Chapter 11 - Pharm
Embed Size (px)
DESCRIPTION
PPT on Pharms
Citation preview
Chapter 11 outline*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Chapter 11:
Antianxiety Agents
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
DHY 1330 - Therapeutics
Chapter 11 Outline
Is this slide correct as displayed?
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Antianxiety Agents
Haveles (pp. 136-137) (Fig. 11-1)
Objectively assessing the patient’s anxiety is necessary on both
the first and subsequent visits
The dental team will most commonly use orally administered drugs to
provide relaxation for an anxious patient
Intravenous (IV) administration is used infrequently; most states
require a separate certificate to administer IV agents or provide
conscious sedation
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Definitions
Sedative-hypnotic agents can produce varying degrees of central
nervous system (CNS) depression, depending on the dose
administered
A small dose will produce mild CNS depression described as
sedation—reduction of activity and simple anxiety
This level has some anxiolytic effects
A larger dose of the same drug, the hypnotic dose, will produce
greater CNS depression
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Benzodiazepines
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Chemistry
Named according to their structure—a 1, 4—benzodiazepine
nucleus
chlordiazepoxide (Librium) was synthesized in 1955
diazepam (Valium) was synthesized in 1959 and marketed in
1963
When an additional ring was added, triazolam was synthesized
Next, midazolam and flumazenil were synthesized
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Pharmacokinetics
Benzodiazepines are well absorbed when administered by the oral
route
The onset of action is related to their lipid solubility
Benzodiazepines are available as tablets, capsules, oral solution,
rectal gel, and injectable form
For benzodiazepines available in parenteral form the IV route
produces a rapid, predictable response; ideal for conscious
sedation
Benzodiazepines cross the blood-brain and placental barriers to
produce an effect on the CNS and the fetus
cont’d…
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Pharmacokinetics
Haveles (pp. 138-139)
Benzodiazepines are metabolized by phase II metabolism alone or by
phase I metabolism followed by phase II metabolism
Phase I metabolism involves oxidation, reduction, hydrolysis,
dealkylation, and hydroxylation
It is hard metabolism; it is affected by external factors such as
other drugs and hepatic disease
Phase II involves glucuronidation
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Mechanism of Action
Haveles (p. 139)
Benzodiazepines enhance or facilitate the action of the
neurotransmitter by exerting their effects in the CNS mediated by
γ-aminobutyric acid (GABA), a major inhibitory
neurotransmitter
The inhibitor effect of GABA is enhanced
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Pharmacologic Effects
Behavioral effects
Clinical effects in humans are anxiety and panic reduction at low
doses and drowsiness and even sleep at higher doses
Antiseizure effects
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Adverse Reactions of Benzodiazepines
Haveles (p. 139)
In general, benzodiazepines, used alone, have a wide margin of
safety
They all have similar adverse effects but differ in their
frequency
cont’d…
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Adverse Reactions of Benzodiazepines
CNS effects
The most common side effect is depression manifested as fatigue,
drowsiness, muscle weakness, and ataxia
The use of parenteral benzodiazepines during a dental appointment
reduces anxiety and alters perception of time
Diazepam’s long half-life and metabolism to an active metabolite
prolongs its duration of action
Midazolam is metabolized primarily to inactive metabolites
flunitrazepam (Rohypnol) is available in Europe
cont’d…
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Adverse Reactions of Benzodiazepines
Respiratory effects
Doses of diazepam have occasionally been reported to produce
respiratory depression
Cardiovascular effects
Relief of anxiety may result in a fall in blood pressure and pulse
rate
cont’d…
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Adverse Reactions of Benzodiazepines
Contraindicated in angle-closure (narrow-angle) glaucoma and can
produce diplopia (single object viewed as two), nystagmus (rhythmic
oscillation of the eyeballs), and blurred vision
Dental effects
Have been reported to produce xerostomia, increased salivation,
swollen tongue, and a bitter or metallic taste
Thrombophlebitis
Parenteral diazepam may cause thrombophlebitis because propylene
glycol is used to solubilize it
cont’d…
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Adverse Reactions of Benzodiazepines
Can produce cramps or pain, difficulty in urination, allergic
reactions
Pregnancy and lactation considerations
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Abuse and Tolerance
Haveles (p. 140)
Benzodiazepines can be abused; physical dependence and tolerance
have been documented
Their abuse and addiction potential is less than that of the other
sedative-hypnotic agents such as barbiturates
Benzodiazepines have a wider TI than barbiturates
Combining with other CNS depressants can reduce the safety
cont’d…
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Abuse and Tolerance
Haveles (p. 140)
Treatment of overdose
Activated charcoal and a saline cathartic
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Drug Interactions
Haveles (pp. 140-141)
Benzodiazepines will interact in an additive fashion with other CNS
depressants
Drugs that inhibit oxidative metabolism (phase I metabolism) may
increase the effect of benzodiazepines that undergo phase I
metabolism
Selective serotonin uptake inhibitors alter clearance of
diazepam
May reduce the effectiveness of levodopa
May increase the effect of digoxin, phenytoin, and probenecid
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Medical Uses
Haveles (p. 141)
Useful in short-term treatment of anxiety, panic attacks, insomnia,
and alcohol withdrawal
Used for acute treatment of seizures
Used for conscious sedation, general anesthesia, or during
surgery
cont’d…
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Medical Uses
Anxiety control
Insomnia management
Treatment of epilepsy (seizures)
cont’d…
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Medical Uses
Control of muscle spasms
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Management of the Dental Patient Taking Benzodiazepines
Haveles (pp. 141-142) (Box 11-2)
Dental procedures
Premedication
Conscious sedation
Muscle relaxation and anterograde amnesia (events after the
injection)
cont’d…
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Management of the Dental Patient Taking Benzodiazepines
Conscious sedation
Require continuous monitoring of respiratory and cardiac
function
Dentists without additional training cannot use conscious
sedation
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Benzodiazepines
alprazolam
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Benzodiazepines
halazepam (Paxipam)
lorazepam (Ativan)
midazolam (Versed)
oxazepam (Serax)
quazepam (Doral)
temazepam (Restoril)
triazolam (Halcion)
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Barbiturates
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Barbiturates
Problems with their use are well documented
Associated with a high rate of abuse and complete cardiovascular
and respiratory depression with overdose
Benzodiazepines have almost completely replaced barbiturates for
treating anxiety and insomnia
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Chemistry of Barbiturates
Haveles (p. 142)
Formed by substitution of R groups on the barbiturate nucleus sites
A and B
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Pharmacokinetics of Barbiturates
Haveles (p. 142)
Absorption: barbiturates are well absorbed orally and rectally;
used intravenously but not intramuscularly
Distribution: IV agents are inactivated by redistribution from site
of action in the CNS, to muscles, and adipose tissue
Metabolism: short- and intermediate-acting barbiturates are rapidly
and almost completely metabolized by the liver
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Mechanism of Action
Haveles (p. 142)
Barbiturates produce their effect by enhancing GABA receptor
binding and prolong the opening of chloride channels
In higher dose may also act directly on chloride channels
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Pharmacologic Effects
With normal doses, relaxation occurs
With larger doses, inhibitory fibers of the CNS are depressed,
resulting in disinhibition and euphoria
When higher doses are administered, hypnosis can be produced
Even higher doses, can result in anesthesia, with respiratory and
cardiovascular depression and finally arrest
cont’d…
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Pharmacologic Effects
Anticonvulsant effect
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Adverse Reactions
In usual doses, barbiturates are relatively safe
CNS depression may be exaggerated in elderly and debilitated
patients or those with liver or kidney impairment
Anesthetic doses
With higher doses, concentrations in the blood can be lethal
Acute poisoning
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Chronic Long-Term Use
Haveles (p. 143)
Chronic use of barbiturates can lead to physical and psychologic
dependence
The addict becomes progressively depressed and is unable to
function
Tolerance develops to most effects but not to the lethal dose
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Contraindications
Barbiturates are absolutely contraindicated in patients with
intermittent porphyria or a positive family history of
porphyria
Porphyria: a group of disorders involving heme biosynthesis
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Drug Interactions
Barbiturates are stimulators of liver microsomal enzyme
production
These enzymes are responsible for the metabolism of many
drugs
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Uses of Barbiturates
Therapeutic uses are determined by duration of action
Ultrashort-acting barbiturates are used intravenously for induction
of general anesthesia
Short- and intermediate-acting barbiturates: little medical use;
replaced by benzodiazepines
Long-acting barbiturates: used for treatment of epilepsy
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Nonbenzodiazepine-Nonbarbiturate Sedative-Hypnotics
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
chloral hydrate
Haveles (p. 144)
An inexpensive, orally effective sedative-hypnotic drug with a
rapid onset and short duration of action
Therapeutic doses do not produce pronounced respiratory or
cardiovascular depression
Gastric irritation can be minimized by taking with milk or
food
Used in dentistry for preoperative sedation of children
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
buspirone
(BuSpar)
Unique in structure and action
Mechanism of action is unknown; believed to be related to
interactions with neurotransmitters in the CNS
Anxioselective because of its selective anxiolytic action without
hypnotic, anticonvulsant, or muscle-relaxant properties
Most patients prefer the benzodiazepines
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Nonbenzodiazepine-Benzodiazepine Receptor Agonists
Haveles (p. 144)
Zolpidem, zaleplon, and eszopiclone comprise a new class of drugs
that are not benzodiazepines but appear to bind to benzodiazepine
receptors and decrease sleep latency with little effect on sleep
stages
All are thought to have agonist effects on GABA
These drugs are used to treat insomnia only
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
zolpidem
(Ambien)
Has hypnotic and anxiolytic effects, but receptor specificity
produces less muscle-relaxant and anticonvulsant effects
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
zaleplon
(Sonata)
Haveles (p. 145)
A rapid-acting hypnotic that is less potent and has a shorter
duration of action than zolpidem
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
eszopiclone
(Lunesta)
Haveles (p. 145)
The newest agent of this class available in the United States
Anterograde amnesia has been reported
Some patients report an unpleasant taste
Eszopiclone could impair driving the morning after nighttime
administration
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Melatonin Receptor Agonist
Haveles (p. 145)
ramelteon (Rozeram) has been approved for treatment of insomnia
characterized by difficulty falling asleep
An indenofuran derivative highly selective for melatonin type 1
(MT1) and melatonin type 2 (MT2) receptors
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Centrally Acting Muscle Relaxants
Haveles (p. 145)
Exert their effects on the CNS to produce skeletal muscle
relaxation
cont’d…
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Centrally Acting Muscle Relaxants
Pharmacologic effects
All CNS muscle relaxants produce some degree of sedative effect
because their action is on the CNS
The sedative effects dominate over the “selective” muscle-relaxant
activity
Useful in treating muscle spasms and back and neck pain
cont’d…
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Centrally Acting Muscle Relaxants
Overview
Exert their muscle-relaxing properties indirectly by producing CNS
depression
Have no direct effect on striated muscle; do not directly relax
tense skeletal muscles
Use
An adjunct to rest and physical therapy for relief of muscle spasm
associated with acute painful musculoskeletal conditions
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Examples of Centrally Acting Skeletal Muscle Relaxants
Haveles (p. 145) (Table 11-3)
carisoprodol (Soma)
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Miscellaneous Agents
Inhibits both monosynaptic and polysynaptic reflexes at the spinal
level
Indicated for spasticity from multiple sclerosis or spinal cord
injuries or diseases
tizanidine (Zanaflex)
dantrolene (Dantrium)
Affects contractile response of skeletal muscle by acting on the
muscle itself
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
General Comments About Antianxiety Agents
Haveles (pp. 146-147)
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Analgesic-Sedative Combinations
Haveles (p. 146) (Box 11-4)
Both sedation and analgesia can be obtained from opioid analgesics
alone
Prescribing an opioid to add sedation to analgesia is undesirable
unless the analgesic potency is required
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Special Considerations
Haveles (p. 146)
Patients who are to use antianxiety agents should be driven to and
from the dental appointment
Drugs are not a substitute for patient management
*
*
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All
rights reserved.
Precautions
Patients with impaired elimination may experience exaggerated
effects of these medications
Depression caused by all sedative-hypnotics will add to depression
caused by other CNS depressants
The patient should be accompanied by a responsible adult who can
drive the patient home
Psychic and physical dependence has been observed with almost all
drugs used to allay anxiety
Suicide may be attempted by taking sedative-hypnotic drugs
These drugs should never be administered to pregnant women or to
those who may be pregnant unless the potential benefit to the
mother outweighs the risk to the fetus
Sedatives do not provide analgesia
*