Parkinson’s Disease Neurodegenerative Disorder The main nuclei involved is the Substantia nigra

o It sends signals in the form of dopamineo Controls normal movements of the body

YOU NEED DOPAMINE FOR NORMAL MOVEMENT!!!! PARKINSON’S PTS WILL NOT HAVE ADEQUATE DOPAMINE LEVELS!!!!

Dopamine is the INHIBITORY neurotransmitter – Acetylcholine is the EXCITATORY neurotransmitter Parkinson’s 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

Parkinson’s 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 inhibitoryo Now there is a lot of GABA and the thalamus realizes there is too much GABA and slows it back downo Now we are back to too much acetylcholine and not enough dopamine AND GABA

MOVEMENT DISORDERS is the big problem with Parkinson’s!

Symptoms Dyskinesias

o Tremors at resto Rigidityo Postural instabilityo Bradykinesia – slow movemento Akinesia – without movemento 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 It’s 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 Therapeutics Pharmacokinetics Dosage Side Effects Interactions ConsiderationsLevodopa

Dopamine Replacement

Used for advanced Parkinson’s-Will have good control of symptoms for 2 yrs

GRADUAL LOSS – pt is starting to lose the drug’s effects right before it’s time for their next dose – not holding them the entire time. Symptoms start returning which means they are subtherapuetic – what to do to fix this:---Shorten dosing interval---Add a drug to

ABRUPT LOSS – ON/OFF PHENOMENON: Episodes of the ability to be mobile (on) and an unpredictable 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 onON/OFF periods are unpredictable & not related to dosing or meds!

-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 THERAPEUTIC EFFECTS!!! CAN TRIGGER AN OFF PERIOD!!!!

-FOOD IS A BIG PROBLEM WITH

--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

--SWEAT AND URINE WILL BECOME DARK!

-THIS MED REACTIVATES

--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

--ANTI-CHOLINERGIC DRUGS ARE A GOOD INTERACTION – it enhances the response

Every Parkinson pt will get this eventuallyBetween years 2-5 they will regress and by year 5 they are back to where they were before they started any meds

-As Parkinson’s progresses, you’ll 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 come to the hospital bc stopping the med immobilizes the pt – stopping med for 10 days helps them get more benefit

prolong Levodopa’s ½ life---Give a direct acting dopamine agonist

LEVODOPA! IT DELAYS ABSORPTION BY DELAYING GASTRIC EMPTYING!!!

MALIGNANT MELANOMA!!

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 Therapeutics Pharmacokinetics Dosage Side Effects Interactions ConsiderationsLevodopa PLUS Carbidopa (Sinemet)

Dopamine Replacement

Carbidopa has no therapeutic effect on its own

INCREASED AVAILABILITY OF DOPAMINE IN CNS

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

LESS POSTURAL HYPOTENSION & ARRHYTHMIA!!

LESS N/V!!

LESS CONCERN ABOUT VITAMIN B6 INTERACTION!!

Dopamine Agonists Once Parkinson’s 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 planto Nonergot

Newer Less side effects Selective for dopamine receptors

Name of Agent Therapeutics Pharmacokinetics Dosage Side Effects Interactions ConsiderationsPramipexole (Mirapex)

Dopamine Agonist - NONERGOT

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

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

Ropinirole (Requip) – main competitor (also Nonergot)

Name of Agent Therapeutics Pharmacokinetics Dosage Side Effects Interactions ConsiderationsBomocriptine (Parlodel)

Dopamine Agonist - ERGOT

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

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

Limited psychological reactions

This has more side effects because it’s 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 Therapeutics Pharmacokinetics Dosage Side Effects Interactions ConsiderationsEntacapone (Comtan)

Catecholamine-O-methyl transferase (COMT) Inhibitors

PROLONGS THE HALF LIFE OF LEVODOPA IN THE BLOOD!!!!!

“ON” TIMES ARE EXTENDED AND “OFF” TIMES ARE DELAYED!!!

