Neuropharmacology High Yield

Front 1

drugs which prolong the state of inactivation of Na+ channels

Back 1

PVC = phenytoin, valproate, carbamazepine (NB: remember that the Na+ channels exist in three states = activated, inactivated and resting)

Front 2

DOC for generalized tonic-clonic seizures

Back 2

phenytoin

Front 3

phenytoin med use and tx

Back 3

DOC for generalized tonic-clonic seizures, status epilepticus (diazepam is DOC), tx of episodic clonic movements following severe head injury

non-linear kinetics at large doses, i.e., at large doses elimination not first order

Front 4

phenytoin S/E

Back 4

gingival hyperplasia; ataxia, nystagmus, diplopia; psychological disturbances; megaloblastic anemia (interferes w folate metabolism); osteomalacia (responds to vitamin D), teratogenic (cleft lip/palate), not much sedation

Front 5

DOC for trigeminal neuralgia

Back 5

carbamazepine

Front 6

carbamazepine MOA

Back 6

MOA: prolong the state of inactivation of the Na+ channel = no impulse propagation

Front 7

carbamazepine med use

Back 7

tx of temporal lobe seizures, DOC for trigeminal neuralgia

Front 8

carbamazepine S/E

Back 8

S/E = monitor LFT’s, esp. in young patients or patients tx w valproate + other seizure meds

5) can cause increased release of AVP and potentiate the antidiuretic effects of AVP; the result is dilutional hyponatremia

Front 9

Phenytoin and phenobarbital S/E

Back 9

: induction of CYP450 which increases the metabolism of vit D and vit K (vit K a cofactor for the synthesis of osteocalcin);

Front 10

Phenytoin and phenobarbital MOA

Back 10

osteomalacia, decreased vit D lowers the GI absorption of Ca++. In order to maintain plasma [Ca++], bone is resorbed

Front 11

DOC for absence seizures

Back 11

ethosuximide

Front 12

ethosuximide MOA

Back 12

blocks T-type Ca++ channels in thalamus

Front 13

baclofen MOA

Back 13

interacts with GABAB-receptors linked to K+ channels, enhanced K+ conductance hyperpolarizes cells presynpatic membrane of glutaminergic neurons in spinal cord to prevent the release of glutamate onto alpha-motor neurons = decrease efferent excitation of spastic skeletal muscle

Front 14

baclofen med use

Back 14

tx of spasticity from spinal cord injury, CP, MS

Front 15

dantrolene MOA

Back 15

inhibits release of “trigger” Ca++ from SR in skeltal muscle

Front 16

dantrolene med use

Back 16

tx of spasticity from spinal cord injury, malignant hyperthermia, neuroleptic malignant syndrome

Front 17

dantrolene S/E

Back 17

generalized muscle weakness

Front 18

desipramine (DMI), specificty of amine transporter

(know this one)

Back 18

NE reuptake blocked, secondary amine

Front 19

fluoxetine, paroxetine, citalopram, fluvoxamine; specificty of amine transporter

Back 19

5-HT reuptake blocked = SSRI's

Front 20

imipramine (tertiary amine), cloimpramine, venlafaxine; specificty of amine transporter

Back 20

both NE & 5-HT reuptake blocked

Front 21

S/E of antidepressants

Back 21

FINE TREMOR, confusion in elderly patients, postural hypotension (alpha-blockade), sedation (central antimuscarinic effect), urinary retention and tachycardia (atropine-like effect), fine tremor, AV block (direct toxic effect)

Front 22

MAO inhibitors are antidepressant because

Back 22

they inhibit MAO-A which degrades NE & 5-HT (NB: MAO-B degrades DA)

Front 23

schizophrenic patient w depression

Back 23

tx w SSRI like fluoxetine

Front 24

depressed pt w hypotension

Back 24

tx w SSRI like fluoxetine

Front 25

Depressed patient being tx w antidepressant suffers from sedation and hypotension

Back 25

could be MAOI or TCA since both cause sleepiness and hypotension, but pick TCA bx TCA’s cause greater orthostatic hypotension than do MAOI’s

Front 26

small child w nocturnal enuresis

Back 26

tx w TCA for atropine-like effect in urinary bladder

Front 27

Which NT involved in OCD?

