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clinical pharmacologyu Flashcards

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1
Q

what is the active metabolite of diazepam

A

Desmethyldiazepam

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2
Q

what is the active metabolite of dothiepin

A

Dothiepinsulfoxide

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3
Q

what is the active metabolite of fluxotine

A

norafloxetine

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4
Q

what is 9-Hydroxyrisperidone an active metabolite of?

A

Risperidone

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5
Q

what is desipramine an active metabolite of?

A

Imipramine

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6
Q

is Nortriptyline a metabolite or a drug? If so, what is the other one associated?

A

it is an active metabolite
its paired with Amitriptyline (drug)

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7
Q

Which is the active metabolite -codeine or morphine?

A

morphine is the active metabolite
codeine is the drug

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8
Q

list 5 medications used in ADHD

A
  1. Dexamfetamine / lisdexamfetamine (prodrug of Dex)
    2.Methylphenidate
    3.Atomoxetine
  2. Guanfacine
  3. Clonidine
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9
Q

which of the ADHD medications are stimulants

A
  1. Dexamfetamine / lisdexamfetamine
    2.Methylphenidate
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10
Q

which of the adhd medications are non stimulant

A

3.Atomoxetine
4. Guanfacine
5. Clonidine

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11
Q

what is occassionally used off licence for adhd and its mechanism

A

Bupropion
dopamine reuptake inhibitor

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11
Q

where are therapeutic effects for adhd known to take place

A

prefrontal cortex
noradrenaline&raquo_space;

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12
Q

which mechanism do each ADHD medication work by

A
  1. Increases synaptic levels of dopamine and noradrenaline- dexamfetamine/lidexamfetamine/methylphenidate
  2. Increasing NA levels in the synaptic cleft -
    highly selective norepinephrine reuptake inhibitot
    - atomoxetine
  3. Selective agonist of α2A-adrenergic receptors. Binds to postsynaptic α2A-adrenergic receptors, mimicking NA - guanfacine
  4. clonidine- agonist of α2-adrenergic receptors, mimic NA
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13
Q

Dexamfetamine / lisdexamfetamine contraindications

A

Significant cardiovascular disorders
Cerebrovascular disorders
Use of MAO inhibitors
Hx of drug abuse
Hyperthyroidism
Glaucoma
Porphyria **
Gilles de la Tourette syndrome or similar dystonias **
Pregnancy and lactation **
Psychosis or bipolar I (if not well controlled)
Anorexia
Significant suicidal ideation

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14
Q

s/e of dexamfetamine /lisadexamfetamine

interactions

A

decreased appetite
- reduced weight gain and weight loss during prolonged use in children
- insomnia
- nervousness

minimal impact with CYP

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15
Q

contraindications for methylphenidate

A

significant cardiovascular disorders
Cerebrovascular disorders
Glaucoma
Phaechromocytoma
Use of MAO inhibitors
Psychosis or bipolar I (if not well controlled)
Anorexia
Significant suicidal ideation
Hyperthyroidism or thyrotoxicosis

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16
Q

methylphenidate s/e and interactions

A

decreased appetite
- insomnia
- nervousness
- headache
- nausea
- dry mouth

nil - No significant effect on CYP

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17
Q

s/e and interactions of Atomoxetine

A

appetite decreased
- headache
- somnolence
- abdominal pain (includes epigastric discomfort)
- vomiting
- nausea
- blood pressure increased
- heart rate increased

metabolised by CYP2D6

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18
Q

CI, s/e and interactions of guanfacine

A

contradindications nil
S/E
somnolence (40%)
- headache (27%)
- fatigue (18%)
- abdominal pain (12%)

Interaction with
Can increase levels of valproic acid
metablised by CYP3A4/5

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19
Q

clonidine
CI
S/E
Interaction

A

ci Severe bradyarrhythmia resulting from either sick-sinus syndrome or AV block of 2nd or 3rd degree

s/e
dizziness
- sedation
- orthostatic hypotension
- dry mouth

No significant effect on CYP
Much of the drug excreted unchanged in urine

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20
Q

what is important to note about methylphenidate ?

A

relative constitution of various brands of methylphenidate vary
immediate and long acting

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21
Q

Which ADHD medication can have more impact on BP
which receptor?

A

. Clonidine has more effect on α2B receptors which are located on blood vessels and this can lead to more pronounced effects on blood pressure compared to guanfacine.

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22
Q

how does methylphenidate work specifically?