Blocks COMT

LONG HALF LIFE OF LEVODOPA, LESS GRADUAL LOSS SYMPTOMS

INCREASE LEVODOPA LEVELS!!!

Selegiline (Eldepryl, Carbex)

MAO-B Inhibitors

3 rd or 4 th line drug to treat Parkinson’s

It MAY slow down progression

Irreversible inhibition of MAO enzyme

Conflicting data on the effects/benefits – why it was moved to 3 rd or 4 th line treatment!!!

Amantadine (Symmetrel)

Causes patient to make their own Dopamine OR to

2-3 day response time but diminishes

-Confusion, light-headed, anxiety-Blurred vision, dry

WORKS QUICKLY BUT BURNS OUT JUST AS QUICKLY!!

Dopamine Releaser

block reuptake of Dopamine

between 3-6 months

mouth, constipation-LIVEDO RETICULARIS is mottled looking skin!!!

-Side effects USUALLY goes away when drug is stopped – NOT ALWAYS!!

Name of Agent Therapeutics Pharmacokinetics Dosage Side Effects Interactions ConsiderationsArtane and Cogentin

Centrally Acting Anti-Cholinergic

Reduces tremor and rigidity but NOT BRADYKINESIA!!!

Second line drugs Peripheral effects – dry mouth, blurred vision, photophobia, urinary retention, constipation and tachycardia

Withdraw drugs slowly do not discontinue abruptly may intensify Parkinson’s symptoms!!!!!

START LOW AND GO SLOW – when it comes to anti-cholinergics !!!!

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, don’t 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) seizureo Absence seizures – no movement, eyes are open but have a staring look like “no one is home” when looking at the childo Atonic seizureso Myclonic seizureso Status Epilepticus – medical emergency, pt can’t break the seizure on their own, pt loses airway and cardiac disturbances starto 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 Therapeutics Pharmacokinetics Dosage Side Effects Interactions ConsiderationsPhenytoin (Dilantin)

Anti-epileptic / Sodium Channel Blocker

ALL SEIZURES EXCEPT ABSENCE!

Prophylactic tx to prevent pt from having seizures

Certain dysrhythmias—as an alternate to lidocaine.

Inhibits Na+ channels delaying the onset of action potentials.

PO, IV, suspensionDoses individualized—Adhere strictly as small can cause seizures, toxicity or failure of RX.

High incidence of phlebitis w/ IV Dilute in NSS. Destroys veins-crystal formationsAVOID IV DILANTIN @ ALL COSTS!CAUTION-not compatible w/ dextrose! Will form precipitates.

Mild CNS effects w/ therapeutic levels (10-20)Toxic levels >20 causes ataxia, nystagmus, diplopia, sedation!

Gingival hyperplasia (overgrowth of gums)manage w/ oral care, surgery.RashIV infusion can cause hypotension and dysrhythmias – infuse s l o w l y, diluted and pt on a cardiac monitor!

Hepatic drug- metabolizing enzymes effects of oral BCP, warfarin, glucocorticoids.RX that plasma phenytoin levels—tagamet, INH, diazepam, valproic acid.RX that plasma phenytoin—carbamazapine, phenobarbitalCNS depressants have an additive effect & should be avoided.

DILUTE DILANTIN W/ NSS WHEN GIVING IV. NOT COMPATIBLE W/ DEXTROSE!

ASSESS HR AND BP BEFORE AND AFTER GIVING!

TERATOGENIC!

Name of Agent Therapeutics Pharmacokinetics Dosage Side Effects Interactions ConsiderationsFosphenytoin (Cerebyx)

Anti-epileptic / Sodium Channel Blocker

Treat all seizures except absence

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

IV admin—immediate conversion to phenytoin.less irritating you can push this

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

NO CV EFFECTS WITH THIS ONE COMPARED TO PHENYTOIN

$$$-Hospitals don’t carry

drug faster which will help pt faster!

