Pharmacology.block 5 Take 2

Front 1

D. Pressed is a 30-year-old female with severe depression; she has also been diagnosed with neuropathic pain. Which one of the following drugs would most likely treat both conditions?

Back 1

Amitriptyline (Elavil®)

Classification and SE?

Hint 1

TCA

SE: Anticholinergic (dry eyes, dry mouth), day time drowsiness

Front 2

What is the site of action of TCAs?

Back 2

NE and 5HT reuptake receptors
(include imipramine, desipramine, amitripyline, and nortripyline)

What are the side effects

Hint 2

Weight gain
Sexual Dysfunction
Orthostatic hypotension (alpha 1 receptors)
Anticholinergic effects - dry mouth, blurry vision, glaucoma (muscarinic receptors)
Sedation (H1 receptors) - particularly amitryptiline
Seizures
Cardiac conduction problems

Front 3

Enuresis treatment for children over the age of 6?

Back 3

Imipramine


Classification?

Hint 3

TCA

Front 4

Treatment of neuropathic pain?

Back 4

Amitryptiline

Classification and SE?

Hint 4

TCA - target NE reuptake receptor

Sedation, daytime drowsiness, (H1)
Orthostatic hypotension (a1)
Anticholinergic effects (dry mouth, dry eyes, glaucoma - muscarinic receptors

Front 5

SNRIs?

Back 5

Venlafaxine, Duloxetine


SE seen at higher doses?

Hint 5

hypertension

Front 6

MAOIs?

Back 6

Phenelzine, Tranylcypramine, Selegiline

Which is more important for the treatment of depression, MAOA or MAOB?

What are SE of MAOIs?

Hint 6

MAO-A


Cheese effect! --> Hypertensive crisis - anything that causes an increase in NE or serotonin can lead to this!

Also causes weight gain, sexual dysfxn, orthostatic hypotension, sedation,

Front 7

What drug (and class) is a specific inhibitor of MAO-B?

Back 7

Selegiline -MOAI

What is this used to treat?

Hint 7

Parkinson's Dz

At higher doses, it can treat depression - by affecting MAO-A as well

Front 8

Which one of the following would best treat depression with insomnia? 1. Amitriptyline 2. Phenylzine 3. Venlafaxine 4. Duloxetine

Back 8

Amitriptyline
- TCA

One of the primary side effects of TCAs is sedation.
Venlafaxine and Duloxetine are SNRIs and do cause some sedation but to a lesser extent than TCAs

Front 9

SSRIs?

Back 9

Citalopram - Celexa
Fluoxetine - Prozac
Paroxetine - Paxil
Sertraline - Zoloft
Escitalopram - Lexapro

Front 10

Akathesia - restless state - is associated with what antidepressant?

Back 10

Fluoxetine
-- SSRI

Front 11

_ cause increased concentration of clozapine and may precipitate seizures

Back 11

SSRIs

Hint 11

Citalopram (Celexa®-G)
Fluoxetine (Prozag®-G)
Paroxetine (Paxil®-G)
Sertraline (Zoloft®)
Escitalopram (Lexapro®)

Front 12

Restlessness, muscle twitches, hyperreflexia, sweating, and tremor are the manifestations for...

Back 12

Serotonin Syndrome

Caused by any two agents that increase serotonin levels (MAOIs, St. John's Wort, TCA, SSRIs, etc)

Front 13

Has an active metabolite that increases it's half life to 7-10 days

Back 13

Fluoxetine
- and SSRI

Front 14

First line choice for depression?

Back 14

SSRIs


Citalopram (Celexa®-G)
Fluoxetine (Prozag®-G)
Paroxetine (Paxil®-G)
Sertraline (Zoloft®)
Escitalopram (Lexapro®)

Front 15

DoC for a depressed patient who has trouble with daytime drowsiness?

Back 15

Fluoxetine
- the most stimulating of the SSRIs

SEs?

Hint 15

Akathesia

Also...Nausea/Vomiting, Sexual dysfunctions, Headache

Front 16

Antidepressant that have relatively low sexual side effects and no weight gain?

Back 16

Buproprion (Wellbutrin, Zyban)
- atypical, blocks reuptake of NE

Front 17

5HT1d Antagonist?

Back 17

Nefazodone
- Atypical Antidepressant
Leads to an increase in serotonin

Front 18

Antidepressant that has relatively low sexual side effects, but causes weight gain?

Back 18

Mirtazapine
- atypical - antagonist at presynaptic alpha AR receptors --> increases NE

Side effects other than weight gain?

Hint 18

agranulocytosis, serotonin syndrome

Front 19

How would you treat Malignant Hyperthermia, induced by succinylcholine?

Back 19

Dantrolene

Front 20

Of the MAOI's, which one is most associated with hepatotoxicity?

Back 20

Phenylzine

(the other MAOIs are Selegiline and Trancypromine)

Front 21

first choice agent to prevent the recurrence of bipolar depression?

Back 21

Lithium
(Note carbamazapine and valproic acid - anticonvulsants are accepted alternatives)
MOA

Hint 21

inhibits formation of inositol, which prevents phosphoylation of GSK. Ultimately it prevents apoptosis (?)

Front 22

What happens if a patient who is on Lithium for bipolar disorder starts taking thiazide diruretics?

Back 22

This decreases the excretion of Li (increases Na excretion increases Li [] ) --> TOXICITY

What are some side effects you should expect when a patient first starts on Lithium?

Hint 22

Polydipsia and polyuria

Nephrogenic Diabetes Insipidus

Front 23

Your patient who is on Lithium for bipolar disorder wants to get pregnant. What drug(s) should you switch her to?

Back 23

Carbamazepine or Valproic Acid
(anticonvulsants)

What Congenital abnormality is a/w lithium use?

Hint 23

Ebsteins anomaly (defect in tricuspid valve)

Front 24

If a patient has generalized anxiety disorder, what are the FDA approved agents to treat this?

Back 24

Venlafaxine (SNRI)

Escitalopram, Paroxetine (SSRIs)

Potential SEs?

--> Antidepressant are considered first line for long term therapy

Hint 24

gi distress, sexual disturbance, bruxisism, jitteriness, increased BP at higher doses, etc

Front 25

What are the FDA approved drugs to treat acute anxiety or panic symptoms?

Back 25

Clonazepam/Alprazolam (Benzos)

Say you're patient is on one of these and they forgot to tell the UC Dr who prescribed them erythromycin for a URI. They then are brought into the ER with impaired coordination, dizziness, and start seizing. How do you treat this presumptive benzo overdose?

Hint 25

Flumazenil - a competitive antagonist of the benzo receptor

(Benzos except for o Lorazepam/Oxazepam are metabolized by P450, so inhibitors such as macrolides, azoles, grapefruit make it more likely to OD)

Front 26

What are side effects of Benzodiazepines when used in pregnancy? Does it differ depending on what trimester they are used in?

Back 26

Avoid use in first trimester because they are associated with cleft palate, third trimester they should not used because they are associated with floppy baby syndrome

What are the preferred drugs in pregnancy for GAD?

Hint 26

SSRIs and
Buspirone - a 5HT1a agonist
---- this treats GAD without causing motor impairment or sedation, and is safely used in pregnancy

Front 27

Used to treat short term insomnia ( and MOA)

Back 27

Zaleplon or Zolpidem

(BZ agonists...think about it: benzodiazpines increase GABAergic (inhibitory) signaling by opening up Cl- channels and causing hyperpolarization)

SEs?

Hint 27

Headache and dizziness.
Zaleplon may cause back and chest pain, migraines, anticholinergic GI effects, (Zolpidem doesn’t have these, but may cause confusion and ataxia)

Front 28

Which one of the drugs will bind directly bind to the gaba site in high doses?

Back 28

Barbituates!

Front 29

What do you use to treat the Symptoms of an acute panic attack?

Back 29

Beta Blockers

(these are used to treat the tachycardia, palpitations, nausea, vomiting, etc)

Understand the difference between benzodiazepines. Benzos are prescribed to people who have been diagnosed with GAD for their attacks, Beta blockers are used in acute situations to control the symptoms.

Front 30

If you're patient is in respiratory depression, would you want to use a strong or weak opioid to minimize the respiratory depression?

Back 30

weak

Front 31

Patient presents with Pinpoint pupils, constipation, urinary retention, pruritis, N/V. How do you treat?

Back 31

Naloxone - this is describing an Opioid Overdose

What is the oral version of an opioid antagonist?

Hint 31

Naltrexone

patient get's no euphoric effect when they take heroine so it acts as a negative reinforcement

Front 32

How do you treat Post herpetic neuralglia:

Back 32

Gabapentin (anticonvulsant)

What about trigemical neuralgia?

Hint 32

Carbamezapine is DOC

(prototype antiepileptic drug – knocks out Na and Ca channels).

Front 33

With regards to the Opioid receptors, what effects are caused by Mu?

Kappa?

Back 33

(act on Gi receptors --> inhibitory --> decreased pain perception)
Mu”REAP”: responsible for respiratory depression, euphoria, analgesia, and physical dependence

Kappa “SAM”: responsible for sedation, analgesia (smaller role), and miosis

What are the three primary sites of action for the opioid analgesic effects?

Hint 33

Spinal Cord

Thalamus and limbic system

Brainstem

Front 34

What is the drug combination of choice for migraines? (and MOA)

Back 34

NSAIDs and triptans
- agonist at 5HT1D receptor and vasoconstrict cranial arteries, reducing migraine pain

What situations are triptans CI in?

Hint 34

CI in pregnancy and gangrene

Front 35

A patient who drops dead after taking Codeine for a cough likely had what problem?

Back 35

They didn't have 2D6,

Codeine undergoes demethylation by 2D6, some patients genetically don't have this enzyme and can't metabolize it.

Front 36

Patient who has developed traveler’s diarrhea, and needs to maintain cognition should be treated with ... (and MOA)

Back 36

Loperamide - considered a weak opioid agonist, but only has GI effects, no CNS

What if the patient needs to sleep?

Hint 36

Diphenoxylate

Front 37

What are the mixed acting opioid agonists/antagonists, and what are these used for?

Back 37

Pentazocine and Nalbuphine - used to treat heroine and opioid addicts

Front 38

What opioid is often used during Labor and Delivery, because it is a strong agonist, but has a short duration therefore is unlikely to accumulate and cause fetal respiratory depression? (and MOA)

Back 38

Meperidine
- demethylized to normeperidine, strong opioid agonist

What are the side effects?

Hint 38

Excess accumulation of Normeperidine causes SEIZURES (lowers threshold), inhibits serotonin so can cause SEROTONIN SYNDROME, and has antimuscarinic effects leading to BRADYCARDIA

Front 39

A 12 yo girl is brought in by her mom because she has been spacing out and staring for a few minutes at a time. What is this seizure called, and what do you expect to see on an EEG?

Back 39

Absence Seizures (petit mal)
---> "Spike and Wave" rhythmic discharge

What are some of the antiepileptic drugs used in this scenario? (and MOA)

Hint 39

T type CA channel blocker

Ethosuximide, Valproic Acid

Front 40

What are some important side effects of anti-epileptics (as a class)

Back 40

CNS Effects
Hepatotoxicity
Hypersensitivity reactions (SJ syndrome

Others such as GI sx should disappear within a few weeks

Hint 40

(all induce microsomal enzymes except Valproic acid, which also causes hepatotoxicity but is greatest for patients under 2 yo and can be fatal within months)

Front 41

The only use for this drug is for monotherapy in absence seizures - particularly in children.

(and MOA)

Back 41

Ethosuximide
---> Inhibits T type Calcium channels


SE?

Hint 41

Weight LOSS, gi distress

Front 42

1st line in tonic clonic seizures and partial seizures but NOT useful in absence seizures.

Also used in seizures with known etiology such as Reye's , after head trauma, or during seizure

(and MOA)

Back 42

Phenytoin - VG sodium channel blocker (note: this is also describing Carbamazepine)

Metabolism is saturable, if the dosing rate exceeds elimination capacity, the plasma levels quickly reach toxic levels (narrow therapeutic index). What are some dose related SEs?
SE a/w chronic use?

Hint 42

Dose related: Nystagmus, blurred vision (>100), and levels >150 patient will experience paradoxical increase in seizure frequency

Chronic: Gingival hyperplasia, hirsutism,
Also hyperglycemia, and osteomalacia

Front 43

What are the uses of Carbamazepine?

Back 43

(VG Na blocker)
1st line in tonic clonic seizures and partial seizures but NOT useful in absence seizures. May also be used for trigeminal and glosspharyngeal neuralgia,

SE?

Hint 43

SJ Syndrome!! (B1502 allele)
Fluid retention and associated hyponatremia

Undergoes autometabolism - ie an inducer of it's own metabolism. When you first start a patient on it, each dose has less and less of a half life. Therefore, significant dosage adjustments are made in the first week

Front 44

An anti-epileptic that Undergoes autometabolism - ie an inducer of it's own metabolism. When you first start a patient on it, each dose has less and less of a half life. Therefore, significant dosage adjustments are made in the first week ?

Back 44

Carpamazepine
(VG sodium channel blocker)
SE?

Hint 44

SJ syndrome

Front 45

DoC for treatment of acute febrile seizures in children
(and MOA)

Back 45

Phenobarbital (works on GABAa receptors to prolong Cl- channel opening)

What is a special note about it's metabolism?

Hint 45

VERY powerful inducer of CYP enzymes

Front 46

What are the 3 benzodiazepines that are also used to treat seizures?

Back 46

Diazepam, Lorazepam, and Clonazepam.
- Act at the GABAa receptor to increase Cl-

Specifically, what type of seizures are these useful in?

Hint 46

Diazepam and Loraz: Acute situations: Status Epilepticus and febrile seizures

Clonazepam is used for long term tx of certain types of seuziures that are resistant to other AEDs (like absence seizures refractory to etho or valproate), also Lennox-Gastaut syndrome

Front 47

Your 14 yo patient who has absence seizures appears to be refractory to treatment by Ethosuximide or Valproic acid. What would be your next DoC?

Back 47

Clonazepam - benzo, acts at GABAa

Front 48

What is the immediate treatment for a patient who is brought into the ER with status epilepticus?

Back 48

Diazepam or Lorazepam (benzos)
Once it's controlled, you switch them to ...

What if it doesn't get controlled with the benzos??

Hint 48

Phenytoin or Fosphenytoin (VG Na channel blockers)


not controlled? Add on Phenobarbital. If that still doesn't work, give anesthesia to knock the person out

Front 49

Zonisamide is a Newer Antiepileptic drug approved in patients over 12. What type of patients is this CI in?

Back 49

Those with sulfonamide allergies

What is the main side effect in adults?

Hint 49

Kidney Stones

Front 50

50 year old dx with Parkinson's disease is put on a drug that combines carbidopa with levodopa. What is the MOA of carbidopa in this case?

Back 50

inhibits the metabolism of levodopa in peripheral tissues

Front 51

Which one of the following drugs can be used as an antiemetic in a pt w Parkinson?

Back 51

Ondesetron (5-H3 antagonist)- only w/ Apomorphine do not use because they both cause hypotension. DO not use D2 r

Front 52

COMT inhibitors?

What are these used for?

Back 52

Tolcapone, Entacapone

These are used in Parkinson's

they block peripheral conversion of LDOPA to 3O methyldopa

Which is preferred, and why?

Hint 52

Entacapone is more preferred because tolcapone has a longer DOA and a higher incidence of hepatotoxicity

Front 53

You are on a surgical rotation and a patient who has had Parkinson's for 10 years has to undergo heart surgery for a valve replacement. What anti-Parkinson drug was this patient likely on?

Back 53

Pergolide (DA Agonist)

- withdrawn from the market in 2007 because of Cardiac problems

Front 54

Which DA agonist is approved for rescue therapy of "off" episodes

Back 54

Apomorphine

What side effects is this most famous for and how do you treat?

Hint 54

Nausea and vomiting, pretreat with an antiemetic (trimethobenzamide)

Front 55

What is the DoC for a younger patient newly diagnosed with parkinsons?

Back 55

DA agonist such as Pramiprexole
--> this as opposed to Levodopa since LD only has a few active years that it can be used.

SE?

Hint 55

Hallucinations, somnolence

Front 56

DoC for acute symptoms of schizophrenia?
(and MOA)

Back 56

Haloperidol
-Typical Antipsychotic, D2 blocker

Also Olanzapine - Atypical 5HT2a and D2, takes care of neg sx too.

Side Effects of Haloperidol?

Hint 56

Haloperidol: Extrapyramidal Symptoms (nigrostriatal pathway):
-acute dystonia, akathesia, parkinsons like sx
HyperProlactinemia (tuberoinfundibular pathway)

With chronic use: tardive dyskinesia

Don't forget the sx that are common to all antipsychotics (and antidepressants): alpha 1 blockade - orthostatic hypotension, h1=sedation, muscarinic = dry mouth, etc. Also Neuroleptic malignant Syndrome - similar to malignant hyperthermia

Front 57

Typical Anti psychotics mainly target what receptor(s)?

Atypical antipsychotics?

Back 57

Typical - D2 receptor blocker
(these cause EPS side effects): haloperidol

Atypical - 5HT2a, D2 blockers
(these cause less EPS but more weight gain): -pines and -dones - clozapine, olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole

Which one of these is more effective against + symptoms vs (-) symptoms?

Hint 57

Typicals are more efficient against +

Atypicals are more efficient against (-).

Front 58

What antipsychotic is DoC in treatment resistant groups?

Back 58

Clozapine
- atypical Antipsychotic, used only if the patient is unresponsive to other drugs, has tardive dyskinesia, or severe EPS

What SE?

Hint 58

Seizures - lower threshold
Fatal Neutropenia
HYPERsalivation (unique)

(also ses that are common to all antipsychotics: alpha 1 blockade - orthostatic hypotension, h1=sedation, muscarinic = dry mouth, etc. Also Neuroleptic malignant Syndrome - similar to malignant hyperthermia

Front 59

Usually, typical antipsychotics are bothersome and not preferred to atypicals. If a patient has to be on a typical antipsychotic, which drug is the DoC?

Back 59

Haloperidol
(D2 blocker)

What feature makes this drug favorable?

Hint 59

Very Little sedation (does not block H1 receptors)

Front 60

Commonly used to treat psychoses in Parkinson’s disease ? and MOA

Back 60

Quetiapine
- atypical antipsychotic - blocks D1, D4 & 5HT2A receptors and NOT D2 receptors

SE?

Hint 60

Sedation, postural hypotension

Front 61

1st antipsychotic to have a black box warning, what is the drug and what is the warning>

Back 61

Aripiprazole
(atypical - blocks 5HT2A it is a partial agonist at 5HT1A & D2 receptors)

--Dementia patients who take this have and increased chance of death

What is the only advantage this drug has?

Hint 61

minimal weight gain

Front 62

Atypical antipsychotics?
MOA?

Back 62

Clozapine (Clozaril)
Olanzapine (Zyprexa)
Risperidone (Risperdal)
Quetiapine (Seroquel)
Ziprasidone (Geodon)
Aripiprazole (Abilify)

-- these are particularly useful in treating negative symptoms

Block 5HT2A receptors
Block D2 family of receptors

SE?

Hint 62

weight gain
(minimal hyperprolactinemia and EPS compared to typicals - ie haloperidol)

Front 63

Typical Antipsychotics are known for their EPS symptoms and Hyperprolactinemia.

What pathways are affected to cause these SEs?

Back 63

EPS: nigrostriatal

Hyperprolactinemia: tuberoinfundibular

Front 64

Depolarizing NMJ blocker?

Back 64

Succinycholine

SE?

Hint 64

Muscle pain postoperatively due to damaged mm fibers during fasciculations.
Hyperkalemia

Malignant hyperthermia - treat with dantrolene

Front 65

Chronic Spasmolytic that acts as a GABAb agonist, increasing K conductiance to hyperpolarize the cells.

Back 65

Baclofen

Front 66

What are the drugs used for chronic spasms?

Back 66

Diazepam
Baclofen (GABAb)
Tizanidine
Dantrolene (blocks ryanodine receptors in skeletal mm)
Botulinum toxin
Gabaptentin (spasms in MS)

Front 67

Which chronic spasmolytic can cause hypotension?

Back 67

Tizanidine (alpha2 agonist activity)

Front 68

Agents used for acute muscle spasms?

Back 68

cyclobenzaparine,
metazolone
carisoprodol
methocarbamol

Front 69

Short acting Nondepolarizing NMJ Blockers?

Back 69

(skeletal mm relaxants)
Mivacurium
Atracurium

What is potentially dangeous regaurding the metanolism of Atracurium?:

Hint 69

Hofmann elimination - rapid spontaneous breakdown independent of renal or liver breaks it down into Laundanosine which can cause seizures with long term use

Front 70

Intermediate acting Non-depolarizing blockers?

Back 70

(skeletal mm relaxants)
Cistacurium
Vecuronium
Rocuronium

Front 71

Long acting Non depolarizing nicotinic blockers

Back 71

(skeletal mm relaxants)
Doxacurium
Pancuronium
Tubcurarine