Classification:Full agonist at the μ (mu)-opioid receptor (phenanthrene)

MOA:produce analgesia through actions at receptors in the central
nervous system (CNS) that contain peptides with opioid-like pharmacologic properties.Morphine does act at μ and δ receptor sites but role is unclear
- Interaction is supported by the study of genetic knockouts in mice. May act primarily and directly at the μ receptor
◦ Action may evoke the release of endogenous opioids acting at δ and κ receptors.

μ+++

κ+

Indication/Clinical Application:Opioids administered to the neuraxis by the spinal or epidural route
(Usefulness may be limited by intense pruritus over the lips and torso). Can be useful for Painful myocardial ischemia with pulmonary edema.Use in patients with impaired hepatic or renal function
● Patients with prehepatic coma
- Morphine and its congeners are metabolized primarily in the liver
- Use may be questioned
● Patients with impaired renal function
- Half-life is prolonged
- Morphine and its active glucuronide metabolite may accumulate
- Dosage can often be reduced

SE and AED's:Metabolite effects:in Patients with renal failure
- Patients receiving exceptionally large doses
- Patients receiving high doses over long periods
◦ Example: M3G-induced CNS excitation (seizures)
◦ Example: M6G enhanced and prolonged opioid action, Disrupts normal rapid eye movement (REM) and non-REM sleep patterns (Disrupting effect is probably characteristic of all opioids)Produces hyperthermia (Administration of μ-opioid receptor agonists). Morphine(Withdrawal signs usually start within 6 to 10 hours after the last dose
- Peak effects are seen at 36 to 48 hours
- By 5 days most of the effects have disappeared
◦ Some may persist for months)

Contraindications:Combination of morphine with other central depressant drugs (sedativehypnotics-May result in very deep sleep)

Therapeutic Considerations:been known to relieve severe pain with remarkable
efficacy.remains the standard against which all drugs that have strong analgesic action are compared.Opium is obtained from the poppy
● Papaver somniferum and P album
● Morphine is the main alkaloid at 10%.Oral dose may need to be much higher than the parenteral dose. Low parental potentcy ratio.High max efficacy.Sustained-release forms-Advantage is a longer and more stable level of analgesiaRelief produced by intravenous morphine(Reduced anxiety, Reduced cardiac preload due to reduced venous tone, Reduced afterload due to decreased peripheral resistaance)● Long-lasting analgesia with minimal adverse effects can be achieved
- Epidural administration of 3 to 5 mg of morphine
- Followed by slow infusion through a catheter placed in the epidural space.Rectal suppositories of morphine-Used when oral and parenteral routes are undesirable.Morphine and congeners
◦ Cross-tolerance to analgesic, euphoriant, sedative and respiratory effects
◦ Cross-tolerance can often be partial or incomplete
◦ Led to the concept of "opioid rotation"

PK: duration: 4-5h.Free hydroxyl groups are conjugated to form morphine-3- glucuronide (M3G)
- Neuroexcitatory properties but through the GABA/glycinergic system
● 10% of morphine is metabolized to morphine-6-glucuronide (M6G)
- Active metabolite with analgesic potency four to six times that of morphine
● These polar metabolites have limited ability to cross the blood-brain barrierProbably do not contribute to the usual acute CNS effects of morphine
- Exception coadministration of probenecid or inhibit of P-glycoprotein drug transporter ◦ CNS uptake of M3G and, to a lesser extent, M6G can be enhanced.Persistent administration of opioid analgesics leads to hyperalgesia

Classification:opioid agonist (phenylpiperidine opioid)

MOA: subtypes of the alpha 2 adrenoceptor --- strong mu agonist

Indication/Clinical Application:anti-shivering properties

SE and AED's: -Tachycardia, hypoTN w/ stress, peripheral arterial & venous dilation, Histamine release

Contraindications: -Renal dysfunction                          -Multiple high doses (Normeperidine accumulates & causes SZ)   -Low blood volume: hypoTN -Tachycardia (anti-muscarinic)