Carbamazepine (Tegretol)

Anti-epileptic / Sodium Channel Blocker

TX of epilepsy – NOT effective tx for absence, myoclonic or atonic seizures.Bipolar d/oTrigeminal & glossopharyngeal 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.

Hematologic effects, teratogenic effects how it differs from phenytoin**

CNS effects- visual disturbances, ataxia, vertigo tolerance to CNS se’s 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 bipolar-mood stabilizer and migraines

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

SAFER THAN PHENYTOIN – wider therapeutic range (50-150)

Hepatotoxicity and Pancreatitis – rare but serious.

N & V

Preg. Cat D –Teratogenic!

phenobarb metabolismDisplaces phenytoin may result in toxicity!

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

Name of Agent Therapeutics Pharmacokinetics Dosage Side Effects Interactions ConsiderationsPhenobarbitol

Barbituate

TX partial or tonic clonic seizures.

Suppresses seizures by potentiating the effects of GABA!

PO, IM, IV

-Drowsiness-Physical dependence-Congenital defects in fetus

TOXICITY—Nystagmus & ataxia generalized CNS depression death!!

NO ALCOHOL!! TOO MUCH CNS DEPRESSION!

NO PREGNANCY!!

NO ANTIDOTE FOR TOXICITY-SUPPORTIVE CARE.

Lamotrigine(lamictal)

Anti-epileptic

TX of epilepsy (adjunct tx for partial and tonic-clonic seizures) Bipolar d/o

SERIOUSAseptic meningitisStevens Johnson Syndrome

Newer agent, limited uses.

Gabapentin (Neurontin)

Used as adjunctive therapy in partial seizures.

Bipolar, neuropathic pain, leg cramps and migraines

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

Levetiracetam (Keppra)

Used for tx of 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.

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

Name of Agent Therapeutics Pharmacokinetics Dosage Side Effects Interactions ConsiderationsNeostigmine (Prostigmin)

Cholinesterase Inhibitors

Will increase muscle strength

Cholinesterase breaks down Acetylcholine, so this will prevent Ach from being inactivated which means there is more available at muscarinic receptors & at the neuromuscular junction

Dose is titrated based on pt’s response

SX of undermedication weakness, trouble swallowing, breathing, speaking, ptosis =MYASTHENIC CRISISSX of overmedication—secretions everywhere! Excess saliva, SOB=CHOLINERGIC CRISIS

Acetylcholine levels will go up!!!!

• 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 SpasticityMuscle 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 Therapeutics Pharmacokinetics Dosage Side Effects Interactions ConsiderationsCyclobenzaprine (Flexeril)

Centrally Acting Muscle Relaxants

Treats local spasm from muscle injury

Mechanism is unknown

Oral CNS depression-drowsiness, sedation; hepatic toxicity, anticholinergic effects—dry mouth, blurred vision, urinary retention, constipation.

Can cause physical dependencew/d over a 2 week period to avoid w/d sx.

Methocarbamol and diazepam (are also centrally acting muscle relaxants) can be given IV or IM

Diazepam (Valium)

BENZOCentrally Acting Muscle Relaxants

Used as a muscle relaxant ACUTELY and is also an ANTISPASMODIC

-Also used in status epilepticus

IV CENTRAL ACTING!

MANY ADDICTED PTS OUT THERE! THIS CAUSES PHYSICAL DEPENDENCE!

CNS DEPRESSANT!

DC s l o w l y! Physical and psychological dependence Withdraw over a 2 week period

Baclofen (Lioresal)

Centrally Acting

MS and traumatic lesions of the spinal cord, & CP. NOT effective in

Mimics GABA on spinal neurons. Suppresses hyperactive

Used in people who have been maxed out on their oral opiates

CNS depressantAnti-cholinergic effectsToxicity—coma,

Use caution in pt w/ seizure d/o – deteriorates seizure control even if pt

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

Spasmolytics spasticity of Parkinson’s or Huntington’s chorea

reflexes or centrally acting spasmolyticsGIVEN INTRATHECALLY!

respiratory depression, vent support.

never had a seizure before!

