A: 29-33 Flashcards
Tricyclic
Tetracyclic
Unicyclic
MAO-inhib
- Tricyclic-
- Amitriptyline
- Clomipramine. Ami tripped the line, כלום לא ישנה את הפרייד שלי
- Imipramine
- Tetracyclic-
- Maprotiline. מה פרו? טיל!
- Unicyclic- Bupropion. Bu!prop!yon!
- MAO-inhib-
- Moclobemide MAoclobemide
- 5HT-2 inhibitor
- Trazodone
AC-M-B-M-T
CAM Be with Me
Trazodone is a 5HT inhibitor
Maprotiline MOA
- tetracyclic antidepresant
NET>>SERT
Maprotiline indication
- tetracyclic antidepressant : inhibit NET
- Major depression
- Sedation
overdoses of maprolitine can cause seizures (it lowers convulsive threshold)
Maprotiline SE
- seizures
- cardiotoxic
in case of overdose
Bupropion, structure , mechanism , indication
- Heterocyclic antidepressant
- mechanism is unknown—the drug has NO effect on either 5-HT or NE receptors or on amine transporters
1. Major depresion
2. smoking cessation
Tricyclic MOA
Like SNRI
Inhibit NET and SERT
Tricyclic SE are due to
Muscarinic, a1, H1 blockade (sedation and weight gain)
TCA indication
- Major depression
- chronic pain
- OCD ( clomipramine)
SSRI’s
Work in the brain so CSF!
Sir. Tralin! the Chita-lo-pram has Flu so EXIT!
Sertraline
Citalopram
Fluoxetine
T1/2 +15 hrs
SSRI’s indication
Major depressive disorder
Anxiety
OCD
PMDD (Premenstrual Dysphoric Disorder )
PTSD
Bolemia
SSRI’s metabolism
Inhibitors of CYP450
half life +15 hrs
- cyp2d6 , CYP3A4 inhibition ( Fluxetine, paroxetine)
- CYP1A2 : fluvoxamine
SSRI SE
sexual dysfunction
agitation
insomnia
headache
nausea
anxiety
citalopram - QT prolongation
SNRTI’s
בוא נלך לאכול בוואן לאפה ונשתה רבוקס דלוקס
Venlafexine
Reboxetine(Only NET)
Duloxetine
SNRI indication
- Major depression
- chronic pain
- fibromyalgia
- menopausal symptoms
SNRI SE
- Anticholinergic
- sedation
- hypertension (Venlafaxine)
NE-R antag. for antidepression
Mitrazapine is an a2 antagonist (block presynaptic a2 r)
5-HT antagonist for antidepression
Agomelatine is also agonist at MT1/2 r in suprachiasmatic nucleus + 5-HT 2/3 antagonist
- major depressive disorder
- 5-HT2 antagonist
-
Trazodone
- ind: 1. Major depression
- hypnosis (trazodone)
- short T1/2
-
Trazodone
Trazodone indication
- 5-HT2 antagonist
- Major depression
- hypnosis
Trazodone SE
- 5-HT2 blocker
- sedation
- modest alpha and H1 blockade
agomelatine
Agomelatine is
- agonist at MT1/2 r in suprachiasmatic nucleus
- 5-HT 2/3 antagonist
major depressive disorder
SE: weight gain
MAO-I indication and SE
- Major depression unresponsive to other drugs
- SE:
- Hypotension
- insomnia
- Serotonin syndrome if combined with SSRI
- Hypetension with tyramine and sympathomimetics
MAO-I
drugs and mechanism
- Moclobemide (MAO-A selective inhibitor) - antidepressant
- Selegilime (more active as MAO-B inhibitor)- anti-parkinsons
MAO-I drug interactions
Hypertension with tyramine and sympathomimmetics
serotonin syndrome if combined with SSRI
very long T1/2
MAO A metabolises?
MAO-B metabolises?