A

it blocks DAT and NAT receptors (dopamine transporter) and noradrealine transporter to increase levels in synaptic cleft

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23
Q

how does dexamfetamine differ to methylphenidate?

A

has same mechanism as methylphenidate but ALSO
blocks SERT (serotonin transporter).

  1. promotes release of monoamines from the presynaptic neurone into the synapse
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24
what can ADR be split into? what percentage of which>
Type A (80%) and B A pharmcological B(Idiosyncratic Reactions) Type B reactions cannot be predicted from the known pharmacology of the drug. They are often unrelated to the drug's intended pharmacological action. Allergic reactions fall under this category. Type B reactions can be more challenging to anticipate or prevent.
25
what is a key category for type B reactions?
Allergies
26
what classification/criteria is used for allergies?
Gell and Coomb
27
What are the subtypes for allergies
type I -IgE - immediate hypersensitivity reactions Type II (Cytotoxic) - Type III immmune complexes Type IV cell mediated
28
examples of each immune reaction and times
pe I -IgE - immediate hypersensitivity reactions - anpylhaxis seconds minutes after Type II (Cytotoxic) - drug-induced haemolytic anaemia or thrombocytopenia. The timing of these reactions is variable. Type III immmune complexes serum sickness or drug-induced lupus. These usually occur 1 to 3 weeks after exposure. Type IV cell mediated -days or even weeks later . Contact dermatitis and some forms of drug-induced hepatitis are examples.
29
mechanism of subtype for immune mechanism
type I -IgE - immediate hypersensitivity reactions mediated by the IgE antibody. They can lead to symptoms such as hives, itching, swelling, and in severe cases, anaphylaxis. minutes after exposure Type II (Cytotoxic) - actiation of complement proteins and destruction of cells by antibodies Type III immmune complexes, which are antigen-antibody aggregates, can form and deposit in tissues, leading to inflammatio Type IV cell mediated These reactions are mediated by T cells and occur over a delayed period, often days to weeks after exposure to the drug.
30
what is Agomelatine ? receptors?
agonist at melatonin M1 and M2 receptors and as an antagonist at 5HT2C receptors. used to treat depression
31
what is the mechanism of agomelatine ?
The melatonin effects appear to promote sleep whereas the 5HT2C antagonism leads to the release of dopamine and norepinephrine in the frontal cortex. Interestingly serotonin levels appear not to be affected.
32
what is an An agonist?
compound that binds to a receptor and produces the biological response.
33
what is a partial agonist ?
produces the biological response but cannot produce 100% of the response even at very high doses
34
what is an antagonist
Antagonists block the effects of agonists. They have no effect on their own. Competitive antagonists bind to the receptor in a reversible way without affecting a biological response. They make the agonist look less potent.
35
what is a Inverse agonists ?
they have opposite effects from those of full agonists. They are not the same as antagonists, which block the effect of both agonists and inverse agonists.
36
how are TCA divided?
1. first generation tricyclics (tertiary amines), 2. second generation tricyclics (secondary amines).
37
what is importantto know about secondary amine?
The secondary amines are said to have a lower side effect profile and to act primarily on noradrenaline. The tertiary amines are thought to boost serotonin and noradrenaline.
38
which antidepressants are advised for diabetic pt?
SRRI SSRIs are first line (most data support fluoxetine)
39
which antidepressants should eb avoided in diabetes?
TCAs and MAOIs should be avoided
40
what percantage of patients experience discontinuation symptoms after sotpping SSRIs
20%
41
SSRI discontination symptoms
Flu-like symptoms Anxiety and suicidality Mood and concentration changes Stomach upset (nausea, diarrhoea) Dizziness Insomnia Vivid dreams Irritability Crying spells Sensory symptoms (e.g. sensations resembling electric shocks in the arms, legs, or head) advised to wean down 5 days is average time to experience symptoms advised to recommence and wean
42
which two SSRI have worse discontinuation sx
depends on dose too but aroxetine (SSRI) Venlafaxine (SNRI)
43
TCA discontinuation sx which two commonly associated
ommon symptoms include:- Flu-like symptoms Insomnia Excessive dreaming Amitriptyline Imipramine