Dantrolene (Dantrium)

Peripherally Acting Spasmolytics

Drug of choice for Malignant HyperthermiaEffective 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 with intracellular Ca++ movement

Muscle WeaknessSerious—Hepatotoxicity

Contraindicated when spasticity is used to maintain an upright posture & balance as in cerebral palsy—bc dantrolene works peripherally directly @ the muscle!

Withdraw over a 2 week period

CNS STIMULANTS/ ADHD

CNS STIMULANTS Increase CNS activity Neuronal inhibition—blocking NT that are inhibitory Neuronal excitation—directly excite the neurons Indications for CNS stimulant use—

o ADHDo Narcolepsy o CNS stimulants do not TX depression!

Name of Agent Therapeutics Pharmacokinetics Dosage Side Effects Interactions ConsiderationsAmphetamines ADHD

Narcolepsy↑ wakefulness and alertness, ↓ fatigue, ↑ mood, augment self confidenceTalkative, peripheral – increased motor activity, ↓ appetite, ↑ respirations, ↓ pain perceptionNE release ↑ HR, ↑BP, dysrhythmias (in high doses)Tolerance develops with regular use—require a higher dose of drug to

Promote/increase the release of NE and dopamine (**dopamine blocks GABA)

CNS Stimulation—insomnia, increased wakefulness, excessively talkativeWeight lossCV Effects—dysrhythmias, chest pain, HTNPsychosis—w/ higher dosesAcute toxicityDizzy, confused, paranoid delusions, hallucinations, palpitations, HTN – convulsions, coma, deathRemove source of medicationTreatmentAlpha-adrenergic blocker, chlorpromazine (to

Abuse/physical dependencePhysical dependence-body becomes dependent and when drug is removed pt will have physical sx —abstinence syndrome—s/s are opposite the effects of the drug Psychological dependence—intense cravings for euphoria amphetamines giveSchedule IIAbrupt withdraw after prolonged use – exhaustion, depression, prolonged sleep, excessive eating craving for more amphetamines

get the same effect

manage psychosis),benzos to tx seizure activity

Methylphenidates ADHDNarcolepsy

Short duration—BID, TID 3—5 hoursIntermediate duration-BID/QID 4—8hoursLong duration—Daily 14 hours

Schedule II-high abuse potential

Dexmethylphenidate

ADHD Structurally different from methylphenidate

Half the dose of methylphenidate

Schedule II

MethylxanthinesCAFFEINE

CNS-increased wakefulness, nervous, tremorsHeart—increases HR, dysrhythmias in high doseBlood vessels—Peripheral— vasodilationCNS — vasconstriction in brain — used to TX HA!Bronchi — dilate bronchi —THEOPHYLLINE! Kidney — diuretic Reproduction—during early pregnancy can cause birth defects; miscarriage. Not recommended for pregos.

Modafinil (Provigil)-tx of narcolepsyCocaine-Local anesthetic-vasconstrictive properties

Strattera (atomoxetine)

ADHD—non stimulant

Selectivey inhibits the reuptake of NE.

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 StratteraGI effects-appetite suppression-wt loss,

MAO inhibitors—cause a HTN crisis SSRIs—increase levels of Strattera

Metabolized bt the liver

No data on long term effects—not as effective as amphetamines—need more controlled trials

growth retardation in children

Drugs of Abuse

Addiction

• Tolerance –body adjusts to drug, requiring a higher dose to achieve desired effect• Cross-tolerance –one substance for another; heroin—will 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• DEA—requires 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 – 5—HT3 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.