- MAO-A
- NE
- 5-HT
- Tyramine
- MAO-B
- Dopamine
Mirtazapine mechanism, indication
- a-2 selective blocker > increased amine release
- 5-HT2, 5-HT3 inhibitor
- H1-r inhibition
- major depressive disorders
- sedation
SE: weight gain , sedation
Lithium indication
- Bipolar affective disorder
- prevents modd swings (prophylaxis)
lithium mechanism of action
- Uncertain, it inhibit several enzymes involved in recycling of neuronal membrane phosphoinositides.;
- supresses IP3 , DAG signalling (interfere with Gq)
- inhibits GSK-3
- NO action on ANS receptors or CNS receptors
- NO sedation
renal elimination
T1/2 = 20hrs
Lithium SE
Reversible hypothyroidism
DI (bcs Li+ antag ADH-R) - renal dysfunction
Tremor
Ataxia
Nephrogenic DI
Edema
CI: pregnancy (neural tube defect)
- Narrow therapeutic window - monitor blood levels
- clearance is decreased by
- thiazides
- NSAIDS
Valproate MOA
- Inhibits of voltage-gated Na channels in neuronal membranes
- Inhibits T-type Ca channel (in thalamic neuron)
- increased brain levels of GABA by Inhibiting GABA-aminotransaminase which normally terminates GABA action. ( for the Tx. of the manic phase)
- Increases neuronal K+ permeability (neuronal membrane hyperpolarization.
Blocks high-frequency firing
Valproate indication
- Generalized tonic-clonic
- focal
- myoclonic seizure
- Bipolar disorder: competes with lithium as first choice in bipolar (acute phase)
Valproate phase 2 (conjugation)
valproate SE
- hepatic dysfunction,
- weight gain,
- and inhibition of drug metabolism (valproic acid)
- teratogenic
- pancreatitis
- GI distress
- thrombocytopenia - monitor PLT
Carbamazapine MOA
Extends the inactivated phase of Na+ Ch. on the axon so no AP
- Blocks axonal VG- Na channel
- decreases glutamate release
- prevents seizure propagation, but NOT initiation
Carbamazapine indication
- Generalized tonic-clonic
- focal seizures
- Bipolar disorder (acute and prophylaxis)
- trigeminal neuralgia (1st line)
oral, P450 metabolism
Carbamazepine forms active metabolite (phase I);
Carbamazapine SE
- Hematotoxicity and
- induction of drug metabolism (carbamazepine)
- CNS dep (dose-dep)
- diplopia
- SJS
- SIADH
- Aplastic anemia
- teratogenic
Anti epileptic which are NOT broad spectrum
Phenytoin- Inhib. of axonal NaCh
Carbamazapine- -“-
Vigabatrin- Inhibits GABA metab.
Phenobarbital- GABA NaCh open longer
Very Privet Cards Play
Privet bcs it is narrow spectrum
T1/2 of SSRI vs SNRI
- SSRI (citalopram, fluoxetine, sertraline) : 15+ hrs
- SNRI (Venlafaxine, desvenlafaxine, duloxetine) : 10+ hrs
Tonic-clonic seizure (grand mal) characteristerics and drugs which can be used
- Bilateral symmetric convulsive movements of all limbs with impairment of conciousness
- Tonic phase (<1min) : loss of consciousness , muscle stiffening
- Clonic phase ( 2-3 min) : jerking of body muscles
- Valproic acid
- phenytoin
- Carbamazepine
- Phenobarbital
- Lamotrigine
- Leve-tiracetam
partial seizure /focal
characteristerics and drugs which can be used
- Involves focal cortical region at onset
- simple partial seizure > no loss of conciousness
- complex partial seizure > loss of conviousness/impaired awareness
- Phenytoin
- Carbamazepine
- Gabapentin
- pregabalin
- vigabatrin
- Valproate
- lamotrigine
- levetiracetam
Generalized absence seizure “petit mal”
characteristerics and drugs which can be used
- Impaired concioussness
- starts with unresponsiveness to external verbal stimuli ( sometimes with eye blinking and head nodding)
- Ethosuximide (minimal sedation; preffered)
