Pharmacology Flashcards
(391 cards)
1
Q
Who discovered Reserpine and when?
A
Kline in 1954
2
Q
Who discovered Lithium and when?
A
In 1949, Cade in Australia discovered the use of lithium compounds in mania
3
Q
Who discovered chlorpromazine and when?
A
Delay and Deniker’s team, and Charpentier 1950-1952
4
Q
What was the first true antidepressant and when it discovered?
A
The first true antidepressant was discovered in 1952 Iproniazid (anti-TB treatment)
Iproniazid is a monoamine oxidase inhibitor.
5
Q
Who discovered chlordiazepoxide and when?
A
Leo Sternbach in 1954
6
Q
Who discovered the first TCA (what was it?) and when?
A
Kuhn discovered imipramine in 1958
7
Q
Who synthesised butyrophenone haloperidol from pethidine and when?
A
In 1958, Janssen synthesised butyrophenone haloperidol from pethidine.
8
Q
Who proposed the cheese reaction for MAOI associated hypertension?
A
1963 Cheese reaction was proposed to be the mechanism for MAOI associated
hypertension by Blackwell.
9
Q
Who synthesised the first atypical agent?
A
Janssen synthesized an atypical agent RISPERIDONE in 1989
10
Q
What was the first SSRI? Who synthesised it?
A
Carlssen synthesized purpose made SSRI Zimeldine – but this was withdrawn due to the
incidence of hypersensitivity syndrome and demyelinating disease that followed its use
11
Q
What was the first SSRI on the market?
A
Fluoxetine
12
Q
Who discovered Clozpaine and when?
A
Kane et al. 1988 rediscovered clozapine via a multicentre randomized design comparing
chlorpromazine vs. clozapine in ‘treatment resistant’ schizophrenia. 4% showed response
to chlorpromazine while 30% showed response to clozapine
13
Q
Aliphatic phenothiazines is the chemical class of which drugs?
A
Chlorpromazine
Promazine
Triflupromazine
14
Q
Piperidine derivatives is the chemical class of which drug?
A
Thioridazine
15
Q
Piperazine derivatives is the chemical class of which drugs?
A
Trifluoperazine
Fluphenazine
Perphenazine
Thioridazine
16
Q
Butyrophenones is the chemical class of which drugs?
A
Haloperidol
Droperidol
17
Q
Thioxanthenes is the chemical class of which drugs?
A
Thiothixene
Flupenthixol
Zuclopenthixol
18
Q
Dihydroindoles is the chemical class of which drug?
A
Molindone
19
Q
Diphenylbutylpiperidine is the chemical class of which drug?
A
Pimozide (long t1/2)
20
Q
Dibenzoxapine is the chemical class of which drug?
A
Loxapine
21
Q
Benzisoxazole derivative is the chemical class of which drug?
A
Risperidone
22
Q
Substituted benzamides is the chemical class of which drugs?
A
Amisulpride, Sulpiride
23
Q
Dibenzodiazepine is the chemical class of which drug?
A
Clozapine
24
Q
Dibenzothiazepine is the chemical class of which drug?
A
Quetiapine
25
Thienobenzodiazepine is the chemical class of which drug?
Olanzapine
26
Benzisothiazole is the chemical class of which drug?
Ziprasidone
27
Arylpiperidylindole (quinolone) is the chemical class of which drug?
Aripiprazole
28
Tertiary amines is the is the chemical class of which drugs?
Imipramine, Amitriptyline, Clomipramine, Dosulepin,
Trimipramine (also Venlafaxine)
The tertiary amines are thought to boost serotonin and noradrenaline.
29
Properties of secondary amines vs. tertiary amines?
more potent; less sedating; more noradrenergic, less antihistaminic or anticholinergic than tertiary
The secondary amines are said to have a lower side effect profile and to act primarily on noradrenaline
30
Secondary amines is the chemical class of which drugs?
Desipramine, Amoxapine, Nortriptyline and Protriptyline
| also Duloxetine
31
Hydrazine derivatives is the chemical class of which drugs?
Phenelzine, Isocarboxazid (greater hepatotoxicity than
| Tranylcypromine, a non hydrazine compound)
32
Aminoketone is the chemical class of which drug?
