Pharmacology Module 13

A general term referring to any substance, natural or synthetic, that has morphine like activity

opioid or opiate (used interchangeably)

What type of pain is opioids used for?

It is premodimanetly used for moderate to severe pain. It can releive any degree of pain but is most effect when used for constant dull pain

In large quantities opioids produce what effects?

euphoria and severe CNS depression leading to stupor, coma, or death

Define narcotic

In clinical practice: It is a broad term to describe morphine like drugs that produce analgesia and CNS depression (same as opioid)

From the persepective of pain management, what are the two most important receptors that opioids interact with in the CNS?

Mu and Kappa

Opioid activation of the Mu receptors is responsible for what actions?

Analgesic properties of the opioids as well as some of the adverse effects like respiratory depression and physical dependence

What is the most serious side effect of Opiods?

Respiratory depression

Should oral doses of morphine be the same size as parenteral doses?

Because of first pass metabolism, oral doses of morphine must be larger that parenteral doses to produce equivalent analgesic effects.

With prolonged opiod use, tolerance develops to ___, ___, ___, and ___. But not to ___ and ___.

Tolerance develops to analgesia, euphoria, sedation, and respiratory depression. But not to constipation and miosis

Opioid overdose produces a classic triad of signs

Coma, respiratory depression, and pinpoint pupils

Use of meperidine [Demerol] should not exceed ___ hours so as to avoid accumulation of normeperidine, a toxic metabolite.

48 hours

Like morphine, codeine and other moderate to strong opioid agonists produce:

analgesia, sedation, euphoria, respiratory depression, constipation, urinary retention, cough suppression, and miosis.

Cross-tolerance exists among the various opioid agonists, but not between opioid agonists and ________________

general central nervous system (CNS) depressants

Abstinence syndrome occurs when prolonged opiod use is abruptly discontinued. Is is dangerous?

It is unpleasant, not dangerous

Opioid overdose produces a classic triad of signs:

coma, respiratory depression, and pinpoint pupils.

Are all strong opioid agonists essentially equal to morphine with regard to analgesia, abuse liability, and respiratory depression?

Yes

most agonist-antagonist opioids act as agonist at ___ receptors and antagonists at ___ receptors. If physically dependent on pure opioid agonists, what will happen if agonist-antagonist is administered?

agonist: kappaantagonist: muPrecipitate withdrawal & reduce analgesia. Don't give agonist-antagonist when patient is already on pure agonist

A common adverse effect of morphine is nausea. Can this be helped by having the patient lie down or stand up?

nausea is less in recumbent patients (laying down)

Narcotics (esp morphine) are not to be used if the patient has a ____ injury.

Head

used to prevent opioid abuse and alcohol abuse.

Naltrexone

Severe opioid induced respiratory depression (e.g. resp under 10/min) can be reversed with what drug?

naloxone (Narcan) - causes immediate withdrawal and reverses analgesia, sedation, CNS depression, and euphoria. titrate Narcan dose so analgesic effects are not reversed * can be used to treat neonatal resp. depression

Opiod tolerance develops to analgesia, euphoria, respiratory depression, and sedation, but not to

constipation

There are five are available agonists-antagonists opioids. They are:

pentazocinenalbuphinebutorphanoldezocinebuprenorphine.

The agonists-antagonists if administered alone produce _1_ but if they are given to a person who has recently taken opioids the agonists-antagonists produce an _2_ effect. The agonists-antagonists are used to prevent a patient from becoming addicted to the narcotics.

1. analgesia2. antagonistic

If narcotics are given for more than ____ days they can cause physical dependence

20 days

Pain has two major forms: nociceptive pain, which results from injury to ______; and neuropathic pain, which results from injury to ______.

nociceptive pain- tissuesneuropathic pain- peripheral nervesThe 2 types respond differently to analgesic drugs

NSAIDS common adverse affects are:

GI injury, acute renal failure, bleeding. All NSAIDS except aspirin pose risk for thrombotic events

NSAID COX-2 inhibitors cause less ____ injury, but pose a greater risk for____

Less GI injuryGreater risk for thrombotic events, so long term use is not recommended

Opioids are especially effective against ______ pain; efficacy against ______ pain is limited.

effective: nociceptive painlimitted effectiveness on neuropathic pain

Fentanyl is a strong opioid analgesic, which is about 100 times more potent than ____

morphine

Define: Migraine

a neurovascular disorder involving dilation and inflammation of intracranial arteries. Studies suggest that calcitonin gene-related peptide and serotonin play important roles.

Antimigraine drugs are used in two ways:

abortive and prophylactic

The goal of abortive migraine therapy is to:

eliminate headache pain and associated nausea and vomitting

What are the two types of abortive migraine therapy?

nonspecific analgesics (aspirin-like drugs and opioids) and migraine-specific drugs(ergot alkaloids and triptans)

apirin-like analgesics (e.g. acetaminophen, aspirin, and ibuprofen) are effective for abortive therapy of ____ migraines

mild-moderate migraines

opioid analgesics (e.g. butorphanol) are reserved for what type of migraine?

severe migraine that has not responded to other drugs

First-line drugs for abortive therapy of moderate to severe migraine. They activate 5-HT 1B/1D receptors and thereby CONSTRICT intracranial blood vessels and suppress release of inflammatory neuropeptides. Oral formulas have slow onset.

Triptans (e.g. sumatriptan) *cause contriction of blood vessels

What are the two Triptans that are available in fast acting formulations- either as a nasal spray or subQ injection

sumatriptan and zolmitriptan

Triptans cause coronary vasospasm so they are contraindicated in patients with ischemic heart disease, prior myocardial infarction, or unctontrolled hypertension.

...

What is the goal of prophylactic migraine therapy?

to reduce the incidence and intensity of migraine attacks.

prophylactic migraine therapy is indicated for:

those who have frequent attacks (2 or more a month), especially severe attacks, or attacks that do not respond adequately to abortive agents

what are 3 preferred drugs for migraine prophylaxis?

propranolol, divalproex, amitriptyline

Overdose of ergotamine (a first line drug therapy for sever migraines) can cause, a ergotism, which is a serious condition characterized by:

severe tissue ischemia secondary to generalized constriction of peripheral arteries

Ergotamine must not be taken routinely because _1__ will occur. It can cause uterine contractions, so should not be taken during pregnancy. Must not be combined with potent inhibitors of CYP3A4, owing to a risk of ___2____

1. physical dependence 2. intense vasoconstriction and associated ischemia

tolerance to alcohol confers cross-tolerance to:

general anesthetics, barbituates, and other general CNS depressants - but not opioids

What are the 3 drugs used for maintaining alcohol abstinence?

disulfiram, naltrexone, acamprosate

Used to maintain alcohol abstinence. Blocks aldehyde dehydrogenase. As a result, if alcohol is consumed, acetaldehyde will accumulate, therby causing a host of unpleasant and potentially dangerous symptoms

Disulfiram

Used to maintain alcohol abstinence. Blocks opioid receptors, and thereby decreases craving for alcohol and blocks alcohol's reinforcing effects

Naltrexone

Used to maintain alcohol abstinence. Decreases tension, anxiety, and other unpleasant feelings caused by the absence of alcohol. Mechanism of action is unclear.

Acamprosate

what is the opioid of choice among abusers?

Heroin. It is lipid soluble so initial effects occur faster than other opioids.

Is opioid withdrawal dangerous?

it is extremely unpleasant, but rarely dangerous

what is the abused opioid of choice among healthcare providers? why?

meperidine (Demerol) because it is orally active, causes minimal pupillary constrictions, less constipation and urinary retention than other opioids