Therapeutic Considerations:Normeperidine is the demethylated metabolite; it may accumulate in body and high concentrations of normeperidine may cause seizures;    has less sedation (because synthetic);   less respiratory depression than morphine - espeically in newborns;   withdrawl subsides in 24 hours

Classification:opioid agonist (phenanthrene)

MOA:patial mu agonist

Indication/Clinical Application:pain

SE and AED's: the adverse effects limit the maximum tolerated dose

 Therapeutic Considerations:effective orally (reduced first pass effect);   metabolized in liver by CYP2D6 and produces metabolites but parent cmpd do analgesia;  less efficacious than morphine (partial agonist); rarely used alone (combo with ASA or APAP); available in sustained release

Classification: benzomorphan mixed agonist - antagonist

MOA:partial mu and strong KAPPA

Indication/Clinical Application:moderate pain 

SE and AED's: psychotomimetic (anxiety, hallucinations, nightmares); irritant properties; may percipitate absitence syndrome

Contraindications: -Weak partial agonist + full agonist: Morphine + Pentazocine (withdrawal)

Therapeutic Considerations:PO or parenteral *NO SubQ injection*;   -Can antagonize strong agonists (no tolerance to antagonist actions); duration is 3-8 hours; -Withdrawal: (induced after chronic Naloxone admin.: anxiety, loss of appetite & weight, tachycardia, chills, abdominal cramps)

Classification: phenylheptylamine strong agonist

 Indication/Clinical Application:mild to moderate pain?

SE and AED's: serious and fatal heart rhythm abnormalities (at therapeutic doses)

 Therapeutic Considerations:controlled substance (death and misuse); recalled and withdrawn from US market (fatal heart rhythm abnormalities); low efficacy and low analgesic activity (half as potent as codeine); chemically related to methadone

Classification:Opioid analgesic

MOA: Mu strong agonist (Phenanthrene); Primarily acts on CNS opioid receptors producing analgesia and sedation

Indication/Clinical Application:Acute and chronic pain

SE and AED's: Dizziness, somnolence, N/V, constipation, flushing, HA, sedation, etc.; Black box warning - respiratory depression (potent schedule II opioid agonist)

Contraindications: Alcohol

Therapeutic Considerations:Duration of analgesia is 4–5 hrs; t1/2 = 2.3 hrs; High maximal efficacy; Low oral:parenteral potency ratio; Metabolized by conjugation into hydromorphone-3-glucuronide (H3G), which has CNS excitatory properties; Does not form significant amounts of a 6-glucuronide metabolite

Classification:Opioid analgesic

MOA: Mu strong agonist (Phenanthrene); Primarily acts on CNS opioid receptors producing analgesia and sedation

Indication/Clinical Application: Acute and chronic pain; Anethesia (adjunct); Obstetric pain; Anxiety

SE and AED's: Dizziness, somnolence, N/V, constipation, flushing, HA, sedation, respiratory depression (no Black box warning), etc.

Contraindications:Alcohol 

Therapeutic Considerations:Duration of analgesia is 3–4 hrs; t1/2 = 7.3-11.3 hrs (urine); High maximal efficacy; Low oral:parenteral potency ratio; Extensive liver metabolism

Classification:Opioid analgesic

MOA: Synthetic Mu strong agonist (Phenylpiperidine); Primarily acts on CNS opioid receptors producing analgesia and sedation

Indication/Clinical Application: Acute and chronic pain; Anethesia (adjunct); Obstetric pain

SE and AED's:TACHYCARDIA (negative ionotropic effect due to antimuscarinic actions), stress-induced hypotension, dizziness, somnolence, N/V, constipation, flushing, HA, sedation, respiratory depression (no Black box warning), etc. 

