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287 Cards in this Set

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Benzodiazepines
MOA
Bind to gamma subunit of GABA(A) complex to increase frequecy of Cl- channel opening; no GABAmimetic activity; BZ1 mediates sedation; BZ2 mediates antianxiety and impairment of cognitive functions
Benzodiazepine drugs
Alprazolam, diazepam, lorazepam, midazolam, temazepam, oxazepam
Uses of alprazolam
Anxiety, phobias, panic attacks
Uses of diazepam
Anxiety, preop sedation, muscle relaxation, withdrawal states
Uses of lorazepam
Anxiety, preop sedation, status epilepticus
Uses of midazolam
Preop sedation and anesthesia, anterograde amnesia
Uses of temazepam
Sleep disorders
Uses of oxazepam
Sleep disorder and anxiety
Pharmacokinetics of benzodiazepines
Liver metabolized to active compounds except oxazepam, temazepam, lorazepam; t1/2: diazepam > lorazepam > alprazolam > temazepam > oxazepam > midazolam
Uses of barbiturates
Phenobarbital for seizures;
Thiopental for induction of anesthesia
Barbiturates
MOA
Bind to beta subunit of GABA(a) complex; GABAmimetic activity at high doses, Prolong GABA activity by increase duration of Cl- channel opening; ; inhibit complex I of ETC
Pharmacokinetics of barbiturates
General inducers of P450
Contraindicated in porphyrias
Withdrawal signs of benzodiazepines
Rebound insomnia, anxiety, seizures
Withdrawal signs of barbiturates and ethanol
Anxiety, agitation, life threatening seizures
Drug interactions of GABAa drugs
Life threatening respiratory depression if used with other CNS depressants (antihistaminics, opiates, beta blockers); Barbiturates induce metabolism of lipid-soluble drugs (oral contraceptives, carbamazepine, phenytoin, warfarin)
Flumazenil
Benzodiazepine receptor antagonist.
Used as antidote for benzodiazepine overdose.
Zolpidem
BZ1 receptor agonist used in sleep disorders. No cognitive impairment (no BZ2 actions), overdose reversed by flumazenil, less tolerance and abuse liability
Buspirone
No effect on GABA, 5-HT1a partial agonist, used for generalized anxiety, nonsedative, 1-2 weeks for effects
Anticonvulsant drugs
Phenytoin, carbamazepine, benzodiazepines, barbiturates, lamotrigine, topiramate, felbamate, ethosuximide, valproic acid
Drugs used for partial seizures
Valproic acid, phenytoin, carbamazepine
Drugs used for general tonic-clonic seizures
Valproic acid, phenytoin, carbamazepine
Drugs used for general absence seizures
Ethosuximide
Drugs used for status epilepticus
Lorazepam, diazepam, phenytoin
Phenytoin MOA
Inhibits fast Na channels in axons which decreases conduction and prevents seizure propagation
Pharmacokinetics of phenytoin
Variable absorption, nonlinear kinetics at low doses, zero-order kinetics at high doses, inducer of P450
Phenytoin side effects
CNS depression, gingival hyperplasia, hirsutism, osteomalacia (decreases vitamin D), megaloblastic anemia (decreases folate), aplastic anemia, teratogenic (cleft lip and palate).
Carbamazepine MOA
Inhibits fast Na channels in axons which decreases conduction and prevents seizure propagation
Pharmacokinetics of carbamazepine
Induces P450
Carbamazepine side effects
CNS depression, osteomalacia, megaloblastic anemia, aplastic anemia, exfoliative dermatitis, increases ADH secretion (dilutional hyponatremia), teratogenic (cleft lip and palate, spina bifida)
Valproic acid MOA
Inhibits fast Na channels in axons which decreases conduction and prevents seizure propagation; Inhibits GABA transaminase; Blocks presynaptic Ca+ channels
Uses of valproic acid
Seizures, bipolar mania, migraines
Pharmacokinetics of valproic acid
Inhibits P450
Valproic acid side effects
Hepatotoxic metabolite, thrombocytopenia, pancreatitis, alopecia, spina bifida
Ethosuxamide MOA
Blocks presynaptic T-type Ca+ channels in thalamic neurons
Lamotrigine MOA
Blocks Na+ channels and glutamate receptors. Side effect: Steven-Johnson
Inhaled anesthetic drugs
Nitrous oxide, halothane, Desflurane, Sevoflurane, Eflurane, Isoflurane
Properties of halothane
High potency (0.8% MAC), high blood-gas ratio (2.3), sensitizes heart to catecholamines
Side effects of halothane
Malignant hyperthermia, hepatitis, cardiac arrhythmias