Bupropion
33
SSRIs
Citalopram, Paroxetine, Fluoxetine, Sertraline
and Fluvoxamine, S enantiomer of citalopram
- Escitalopram
34
SNRIs - serotonin and noradrenaline
| reuptake inhibitor
Venlafaxine, Milnacipran, Duloxetine,
| Sibutramine
35
NaSSA – Noradrenergic and specific
| serotonergic antagonist
Mirtazapine and
| Mianseri
36
NARI - Noradrenaline reuptake inhibitor
Reboxetine
37
NDDI - Noradrenaline Dopamine DisInhibitor -
Agomelatine
38
DARI – Dopamine reuptake inhibitor
| *norepinephrine and dopamine re-uptake inhibitor
Bupropion
39
RIMA – reversible inhibitor of Monoamine A
| oxidase
Moclobemide
| brofaromine
40
SARI – serotonin antagonist and reuptake
| inhibitors
Nefazodone, Trazodone
41
What is the novel agent Xanomeline?
A treatment option for schizophrenia. It acts via M1/M4
agonism
*also showed a trend toward improving cognitive function in Alzheimer’s
42
Which condition has ketamine been used in?
(NMDA) receptor antagonist that has shown
| rapid antidepressant effects in treatment-resistant depression
43
What is the novel agent Pomaglumetad methionil?
a metabotropic glutamate receptor 2/3
agonist,
used to treat positive and negative symptom as an add-on therapy in schizophrenia.
44
What is deliquescence?
sensitivity to environmental moisture to such an extent that drugs turn from crystalline states into pastes or
liquids if left in contact with moist air even for a
short period of time.
45
Which drug has deliquescence?
Sodium valproate
46
What's an active placebo?
An ‘active placebo’ has some activity inherently, but not against the treated condition.
47
What's a nocebo?
When a substance administered for placebo effects produces prominent side-effects, it is
known as a ‘nocebo’.
48
What's placebo sag?
Placebo sag is a term used to refer to decrease in placebo effect with repeated or chronic
administration of placebo drugs.
49
What is efficacy paradox?
The placebo effect may be disproportionately large for non-blinded therapies potentially
resulting in what has been called the efficacy paradox.
50
What do placebos work best for?
Placebos work best for pain, disorders of autonomic sensation, and disorders of factors
under neurohumoral control e.g. nausea, blood pressure, and bronchial asthma.
51
Placebo rates in psychiatric disorders
Depressive illness: 25 - 60%
Mania: up to 25%
Schizophrenia: 25 - 50%
Panic disorder: up to 70%
52
What colour tablets do anxiety and depression respond better to?
Anxiety symptoms responded better to green tablets and depressive symptoms responded
better to yellow tablets.
53
Why do placebos work?
1. Natural remission theory
2. Measurement regression (to the mean)
3. Conditioning theory
4. Endogenous opioids
54
Which medication form is associated with increased response?
Capsules
55
Phases before drug approval
1. Preclinical Animal Studies - Mutagenicity, carcinogenicity and organ system toxicity are studies at this phase
2. Human trials – volunteers phase 1 (safety) - tolerability and pharmacokinetics of the
drug are ascertained
3. Human trials – patients phase 2 (effectiveness) - RCTs
4. Human trials – patients phase 3 (superiority or equivalence to standard looking for
comparative efficacy and tolerance profile). Extensive double blind RCT to determine how well does it work and what are the common side effects.
5. Human trials – post-marketing surveillance phase 4:
56
Adverse effects detected by post marketing surveillance of psychotropic medications:
1. Nefazadone
2. Droperidol, Thioridazine
3. Sertindole
4. Thalidomide (analgesic)
5. Nomifensine
6. Zimeldine
7. Remoxipiride(sulpiride group)
8. Mianserin
9. MAOIs
10. Clozapine
1. Nefazadone - Hepatotoxicity
2. Droperidol, Thioridazine - prolonged QTc
3. Sertindole - Sudden cardiac death
4. Thalidomide (analgesic) - Phocomelia
5. Nomifensine - Hepatotoxicity
6. Zimeldine - Hypersensitivity reactions and Guillain-Barre syndrome
7. Remoxipiride(sulpiride group) - Aplastic Anaemia
8. Mianserin - Blood dyscrasias
9. MAOIs - Cheese reactions
10. Clozapine - Agranulocytosis
57
Non-adherence rates for antipsychotics?
40–60%
*Nonadherent patients with schizophrenia are 3.5 x
more likely to relapse within 2 years
58
Non-adherence rates for mood stabilisers?
18–56%
59
Non-adherence rates for antidepressants?