Contraindications: Alcohol

Therapeutic Considerations:Duration of analgesia is 2–4 hrs; t1/2 = 2.5-4 hrs, 23 hrs in neonates (urine); High maximal efficacy; Low oral:parenteral potency ratio; Extensive liver metabolism to normeperidine, which can accumulate and cause seizures in pts with decreased renal function; Most pronounced anti-shiver properties; Short withdrawal symptom period (24 hrs)

Classification:Mu partial agonist
Phenanthrene

MOA:partial or weak agonist @ mu receptors

 Indication/Clinical Application:pathologic cough suppression, effective in pts needing maintenance of ventilation via endotracheal tube
antitussive at low dose

SE and AED's: Contraindications:Avoid MAOi if taking with dextromethorphan AND codeine

Therapeutic Considerations:synthesized from Morphine (methylated morphine=codeine), low affinity for other opioid receptors, less efficacious than morphine, rarely used alone, combined in formulations containing aspirin, ASA, or others, SE limit max tolerated dose when seeking analgesia
reduced 1st pass mtblsm, CYP2D6 mtblsm, metabolites more potent than parent, high oral/parenteral potency, 4-6 hrs of analgesic duration,

Classification:Mu partial agonist
Phenanthrene

  Indication/Clinical Application: analgesia

SE and AED's: Contraindications: Therapeutic Considerations:"less efficacious than morphine, SE limit max tolerated dose used for analgesia, compounds rarely used alone,
moderate oral/parenteral potency, 4-6 hrs analgesia duration, CYP2D6 mtblsm, minor activity by metabolites, parent compound active for analgesia"

Classification: "Mixed agonist-antagonist: Mu partial agonist, delta antagonist, kappa antagonist
Phenanthrene"

MOA: "agonist: high binding affinity, low intrinsic activity at Mu, slow rate of dissociation from Mu=long-acting drug (this makes it good alternative over methadone for management of opioid withdrawal);

high doses=mu-opioid antagonist action

antagonizes action of more potent mu agonists (morphine); binds to ORL 1 of orphanin receptor"

Indication/Clinical Application:"analgesic, effective for manitenance of detoxification, detoxification and maintenance of heroid abusers (as effective as methadone)
approved for opiod analgesic detoxification and management of opiod dependence"

SE and AED's: psychotomimetic effects: hallucinations, nightmares, anxiety

Therapeutic Considerations:lower risk of overdose fatalities, renders its effects resistant to naloxone reversal, sublingual route preferred to avoid 1stpassmtblsm,  high dose=mu antagonist limits analgesia and respiratory depression properties; available with naloxone (suboxone) to prevent IV drug abuse

Classification: MOA:Effects of the Kappa receptor (strong agonist) And mu receptor antagonist. Mixed agonist-antagonist properties

Indication/Clinical Application: Some clinical syccess as analgesics

SE and AED's: Can cause dysphoric reactions and have limited potency.

 Therapeutic Considerations:Parenteral only, 3-6h duration of analgesia, with high max efficacy. Causes significantly greater analgesia in women than in men. At higher doses there seems to be a definte ceiling to the respiratory depressant effect (not seen with morphine) . If respiratory depression does occur it is relatively to naloxone reversal. There has been some clinical success as analgesics/can cause dysphoric reactions and has limited potency.

Classification: Opioid Antagonist

MOA:Mu opioid binding (high affinity) & delta & kappa (lower affinity) binding; Increases baseline beta-endorphin release

Indication/Clinical Application:Maintenance drug for addicts in treatment programs; FDA approved to decr. the craving for alcohol in chronic alcoholics 

SE and AED's:Almost instantaneously precipitates abstinence syndrome

  Therapeutic Considerations:Long DoA; well absorbed after oral admin.; may undergo rapid first pass metabolism; T1/2 = 10 hrs; Single oral dose of 100 mg blocks the effects of injected heroin for up to 48 hrs; It's derivative is Nalmefene; Predicted this would not be popular w/ a large percentage of drug users (must be motivated to become drug-free);

Classification: Opioid Antagonist

MOA: Mu opioid binding (high affinity) & delta & kappa (lower affinity) binding

Indication/Clinical Application: Opioid overdose

 Therapeutic Considerations:Derivative of Naltrexone, T1/2 8-10 hrs, Only IV admin. available

