ seizure d/o! Avoid drugs that lower the seizure threshold and anticoagulant s

Avoid using w/ Prescription antidepressants Can increase the risk of Serotonin syndrome Photosensitivi ty risk for burning Do not use with antiretroviral meds for HIV! Accelerates the anitviral therapy making antivirals subtherapeuti cincreasing risk for resistanct

Echinacea

Sx relief decreased length and severity of a cold

Antiinflammat ory and immune system stimulant that increase phagocytosis, activates non specific T cells

Similar to Ragweed allergic rxns common! Contraindicated in patients w/ autoimmune disease and/or on immunosuppres sant drugs post transplant, Lupus, AIDS GI sx NV Avoid use with: Insulin/oral hypoglycemic meds & antihypertensiv e meds. Potentiates the action of these drugs and may cause hypoglycemia & hypotension FINASTERIDE PROSCAR Use cautiously w/ anticoagulants/ antiplatelet RX increases the risk for bleeding Tachycardia, palpitations, dizziness

Not recommended for longer than 6-8 wks! Long term use suppresses immune function! Use not recommended no documented benefits!

Black Cohosh

Sx relief menopausal hot flashes

Unknown

Saw Palmetto

Sx relief of urinary hesitancy w/ BPH Effectiveness is questionable

Ma--Huang

Ephedra Sx relief of asthma,

Active ingredients inhibit steroids needed for prostate cell proliferation similar to 5alpha reductase inhibitors chemical constituents of ephedrine &

SHOULD NOT BE TAKEN BY WOMEN @ ALL!

FDA STEPPED IN AND SALES WERE BANNED IN THE US

appetite suppression, increases energy

pseudoephedri ne causing release of norepinephrin e.

progressing to dysrhythmias, HTN high risk of stroke and MI

IN 2004