30–97% (median 63%)
60
Factors that reduce adherence
```
•Asymptomatic stage of illness
•Cognitive deficits
•Comorbidity – alcohol and substance
misuse
•Devaluation of medication effects by
the physician
•Fear of side-effects.
•High frequency of daily doses
•Homelessness
•Lack of insight (most common cause)
•Long duration of illness (chronic
diseases)
•Oral formulations have poorer
adherence than depots
•Past history of non-adherence
•Polypharmacy
•Prophylactic or maintenance treatments
•Psychopathology of hostility,
suspiciousness and disorganization
```
61
Factors that improve adherence
* Presence of family support
* Liquid or sublingual forms
* High enthusiasm fromclinican
* Good patient-clinician relationship
* Continued access to clincian
62
Factors that have no influence on adherence
* Age at illness onset
* Age at first hospitalization
* Sex
* Socioeconomic status,
* Marital status
* Ethnicity
63
What are the four main categories of the health belief model of adherence?
1. Benefits
2. Costs
3. Susceptibility
4. Secondary benefits of medication and adherence.
64
What are some methods of improving adherence?
```
Psychoeducational programmes:
Cognitive-based interventions
Behaviour-modification interventions
Motivational interviewing
Compliance therapy
```
65
What are pharmacokinetics?
the time course and disposition of drugs in the body (what the body does to the drug)
*affected by the method of administration
66
What processes are involved in pharmacokinetics?
ADME; Absorption, Distribution, Metabolism,
| and Elimination
67
Which factors affect the rate of absorption?
- The form of the drug
- The rate of blood flow at the site of administration
- Solubility of the drug which depends on the pH of the drug, size of particles in the formulation and the pKa of the drug (pKa is the pH at which precisely half of the drug is in its ionised form)
68
What is first-pass effect?
metabolism by liver and gut
| mucosa - drugs absorbed from the gut undergo extensive metabolism before entering the systemic circulation
69
What are the mechanisms of absorption of drugs from the GI tract?
1. Active transport 2. Passive
| diffusion (most common mechanism) 3. Pore filtration
70
Which factors influence absorption of drugs from GI tract?
Intestinal motility
Gastric emptying
Gastric and intestinal pH
Intestinal microflora e.g. Chlorpromazine is sulfated in the gut which reduces its absorption
Area available for absorption
Integrity of blood flow
Presence or absence of food (food delays gastric emptying)
71
What is dissolution rate dependent on?
1. Size of drug particle
2. Solubility of the drug
3. Properties of intestinal fluid (e.g. p H)
72
How quickly does absorption happen with IM administration?
10-30 minutes (avoids most of the first pass
| metabolism)
73
What factors influence the rate of absorption of drugs administered intramuscularly?
Blood flow and aqueous solubility.
Lipid soluble drugs are rapidly absorbed; drugs with a relative low molecular weight are better absorbed. Increased muscle blood flow e.g. after muscular exercise increases the rate of absorption
74
Which method of administration gives 100% bioavailability?
IV
75
Which factors affect permeation?
Lipophilicity
Concentration gradient - either simple or facilitated diffusion
Surface area and vascularity
76
Which is more water soluble the ionised or non-ionised form of a drug?
The ionized form is more water-soluble than the nonionized form
77
Is the renal clearance higher or lower for ionised drugs?
Renal clearance is higher for ionised drug (drug is "trapped" in the glomerular filtrate and does not get reabsorbed)
78
What is distribution of a drug?
to ‘where’ in the body it can be found.
Some drugs are confined to the body fluids only, but others accumulate in particular tissues.
*Distribution of a drug leads to a fall in
the plasma concentration (central to peripheral shift) and is most rapid after intravenous
administration
79
Which factors influence Drug distribution?
1. Hemodynamic factors - cardiac output, regional blood flow. Organs with the highest blood perfusions such as the brain, kidneys, and liver receive the highest distribution
2. Plasma protein binding
3. Permeability factors- higher the lipid solubility of the drug, the greater its rate of entry into cells
4. Blood-brain barrier
5. Blood- CSF barrier
80
What are the two compartments the body is divided
| into?
Central compartment - plasma
| Peripheral compartment - fat and other tissues, which vary with age, sex and weight.
81
Which drugs are highly protein bound?
95 - 99% --> diazepam, chlorpromazine, amitriptyline and imipramine
90 - 95% --> Phenytoin, valproate and clomipramine
82
What can occur with drugs that are highly protein bound?