– Wernicke’s Encephalopathy• Directly r/t thiamine deficiency!• Confusion, nystagmus, abnormal ocular movements• Reversible with thiamine—IV

– Korsakoff’s 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• ↑TPA—tissue 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 ADH—”break 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 infant’s 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 rate—metabolism doesn’t 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 depressants—additive 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.• Antihypertensives—negates 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 Therapeutics Pharmacokinetics Dosage Side Effects Interactions ConsiderationsHeroin Drug of choice for

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

Routes- IV, smoking, nasal inhalation

Effects are immediate w/ an intense euphoria

Meperidine (Demerol)

Often a drug of choice for healthcare workers – euphoria!

Effective PO administration so don’t 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 gooseflesho Peak effects include violent sneezing, weakness, NVD, abdominal cramps; muscle spasm and kicking movements

o Lasting 7—10 days o Unpleasant but rarely dangerouso Mild w/d follows and may last for months w/ insomnia, irritability, fatigue, GI hyperactivity – diarrhea, premature ejaculation

TX OF ACUTE TOXICITYo 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 AGENTSName of Agent Therapeutics Pharmacokinetics Dosage Side Effects Interactions ConsiderationsMETHadone Easing Heroin

w/d to prevent abstinence syndrome

PO opioid w/ long durationOnce the pt is stabilized on methadone—doses are titrated down

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 addictionName of Agent Therapeutics Pharmacokinetics Dosage Side Effects Interactions ConsiderationsMethadone Maintenance

therapy and suppressive therapy

Suppressive therapy is done to prevent the reinforcing effects of opioid

Used to modify drug using behavior in pts who are not ready to withdrawal

induced euphoria

Buprenorphine (Subutex)Agonist—antagonist Opioid

Maintenance therapy and to facilitate detoxification

Low potential for abuseSuppresses craving for heroin

ABUSE OF GENERAL CNS DEPRESSANTS

Name of Agent Therapeutics Pharmacokinetics Dosage Side Effects Interactions ConsiderationsBarbiturates

Subjective effects similar to effects of alcohol

MILD SEDATION COMA AND DEATH

Acute toxicity – no antidote – supportive therapy and removing the drug from the body

No tolerance to respiratory depression but pt will have a tolerance to euphoria!

BENZODIAZEPINES OD on benzos alone is rarely fatal—death is greatly increased when combining PO benzos w/ other CNS depressants! or administered IV.

Antidote –Flumazenil (Romazicon)

Withdrawal slowly

Alcohol

Psychostimulants

Name of Agent Therapeutics Pharmacokinetics Dosage Side Effects Interactions ConsiderationsCOCAINE Produces a

euhporiaInhibits neuronal reuptake of dopamine – increasing activation of dopamine receptors in the

Cocaine HCL –intranasally; IV

Cocaine base “crack” Smoked

MILD OD – agitation, dizziness, tremor, blurred vision

SEVERE OD- hyperpyrexia, convulsions,

OD IS FREQUENT

W/ chronic use –nasal damageUse during prego is not recommended

brains reward circuit

ventricular dysrhythmias and hemorrhagic strokeAnginaAnxiety, paranoid ideations and hallucinations

Physical dependence is unclear—may 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

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

Hallucinations, paranoid ideation; psychosis, vasoconstriction(increased BP and HR)Tolerance develops –requiring higher dosesPhysical dependence is moderatePsychological dependence can be intense!

Marijuana and related preparations

Therapeutic use-antiemetic, appetite stimulant, chronic pain managementEuphoria, sedation, hallucinations, antimotivational syndrome w/ chronic use

Tachycardia, reddening of conjunctivae, orthostatic hypotensionRespiratory- chronic use asthma, lung CADecrease in sperm production

Tolerance and dependence –can occur w/ extremely high doses – restlessness, irritability.