What is MAC?
Minimal alveolar concentration is the amount of anesthetic at which 50% of patients don't respond to surgical stimulus. Analogous to ED50, measures potency, the more lipid soluble the lower the MAC, lower in elderly
What is the blood-gas ratio?
Measure of the onset of recovery. The more soluble in the blood the slower the anesthesia and recovery.
Name the 4 stages of anesthesia?
1 analgesia
2 disinhibition
3 surgical anesthesia
4 medullary depression
General anesthesia protocol
Includes sedation and anterograde amnesia (midazolam), induction (propofol), analgesia (fentanyl), muscle relaxant for intubation (succinylcholine) and may or may not include atropine in case of CV depression due to propofol
Intravenous anesthetic drugs
Midazolam, thiopental, propofol, fentanyl, ketamine
Midazolam
IV benzodiazepine used for preoperative sedation and commonly in anesthesia protocols (e.g.,
conscious sedation) affording anterograde amnesia. Depresses respiratory function but reversed
by the BZ receptor antagonist flumazenil
Thiopental
Highly lipid-soluble, rapid-onset, and short-acting barbiturate used mainly for induction.
Depresses respiratory and cardiac function but does not increase cerebral blood flow. Rapid
recovery associated with redistribution from CNS to peripheral tissues, but liver metabolism
required for elimination.
Propofol
Very rapid onset and recovery, plus antiemetic effects, used for both induction and maintenance;
especially useful in outpatient surgery.
Fentanyl
One of several related opioid analgesics used in anesthesia. Potent analgesic, with shorter durations
of action than most opioids; oral and patch formulations are also used. Chest wall rigidity
with IV use.
Neurolept anesthesia = combination of fentanyl, droperidol, and nitrous oxide.
Ketamine
Rapid-onset and short-duration agent that causes "dissociative anesthesia" with amnesia, catatonia,
and analgesia. Only anesthetic that causes CV stin~ulation!E mergence reactions (vivid
dreams, hallucinations) partly offset by benzodiazepines.
KETAMINE does not produce its effect via facilitation of GABA receptors, but possibly via its antagonism of the action via what neurotransmitter at what receptor?
Excitatory neurotransmitter GLUTAMATE on the NMDA receptor.
How is the production of anesthesia and recovery of anesthesia of PROPOFOL in comparison with barbiturates (thiopental)?
Its anesthetic effect is faster and it recovers faster.
What are the ester local anesthetics?
Procaine, cocaine, benzocaine. Metabolized by plasma esterases. All have only one "i"
What are the amide local anesthetics?
Lidocaine, bupivacaine, mepivacaine. Metabolized by liver amidases. All have two "i".
MOA of local anesthetics
Nonionized form crosses axonal membrane --> ionized form blocks inactivated Na+ channel --> prevent propagation of action potentials
Side effects of local anesthetics
Neurotoxicity, cardiovascular toxicity, allergies. Use alpha-1 agonists to prevent absorption.
Skeletal muscle relaxants MOA
Nicotinic antagonists (competitive, nondepolarizing); Nicotinic agonists (noncompetitive, depolarizing)
Non-depolarizing muscle relaxant drugs
Atracurium, mivacurium, tubocurarine
Non-depolarizing muscle relaxant properties
Nicotinic antagonists, reversible with AChE inhibitors, progressive paralysis, no effects on heart or CNS
Properties of succinylcholine
Depolarizing muscle relaxant, nicotinic agonist; Phase I: depolarization, fasciculation, flaccid paralysis; Phase II: desensitization. Caution in atypical pseudocholinesterase, hyperkalemia, malignant hyperthermia
Malignant hyperthermia
Succinylcholine side effect in genetically susceptible people. Muscle rigidity, hyperthermia, hypertension, acidosis, hyperkalemia. Rx.: dantrolene
Neostigmine
AChE inhibitor reverses non-depolarizing muscle relaxants
Opiod analgesic drugs
Morphine, meperidine, methadone, codeine, fetanyl, heroin
Contraindications of opiod analgesics
Head injuries, pulmonary dysfunction, hepatic or renal dysfunction, adrenal or thyroid deficiencies, pregnancy
Effects of morphine
Analgesia, sedation, respiratory depression (decreased response to PCO2), miosis, cough supression, nausea, vomiting

Analgesia
Increase pain tolerance and perception and reaction to pain. Variable efficacy-morphine is
a full agonist providing maximum pain relief. Persistent, dull, aching pain responds better than
intermittent.

Sedation
Drowsiness, possible euphoria, short-term memory loss.

Respiratory Depression
Decreased response to '? pCOz (even at Rx dose) via depression of neurons in brainstem respiratory
center-major problem in overdose.

Cardiovascular
Minimal effects on heart-cerebral vasodilation +'?in tracerebral pressure (avoid in head trauma).
Morphine (but not other drugs) releases histamine +J BP.

GI Tract
Decreased peristalsis 4 constipation (or clinical use in diarrheal states, e.g., loperamide and
diphenoxylate).

Smooth Muscle
Increased tone of biliary, bladder, and ureter with possible spasms (except meperidine, which
blocks M receptors); 4 tone of vasculature (hypotension via histamine) and uterus (slow delivery).

Pupils
Miosis via '? cholinergic activity (except meperidine).

Cough Suppression
Antitussive action-independent of analgesia (e.g., dextromethorphan) and at subanalgesic
doses with codeine.

Nausea and Emesis
Stimulation of the chemoreceptor trigger zone (CTZ) in the area postrema.
Pharmacokinetics of morphine
Phase 2 metabolism by glucoronidation. Caution in renal dysfunction as morphine-6-glucoronide is highly active
Opiod toxicity
Pinpoint pupils, repiratory depression and coma. Rx. Naloxone
Meperidine
Opiod without miosis or spasms. Metabolized via P450 to normeperidine which can cause seizures
Methadone
Used for opiate withdrawal in addicts
Codeine
Cough suppressant, analgesia, use in combination with NSAIDs
Symptoms of opiod withdrawal
Yawning, lacrimation, rhinorrea, salivation, anxiety, muscle spasms and CNS-originating pain. Rx.: methadone
Naloxone
Antidote for opiods
Drugs used in Parkinson disease
Levodopa, tolcapone, selegiline, bromocriptine, benztropine, amantadine
Levodopa
Crosses CNS barrier. Converted to dopamine in CNS and periphery, so use tolcapone, carbidopa and selegiline
Tolcapone
Inhibits COMT which blocks levodopa conversion to methyldopa which has no pharm actions
Carbidopa
Inhibits conversion of levodopa to dopamine in peripheral tissues, increasing CNS availability
Selegiline
MAOb selective inhibitor, adjunt to levodopa to decrease dopamine metabolism in CNS
Bromocriptine
Dopamine receptor agonist used in hyperprolactinemia, acromegaly
Benztropine
Muscarinic blocker used to decrease Ach activity in Parkinson. Decreases tremor and rigidity but not bradykinesia
Atypical antipsychotics
Clozapine, olanzapine, risperidone, aripiprazole
Atypical antipsychotic MOA
Inhibition of dopamine and 5HT2 receptors
Side effects of antipsychotic drugs
Extrapyramidal symptoms, akathisia, tardive dyskinesia, dysphoria, endocrine dysfunction, weight gain, hypotension, muscarinic blockade tachychardia
Specific side effects of thioridazine
Torsades, retinal deposits
Typical antipsychotics
Chlorpromazine, thioridazine, fluphenazine, haloperidol
Specific side effects of haloperidol
Neuroleptic malignant syndrome, tardive diskynesia
Specific side effects of clozapine
Agranylocytosis, seizures, salivation
MAO inhibitor drugs
phenelzine, tranylcypromine
Drug interaction of MAO inhibitors
Tyramine, TCAs, alpha-1 agonists, levodopa: increase NE --> hypertensive crisis; Serotonin syndrome with SSRI, TCA, meperidine --> sweating, rigidity, myoclonus, hyperthermia
Tricyclic antidepressant drugs
Amitriptyline, imipramine, clomipramine
TCAs MOA
Nonspecific blockade of 5HT and NE reuptake
Side effects of TCAs
Muscarinic blockade, alpha blockade, serotonin syndrome, hypertensive crisis
SSRI drugs
Fluoxetine, sertraline, paroxetine
Side effects of SSRI
Anxiety, agitation, bruxism, sexual dysfunction, weight loss
Serotonin syndrome
Sweating, rigidity, myoclonus, hyperthermia. Interaction between MAOi, TCAs, SSRIs, meperidine, dextromethorphan
Drug-induced hypertensive crisis
Due to interaction between MAOi, TCAs, alpha-1 agonists
Venlafaxine
Selective reuptake inhibitor of NE and 5HT. Can cause hypertensive crisis and serotonin syndrome
Bupropion
Dopamine reuptake blocker. Used in smoking cessation
Lithium MOA
Prevents recycling of inositol (decreases PIP2), decreases cAMP
Lithium side effects
Narrow therapeutic index requires monitoring, tremor, hypothyroidism (decreases TSH effects and inhibits 5'-deiodinase), nephrogenic diabetes insipidus (manage with amiloride), teratogenic
Methylphenidate
Reuptake inhibitor and releaser of DA and NE. Side effects: agitation, restlessness, insomnia, CV toxicity. Treats ADHD.
Atomoxetine
Selective NE reuptake inhibitor. Treats ADHD.
Drugs that cause disulfram-like effects
Disulfram-like effects = acetaldehyde toxicity. Disulfram inhibits acetaldehyde DH. Metronidazole, cefamandole, cefoperazone, cefotetan, chlorpropamide
Additionally the barbiturates have effect on what receptor, except for the GABAA?
AMPA receptor
How does the solubility of a drug affect anesthetics?
The more rapid a drug equilibrates with the blood, the more quickly the drug passes into the brain to produce anesthetic effect.
How does the inspired gas partial pressure affect anesthetics?
A high partial pressure of gas in the lungs results in more rapid achievement of anesthetic levels in the blood.
How does the ventilation rate affect anesthetics?
The greater the ventilation rate, the more rapid is the rise in alveolar and blood partial pressure of the agent and the onset of anesthesia.
How does pulmonary blood flow affect?
At low flow rates, the onset is faster.
The rate of recovery from anesthesia using agents with low blood:gas partition coefficients is faster or slower than that of anesthetics with high blood solubility?
faster
anesthetic gases!
• Methoxyflurane
• Sevoflurane
• Halothane
• Isoflurane
• NO
• Enflurane
• Desflurane
What gases are metabolized by the liver to significant extent? (
halothane and methoxyflurane
How is difference of MAC concerning age?
Infants and elderly patients have lower MAC than adolescents and young adults.
What are the MACs of halothane and NO?
NO = 104% (high)
halothane = 0,75% (low)
What are the blood:gas portion coefficents of halothane and NO?
NO = 0,5 (low)
halothane = 2,3 (high)
What effect do INHALED ANESTHETICS have on INTRACRANIAL PRESSURE?
Inhaled anesthetics decrease brain metabolism. They reduce vascular resistance and thus increase cerebral blood flow. This may lead to an INCREASE in intracranial pressure.
What inhaled anesthetics are MYOCARDIAL DEPRESSANTS?
HALOTHANE and ENFLURANE are myocardial depressants that decrease cardiac output.

Sevoflurane, Isoflurane, Desflurane and cause periphereal vasodilation
What inhaled anesthetic does NOT lower blood pressure?
NO
What inhaled anesthetics may sensitize the myocardium to the ARRHYTMOGENIC EFFECTS of catecholamines?
HALOTHANE and to a lesser degree isoflurane.
Most inhaled anesthetics are bronchodilators or bronchoconstrictors?
bronchodilators
Postoperative HEPATITIS has occurred after administration of what inhaled anesthetic in patients experiencing hypovolemic shock or other severe stress?
Halothane
What inhaled anesthetic may cause RENAL INSUFFIENCY after prolonged anesthesia?
Fluoride released by metabolism of METHOXYFLURANE (and possible enflurane and sevoflurane)
Prolonged exposure to what inhaled anesthetics may lead to MEGALOBLASTIC ANEMIA?
NO decreases methionine synthase activity and may lead to megaloblastic anemia.
Susceptible patients may develop MALIGNANT HYPERTHERMIA when anesthetics are used together with what?
neuromuscular blocker, especially SUCCINYLCHOLINE
What drug is indicated for treatment of MALIGNANT HYPERTHERMIA?
Dantrolene
The barbiturates – thiopental and methohexital - have high or low lipid solubility?
HIGH - this promotes rapid entry into the brain and results in surgical anesthesia in one circulation time (less than one minute).
What effect do the barbiturates (thiopental and methohexital) have on respiratory and circulatory systems?
They are respiratory and circulatory DEPRESSANTS
What effect do the barbiturates (thiopental and methohexital) have on intracranial pressure?
Because they depress cerebral blood flow, they can also DECREASE intracranial pressure.
So the inhaled anesthetics increase intracranial pressure and the barbiturates decrease it. There is one more drug that increases intracranial pressure. Name the drug!
• ketamine
• morphine
What drugs are especially valuable in high-risk patients who might not survive a full general anesthesia?
These drugs may also cause CHEST WALL RIGIDITY, which can impair ventilation.
opioids – MORPHINE and FENTANYL
Respiratory depression of the opioids morphine and fentanyl may be reversed by what drug administration?
• naloxone
• naltrexone
NEUROLEPTHANESIA is a state of analgesia and amnesia. This is produced when?
When you combine
• FENTANYL
• NO
• DROPERIDOL
What are the components of BALANCED ANESTHESIA?
• muscle relaxant
• IV anesthetic
• gas anesthetic
What drug with a short duration of action is a primary advantage in anesthesia for patients with limited cardiac or respiratory reserve?
etomidate
Etomidate is also used in what procedure with a heart beating too fast or with arrhythmia?
cardioversion
(Cardioversion - abnormal or too fast rhythm is converted to normal rhythm via drugs or electricity.)
What is the SUFFIX of local anesthetics?
CAINE
(Articaine, Bupivacaine, Levobupivacaine, Lidocaine, Mepivacaine, Prilocaine, Ropivacaine, Benzocaine, Cocaine, Procaine, Tetracaine)
The commonly used local anesthetics are bases or acids?
WEAK BASES with at least 1 ionizable amine function that become charged through the gain of a proton.
Many shorter-acting local anesthetics are usually administrated with a vasoconstrictor (alpha-agonist). Why?
The local anesthetics are readily absorbed into the blood. The duration of local action is limited unless blood flow is reduced.
All local anesthetics are vasodilators except one. Which?
cocaine
COCAINE is an important exception because it has sympathomimetic action and inhibits what?
NE REUPTAKE TRANSPORTER that reuptakes norepinephrine into the nerve terminals.
Metabolism of ESTER local anesthetics is carried out by what?
Plasma and tissue esterases
Metabolism of AMIDES are carried out by what?
P450 system in the LIVER
(Conjugation reaction so they are less lipid soluble and can get excreted in the urine easier)
Local anesthetics block what channels? (LA)
SODIUM CHANNELS and reduce influx of sodium ions, thereby preventing depolarization
Which form reaches more rapidly the intracellular concentration? (LA)
uncharged
(ionized form)
Which form is more effective in blocking? (LA)
charged
( non-ionized)
What state of the channel is blocked first? (LA)
Active sate
The uncharged or ionized form blocks what state? (LA)
Inactive state
How do the concentrations of potassium and calcium affect local anesthetic activity?
High extracellular concentrations of potassium may enhance.
High extracellular concentration of calcium may antagonize.
What are blocked first – nerve in small or large diameter?
small diameter
(B, C → A-delta → A-beta , A-gamma → A-alpha)
What are blocked first – myelinated or unmyelinated fibers?
myelinated fibers
(because they only have to block sodium channels at 3 nodes of Ranvier)
What fibers recover first – small or large?
In reverse order! The larger recovers first.
What fibers are blocked first in a thick nerve?
The fibers located in the PERIPHERY of a thick nerve bundle are blocked sooner than those in the core because they are exposed earlier to higher concentration of the anesthetic.
The local anesthetics are commonly used for minor surgical procedures often in combination with vasoconstrictors such as
epinephrine
Onset of action of local anesthetics may be accelerated by the addition of
sodium bicarbonate
(So for the best results you should add both SODIUM BICARBONATE and EPINEPHRINE when using local anesthetics.)
Which one has the fastest onset of action? (LA)
Articaine
Local anesthetic are also used in SPINAL ANESTHESIA and to produce autonomic blockade in ischemic conditions. Slow epidural infusion at low concentrations has been successfully for postoperative analgesia. Repeated epidural injection in anesthetic doses may lead to what
thachyphylaxis
(A rapid decrease in the response to a drug due to previous (long term) exposure to that drug)
The important toxic effects of most local anesthetics are in the CNS. All local anesthetics are capable of producing a spectrum of central effects. Name them!
CNS alert!!!
• Convulsions
• Nystagmus
• Sedation
• Restlessness
What local anesthetics are associated with heart disturbances?
• bupivacaine
• cocaine
Which of the LA drugs will produce hypertension and which will produce hypotension?
BUPIVACAINE may produce arrhythmias and HYPOtension.
COCAINE may produce cerebral hemorrhage, MI, arrhythmias and HYPERtension
What local anesthetic is metabolized to a product that includes O-TOLIDINE?
prilocaine
What is the function of o-tolidine?
An agent converting hemoglobin to methemoglobin.
(methemoglobin cannot carry oxygen!)
Though tolerated in healthy persons, even moderate methemoglobinemia can cause decompensating in patients with what diseases?
• PULMONARY disease
• CARDIAC disease
(Those patients should not use prilocaine.)
What subclass of local anesthetics is metabolized to products that can cause antibody formation?
ESTER
Allergic responses are rare IN LAand can usually be prevented by using an agent from what subclass
ESTER
In high concentrations, local anesthetics may cause a local an action, that include histologic damage and permanent impairment of function.
Neurotoxic
What drug do you use to treat severe toxicity of local anesthetics?
Severe toxicity is treated SYMPTOMATICALLY, there are no antidotes.
EMLA consist of what drugs?
• prilocaine
• lidocaine
What sulfate-containing drugs are esters of PABA?
sulfonamides
The classic antipsychotic drugs have what affinity on what receptor?
D2 receptor
The newer antipsychotics have what receptor affinity?
5-HT2 receptor
Name a drug of the BUTYROPHENONES?
Haloperidol
Name the PHENOTIAZINES!
PhenotiaZINE
• chlorpromaZINE
• fluphenaZINE
• thioridaZINE
• trifluoperaZINE
Name the classic antipsychotic drugs!
• chlorpromazine
• fluphenazine
• thioridazine
• trifluoperazine
• haloperidol

(In other words: the classic antipsychotic drugs are the PHENOTIAZINES and HALOPERIDOL!)
Name the newer antipsychotic drugs!
• Clozapine
• Olanzapine
• Quetiapine
• Risperidone
• Ziprasidone
• Molindone
How is the absorption of antipsychotic drugs when given orally?
Well absorbed.
Are the antipsychotic drugs lipid soluble?
Yes, the readily enter the CNS and most other body tissues. Many are bound extensively to PLASMA PROTEINs.
What is the DOPAMINE HYPOTHESIS?
The dopamine hypothesis of schizophrenia proposes that the disorder is caused by a relative excess of functional activity of the neurotransmitter dopamine in specific neuronal tract in the brain.
• many antipsychotic drugs that block brain dopamine receptors have been detected in certain brain regions of untreated schizophrenics
• dopamine against drugs exacerbate schizophrenia
• increased density of dopamine receptors
Describe the DOPAMINE RECEPTORS!
• Five different
• all are G-protein bound ( D1 = Gs ; D2 = Gi )
• 7 transmembrane domains
How are the affinities of the newer antipsychotic drugs at different dopamine receptors?
Most of the newer drugs have higher affinities for OTHER receptors than D2.
Clozapine block what receptors?
• D4
• 5-HT2
The newer drug ZIPRASIDONE is an antagonist and agonist at what receptors?
antagonist
• D2
• 5-HT1D
• 5-HT2A
agonist
• 5-HT1A
Almost all antipsychotic drugs block what receptors at some extend that aren’t dopaminergic or serotoninergic?
• alpha1
• H1
• muscarinic
Name the POSTIVE SYMPTOMS of schizophrenia!
• hyperactivity
• bizarre ideation
• hallucinations (hearing voices)
• delusions
Name some of the NEGATIVE SYMPTOMS of schizophrenia!
• emotional blunting
• social withdrawal
• lack of motivation
The older drugs vs. newer when talking about EFFECTIVENESS, COST and TOXICITY?
Newer drugs more effective and less toxic but cost more.
How are the effects on positive and negative symptoms by newer and older drugs? How long does it take to see beneficial effects?
• antipsychotic drugs reduce some of the positive symptoms, but it takes weeks to develop beneficial effects
• the older drugs has not got much effect on negative symptoms
• newer drugs have been reported to improve some of the negative symptoms
• both older and newer drugs have effect on positive symptoms
The newer antipsychotic drugs are often used with what drug in the treatment of mania?
Lithium
One of these of the drugs approved for treatment of acute mania are approved for maintenance treatment of bipolar disorder. Name the drug!
Olanzapine
What drug is used in the treatment of Tourette’s syndrome?
Molindone
With the exception of what drug, most phenothiazines have ANTIEMETIC actions. What drug has no anti-emetic effect?
(Chlorpromazine, Thioridazine, Fluphenazine, Trifluoperazine)
THIORIDAZINE has NO ANTIEMETIC ACTIONS!
Dose-dependent extrapyramidal effects include a Parkinson-like syndrome with bradykinesia, rigity and tremor. How can this toxicity be reversed?
• decrease in dose
• antagonized by use of muscarinic blocking agent
Extrapyramidal toxicity occurs most frequently with what drugs?
The classic antipsychotic drugs:
• haloperidol
• phenothiazines (fluphenazine, trifluoperazine, thioridazine, chlorpromazine)
TARDIVE DYKINESIA includes movements of the muscles of the lips and buccal cavity. Tardive dyskinesia tend to develop after several years of antipsychotic drugs therapy but have appeared as early as 6 months. What is the drug for treatment of tardive dyskinesia?
The symptoms may be irreversible. There is NO EFFECTIVE DRUG treatment for tardive dyskinesia.
You can change to what drug when having TARDIVE DYSKINESIA, so that the symptoms won’t get worse?
Clozapine
Which of the older antipsychotic agents have STRONGEST AUTONOMIC EFFECTS?
Thioridazine
Which of the older antipsychotic agents have the WEAKEST AUTONOMIC EFFECTS?
Haloperidol
The symptoms of NEUROLEPTIC MALIGNANT SYNDROME may be life threatening. Name the drugs involved in treatment of neuroleptic malignant syndrome!
The “3 D’s” (Remember that Neuroleptic Malignant Syndrome consist of 3 words, the same number as the “D’s”)
• Dantrolene
• Diazepam
• Dopamine agonists


FEVER
• FEVER
• ENCEPHALOPATHY
• VITALS are unstable
• ELEVATION of enzymes (elevated CPK)
• RIGIDITY of muscles
Which is the antipsychotic drug marked with most SEDATION?
chlorpromazzzzzzzzzzzzzine
Deposits in the eye: RETINA and LENS – what antipsychotic drug(s)?
retina thioridazine
lens chlorpromazine
What antipsychotic drug causes a small but important (1-2%) incidence of AGRANULOCYTOSIS and at high doses causes seizures?
clozapine
Poisoning with antipsychotic drugs is usually not fatal, except for one drug. Name the drug!
thioridazine
Why can poisoning with THIORIDAZINE be fatal?
Because of the CARDIOTOXICITY
What drug is very effective in the treatment of MANIC PHASE of bipolar disorder and continues to be used for acute-phase illness and for prevention of recurrent manic and depressive episodes?
lithium
How is the ABSORBTION of lithium?
Lithium is absorbed RAPIDLY and completely from the GUT.
How long is the half-life of lithium?
20 h
How is the treatment with lithium?
The plasma levels should be MONITORED, especially during the first weeks of therapy, to establish an effective and safe dose regimen.
How is the effect of sedation of lithium?
Causes no sedation.
The plasma levels of lithium can be changed. How?
Plasma levels of the drug may be altered by changes in BODY WATER.
• dehydration
• thiazides
• NSAIDS
• ACE inhibitors
• loop diuretics
What increase the renal CLEARANCE of lithium?
• caffeine
• theophylline
(Theophylline is similar in structure to caffeine and is found in tea and in cacao beans. It is used in respiratory diseases such as COPD or asthma.)
What is the mechanism of action of lithium?
The drug inhibits several enzymes involved in the recycling of neuronal membrane phosphoinositides. Decrease of PIP2, IP3 and DAG.
Lithium carbonate continues to be used for the treatment of bipolar disorder although other drugs are equally effective. Name two other drugs!
• Carbamazepine
• Valproic acid
Why are antipsychotic agents and/or benzodiazepines commonly required at the initiation of treatment with valproic acid or lithium?
Because they have a slow onset of action.
What two drugs are both approved for MONOTHERAPY for acute mania?
• Olanzapine
• Quetiapine
What are the side-effects of LITHIUM?
• Leukocytosis
• Insipidus (diabetes insipidus)
• Tremor / Teratogenic
• Hypothyroidism
Why is lithium teratogenic?
The use of lithium during pregnancy is thought to increase the incidence of congenital cardiac anomalies (Ebstein’s anomaly).
Side-effects of VALPROIC ACID?
VALPROATE”
• Vomiting
• Alopecia (hairloss)
• Liver (liver toxicity leading to jaundice)
• Pancreas (pancreatitis
• Retention of fats (weight gain)
• Obesity
• Appetite
• Tremor, Teratogenic
• Edema (peripheral edema)
What is the HYPOTHESIS OF MOOD?
NE and 5-HT are neurotransmitters in the pathway of mood. Functional decrease results in depression and functional elevation in mood elevation.
What drug has the longest half-life of all SSRI?
norfluoxetine
Norfluoxetine has what relation to FLUOXETINE?
It is the active product of fluoxetine.
Do the other members of SSRI (citalopram, escitalopram, fluvoxamine, paroxetine and sertraline) form long-acting metabolites?
No
MAOA inhibit what neurotransmitters and/or substances?
• NE
• 5-HT
• tyramine
MAOB inhibit what neurotransmitter and/or substances?
dopamine
Name the MAOI that is REVERSIBLE and SELECTIVE?
Moclobemide
Where is MOCLOBEMIDE metabolized?
In the LIVER.
Name the MAO inhibitor that is IRREVERSIBLE and NON-SELECTIVE?
tranylcypromine
What MAOI has the FASTEST onset of effect but has a SHORT duration of action?
tranylcypromine
Normal duration of other MAOI?
VERY LONG. About 2-3 weeks.
Isocarboxiazid, phenelzine and selegeline are all MAO inhibitors. They inhibits MAOA , or MAOB?
They inhibit both.
(SELEGELINE more active on inhibiting MAOB. Because the drug inhibits a receptor that has an impact on dopamine, selegeline is used in Parkinsson.)
MIRTAZAPINE inhibit what structure?
• presynaptic alpha-2 receptors
• 5-HT2
(unique action to increase amine release from nerve endings by antagonizing presynaptic alpha-2 receptors. Mirtazapine belong to the “group” of other heterocyclics.)
MIRTAZAPINE has what known clinical application decides use in depression?
Sedative effects used in INSOMNIA
NEFAZODONE and TRAZODONE block what?
5-HT2A
(Trazodone and nefazodone belong to the group of 5-HT2 antagonists.)
Longterm use of TCA and MAOIs, but not SSRIs leads to downregulation of what receptors?
Downregulation of BETA-RECEPTORS
Action of TCAs?
Block NE and 5-HT transporters
Action of SSRI?
Block 5-HT transporters
Action of SNRI?
Block NE and 5-HT transporters
(SNRI and TCA both have the same action!)
Name the TCA’s!
• Clomipramine
• Imipramine
• Amitriptyline
What is characteristic for TCA overdose?
The “3 Cs”! (Remember that when you think of the number 3 (like in 3 C:s) you think of the amount of letters in TCA!)
• Coma
• Convulsions (contraction of muscle resulting in shaking of the body)
• Cardiotoxicity
What drugs used in depression are INHIBITORS of hepatic cytochrome P450 isozymes?
SSRI
SSRI toxicity?
SSRI
• Serotonin syndrome
• Stimulate CNS (nausea, headache, anxiety)
• Reproductive dysfunctions in male
• Insomnia
Describe SEROTONINE SYNDROME!
DMARD 5-HT
• DELIRIUM
• MYOCLONUS (brief, involuntary twitching of muscles)
• AGITATION
• RIGIDITY (of muscles)
• DIAPHORESIS (excessive sweating)
• HYPERTHERMIA
• TACHYCARDIA (cardiovascular instability)
Drugs implicated for SEROTONINE SYNDROME include what drugs?
• Meperidine
• TCA
• MAOI
• St. Johns Wort
• Dextromethorphan
What are the indications for MAOIs?
MAOIS
• Major depression
• Anxiety
• Obesity disorder (bulimia)
• Imagined illnesses (hypochondria)
• Social phobias
MAOI toxicity?
• Agitations
• Convulsions
• Hyperthermia
• Hypertensive crisis
What patients taking MAO inhibitors may get HYPERTENSIVE CRISIS?
Those who consume food that contains high concentrations of the indirect sympathomimetic TYRAMINE.
How are absorptions in TCA drugs?
WELL absorbed.
How are half-lifes in TCA drugs?
LONG half-lifes
When should you take the TCA – morning or evening?
In the evening, because of the sedative effect. (Tzzzzzzzzzzzzzza….)
What drugs have the LOWEST PROTEIN BINDING of all antidepressant with only 27-30% that are protein bound?
• venlafaxine (SNRI)
• desvenlafaxine (SNRI)
What antidepressant drug is available in both transdermal and sublingual forms that bypass both gut and liver?
(these routes decrease the risk of food interactions and provide substantially increased bioavailability.)
selegiline
PANIC DISORDER?
SSRI
Best drug for GAD?
SSRI
Best drug for SOCIAL ANXIETY DISORDER?
SSRI
Best drug for POST TRAUMATIC STRESS DISORDER (PTSD)?
SSRI
Best drug for OCD?
SSRI but also CLOMIPRAMINE (TCA) is available.
What drugs are approved for PREMENSTRUAL DYSPHORIC DISORDER (PMDD)?
sertraline (SSRI)
What drug against obesity?
bupropion
(belong to group of other heterocyclics)
Neuropathic pain or pain associated with fibromyalgia?
• SSRI
• bupropion
What drug is the best for STRESS URINARY INCONTINENCE?
duloxetine (SNRI
What drug for BULIMIA that was approved in 1996?
SSRI
What drug has sedative effect and is a good choice against insomnia?
TCA
What drug is the best for ENURESIS in children?
imipramine (TCA)
What drug for smoking cessation?
bupropion (drug belong to other heterocyclics)
What drug when problems with PREMATURE EJACULATION?
• SSRI
• bupropion
NAME Opioids?
Fentanyl, Hydromorphone, Meperidine, Morphine, Methadone Oxymorphone, Codeine, Hydrocodone, Buprenorphine, Nalbuphine, Naloxone, Naltrexone, Nalmefene, Codeine, Dextromethorphan, Tramadol
Opioids may be classified under what subgroups?
• agonists
• mixed agonist-antagonist
• antagonists
The agonists can be classified as what?
• strong
• moderate
• weak
Name the prototype of a strong analgesic or full agonist?
Morphine
How is the absorption of opioids when taken orally?
Most are WELL absorbed.
So most opioids are well absorbed when taken orally. However, some drugs do undergo extensive FIRST-PASS METABOLISM. Name them!
• morphine
• hydromorphone
• oxymorphone
Are the opioids widely distributed to body tissues?


Can they cross the placental barrier?
YES


YES
(They cross the placental barrier and exert effects on the fetus that can result in both respiratory depression and, with continuous exposure, physical dependence in neonates.)
Most opioids are metabolized by hepatic enzymes, usually to inactive glucuronide conjugates, before elimination by the kidney. What metabolic product of MORPHINE has analgesic activity equivalent to that of morphine?
morphine-6-glucuronide
The primary metabolite of morphine is NEUROEXCITATORY. Name the metabolite!
morphine-3-glucuronide
Name the full agonist and strong opioids!
• Fentanyl
• Meperidine
• Morphine
• Methadone
• Hydromorphone
• Oxymorphone
Name the partial or MODERATE opioids
• codeine
• hydrocodone
• oxycodone
What drugs are metabolized by the isozyme CYP2D6 in the liver?
• codeine
• hydrocodone
• oxycodone
CYP2D6 is responsible for variability of analgesic response of CODEINE. CYP2D6 demethylates codeine to its active metabolite. Name the active metabolite of codeine!
morphine
How can ingestion of ALCOHOL affect the opioids, including HYDROMORPHONE and OXYMORPPHONE?
Increase the peak serum levels.
MEPERIDINE is metabolized to what?
normeperidine
Adverse effects of normeperidine?
It can cause SEIZURES at high plasma levels.
What are the 3 major receptors of opioids?
• mu
• delta
• kappa
Mu-receptor activation plays a major role in what?
Action as RESPIRATORY DEPRESSANT.
Kappa-receptors activations play a role in what?
sedation
Mu-receptors together with kappa-receptors play a major role in activation of what?
slowing peristalsis of GI tract (=constipation)
Delta-receptors activation plays a role in what?
development of TOLERANCE
Opioid receptors are thought to be activated by endogenous peptides under physiological conditions. Name these peptides that include!
• endorphins
• enkephalins
• dynorphins
What peptides to you find in the presynaptic membrane of neurons?
All of them (mu, delta, kappa).
What peptides do you find in the postsynaptic membrane of neurons?
mu
These peptides have highest affinity for what receptors?
endorphins → mu
enkephalins → delta
dynorphins → kappa
What effect do these opioid peptides have to neurons?
They are INHIBITATORY to neurons.
Opioid analgesics have what effects on synaptic activity through direct activation of opioid receptors?
They INHIBIT synaptic activity.
All 3 major opioid receptors are coupled to their effectors by what G-proteins?
Gi
(inhibit adenylyl cyclase)