They are prone to interactions mediated b ythis mechanism
e.g. Diazepam displaces phenytoin from plasma proteins, resulting in an increased plasma concentration of free phenytoin and an increased risk of adverse effects.
*The effects of protein displacement are usually not of clinical significance, as the metabolism of the affected drug increases in parallel with the free drug concentration.
83
What are the plasma proteins responsible for binding to drugs?
acidic drugs - albumin.
alkaline drugs - α1-acid glycoprotein
*most psychotropic drugs are basic
84
Which factors can affect the permeability of the BBB?
fever, head injury, hypoxia, hypercapnia, retroviruses, inflammation, vasculitis, hypertension, cerebral irradiation and aging
85
What determined the ability of a drug to pass blood brain barrier?
molecular size, lipid solubility and ionic status (Unionized molecules that are freely available and less protein bound are transported across the barrier)
86
Which areas lack BBB?
Circumventricular organs - subfornical organ, area postrema of the medulla and the median eminence.
87
What is bioavailability of a drug?
how much of an administered drug reaches its target - affected by absorption, distribution and elimination
88
What is metabolism of a drug?
process that renders drug less lipid-soluble and more water-soluble so that products are more easily excreted from the body
89
What happens during phase 1 of metabolism?
oxidation, reduction and hydrolysis
90
What happens during phase 2 of metabolism?
conjugation - to produce a water soluble conjugate
91
Where can conjugated drugs be excreted through?
renal excretion if relative molecular mass < 300
| bile excretion if relative molecular mass > 300
92
Most psychotherapeutic drugs are oxidized by which enzyme system?
Hepatic cytochrome P-450 enzyme system
93
Between 5and 10% of Caucasians lack which P-450 enzyme and are poor metabolisers of corresponding substrates?
CYP2D6
94
Up to 15-20% of East Asians are poor metabolisers of substrates of which P-450 enzymes?
CYP2C19
95
Which psychotropic medications are metabolised by CYP2D6?
All TCAs, fluoxetine, paroxetine, trazodone, nefazodone, valproate, antipsychotics, risperidone, carbamazepine
96
Which psychotropic medications inhibit CYP2D6?
Paroxetine, to some extent fluoxetine, antipsychotics, amitriptyline and clomipramine
97
Which psychotropic medications are metabolised by CYP3A4?
Clomipramine, fluvoxamine, mirtazapine, nefazodone, Carbamazepine, most benzodiazepines.
98
Which psychotropic medications stimulate CYP3A4?
Carbamazepine and barbiturates
99
Which psychotropic medications inhibit CYP3A4?
Calcium channel blockers, fluoxetine and nefazodone.
100
What does smoking do to CYP1A2?
Inhibits
101
What does Fluvoxamine do to plasma Clozapine concentrations?
Increases plasma clozapine concentrations (by inhibiting CYP system)
*Clozapine levels may be increased 10-fold by the addition of fluvoxamine, which can induce seizures.
102
What does Fluoxetine do to plasma TCA levels?
Fluoxetine increases plasma tricyclic antidepressants via 2D6 and 2C19
103
What does carbamazepine do to the plasma concentration of the oral contraceptive?
Decreases the plasma concentration of several drugs including contraceptive pills.
104
Which drugs undergo autoinduction?
Carbamazepine and phenobarbitone
105
How does carbamazepine undergo autoinduction?
Carbamazepine is metabolised by CYP2D6, synthesis of which in turn is induced by carbamazepine
As a result of this autoinduction, the rate of metabolism of carbamazepine (and other P450 substrates) gradually increases over the first several weeks of treatment.
106
Which enzyme do smoking and caffeine affect?
Smoking and caffeine affect glucuronidation reaction via UGT enzyme and CYP1A2
* caffeine competitively inhibits CYP1A2
* Polyaromatic Hydrocarbons (PAH)in cigarettes induce CYP1A2
107
What are aripiprazole and risperidone metabolised by?
CYP2D6 and CYP3A
108
What are Quetiapine and ziprasidone metabolised by?
mainly metabolized by CYP3A
109
What are Olanzapine and Clozapine metabolised by?
CYP1A2 and UGTs
110
What's the effect of caffeine on Clozapine/olanzapine?
increases levels
111
What's the effect of caffeine on Clozapine/olanzapine?
decreases levels
112
What are the major routes of drug excretion?
urine, faeces and bile
*may also be excreted in sweat, sebum, tears, saliva and breast milk
113
What are the factors that influence excretion?