Back 27

5-HT

Front 28

tx for OCD

Back 28

clomipramine or SSRI (e.g., fluoxetine)

Front 29

depresssed patient w CHF tx w digoxin is given TCA

Back 29

inverts or flattens T-wave, slows conduction in fast fibers so QRS increased

Front 30

imipramine (tertiary amine which blocks 5-HT & NE uptake1) converted to:

Back 30

desipramine (secondary amine which blocks NE uptake1)

Front 31

OD with imipramine:

Back 31

usual effects are dec BP from alpha-blockade; inc HR from dec BP and anticholinergic effects; decreased AV conduction with inc Q-T interval

Front 32

serotonin syndrome

Back 32

results from excessive stimulation of central 5-HT receptors = inc BP, HR and respiration; increased muscle activity (muscle twitching, shivering, myoclonus) causing hyperthermia and sweating; pupillary dilation; confusion, agitation, hallucinations

Front 33

the serotonin syndrome is caused by

Back 33

an SSRI (e.g., fluoxetine) or a TCA whch blocks both NE and 5-HT uptake, e.g., imipramine), especially in patients taking an MAOI. MAOI (e.g., phenelzine) prevent the degradation of 5-HT in the CNS, and 5-HT accumulates in the cytoplasm of central 5-HT neurons

Front 34

Antipsychotic drugs MOA

Back 34

Block D2-receptors in mesolimbic DA pathway

Front 35

DOC for Tourette’s syndrome (vocal and motor tics, coprolalia)

Back 35

haloperidol

Front 36

haloperidol S/E

Back 36

least sedating, greatest likelihood of ESP

Front 37

clozapine med use

Back 37

effective in tx of negative symptoms; measure CBC weekly w clozapine tx

Front 38

chlorpromazine prevents

Back 38

emetic effects of D2-receptor stimulation at CTZ

Front 39

Antipsychotic drugs S/E's

Back 39

alpha-blockade = dizziness, orthostatic hypotension, inc HR , nasal stuffiness, impotence
- muscarinic blockade = dry skin & mouth, mydriasis, inc HR, urinary retention, sedation
- central D2-blockade = fine tremor, muscular rigidity, EPS, tardive dyskinesis, hyperprolactinemia, galactorrhea, amenorrhea

- neuroleptic malignant syndrome (vide infra)

Front 40

Li+ MOA

Back 40

inhibits enzymes important in recycling phosphoinostides, so PIP2 is depleted

Front 41

Li+ S/E

Back 41

- both HCTZ and furosemide enhance the reabsorption of Li+ in the PT causing toxicity

- S/E = tremor, motor and psychiatric disturbances; causes nephrogenic DI by inhibiting adenyl cyclase coupled to V2-ADH receptors in CD

- in a female patient with bipolar dz, must d/c Li+ tx during first trimester to prevent teratogenesis (Ebstein’s anomaly = leaflets of mitral valve displaced downward into right ventricle, tricuspid regurgitation, right ventricular dysfunction)

Front 42

Drugs which can cause Parkinsonian-like side effects

Back 42

D2-receptor antagonists like haloperidol, chlorpromazine, trifluperazine

Front 43

Drugs used to treat PD

Back 43

levodopa, carbidopa, selegiline, benztropine, bromocriptine, amantadine

Front 44

levodopa MOA

Back 44

precursor of DA which is pumped into the brain via the aromatic amino acid pump; tx w vitamin B6 interferes w therapeutic action of levodopa because B6 increases peripheral decarboxylation of levopdopa to DOPA

Front 45

carbidopa MOA

Back 45

inhibits DOPA (L-aromatic amino acid) decarboxylase outside brain to enhance the amount of DOPA taken up by the brain and converted to DA

Front 46

benztropine MOA

Back 46

central muscarinic receptor blockade

Front 47

selegiline MOA

Back 47

selective MAO-B inhibitor, blocks breakdown of DA in CNS

Front 48

bromocriptine MOA

Back 48

central D2-dopamine receptor agonist

Front 49

amantadine MOA

Back 49

antiviral drug which release DA centrally

Front 50

carbidopa + levodopa

Back 50

- can reduce the dose of DOPA
- prevents decarboxylation of DOPA outside CNS
- carbidopa does not enter CNS
- carbidopa does not attenuate the orthostatic hypotension caused by levodopa

Front 51

levodopa can cause (S/E)