Classification: Opioid Antagonist

MOA:Inhibition of peripheral mu receptors in the gut w/ minimal CNS penetration

Indication/Clinical Application: (FDA): Treatment of postoperative ileum following bowel resection surgery

Therapeutic Considerations:Modified Analog of naloxone and naltrexone

Classification: Opioid Antagonist

MOA:

Inhibition of peripheral mu receptors in the gut w/ minimal CNS penetration

Indication/Clinical Application:

(FDA): Treatment of postoperative ileum following bowel resection surgery

Therapeutic Considerations:

Modified Analog of naloxone and naltrexone

Classification:Opioid Antagonist

MOA:Mu opioid binding (high affinity) & delta & kappa (lower affinity) binding; Increases baseline beta-endorphin release

Indication/Clinical Application:Maintenance drug for addicts in treatment programs; FDA approved to decr. the craving for alcohol in chronic alcoholics 

SE and AED's: Almost instantaneously precipitates abstinence syndrome

Therapeutic Considerations:Long DoA; well absorbed after oral admin.; may undergo rapid first pass metabolism; T1/2 = 10 hrs; Single oral dose of 100 mg blocks the effects of injected heroin for up to 48 hrs; It's derivative is Nalmefene; Predicted this would not be popular w/ a large percentage of drug users (must be motivated to become drug-free);

Classification:cholinesterase

inhibitor

 MOA: centrally acting, reversible

choliesterase inhibitor that

increases CNS AChe

levels

Indication: mild to moderate

Alzheimer's

disease

(significantly delay

global cognitive

impairment)

SE:SERIOUS:

bradycardia, AV block;

COMMON: headache,

insomnia

 CI:CYP 2D6 inhibitors

TC:clinical trials only

ran 6 months;

modest

symptomatic

benefits in AD;

also acts as a nonpotentiating

ligand

of nicotinic

receptors; does

not alter underlying

neurodegenerative

process; clinical

benefit is modest

and temporary

 PK:orally active

(divided doses)

Classification: glutamatetransmission "dampener"

MOA:inhibits glutamate release and increases glutamate

uptake

 Indication:Amyotrophic Lateral Sclerosis--extends the time until invasive breathingassistance is needed

 SE: AT TOXIC LEVELS: decreased lung function, HTN

CI:should not be given with hepatotoxic drugs or drugs that

affect CYP1A2

 TC:palliative, but no significant effect on reducing time to

death

 PK:oral; metabolized by CYP1A2

Classification:Antimuscarinic agent

 MOA: Antagonist at M receptors in basal ganglia

Indication:Used for Parkinson's disease; reduces tremor and rigidity; little effect on bradykinesia

 SE:antimuscarinic effects (aka anti-SLUD + mydriasis, confusion); may worsen dementia and cognitive impairment in the elderly

 CI:Interaction with amantadine -- potentiates CNS side effects

 TC:Given orally pk

Classification: Antimuscarinic agent

MOA:Antagonist at M receptors in basal ganglia

 Indication:Used for Parkinson's disease; reduces tremor and rigidity; little effect on bradykinesia

 SE: antimuscarinic effects (aka anti-SLUD + mydriasis, confusion); may worsen dementia and cognitive impairment in the elderly

CI: TC:Given orally

 PK:

Classification:Increases dopamine levels for PD

MOA: Dopa Decarboxylase Inhibitor Indication:*Coadministered with Levodopa reduces amount needed *Levodopa is best given with carbidopa to patients with cardiac disease *Reduces peripheral metabolism of levodopa *Increases plasma levels of levodopa + increases T1/2

TC:*Increase dopa entry into the brain PK:Carbidopa does not cross the BBB

 MOA: Transported into the CNS and converted to dopamine (which does not enter the CNS); also converted to dopamine in the periphery; inhibits peripheral metabolism of levodopa to dopamine and reduces required dosage and toxicity; carbidopa does not enter CNS Indication: Parkinson's disease: Most efficacious therapy, but not always used as first drug due to development of disabling response fluctuations over time; helpful in relieving bradykinesia