- Increased age (decreases excretion)
- Reduction in renal blood flow e.g. dehydration
- Renal impairment leading to decreased renal function
- Alterations in re-absorption: urine pH
114
Which drugs undergo renal elimination without significant liver breakdown?
lithium, amisulpride, sulpiride, gabapentin, acamprosate and amantadine.
115
What's the half life of a drug?
The time taken for the plasma concentration of a drug to halve
116
What is first order kinetics?
a constant fraction of drug is cleared per unit time
(the higher the amounts of a drug present, the faster the elimination)
e.g. 100mg/ml (2hours) -> 50mg/ml (2hours) -> 25mg/ml (2hours) -> 12.5mg/ml
117
What is zero-order kinetics?
a constant amount, not a fraction, of the drug is cleared per unit time
e.g. 100mg (2hours) -> 80mg (2hours) -> 60mg (2hours) -> 40mg
118
How long does it take drug to reach the steady plasma level?
4-5 half lives
119
What is the median toxic dose?
dose at which 50% of patients experience a specific toxic effect
120
What is the median effective dose?
dose at which 50% of patients have a specified therapeutic effect.
121
What is the therapeutic index?
measure of the toxicity or safety of a drug
| ratio of the median toxic dose to median effective dose
122
Changes in body composition in the elderly?
Increase in total body fat
Decrease in total muscle mass (lean body mass)
Decrease in total body water
123
What's the effect of changes in body composition in the elderly?
Larger volume of distribution and longer half-life of lipophilic chemicals because of their increased sequestration in fat. e.g. benzodiazepines excretion is slower in the elderly
124
Changes in plasma protein in the elderly?
Decrease in plasma protein binding capacity
125
What's the effect of changes in plasma protein in the elderly?
15-25% decrease in protein binding due to higher proteinuria and lesser plasma protein synthesis by the liver.
126
Changes in the liver in the elderly?
Decreased hepatic blood flow occurs.
127
What's the effect of changes in the liver in the elderly?
After 80, CYP system declines.
128
Changes in the kidney in the elderly?
Decreases in renal blood flow have been approximated at 10% per decade beginning after the fourth decade - leads to reduced creatinine clearance and GFR.
129
What's the effect of changes in the kidney in the elderly?
More frequent toxicity of renally eliminated agents(e.g. lithium).
130
Changes in the GI tract in the elderly?
- GI blood flow is diminished
| - Gastric pH is increased as acidity drops
131
What's the effect of changes in the GI tract in the elderly?
- Slower but nearly equal absorption of oral administered drugs
- Decreased gastric first pass metabolism noted
A reduction in the gastric wall content of dopa decarboxylase leads to a 3-fold increase in the concentration of levodopa in the elderly
132
Changes in the brain receptors in the elderly?
- Decreased number of brain acetylcholine postsynaptic receptors
- choline acetyltransferase is diminished
- brain acetylcholinesterase decreased
133
What's the effect of changes in the brain receptors in the elderly?
Anticholinergic side effects more pronounced leading to increased frequency of delirium on polypharmacy.
134
Pharmacokinetic changes in neonates
- higher proportion of total body water and extracellular body water
- lower proportion of adipose tissue
- glomerular filtration rate is lower in those aged less than 3-5 months
- lower gastric acidity and have an increased gastric emptying time
- more permeable blood—brain barrier
- microsomal enzyme activity in the liver is lower in those than 2 months
- lower plasma concentration of albumin
135
Pharmacokinetic changes in pregnancy
- Delayed gastric emptying
- Decreased GIT motility
- Increased volume of distribution (5%)
- Decreased drug-binding capacity
- Decreased albumin level
- Induced liver metabolic pathway
- Increased GFR & renal clearance.
136
Pharmacokinetic changes in renal impairment (benzos)
- Benzodiazepines should be used with caution
- half-life of diazepam remains unchanged in end-stage renal disease, but its metabolite, desmethyldiazepam, may accumulate, causing excessive sedation
- The half-life of lorazepam is increased from 8–25 hours in healthy adults to 32–72 hours in end-stage renal disease
- At a low level of renal function, lorazepam dosage should be reduced by 50% to avoid excessive sedation
137
Pharmacokinetic changes in renal impairment (antidepressants)
- Imipramine and amitriptyline can be given at their usual dosage
- Dosage of fluoxetine and fluvoxamine does not have to be reduced
- Half normal dose is used for citalopram in patients with renal impairment or in elderly
- Half-life of paroxetine is increased with severe renal impairment, requiring dosage reduction
- