CNS Drug

STIMULATION

Sensation acuity increased
(greater awareness of environment)

Motor activity increased
(restlessness)

CNS Drug

DEPRESSION

Sensation acuity decreased

(lack of perception, drowsy, not alert)

Motor activity decreased

(lethargic)

Tolerance

-state where one must increase dosage to keep the desired effect. (always occurs in process of physical addiction)

"Metabolic" Tolerance -enzymes systems working differently, breaking drugs down faster, metabolizing/getting rid of drug faster.

"Receptor" Tolerance - up or down regulation of receptors, altering the need for drugs.

Physical Dependence

-An adaptive physiological state that manifests by physical disturbances when withdrawn (withdrawal syndrome)

**Dependence causing drugs usually are both types at the same time.**

Psychological Dependence

-a state of emotional reliance upon a drug in order to maintain a state of well-being. If tolerance does occur it is of "metabolic" type, no withdrawal symptoms.

**Degree of physical dependence is NOT synomymous with degree of "addiction"**

CNS Stimulants

Amphetamines

(stimulates all areas of the brain)

d-amphetamine (dexedrine), methylpenidat (Ritalin), pemoline (Cylert)

Responses Observed

1.) Increased alertness, wakefulness, decreased fatigue.

2.) Mood elevation or euphoria, increased initiative

3.) Decreased appetite, but little effect in reducing food intake if eating for pyschological reasons.

CNS Stimulants

Amphetamines

(stimulates all areas of the brain)

d-amphetamine (dexedrine), methylpenidat (Ritalin), pemoline (Cylert)

Mechanisms of Action

-incr. the release of NOREPI in the brain (CNS stimulation)

-incr. the release of DOPAMINE (causes side effects)

For AD-HD - incr. NOREPI which increases attention span of child.

-Perhaps incr. dopamine helps

CNS Stimulants

Amphetamines

(stimulates all areas of the brain)

d-amphetamine (dexedrine), methylpenidat (Ritalin), pemoline (Cylert)

Therapeutic Uses

Schedule II

1.) Narcolepsy

2.) Weight control - highly abused, doesn't control psycholigical eating, tolerance occurs (too dangerous)

3.) AD-HD - Ritalin; classroom improvement in 70-80%

-active

-learning and discipline problems

-short attention span

CNS Stimulants

Amphetamines

(stimulates all areas of the brain)

d-amphetamine (dexedrine), methylpenidat (Ritalin), pemoline (Cylert)

Side/Toxic Effects

1.) CNS - nervousness, anxiety, sleeplessness.

High dose: - schizophrenic behavior (incr. dopamine), hellucinations, paranoia, psychoses,tremors, dependence.

2.)Cardiovascular - incr. H.R., B.P., and possibly arrhythmias.

3.)Weightloss and malnutrition

4.)AD-HD - sleeplessness, excessive crying, suppresses growth (reversible if quit before bone closure)

5.)Poss. (rare) bone marrow supression. (periodic blood checks)

CNS Stimulants

Amphetamines

(stimulates all areas of the brain)

d-amphetamine (dexedrine), methylpenidat (Ritalin), pemoline (Cylert)

Contraindications

1.) Insomnia or psychological disorders (suicidal, schizophrenia, etc.)

2.) MAO inhibitors

3.) Hypertension, cardiac arryhthmias

4.) Anorexia

Drug interactions: anticholinergics, anticoagulants, anticonvulsants, tricyclic (req. dose adjustments).

CNS Stimulants

Xanthines

(caffeine, theobronmine, theophylline)

min. therapeutic use

Responses observed

1.) CNS stimulation - incr. alertness, decr. fatigue

caffeine > theophylline > theobromine

2.) Cardiac stimulant (rate and force of contraction) T>T>C

3.) Constricts blood vessels in brain, coffee may help headache (if causes is dilated blood vessels)

4.) Diuresis (theophylline > theobromine > caffeine)

5.)Bronchiorelaxation (req. higher dose than CNS effects) T>T>C

CNS Stimulants

Xanthines

(caffeine, theobronmine, theophylline)

min. therapeutic use

Mechanism of Action

-inhibits breakdown of cyclic AMP.

-incr. CNS activity

-dilates bronchiles, pulmonary blood vessels, but constricts cerebral vessels.

-**Activates P450 enzymes so affecsts metabolism of many drugs.

CNS Stimulants

Xanthines

(caffeine, theobronmine, theophylline)

min. therapeutic use

Therapeutic Uses

1.) Counter drowsiness

2.) Asthma, bronchitis, empysema (aminophylline - H2O soluble version of theophylline)

3.) Pain from headache (caffeine in OTC), no activity alone, only with other analgesics (painkiller)

CNS Stimulants

Xanthines

(caffeine, theobronmine, theophylline)

min. therapeutic use

Side Effects

1.) Incr. heart erate, cardiac arrhythmias

2.) Incr. gastric secretion (caffeine worst culprit)

3.) Diuresis

4.) Excess CNS stimulation - convulsions, insomnia

5.) Withdrawal may causes headache and irritability

CNS Stimulants

Xanthines

(caffeine, theobronmine, theophylline)

min. therapeutic use

Cautions

1.) Cardiac arrhythmias

2.) Ulcers

3.) Possibly birth defects with large doses in small animals, no sign in humans.

CNS Stimulants

Cocaine

(cola leaves - powerful CNS stimulant - schedule II)

Same responses, MOA, side effects, cautions as Amphetamines

Uses - local anesthetics, only allowed in hospital/clinical setting.

-seems to elevate threshold for excitement of neuron by decreasing permeability to all ions.

CNS Stimulants

Cocaine

(cola leaves - powerful CNS stimulant - schedule II)

Side Effects

Early: CNS stim. (anxiety, restlessness, confusion, dizziness, tremors, convulsions; incr. H.R. and B.P.

Later: may get depression, unconsciousness, and death. Cardio - will see later depressant action directly on heart (bradycardia, hyopotension, cardiac arrest)

CNS Depressant Terms:

CNS depressant

Sedative

Hypnotics

General anesthetic

CNS depressant - agent decr. excitability of tissue in CNS. All drugs can be sedative, hypnotic, or gen. anesthetic depending on dose.

Sedative - administered for mild drowsiness or to reduce restlessness or anxiety

Hypnotic - admin. to induce sleep or allow to stay asleep, (can be aroused from sleep). *3-4 times dose of sedative.

Gen. anesthetic - depress CNS to cause unconsciouness (unarousable sleep), as well as analgesia.

CNS Depressant

Barbiturates

-15 kinds commonly avail. in U.S (50 FDA approved)

Differ in:

-speed with which effects occur

-duration of action (into blood same rate, brain diff.)

-all can be taken orally, or I.V

phenobarbital (Lumina) - slow onset, long acting(all day)

seco & pentobarbital (Nembutal) - interm. acting (2-4hrs)

thiopental (Pentothal) - onset in secs., duration in mins.

CNS Depressant

Non-Barbiturates

(aka minor tranquillizers)

*Does not have barbiturate structure*

-Ethyl alcohol

-Benzodiazepines: flurazepam (Dalmane)

                          diazepam (Valium)

                          chlorodiazepoxide (Librium)

CNS Depressant

Non-/Barbiturates

(classified as sedative-hypnotics)

Useful Therapeutic Reponses

-Reduced anxiety

-Sedation (drowsiness)

-Hypnosis (sleep)

-General anesthesia

CNS Depressant

Non-/Barbiturates

(classified as sedative-hypnotics)

Mechanism of Action - Barbituates

-depress all areas of brain

-inhibit reticular activating system.

-Prob. enhance GABA receptor complex, and enhance Cl- entrance to neurons and hyperpolarize cells.

-GABA independent

CNS Depressant

Non-/Barbiturates

(classified as sedative-hypnotics)

Mechanism of Action - Benzodiazepines

-Bind to special receptor that decr. acitvity of brain. Also incr. activity of GABA.

-When GABA concentration decr. so does degree of depression.

-GABA dependent

CNS Depressant

Non-/Barbiturates

(classified as sedative-hypnotics)

Mechanism of Action - Alcohol

-seems to incr. GABA activity with short term use.

-long term use (alcoholics) decre. GABA, therefore decr. anti-anxiety effects, thats why need to drink more and more to relieve anxiety.

-large ingestion of alcohol incr. dopamine release

**All activate P450 enzyme = incr. metab. of drugs