Back 51

the reappearance of psychotic symptoms in a schizophrenic patient with PD caused by tx w typical antipsychotic drugs (e.g., haloperidol)

Front 52

Drugs which increase plasma prolactin

Back 52

-D2-dopamine receptor blockers like haloperidol
- reserpine
- metoclopramide
- alpha-methyldopa

Front 53

how to treat Parkinson's and reverse hyperprolactinemia

Back 53

bromocriptine

Front 54

Ethanol kinetics

Back 54

oxidized to acetaldehyde by alcohol dehydrogenase; acetaldehyde degraded to water and CO2 by acetaldehyde dehydrogenase
- alcohol dehydrogenase easily saturated a low concentrations of ethanol, so ethanol removed by zero-order kinetics = constant amount of drug/h

Front 55

acetaldehyde dehydrogenase inhibited by: (2 drugs)

Back 55

disulfiram & metronidazole; build up of acetaldehyde causes peripheral vasodilation (red skin), n/v, pulsating headache, sweating, chest pain, vertigo, syncope, blurred vision, confusion

Front 56

patient being treated for Giardia + some other infection (e.g., bacterial) develops n/v and headache after drinking a beer. Which drug causes this rx

Back 56

metronidazole

Front 57

Alcoholism causes:

Back 57

- hyperlipidemia and fatty infiltration of the liver
- cardiomyopathy, portal hypertension, gastric ulceration, esophageal varices
- Wernicke-Korsakoff syndrome - ass w thiamine deficiency - get paralysis of external eye muscles, altered mentation and ataxia

Front 58

fetal alcohol syndrome

Back 58

flattened face, short nose, short palpebral fissures = underdevelopment of mid-facial region, microcephaly with low IQ, retarded growth

Front 59

Methanol toxicity

Back 59

- severe visual disturbance (“like being in a snow storm”) with relatively clear sensorium, headache, dyspnea, cold digits, GI pain, breath smells of formaldehyde.
- treat w ethanol to saturate enzymes which degrade EtOH and MeOH because toxic product of MeOH appears to be a formate compound produced by the sequential actions of alcohol and acetaldehyde dehydrogenases

Front 60

ingestion of ethylene glycol from antifreeze

Back 60

converted to aldehydes, acids and oxalate: oxalate causes acute renal failure

Front 61

Amphetamine toxicity:

Back 61

nervousness, restlessness, insomnia, hypertension, tachycardia, hyperthermia, toxic psychosis = paranoid schizophrenia, weight loss, formication, tonic-clonic seizures.
- pupillary dilation from the release of NE in the radial muscle

Front 62

Use of methylphenidate for tx of ADD and ADHD in children can cause: (S/E)

Back 62

depression, insomnia, loss of apetite, weight loss, slowed growth rate

Front 63

to normalize breathing in neonatal apnea

Back 63

theophylline, aminophylline & caffeine used

Front 64

phentermine suppresses appetite via

Back 64

the release of NE in the hypothalamus

Front 65

MDMA (“ecstacy’) = methylenedioxymetamphetamine - can cause (long term S/E)

Back 65

degeneration of central 5-HT neurons

Front 66

All sedative-hypnotic drugs (barbiturates, benzodiazepines, choral hydrate, glutethimide) cause:

Back 66

dependence, shortened sleep latency, suppression of REM sleep, tolerance, rebound insomnia, respiratory depression. They are NOT analgesic.

Front 67

oil: water partition coefficient predicts:

Back 67

drug with most rapid onset (the higher the coefficient the faster it diffuses into the brain)

Front 68

Barbiturate MOA:

Back 68

Low therapeutic index/window.

enhance GABA-A receptor-mediated increase in Cl- conductance to hyperpolarize neurons: enhances duration of channel opening

Front 69

in older pts, Barbiturates can cause:

Back 69

paradoxical excitation

Front 70

thiopental MOA and med use:

(know this one)

Back 70

- used for induction of anesthesia, short duration of action due to redistribution
(blood-brain/viscera -> skeletal muscle- -> fat

- transient decrease in BP with reflex increase in HR and dP/dT, so CO NOT DEPRESSED

Front 71

Benzodiazepine MOA:

Back 71

enhance GABAA receptor-mediated increase in Cl- conductance to hyperpolarize neurons; enhances rate of channel opening

Front 72

Benzodiazepines in older patients

Back 72

exhibit inc t1/2 due to dec Cl; inc free plasma concentration from dec plasma
protein binding; inc receptor sensitivity to BZ’s = inc risk of falls and hip fracture

Front 73

with benzodiazepines, less PBPs means:

Back 73

more effect

Front 74

benzodiazepines for old people

Back 74

lorazepam and oxazepam

cleared by glucuronidation in blood rather than CYP450

Front 75

BZ withdrawal syndrome

Back 75

anxiety, dysphoria, agitation, insomnia, vomiting, sweating, muscle and abdominal cramps, myoclonic jerks, convulsions. No CV effects!