- valproate (minimal sedation; preffered)
- clonazepam
- lamotrigine
- levetiracetam
myoclonic seizure characteristics and drugs
- Consist of sudden, brief movement which are not ass w/ any disturbance of conciousness
- Clonazepam
- Lamotrigine
- valproic acid
status epilepticus characteristics and drugs
- continuous seizure lasting more than 5 mins OR >2 seizures without full recovery of conciousness between any of them
- life-threatening, medical emergency
- Lorazepam
- Diazepam
- Phenytoin (may cause cardiotoxicity due to solvent propylene glycol) , fosphenytoin (water-soluble)
- Phenobarbital
- In severe cases which DONT respond to anti-convulsant , general anesthesia may be used
A32 antiepileptics used in partial seizures and generalised tonic-myoclonic seizures
EXCEPT broad spectrum agents
-
Phenobarbital
- Enhances GABA-A r responses
- ind:
- generalised tonic-clonic seizure
- focal seizures
- SE: sedation, ataxia
-
Phenytoin
- blocks VG Na ch
- IND:
- generalised tonic-clonic
- focal seizures
- SE: ataxia, diplopia, gingival hyperplasia, hisutism, neuropathy
-
carbamazepine
- blocks VG Na+ ch
- decreases Glutamate release
- IND:
- generalised tonic-clonic
- focal seizures
- SE: Ataxia, diplopia, headache, nausea
-
vigabatrine (GABA derivative)
- inhibit GABA-transaminase ( inhibited by valproate too)
- IND:
- focal seizures ONLY
- renal elimination
- SE: drowsy, dizzy, psychosis, ocular effect
- IND:
- inhibit GABA-transaminase ( inhibited by valproate too)
Broad spectrum antiepileptics
-
Ethusoximide-
- inhibits Thalamic Ca2+ Ch. (T-type) Alot of Ethous to work on the Thelamic
- IND:
- absence seizure
- long T1/2
- SE: GI distress. dizzy, headache
-
Lamotrigine-
- Inhibits Na axonal channels.
- Inhibits Ca +2 channel
- decreases neuronal glutamate release למה לא?TRIGGED?
- IND:
- generalised tonic-clonic
- focal seizure
- myoclonic
- absence seizure
- SE: dizzy, diplopia, headache, rash
-
Levetiracetam-
- Binds synaptic protein SV2A , modifies GABA and Glutamate release. לב לתירצה סתם
- IND:
- Generalised tonic-clonic
- focal seizure
- SE: dizzy, nervous, depression, seizure
-
Valproate-
- inhibits Thalamic Ca2+ Ch (blocks high freq firing)
- IND:
- generalised tonic-clonic
- focal
- myoclonic
- SE: nausea , alopecia, weight gain, teratogenic
-
Clonazepam-
- enhance GABA-A
- IND:
- Absence seizure
- myoclonic seizure
- infantile spasms
- SE: sedation
-
Diazepam-
- enhance GABA-A
- IND: status epilepticus
VECLLD
Levetiracetam-
moa
- Binds synaptic protein SV2A ,
- modifies GABA
- modifies Glutamate release. לב לתירצה סתם
levetiracetam IND
IND:
- Generalised tonic-clonic
- focal seizure
levetiracetam SE
- dizzy,
- nervous,
- depression,
- seizure
Ethusoximide-
MOA, indication
- inhibits Thalamic Ca2+ Ch. (T-type) Alot of Ethous to work on the Thelamic
- IND: absence seizure
- long T1/2
SE ethusoximide
- GI distress.
- dizzy,
- headache
Lamotrigine-
MOA
- Inhibits Na axonal channels.
- Inhibits Ca +2 channel
- decreases neuronal glutamate release למה לא?TRIGGED?
Lamotrigine IND
- IND:
- generalised tonic-clonic
- focal seizure
- myoclonic
- absence seizure
LAMOTRIGINE SE
SE:
- dizzy,
- diplopia,
- headache,
- rash
Valproate-
MOA
inhibits Thalamic Ca2+ Ch (blocks high freq firing)
Valproate ind
IND:
- generalised tonic-clonic
- focal
- myoclonic
valproate SE
- nausea ,
- alopecia,
- weight gain,
- teratogenic
Diazepam-
moa, ind
enhance GABA-A
IND: status epilepticus
Clonazepam-
moa, ind, SE
- enhance GABA-A
- IND:
- Absence seizure
- myoclonic seizure
- infantile spasms
SE: sedation