SE: GI upset, arrhythmias, dyskinesias, on-off and wearing-off phenomena, behavioral disturbances CI: Interactions: use with carbidopa greatly diminishes required dosage use with COMT or MAO-B inhibitors prolongs duration of effect; Carbidopa does not enter CNS

TC:Dopa is the precursor of DA and NE; levodopa is the stereoisomer of dopa; get the best results of the medication in the first few years (3- 4) of treatment Sometimes the daily dose of levodopa must be reduced over time to avoid ADEs; early initiation does lower the mortality rate; long term treatment may lead to problems in management (onoff phenomena); available as controlled-release

PK:Oral, 6-8 hour effect Levodopa is rapidly absorbed from the small intestine; ingestion of food delays the appearance of levodopa in the plasma

MOA: Same carbidopa+levodopa; entacapone added is a catechol-omethyltransferase (COMT) inhibitor

Indication: Parkinson's disease: Most efficacious therapy, but not always used as first drug due to development of disabling response fluctuations over time; helpful in relieving bradykinesia

SE: GI upset, arrhythmias, dyskinesias, on-off and wearing-off phenomena, behavioral disturbances

  CI:Interactions: use with carbidopa greatly diminishes required dosage use with COMT or MAO-B inhibitors prolongs duration of effect; Carbidopa does not enter CNS Levodopa should not be given to psychotic patients, angleclosure glaucoma, use with care in pts  with a history of melanoma or with suspicious skin lesions

 TC:same as above; the use of entacapone prolongs the action of levodopa by diminishing peripheral metabolism

 PK:oral, 6-8 hour effect

Classification:COMT Inhibitor

MOA:Inhibits COMT in

periphery and CNS.

Reduces metabolism of

levodopa

 Indication:PD

SE:Main: nausea,

diarrhea. Also:

Increased levodopa

toxicity

dyskinesias, confusion

 TC:Preferred over

tolcapone 

PK:T1/2=2hrs

Classification:COMT Inhibitor

MOA:Inhibits COMT in

periphery and CNS.

Reduces metabolism of

levodopa

Indication: PD

SE: Hepatotoxicity!!

diarrhea, nausea,

dyskinesias, confusion

TC:Hepatotoxic!!

PK:T1/2=2hrs, more

potent than

entacapone,

longer duration of

action

Classification: ('older') D2 Agonist

(ergot derivative)

 Indication:Treat Parkinson's

disease; reduces

symptoms of

parkinsonism &

smooths out

fluctuations in

levodopa

response; on-off

phenomenon

 SE: N/V, postural hypotension,

diskinesias, confusion,

impulse control disordrs,

sleepiness (sedation),

painless digital vasospasm

(dose-related), decr.

prolactin levels, dry mouth,

hallucinations, vivid dreams;

more toxic than pramipexol

or ropinirole

CI:D-D interaction: DA

antagonists may

reduce effects (duhr)

 TC:Oral: 8 hr effect;

rarely used, replaced

w/ newer DA

agonists; variable

absorption, Tmax 1-2

hrs, excreted in bile

& feces (ew); taken

after meals to decr.

AEs

Classification:Dopamine

Antagonist

 MOA:blocks central D2

receptors

 Indication:Reduces vocal &

motor tic

frequency,

severity; Tourette's

syndrome

 SE: Parkinsonism, other

dyskinesias, sedation,

blurred vision, dry

mouth, GI

disturbances; May

cause cardiac rhythm

disturbances

 TC:Oral

Classification:Dopamine Agonist,

D3 receptor

agonist. Mono-Tx:

mild to moderate

PD

 MOA: Non Ergot. Used to

reduce parkinson

sympotoms.