Front 76

flumazenil

Back 76

BZ receptor antagonist; used to tx OD with BZ's; will also precipitate the BZ withdrawal syndrome in a patients addicted to BZ's

Front 77

zolpidem

Back 77

a non-BZ hypnotic drug; acts to increase Cl- conductance

Front 78

Buspirone MOA

Back 78

a partial agonist at 5-HT1A receptors linked to K+ channel: causes hyperpolarization to suppress neuronal activity

Front 79

Buspirone effects

Back 79

anxiolytic but not addictive

Slow onset of action compared to BZ's; no sedation or interaction w EtOH
3) No hypnotic, anticonvulsant or muscle relaxant effects

Front 80

Drug schedule

Back 80

Class 1: heroin, LSD, marihuana, mescaline, PCP, psilocybin, MDA, DMT, DET, bufotenine = no med uses

Class 2: opiates, amphetamines, cocaine, some barbiturates, dronabinol
= no tel scripts/refills

Class 3: codeine, opium, some barbiturates = rewrite script after 6 mo or 5 refills

Class 4: BZ’s pentazocine, propoxyphene, phenobarbital = rewrite script after 6 mo or 5 refills

Class 5: diphenoxylate

Front 81

mu receptors:

Back 81

- analgesia = supraspinal mu1 in periaqueductal gray and spinal mu2
- morphine causes analgesia in humans via stimulation of supraspinal mu1 and spinal mu2 receptors, but predominant effect is supraspinal mu1
- respiratory depression = mu2
- decreased GI motility = mu2
- miosis = increases PSNS activity from E-W nucleus to sphincter muscle of iris
- euphoria
- physical dependence

Front 82

supraspinal effect of opiates

Back 82

a.GABA neuron normally inhibits pain-inhibiting neurons (PIN)
b.Opiates inhibit GABA neuron, so no GABA released onto PIN = no inhibition of PIN = central descending inhibition of pain pathways
c. (inhibitory effect on GABA neurons can explain seizures caused by some opiates like meperidine)

Front 83

spinal effect of opiates

Back 83

opiates block nociceptive stimuli in ascending spinothalamic pathways

a.mu2, delta2 & kappa1 stimulation decreases NT release (probaby glutamate) from presynaptic terminal of nociceptive primary afferent
b.mu receptor stimulation creates IPSP (hyperpolarization) in secondary ascending pain transmission neuron

Front 84

full agonists at mu receptor

Back 84

“morphine met me finally”

morphine, methadone, meperidine, fentanyl

Front 85

partial agonists at mu receptor

Back 85

“partially b-blocks narcotics”

pentazocine, butorphanol, nalbuphine, buprenorphine

Front 86

toxicity triad of opiates

Back 86

miosis, coma, depressed respiration

Front 87

opiate tolerance

Back 87

tolerance to everything but no tolerance to miosis or constipation

Front 88

opiate withdrawal

Back 88

rhinorrhea, lacrimation, chills, n/v, diarrhea, hyperthermia, sweating and piloerection (“goose flesh”), myalgia, tremor, urticaria, mydriasis, anxiety, hostility

Front 89

diphenoxylate

Back 89

least potential for addiction; used to tx diarrhea

Front 90

morphine is DOC for pain and pulmonary edema caused by acute MI bx:

Back 90

it acts in CNS to dec SNS activity: dec preload and afterload.

Front 91

tx of female w acute pain from gallstones w morphine causes greater pain. Why?

Back 91

Morphine contracts smooth muscle of gall bladder

Front 92

female on methadone has emergent surgery and is tx w butorphanol; patient experiences S/S of opiate withdrawal. Why?