PsychedelicsName of Agent Therapeutics Pharmacokinetics Dosage Side Effects Interactions ConsiderationsLSD No therapeutic

effects!Alterations in thinking, feeling, perception, sense

PO, smoking, IVEffects can last 8—12 hours

Panic rxns, flashbacks, fatalities from accidents and suicide

of self and relationships w/ othersUnpredictable effects – sublime to terrifying

Ecstacy Stimulant and psychedelic properties—elevation of mood, increased sensory awareness and heightened sensitivity to music

Rhabdomyolosis-b/d of muscle, increase in myoglobinrenal failureDehydration/hyponatremia—drink lots of fluidsNeuro effects—teeth grindingIncreases HR and BPHYPERTHERMIA

Phencyclidine PCP Low dose—alcohol effects

As dosage increase clinical picture become more variable and complex

Hallucinations, CNS depression, and excitation and analgesia

TX of toxicity is supportive care – no antidote

INHALANTSAnestheticsVolatile NitratesOrganic solvents

Toxicity management is supportive

Nicotene Low dose –activates nicotinic receptors

Absoprtion depends on system of delivery

CV—increased HR and BPGI—NV—decreases overtimeCNS—more alert, decreased anger, decreased appetite

Tolerance—NV goes awayDependence

Causes harm to the fetus—passes thru breastmilk – avoid all preparations of nicotineAcute poisoning by ingestion –NV, salivation, cold sweat, disturbed hearing and vision, confusion, fainting, rapid, weak irregular pulse; resp paralysis TX—reduce absorption w. charcoal and

supportive therapy

Chronic toxicity from smoking—CA, heart disease, stroke, pulmonary emboli w/ concurrent oral BCP use

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 hazardouso Quality may be questionable – b/w manufacture o Removal when agents are proved unsafe by court order! – ephedra

FDA enforcedo 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 Therapeutics Pharmacokinetics Dosage Side Effects Interactions ConsiderationsGarlic Antioxidant— CV PROTECTIVE INTERACTIONS W?

reduces carcinogens, activation and boosts the immune system

FACTORS—lowers cholesterol, blocks platelet aggregation, lowers BP

ANTICOAGULANTS

Ginko Biloba Sx relief of memory loss, mental alertness, dementia; PAD relief

Works as an antioxidant and free radical scavenger, inhibits platelet aggregation, increases and improves cerebral blood flow and perfusion

Spontaneous bleeding, lowers seizure threshold

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

St. John’s Wort Sx relief of mild to moderate depression

Active ingredients work similar to SSRI’s and MAOI’s

Avoid using w/ Prescription antidepressants –Can increase the risk of Serotonin syndromePhotosensitivity – risk for burning

Do not use with antiretroviral meds for HIV!Accelerates the anitviral therapy– making antivirals subtherapeutic—increasing risk for resistanct

Echinacea Sx relief—decreased length and severity of a cold

Antiinflammatory and immune system stimulant that increase

Similar to Ragweed—allergic rxns common!

Not recommended for longer than 6-8 wks! Long term use suppresses immune function!

phagocytosis, activates non specific T cells

Contraindicated in patients w/ autoimmune disease and/or on immunosuppressant drugs – post transplant, Lupus, AIDS

Use not recommended – no documented benefits!

Black Cohosh Sx relief – menopausal hot flashes

Unknown GI sx – NV Avoid use with: Insulin/oral hypoglycemic meds & antihypertensive meds. Potentiates the action of these drugs and may cause hypoglycemia & hypotension

Saw Palmetto Sx relief of urinary hesitancy w/ BPH

Effectiveness is questionable

Active ingredients inhibit steroids needed for prostate cell proliferation – similar to 5alpha reductase inhibitors

FINASTERIDE – PROSCAR Use cautiously w/ anticoagulants/ antiplatelet RX – increases the risk for bleeding

SHOULD NOT BE TAKEN BY WOMEN @ ALL!

Ma--Huang EphedraSx relief of asthma, appetite suppression, increases energy

chemical constituents of ephedrine & pseudoephedrine – causing release of norepinephrine.

Tachycardia, palpitations, dizziness progressing to dysrhythmias, HTN –high risk of stroke and MI

FDA STEPPED IN AND SALES WERE BANNED IN THE US IN 2004