Indication:Intial therapy of

parkinsons

 SE: -GI: anorexia, NV,

constipation, reflux

esophagitis, bleeds,

indigestion -

CV: periph. edema,

postural hypoTN,

arrhythmias

-Dyskinesias

-Mental: confusion,

hallucinations,

delusions, impulsive

*Worse: old drugs*

 TC: On/off

phenomenon. Ex.

Used when

levadopa is not

working.Possible

neuroprotection 

PK:oral

Classification:Dopamine Agonist,

D2 agonist.Mono-

Tx: mild PD

 MOA:Non Ergot. Used to

reduce parkinson

sympotoms.

 Indication:Intial therapy of

parkinsons

 SE: -GI: anorexia, NV,

constipation, reflux

esophagitis, bleeds,

indigestion -

CV: periph. edema,

postural hypoTN,

arrhythmias

-Dyskinesias

-Mental: confusion,

hallucinations,

delusions, impulsive

*Worse: old drugs*  

 TC:On/off

phenomenon. Ex.

Used when

levadopa is not

working 

PK:Oral. -CYP1A2

metabolism

Classification:MAO-B inhibitor

mostly

 MOA: prevents/slows mtblsm of

DA=incr. DA levels to

enhance and prolong

antipark. effect of

levodopa (which helps to

reduce levodopa dose)

also prevents mtblsm of

NE and 5HT

high doses=MAO-A inhib.

also

Indication: adjunct therapy:

pts with declining

or fluctuating

response to

levodopa

SE:insomnia when taken

later in day

Confusion;

dyskinesias;

hallucinations;

hypotension; insomnia;

and nausea.

may incr. AE of

levodopa

 CI: avoid with

meperidine and

fluoxetine

caution w/ TCA,

SSRIs (rare

theoretical risk of

acute toxic

interactions of

serotonin syndrome

type)

TC:monotherapy=minor

therapeutic effect

on parkinsonism

ambiguous

whether slows

disease

progression;

TAKE W/ FOOD

Classification: Dopamine Agonist

MOA:Potent dopamine agonist

(nonergot)

 Indication: temporary relief

("rescue") of offperiods

of

akinesia/dyskinesia

SE:Nausea (Pretreatment

with the antiemetic

trimethobenzamide)

Dyskinesias,

drowsiness, chest pain,

sweating, hypotension

and injection site

bruising

 TC:subcutaneous

injection

Classification:Dopamine Agonist

MOA: unclear; Antagonism at

NMDA receptors, MAY

potentiate dopaminergic

function, Antagonize the

effects of adenosine at

adenosine A2A receptors,

Release of

catecholamines from

peripheral stores,

Indication: Smooths out

movement in the

course of levodopa

treatment

SE: Central nervous

system effects (

agitation,

hallucinations,

confusion, etc,

REVERSED IF DC

DRUG) Livedo

reticularis (purple

mottled discoloration of

skin usually on legs,

clear w/in 1 month after

DC) Peripheral edema

(respond to diuretics)

GI, HA, heart failure,

etc.

CI:Caution in patients

with heart

failure/seizure

 TC:Anti-viral agent,

less efficacious

than levodopa,

benefits short

lived, May

favorably influence

the bradykinesia,

rigidity and tremor

of parkinsonism,

REDUCE

iatrogenic

dyskinesias in

patients with

advanced disease.

DRUG

INTERACTION:

Benztropine and

trihexyphenidyl

potentiate CNS

side effects

 PK:SHORT HALF

LIFE (2-4 hr)

 CI: Carbamazepine ↓

serum levels of

haloperidol (used for

huntingtons's)

Classification:Typical
Antipsychotic

 MOA:depletes amine

transmitters(esp

dopamine from nerve

endings), Blocks central

d2 receptors; Effect: ↓ the

chorea severity in

huntingtons, ↓ vocal and

motor

tic/frequency/severity in

tourette's

 Indication:Huntington's

disease,

Tourrette's

 SE:EPS and ↑ Prolactin,

other diskenesias,

blurred vision, dry

mouth, GI disturbances

( hypotension,

sedation, depression,

diarrhea- specific to

drugs used in

huntingtons)

 CI: *May ↓ the effects of

drugs used for

parkingson's disease

like Amantadine and

levodopa-cabidopa

(applies to all

antipsych drugs)

*serum levels ↓ by

carbamazepine and

barbituates

TC: *Can titrate the

dose for this drug,

but perphenazine

can sometimes be

added if

haloperidol is not

being effective

Classification:Antipsychotic;

antihypertensive

 MOA:Irreversible VMAT2

inhibitor

 Indication:FDA labeled for

psychosis and

HTN

Classification:neuroleptic;

VMAT2 inhibitor

 MOA:reversible VMAT2

inhibitor; Weak D2

antagonist

 Indication:Dyskinesias,

particularly chorea

and tardive

diskinesia;

Huntington's

disease, Tourette's

 SE: Drowsiness, fatigue,

insomnia, N/V;

Akathesia,

Parkinsonism; NMS,

depression, QT

prolongation

CI: Suicidal, depressed,

liver damage;

MAOI's, reserpine

(within 3 weeks)

TC:Shown to equally

deplete neuronal

NE, DA, 5HT, and

histamine.

[Modest depletion

of ACh, glutamate,

and aspartate, too]

Weak D2

antagonist.

 PK:Shorter onset and

duration of action

than reserpine

Classification:reversible AChE,

BuChE inhibitor

 MOA:increases CNS

acetylcholine levels

 Indication: Mild to moderate

Alzheimer's

disease

SE: bradycardia, AV block,

NVD, cramps,

anorexia, weight loss,

vivid dreams

CI: Anticholinergics

inhibit effects,

Nicotine decreases

oral clearance

TC: significant delay in

global cognitive

impairment

PK:oral, transdermal

Classification:NMDA antagonist

MOA:non-competitive blockade

of excitotoxic activity of

glutamate transmission

(possible cause of

Alzheimers) 

Indication:Moderate to

severe Alzheimer's

disease

 SE: confusion, dizziness,

drowsines, HA,

insomia, vomiting,

constipation 

CI: carbonic anydrase

inhibitors reduce its

renal elimination

TC:better tolerated

and less toxic than

cholinesterase

inhibitors

 PK:Oral tabs or

solution

Classification:AChE inhibitor

(reversible);

selective for CNS

AChE

 MOA:Increases CNS ACh

levels (cerebral cortex)

 Indication:mild to moderate

Alzheimer's

disease

 SE:diarrhea, nausea, vom

(NVD usually mild and

transient), cramperz,

anorexia, vivid dreams

(ah yea); not

associated with

hepatotoxicity; MAJOR

ADV. EFFECTS:

bradycardia, NVD,

gastrointestinal

bleeding

 CI:anticholinergic drugs

inhibit effects.

 TC: significantly better

cognitive function

than placebo

(kinda like Braino,

eh?)

PK:long half-life (70hr)

Classification: AChE inhibitor

MOA: Increases CNS ACh

levels

Indication:Mild to moderate

Alzheimer's

disease

(significantly delay

global cognitive

impairment)

 SE: *Few patients can

tolerate the higher

dose required to

demonstrate cognitive

improvement.

Peripheral cholinergic

side effects: NVD,

cramps, urinary

incontinence. Also GI

bleeding, anorexia,

vivid dreams.

*Bradycardia.

**Hepatic toxicity!

Tacrine almost

completely replaced in

clinical use by newer

cholineresterase

inhibitors.

CI: Anticholinergic drugs

inhibit effects.

Cimetidine increases

serum levels.

Smoking decreases

serum levels. Tacrine

increases the effects

of succinylcholine

and theophylline.

TC: Tacrine, donepezil,

rivastigmine, and

galantamine

produce modest

symptomatic

benefits in

Alzheimer's

disease. *Tacrine

was the first drug

shown to have any

benefit in

Alzheimer's

disease

PK:Oral, shorter t1/2

than donepezil,

lower

bioavailability than

donepezil, must be

administered

several times/day