Back 92

Butorphanol is a partial agonist at mu receptors. The partial agonists pentazocine, nalbuphine and buprenorphine can also cause S/S of opiate withdrawal in a patient taking methadone

Front 93

which opiate does not cause a dose-related inhibition of respiration

Back 93

the partial agonists pentazocine, butorphanol and nalbuphine

Front 94

newborn baby has respiratory depression bx:

Back 94

mom received an opiate during labor

Front 95

patient with MI tx with morphine, why?

Back 95

Chest & arm pain inc the activity of the sympathetic nervous system which constricts arterioles and venules to increase preload and afterload. The damaged heart cannot pump the increased venous return, especially in the face of an increase in afterload. Morphine acts centrally to decrease pain and to decrease sympathetic outflow. Decreased activity of the SNS decreases preload and afterload and improves CO. the analgesic effects of morphine also make the patient more comfortable.

Front 96

Nitrous oxide N2O cannot be used for anesthesia bx:

Back 96

Its MAC is 100%. pt must have at least 20% oxygen.

Front 97

Question re: potency or MAC

Back 97

Most potent drug has the smallest MAC gas with lowest MAC (most potent) = gas with the highest oil/gas partition coefficient. gas with the highest MAC (least potent) = gas with lowest oil/gas coefficient

Front 98

factors controlling the rate of induction of anesthesia:

Back 98

- alveolar ventilation rate
- blood/gas partition coefficient
- partial pressure of gas in lungs
- cardiac output
- increase in FI (concentration of gas in inspired air) = concentration effect = increase dose
- cerebral blood flow
- NOT potency (MAC)

Front 99

high MAC and fast induction and recovery

Back 99

an anesthetic gas with low lipid solubility

Front 100

low MAC and slow induction and recovery

Back 100

an anesthetic gas with high lipid solubility

Front 101

second-gas effect

Back 101

A rapidly absorbed gas inc the rate of uptake of a second gas.Give 70% nitrous oxide + 0.78% halothane + 29% oxygen, and the rapid uptake of nitrous oxide pulls the halothane along with it.

Front 102

diffusion hypoxia

Back 102

When N2O is stopped, a large volume of N2O dilutes the oxygen, and the patient becomes hypoxic. Occurs during first 10 min after dc of N2O, tx patient w 100% oxygen

Front 103

empty air spaces and N2O

Back 103

If the air-filled cavity is non-compliant (e.g., sinuses, middle ear and cerebral ventricles), intracavity pressure increases. Increased middle ear pressure can rupture the tympanic membrane or cause n/v after surgery.

Front 104

factors controlling rate of offset of anesthesia

Back 104

- blood/gas partition coefficient
- hyperventilation
- cardiac output
- drug metabolism by the liver

Front 105

CV effects - halothane, isoflurance, enflurane

Back 105

- all volatile agents decrease MAP by decreasing either CO or TPR, but effect to decrease BP is attenuated in the presence of N2O which tends to increase sympathetic activity
- isoflurane has little effect on CO

Front 106

Ketamine MOA

Back 106

blocks NMDA glutamate receptor coupled to Ca++ channel (NB: glutamate is an
excitatory NT in the CNS)

Front 107

Ketamine med use

Back 107

- produces a dissociative state of consciousness, analgesia and postanesthetic hallucinations
- least likely to supppress respiration (all opiates, barbiturates, BZ’s and gaseous anesthetics suppress respiration)
- MAP via inc CO (inc LV-EDP, dp/dt, HR). Little effect on TPR.

Front 108

Etomidate MOA:

Back 108

enhances GABAA-mediated chloride conductance to hyperpolarize neurons
- minimal effect on BP or respiration

Front 109

Etomidate med use:

Back 109

- causes myoclonic movements (not epilepsy) which can be prevented by pretx w BZ’s
- can cause adrenal suppression w decrease in plasma cortisol

Front 110

Which of the following drugs decreases BP and respiration when given i.v.?

Back 110

1) opiate - BP = nc, dec respir;
2) ketamine - inc BP, respir = nc;
3) etomidate - BP & respir = nc;
4) thiopental - dec BP and respir

Front 111

Nitrous oxide produces analgesia, amnesia and mental confusion, but does not cause what?

Back 111

anesthesia!

Front 112

Halothane predisposes to :

Back 112

Epi-induced cardiac arrhythmias: tx w beta-blocker.