44
MAOI discontinuation includes
Agitation/ irritability Ataxia Movement disorders Insomnia Vivid dreams
45
who is at high risk of discontinuation sx
Those at highest risk include: those on antidepressants with shorter half lives those who have been taking antidepressants for 8 weeks or longer (longer duration of treatment) those using higher doses those who developed anxiety symptoms at the start of antidepressant therapy those receiving other centrally active medications (e.g. antihypertensives, antihistamines, antipsychotics) younger people those who have experienced discontinuation symptoms before those also prescribed antipsychotics
46
which antidepressant does not have discontinuation symptoms
Agomelatine
47
which antidepressant is best for bulimia?
Fluoxetine
48
which antidepressant is best for PTSD
Paroxetine sertraline
49
which antidepressant is best for OCD
Escitalopram, Fluoxetine, Fluvoxamine, Paroxetine, Sertraline, Clomipramine
50
which antidepressant is best for Phobic and obsessional states
Phobic and obsessional states Clomipramine
51
which antidepressant is best for Adjunctive treatment of cataplexy associated with narcolepsy
Clomipramine
52
which antidepressant is best for nocturnal enuresis in kids
Amitriptyline, Imipramine, Nortriptyline
53
which antidepressant is best for Panic disorder and agoraphobia
Citalopram, Escitalopram, Sertraline, Paroxetine, Venlafaxine
54
which antidepressant is best for Generalised anxiety disorder and social phobia
GAD Escitalopram, Paroxetine, Duloxetine, Venlafaxine PHOBIA Escitalopram, Paroxetine, Sertraline, Moclobemide, Venlafaxine
55
minimum dose needed
20 mg / day- citalopram, Fluvoxamine, paroxetine 25mg/day -Agomelatine 30mg/day (15?) - mirtazpine 50mg - sertraline , Fluvoxamine 60 mg / day - Duloxetine 75mg -venlafaxine 150mg - trazadone 300mg -Moclobemide
56
which antidepressants do not affect sexual desire, arousal and orgasm
Agomelatine Moclobemide
57
which antidepressant affects sexual desire only
mirtazpine
58
which antidepressant affects arousal only
Vortioxetine
59
which antidepressant affects exual desire, arousal and orgasm
MOAI TCA SSRI VENLAFAXINE
60
sexual dysfunction and duloxetine and trazadone
desire, orgasm ++ arousal + ( duloxetine) orgasm and arousal + (trazadone)
61
common side affects of TCA
drowsiness dry mouth blurred vision constipation urinary retention
62
rarer s/e of TCA
Arrhythmias and ECG changes Black tongue Tremor Altered LFT's Paralytic ileus Neuroleptic malignant syndrome
63
word for black hairy tongue
(aka lingua villosa nigra)
64
most dangerous TCA in overdose
the most dangerous in overdose
65
what is low dose amitrpylline used for
neuropathic pain and the prophylaxis of headache (both tension and migraine)
66
which antidepressants more likely to cause weight gain
tricyclic antidepressants (TCAs) and perhaps monoamine oxidase inhibitors (MAOIs) may be more likely to cause weight gain than the selective serotonin reuptake inhibitors (SSRIs)
67
which TCA has a lower lower incidence of toxicity in overdose
lofepramine
68
what affect does mirtazpine have on weight
increase
69
which ssri increase weight gain
Paroxetine may be more likely to cause weight gain than the other SSRIs during long-term treatment
70
which antidepressant less likely to cause weight gain in long run
bupropion and nefazodone may be less likely to cause weight gain than the SSRIs in the long term
71
what is histamine
a neurotransmitter a substance that potentiates the inflammatory and immune responses of the body and regulates physiological function in the gut.
72
example of h2 receptor antihistamines
Cimetidine Ranitidine
73
example of h1 receptor antihistamines
Diphenhydramine Cetirizine Chlorpheniramine Cyclizine Hydroxyzine
74
1st gen antihistamines
Diphenhydramine Promethazine Hydroxyzine Chlorpheniramine Cyproheptadine Cyclizine Ketotifen ability to cross the blood brain barrier and their anticholinergic properties e first generation antihistamines tend to be sedating
75
2nd gen antihistamines
Loratadine Cetirizine Fexofenadine Acrivastine
76
what are anti-histamine useful for and why?
anticholinergic effects make then useful for managing extrapyramidal side effects (as antipsychotics block dopamine in the nigrostriatal pathway which results in excess acetylcholine which is thought to underlie extrapyramidal side effects).
77
1st generation antihistamine CI
Benign prostatic hyperplasia Angle-closure glaucoma Pyloric stenosis (in infants)
78

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