Antidepressants and antianxiety Flashcards
Biologic hypothesis of depression
________
_____________ theory
_______ – _______
Genetics
Monoamine theory
Hormonal – Neuroendocrine
Monoamine theory of depression
Due to a deficit in the monoamine transmitters –___________ and _________ in some regions of the brain
norepinephrine and serotonin
Monoamine theory of depression
Supportive evidence
•The monoamines play a role in _________
•Antidepressants act by facilitating __________
•Drugs that ______________
arousal and mood
noradrenergic and serotonergic transmission
block monoaminergic synthesis and storage
Examples of drugs that block monoaminergic synthesis and storage
???
reserpine, alpha-methyltyrosine, methyldopa
Monoamine hypothesis
Research evidence against monoamine hypothesis
Although levels of norepinephrine and serotonin are increased immediately,
therapeutic effects are seen at _____
Likely a trophic factor
2-3 weeks
Neuroendocrine
Depressed patients have a (low or high?) level of cortisol and does not (rise or fall?) when _______________________ test is carried out
This is thought to occur as a result of a deficiency of _____________ to the __________
High; fall
dexamethasone suppression
noradrenergic and serotonergic input
hypothalamus
Neuroendocrine
Hypothalamus secretes corticotrophin releasing hormone (CRH) which stimulates the pituitary gland to produce ACTH and this further stimulates cortisol
________ level is also increased
_______ hormone is reduced
Prolactin
Growth
Other hypothesis of depression
Low levels of brain derived __________ factors
Increased cortical _______ levels
____________________
neurotrophic
glutamate
Neurodegeneration
What antidepressants are?
Drugs used to treat depression- by ___________
Mainly (inhibitory or excitatory?) to increase monoaminergic transmission
elevate mood
excitatory
Classification of antidepressants
Reversible monoamine oxidase inhibitor (RIMA) –_________,_______
Selective serotonin reuptake inhibitor –_____,_______,_______,_______,________,_______,________
moclobemide, clorgyline
fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram, dapoxetine
Classification of antidepressants
____________(RIMA)
_________ antidepressant
Selective ____________ inhibitor
Serotonin and ———————-
______ antidepressants
Reversible monoamine oxidase inhibitor
Tricyclic antidepressant
Selective serotonin reuptake inhibitor
Serotonin and noradrenaline reuptake inhibitors
Atypical
Atypical antidepressants – ______,_______,_________,______,______,_____________
trazodone, mianserin, mirtazapine, bupropion, atomoxetine, tianepine
Serotonin and noradrenaline reuptake inhibitors – ________,_______
venlafaxine, duloxetine
Monoamine oxidase
MAO – a ___________ enzyme , ________________________ of amines like adrenaline, noradrenaline , dopamine, serotonin
mitochondrial
oxidative deamination
Monoamine oxidase
Two type
MAO –A – Present in _____ nerve endings, _________ and human ______. Preference for _______ and _______
MAO –B –Present in _________ areas in the ________ and ________. Preferentially deaminates _________.
adrenergic; intestinal mucosa; placenta
5-HT and NA.
serotonergic
brain and platelets
phenylethylamine
Monoamine oxidase
___________ is degraded equally by MAO –A and MAO-B
Dopamine
Monoamine oxidase inhibitors
Irreversible – _______ ,———,_______
Reversible
MAO –A __________,__________
MAO –B _____________
phenelzine, tranylcypromine, isocarboxazid
Moclobemide, Clorgyline
Selegiline
Selegiline is not used in depression.
T/F
T
Antidepressant only at high doses
Irreversible monoamine oxidase inhibitors
(Selective or Non-selective?)
No longer in use because of _________ and _____________
Non-selective
drug drug interactions and drug –food interaction (cheese) etc
Irreversible monoamine oxidase inhibitors
Inhibits the enzyme irreversibly – action lasts about ________ until new enzymes are synthesised
3 weeks
Irreversible monoamine oxidase inhibitors
Cheese reaction – reaction with ______, some ___,________,_________ extracts.
Release (small or large?) amount of _____ from adrenergic neurons
Leading to dangerous ______________
cheese
beers, wine and yeast
Large ; noradrenaline
hypertensive crises
Reversible inhibitors of MAO –A
Moclobemide –
•reversible and (selective or non-selective?)
•Duration of action is ______
•Indicated for ____________ depression
•Less adverse reaction – can be displaced by _______ from enzyme binding site
•Adverse effects – nausea , dizziness
•Drug interactions – rare, caution when prescribing with _____________ and _________
selective; 1-2 days
mild to moderate
tyramine
other antidepressants and pethidine
Tricyclic antidepressants
Uptake blocker – inhibit ————- and _________ at the ——— and ——— membranes.
Prolonged accumulation of the monoamines lead to the _______ of the inhibitory presynaptic ______,_______, and _________ auto receptors.
There is also an adaptive change in the postsynaptic receptors leading to _________ noradrenergic and serotonergic transmission.
norepinephrine and serotonin transporter
neuronal and platelet ; desensitization
alpha 2, 5HT1A and 5HT1D
enhanced
Tricyclic antidepressants
Inhibits other receptors
_____ adrenergic,
________ receptors
histaminergic effects H__
5-HT__ and 5-HT___
D___ -
Alpha
Muscarinic
H1
5-HT1 and 5-HT2
D2 -
Pharmacological actions of Tricyclic antidepressants
CNS - Clinical effects seen within _________ of treatment because there is upregulation of the ________ and _______ receptors in the CNS.
Improved ______ pattern.
2 -3 weeks
serotonin and Noradrenaline
sleep
Pharmacokinetics of Tricyclic antidepressants
(Poorly or Well?) but (slowly or rapidly?) absorbed
(Mildly or Highly?) plasma and tissue protein bound
(Small or Large?) vol. of distribution
Metabolism – hepatic microsomal enzyme
Well; slowly
Highly ; Large
Pharmacokinetics of Tricyclic antidepressants
Imipramine is ________ to an (active or inactive?) metabolite called __________
Amitriptyline is similarly ________ to __________
(Short or Long?) half-lives
demethylated
Active ; desipramine
demethylated; nortriyptyline
Long
Adverse effects of Tricyclic antidepressant
________,___________,__________
_____eased appetite and weight ____
Sedation, mental confusion , weakness
Incr; gain
Adverse effects of Tricyclic antidepressant
Anticholinergic effects –____ mouth, bad taste , (constipation or Diarrhea?) , urinary _______, ________ vision
Lowers ______ threshold and causes ______ in cases of overdose. – less likely with _______ and ________
dry; constipation; retention; blurred
seizure; seizures
amitriptyline and imipramine.
Adverse effects of of Tricyclic antidepressant
CVS –
______cardia
ECG changes and cardiac arrhythmias – disturbs ___________ especially in the ______
postural _________ –_____ blockade and inhibition of ________
Tachy
intraventricular conductance
elderly
hypotension; alpha 1
CVS reflexes
Tolerance and dependence of Tricyclic Antidepressant
Tolerance to ________ and ________
Dependence (low or high?).
anticholinergic and hypotensive
Low
Drug interactions of Tricyclic antidepressants
Potentiates the action of _____________
Abolishes the antihypertensive effect of _______ and _______ by preventing their _____________________
Potentiates _____ depressants
_____ ,________ displaces TCA from their binding sites causing toxic effects
direct sympathomimetics
guanethidine and clonidine; transport into adrenergic nerves
CNS
Phenytoin , aspirin
Selective serotonin reuptake inhibitors
Selectively inhibit membrane associated serotonin transporter
T/F
T
Selective serotonin reuptake inhibitors
(More or Less ?) efficacy compared to TCA especially in severe depression
(more or less?) tolerable
(more or less?) sedative, cognitive, psychomotor effects
______ anticholinergic and alpha adrenergic effects
_____ effect on seizure threshold.
Less; more
Less
no
no
———- are the First line drugs in depression
Selective serotonin reuptake inhibitors
Selective serotonin reuptake inhibitors is also used for other conditions like anxiety, phobia and obsessive and compulsive disorders
T/F
T
Adverse effects of Selective serotonin reuptake inhibitors
Nausea – _____________ stimulation
Nervousness, restlessness, headache, (constipation or diarrhoea?)
Epistaxis, ecchymosis and increased NSAIDS associated blood loss – impairment of _________
5HT3 receptor
diarrhoea
platelet function
Adverse effects of Selective serotonin reuptake inhibitors
_______– 5HT3 receptor stimulation
Nervousness, restlessness, headache, diarrhoea
_______,_________ and increased ____________ associated blood loss – impairment of platelet function
Nausea
Epistaxis, ecchymosis
NSAIDS
Drug interactions - SSRI
SSRI are enzyme (inducers or inhibitors ?) leading to ______ levels of TCAs, haloperidol, clozapine, warfarin
Serotonin syndrome – when a patients takes a ____________________ with SSRI.
______,_________,________, and _______
inhibitors
elevated
serotonergic drug
Restlessness, agitation, sweating and convulsions
Serotonin norepinephrine reuptake inhibitors
Include _______ and _________
More specific for ________ and ________ transporter
venlafaxine and duloxetine
serotonin and norepinephrine
Serotonin norepinephrine reuptake inhibitors
More likely to cause ____tension compared to SSRI
hypo
Which is more likely to cause hypotension
SNRI or SSRI
Serotonin norepinephrine reuptake inhibitors are More likely to cause hypotension compared to SSRI
Atypical antidepressants
Includes _______,__________,__________
________ mechanism of action
trazodone, mianserin, bupropion
Variable
Uses of antidepressants
Endogenous and major ________
___________ disorders
______ disorders
____________ pain
______________ disorder
______
Migraine
Pruritus
depression; Obsessive compulsive
Anxiety ; Neuropathic
Attention deficit hyperactivity
Enuresis
Antianxiety drugs
Anxiety disorders are _________ _______ characterized by _______,_________ and concerns or fear about some defined or undefined future threat
unpleasant emotional statesm
uneasiness, discomfort
Antianxiety drugs
Drugs used to treat these disorders have ___________ effects
CNS depressive
Classification of antianxiety drugs
List 5
Benzodiazepines
Azapirone
Sedative antihistamines
Beta blocker
Selective serotonin reuptake inhibitors
Classification of antianxiety drugs
Benzodiazepines – ______,_____,_____,____, and _____
Azapirone –_______,_____,______
Sedative antihistamines- _________
Beta blocker – _________
Selective serotonin reuptake inhibitors
diazepam, alprazolam, lorazepam, oxazepam and chlordiazepoxide
Buspirone, Gebiprone, Ispapirone
Hydroxyzine
Propanolol
Buspirone
No ______ action
(More Or Less?) likely to cause sedation , cognitive impairment
No ________ or ____________ effect
(More or Less ?) likely to cause tolerance or dependence
GABA
Less
anticonvulsant or muscle relation
Less
Versus
SSRI
_______,________
_______,_________,_______,_________
SNRI
_______,_____,———-,_________,_________
Fluoxetine, Paroxetine, Sertraline, Citalopram, Escitalopram, Fluvoxamine
Venlafaxine Duloxetine Desvenlafaxine
Levomilnacipran Milnacipran
TCA :Secondary amines
List 4
TCA: Tertiary amines
List 5
MAOl
List 5
– Nortriptyline
– Desipramine
– Protriptyline
-Amoxapine
Amitriptyline Imipramine Trimipramine Clomipramine Doxepin
Tranylcypromine Phenelzine Moclobemide Selegiline Isocarboxazid
SARI
________,__________
Atypical
______,———,_______,———-,_______
Trazodone
Nefazodone
Mirtazapine Bupropion Vilazodone Vortioxetine Varenicline
MECHANISM OF ACTION
SSRI
__________ of ____________ in synaptic cleft
– Thus ______ease in _______ levels
SNRI
_________ of ___________________ in synaptic cleft
– Thus ____eased ___________________________ levels
Inhibition of serotonin reuptake
Increased ; SEROTONIN
Inhibition of norepinephrine reuptake reuptake
Increased; SEROTONIN and NOREPINEPHRINE
Mechanism of Action
TCA
–________ of __________ in synaptic cleft
– Thus _____ease in _______ and _______ levels
MAOI
– (Selective or Nonselective?) inhibition of _________________
– Thus ____eased ______ and _____eased accumulation of, ————-,______,———
Inhibition; norepinephrine reuptake
Increase in SEROTONIN and NOREPINEPHRINE
Nonselective ; monoamine oxidase enzyme
Decreased; breakdown; increased
NOREPINEPHRINE, SEROTONIN, epinephrine
Mechanism of action
SARI and Atypical
– Block _________________ receptors leading to ____eased activity of _______________ receptors in the CNS
postsynaptic type 2 serotonin
Increased
SEROTONIN of type 1 receptors
Mechanism of action
– SARI
(Weak or Strong?) inhibition of ___________ leading to ______ease in ______ levels
– Atypical
(Selective or Non-selective?) ______________ causing ___eased ________________________________
Weak; serotonin reuptake
Increase; SEROTONIN
Selective; α2-adrenergic antagonist
Increased; SEROTONIN and NOREPINEPHRINE release
Adverse effects
SSRI
–_________ disturbance
– ______ dysfunction
–________
– _______
– ____________ syndrome
Gastrointestinal
Sexual
Insomnia
Sedation
Serotonin
Serotonin syndrome occurs when SSRIs are _____________________
combined with MAOI
Serotonin syndrome
List the characteristics
S hivering
H yperreflexia
I ncreased temperature
V ital signs instability
E ncephalopathy
R estlessness
S weating
ADVERSE EFFECT
SNRI
– Similar side effect to _____
– _____tension
– ____lytics
– Insomnia
– Hyper______
SSRI
Hyper
Anxio
lipidemia
ADVERSE EFFECT
TCA
–____________/________ ————
– _____toxicity
– Tremor
– Weight _____
– _____pyrexia
– ______ dysfunction
–_____________ effects
Orthostatic/ Postural hypotension
Cardio
Gain
Hyper ; Sexual
Anti-muscarinic
ADVERSE EFFECT
MAOI
– ________ ——-tension
– _____toxicity
– Insomnia
–_____ dysfunction
–______— syndrome
– __________ crisis
Orthostatic hypo
Hepato
Sexual; Serotonin
Hypertensive
Hypertensive crisis can occur when you combine MAOI with _______ containing foods Also called __________ interaction
TYRAMINE
WINE-CHEESE
ADVERSE EFFECT
Atypical
– Mirtazapine
Increase ________
Weight _____
– Bupropion
Seizure
Weight _____
___________ DYSFUNCTION
appetite; gain
loss; NO SEXUAL
ADVERSE EFFECT
SARI
–________
–_______
– Orthostatic hypotension
– Nausea
Priapism
Sedation
