Morphine

Classification MOA (brief) Effects Produced: Opioid. (Pure Opioid Agonist). Natural found in the seed pod of poppy plant Papaver somniferum Activate opioid receptors: Mu and Kappa receptors. Relieves pain without affecting other senses such as touch, sight, smell, hearing and LOC. More effective against constant dull pain rather than sharp, intermittent pain. 1) Analgesia 2) Euphoria 3)sedation 4) cough suppression 5) biliary colic 6) Emesis (give promethazine or prochlorperazine) 7) Miosis (pinpoint) 8.) Respiratory depression Is what usually causes death (especially in combo w/ alcohol, barbs, benzos). May last 4-5 hrs. If RR is <12 breaths per min, delay morphine esp with asthma or emphysema. If 2-4 breaths per min, hypoxia and patient can go into shock. Resp dep can be reversed with opioid antagonist Naloxone or Nalmefene w/ ventilator support. Resp dep varies w/ route 7 min after IV, 30 min after IM, 90 min after SQ 9) Constipation produced by CNS & GI tract give stool softener (docusate), laxative (senna), or osmotic laxative (Na+ phosphate) 10) Orthostatic hypotension blunts baroreceptor reflex 11) Urinary retention 12) Tolerance/Dependence tolerance develops to euphoria, sedation, analgesia & resp dep. Little tolerance to constipation and miosis. Cross tolerance btw opioid agonists but not btw barbs, ETOH, benzos, and gen anesthetics 13) Physical dependence occurs w/ continued use by adaptive cellular change. Morphine physical dependence is intense but brief due to short half-life but w/ methadone physical dep is longer but less intense. PO, IM, IV, SQ, epidural, intrathecal. IM, IV, SQ, and PO regular lasts 4-5 hr; PO ER lasts 24 hr; epidural and intrathecal last up to 24 hr; IM/SQ painful and unreliable; IV injected slowly over 4-5 min. PO doses larger than parental due to 1st pass effect (may need to lower in pts w/ liver dz). Epidural and intrathecal is usually admin for spinal analgesia w/ epidural being preferred analgesia. Action is rapid & can last up to 24 hr. y Dosing is individualized y Sharp stabbing pain need higher doses; dull pain needs lower doses y Lower doses: elderly b/c of dec liver fcn, neonates b/c of bbb immaturity, y Should be used on a fixed schedule rather than PRN Schedule II drug. Overdose: Naloxone Pts w/ respiratory problems, pregnancy (physical dependence of fetus), labor/deliver (suppress uterine contractions and cause respiratory depression in neonates); head injury, liver impairment, hypotension, urinary problems or BPH CNS depressants, Anticholinergics (constipation and urinary retention), hypotensive drugs, MAOIs, Opioid Agonistantagonists Can be used in pregnancy does not cause birth defects

Dosage/Route

Adverse Effects Precaution pts: Drug Interactions Other

Drug Class/Specific Agents Pure Opioid Agonists (STRONG) Fentanyl Alfentanil & Sufentanil Remifentanil Meperidine Methadone Heroin Hydromorphone (Dilaudid) Oxymorphone Levorphanol POA (Moderate to Strong) C II: Codeine, Oxycodone C III: Hydrocodone, Propoxyphene Agonist-Antagonist Opioids Pentazocine (C IV) Nalbuphine Butorphanol Buprenorphine Opioid Antagonists Naloxone (Narcan) Naltrexone Nalmefene

Drug Info

Route, Etc

100x s more potent than morphine 1000x s more potent than morphine 100x s more potent than morphine

Can be given by transdermal patch Used in hospice. IV Not used much b/c of short ½ life Used b/c of long ½ life Lipid sol crosses bbb more readily than others. PO, rectal supp, soln Rectal supp, parental soln, IV, IM, SQ PO, IV, IM

C1 controlled subst. (no medical use)

Main difference is amt of analgesia and resp depression produced

Agonists at kappa receptors and antagonists at mu receptors Not used in MI due to inc CO (in contrast to pure opioid agonist) For headaches, was freq abused,

PO; little to no euphoria but does mediate physical dependence; usually in combo w/ naloxone IV, IM, SQ IV, IM, nasal; rarely carried in pharmacies anymore IV, IM

Used for opioid OD, to reverse resp dep (post-op), & in opioid addiction No effect if admin in absence of opioids. Used to treat chronic alcoholism

IV, IM, SQ; can trigger withdrawal Sx in pts w/ physical dependence; can block and reverse effects of opioids

Nonopioid Centrally Acting Analgesics Relieve pain by mechanisms largely or completely unrelated to opioid receptors; do not cause resp depression, dependence, or abuse. Tramadol:

MOA

WEAK agonist of mu rec. mostly works by blocking uptake of NE and 5HT3 thereby activating the monoaminergic spinal inhibition of pain. Naloxone will partially block Tramadol s effect. Pain relief is delivered through continuous epidural infusion. Relieves pain by binding to pre & postsynaptic 2 rec in the spinal cord & blocks pain signals from the periphery to the brain. Centrally acting analgesic w/ intrathecal admin. NOT 1st line agent due to adverse rxn (hallucinations, confusion, muscle injury)

Clonidine:

Ziconotide:

Muscle Relaxants 2 Groups: For Muscle Spasm (1)

MOA (says he won t ask MOA) Unclear. May result primarily from sedative properties, not by specifically controlling muscle tone. Promotes presynaptic inh by enhancing effects of GABA

Adverse Effects

Uses/Other Used to relieve localized spasm resulting from muscle injury. Not used for spasticity or other muscle disorders resulting from CNS pathology (except Diazepam). (see above) not muscle relaxer is benzodiazepine; can give you high

Diazepam (Valium)

Tizanidine Metaxalone Chlorzoxazone Others: Cyclobenzaprine, Carisoprodol, Methocarbamol Orphenadrine, Baclofen Drugs for Spasticity (2)

Agonist at the presynaptic 2 rec

CNS depression sedation, lightheaded, dizzy; physical dependence with life-threatening withdrawal if not done slowly Same as above + hepatotoxic check LFT prior to use. Also hepatotoxic Marginally effective & can cause fatal hepatic necrosis Cyclo: causes marked drowsiness Caris: just became ctrled subst.

(see above)

Baclofen

Diazepam Dantrolene

Acts w/in the spinal cord to suppress hyperactive reflexes involved in reg of muscle movemt (listed in 1st group) Acts directly on skeletal muscle; does not allow muscle to contract; can decrease strength

Abrupt d/c of intrathecal dose can cause rhabdomyolysis, multiorgan failure, death (listed in 1st group) Hepatotoxicity

Used for movement disorders of CNS origin (spasticity); disorders w/ heightened muscle tone, spasm, & loss of dexterity MS, usually SCI, cerebral palsy

Preferred in pts w/ marginal strength MS, SCI, cerebral palsy; treats malignant hyperthermia (lifethreatening increase in temp)

Sedative-Hypnotics: Class & Specific Agents Barbiturates Thiopental, Secobarbital Phenobarbital Benzodiazepines Diazepam, Lorazepam, Midazolam, Clonazepam, Clorazepate, Alprazolam Benzo-like Drugs Zolpidem (Ambien) Eszopiclone (Lunesta)CIV Pyrazolopyrimidines Zaleplon (C IV) Melatonin Agonist Ramelteon MOA Bind to and enhance GABA rec High abuse potential; rarely used anymore Enhance effects of GABA Adverse Effects Strong resp dep, tolerance, dependence, DOC for suicide Confusion, anterograde amnesia Uses/Other dec response to other drugs (inc hepatic synthesizing enzymes) Uses: anxiety, insomnia, general anesthesia, seizure disorders, muscle spasm, panic disorders, alcohol withdrawal insomnia E: only drug with no limit to how long it can be taken Approved only for short-term insomnia Amenorrhea, Galactorrhea, reduced libido, fertility problems Avoid during preg/lact

Enhances GABA, but does not bind to benzo receptors

Some daytime drowsiness

Works the same way as zolpidem but quick onset and short DOA Activates MT1 & MT2 rec for melatonin; can inc levels of prolactin & dec levels of testosterone

Miscellaneous Sed-Hyp Chloral Hydrate (C IV)

CNS dep similar to barbs

Tolerance, withdrawal w/ sleep disruption and nightmares

Prodrug that is rapidly metabolized to active form in liver Used for induction of sleep

Trazodone Antihistamines

Benzodiazepines
Classification Drug Names MOA (brief) MOA (detailed) benzodiazepines Diazepam, Lorazepam, Midazolam, Clonazepam, Clorazepate, Alprazolam, Triazolam, Oxazepam Potentiate the actions of GABA (intensify GABA s effects only, not direct GABA agonists) Enhance the actions of GABA by binding to specific rec in the supramolecular structure known as the GABA recchloride channel complex. Since the amount of GABA in the CNS is finite, there is a built-in limit to the depth of CNS depression the benzodiazepines can produce. This is why they are much safer than barbiturates, which directly mimic GABA. Benzos readily cross the bbb (lipid soluble). Benzos metabolites are pharmacologically active, so the effects of the drugs persist long after the parent drug has disappeared. Reduce anxiety; Promotes sleep; induce muscle relaxation PO (have no effect on heart & bv); IV (can produce profound hypotension and cardiac arrest); all benzos can be PO Confusion; anterograde amnesia (impaired recall of events that take place after dose) especially w/ Triazolam; may exacerbate obstructive sleep apnea (OSA); CNS depression with little to no resp dep; paradoxical effects: insomnia/excitation, euphoria/heightened anxiety & rage; abuse; death from OD has never been documented Anxiety; insomnia; induction of general anesthesia (D,L,M)M is for conscious sedation; seizure disorders (D, L, clona, clora); muscle spasm (D); panic disorder (A, L, clona); withdrawal from alcohol Certain benzos go through very little hepatic metabolism & can be used in pts w/ liver disease (L,O,T) Triazolam sleep (b/c rapid onset); Estazolam for someone waking up after falling asleep (slower onset); Lorazepam (L,O,T) good in elderly b/c it does not accumulate w/ repeated dosing - Gastric lavage followed by activated charcoal & saline cathartic & possibly dialysis if Sx are severe. - Flumazenil: competitive benzo rec antagonist & will reverse sedative effects but NOT resp dep. Give IV slowly over 30 seconds and can be repeated every min PRN. 1st dose is 0.2 mg, 2nd dose 0.3 mg 3rd dose and all subsequent doses are 0.5 mg.

Pharmacology Dosage/Route Adverse Effects

When is it used? Metabolic Effects Selective Uses Overdose

Epilepsy: refers to a group of disorders characterized by excessive excitability of neurons in the CNS. Seizure: general term that applies to all
types of epileptic events. Convulsion: applies only to abnormal motor phenomena. For example: jerking movements during tonic-clonic attack. Types of Seizures: Partial (focal): begins in the cerebral cortex and undergoes limited spread to adjacent cortical areas. 1. Simple Partial Seizures no LOC; symptoms determined by brain region affected motor Sx (thumb twitching), sensory Sx (local numbness, auditory, visual or olfactory), autonomic Sx (nausea, flushing, urinary incontinence, salivation), psychoillusory Sx (feeling of unreality, fear, or depression); lasts 20-60 sec 2. Complex Partial Seizures characterized by impaired consciousness and lack of responsiveness (motionless/fixed gaze); followed by period of automatism (repetitive, purposeless movements such as lip smacking & hand wringing); lasts 1-2 min 3. Secondary Generalized Seizures begin as #1 or #2 and then evolved into generalized tonic-clonic seizures; LOC (according to book); lasts 1-2 min Generalized: conducted widely through the hemispheres; May be convulsive or non-convulsive; Produce LOC. 1. Tonic-Clonic (Grand Mal) neuronal discharge spreads through both hemispheres of cerebral cortex; period of muscle rigidity (tonic) followed by synchronous muscle jerks (clonic); cause urination, not defecation; convulsions may be preceded by a loud cry caused by forceful expiration of air across the vocal cords; lasts 90 seconds or less; followed by period of CNS depression - postictal state 2. Absence (Petit Mal) brief LOC (10-30 sec); mild, symmetric motor activity (eye blinking) or may occur w/ no motor activity. Pt may experience hundreds of attacks per day; occur primarily in children and cease during early teens. 3. Atonic sudden loss of muscle tone; if seizure activity is limited to muscles of the neck = head drop, if muscles of limbs and trunk are involved = drop attack (collapse); occur mainly in children 4. Myoclonic sudden muscle contractions that last for 1 second; may be limited to one limb (focal) or may involve entire body (massive) 5. Status Epilepticus (SE) persists for 30 min or longer; Several types including generalized convulsive SE (may be life threatening), absence SE, and myoclonic SE 6. Febrile common in children ages 6 mo 5 yrs; typically manifest as generalized tonic-clonic of short duration; does not increase risk for developing epilepsy later in life. Mixed Seizures (LGS) Lennox-Gastaut Syndrome: severe form of epilepsy; usually develops during preschool years; developmental delay and a mix of partial and generalized seizures; Seizure types include partial, atonic, tonic, generalized tonic-clonic, atypical absence; difficult to treat

Antiepileptic Drugs (AED): AEDs can suppress discharge of neurons within a seizure focus and suppress propagation of seizure activity from focus area to other areas. AEDs act through 4 basic mechanisms: 1. Suppression of Na+ influx: bind to Na+ channels while they are in inactivated state to prolong channel inactivation, thus decreasing the ability of neurons to fire at high frequencies. (seizures that depend on high frequency discharge are suppressed) 2. Suppression of Ca2+ influx: calcium influx promotes NT release at axon terminal. Block Ca2+ = block transmission. 3. Antagonism of Glutamate: glutamate is primary excitatory NT in CNS. Block its receptors=suppression of neuronal excitation. 4. Potentiation of GABA: decrease neuronal excitability and suppress seizure activity Seizure Type Partial: Simple, complex, and secondary generalized Traditional AEDs Carbamazepine Phenytoin Valproic Acid Primidone Newer AEDs Oxcarbazepine Gabapentin Lamotrigine Levetiracetam Pregabalin Topiramate Tiagabine Zonisamide Lamotrigine Topiramate Lamotrigine

Primary Generalized: Tonic-Clonic

Same as above & Phenobarbital (rarely)

Absence

Ethosuximide (DOC) Valproic Acid (obtain baseline LFT s) Valproic Acid

Myoclonic

Topiramate

**red = drugs that suppress Na+ influx. **blue =drugs that suppress Ca++ influx. **green=glutamate antagonist also Felbamate (not listed) ***Valproic Acid has 3 MOAs: sodium, calcium, and GABA

AEDs that potentiate the effects of GABA: 1. 2. 3. 4. 5. Barbiturates Benzodiazepines Gabapentin Tiagabine Vigabatrin

Phenytoin
Classification MOA (brief) Therapeutic Range Adverse Effects Drug Interactions When is it used? Metabolic Effects AED (most widely used and 1st drug to suppress seizures w/out depressing the entire CNS Blockade of hyperactive Na+ channels NARROW (the capacity of the liver to metabolize phenytoin is very limited) Gingival hyperplasia (excess swelling, tenderness, bleeding of gums 20% and can be reduced w/ proper hygiene) INC plasma levels: Diazepam, Valproic Acid, alcohol (acute). DEC plasma levels: Carbamazepine, phenobarbital, alcohol (chronic) Epilepsy, Cardiac Dysrhythmias ½ life shortens the longer the pt takes the drug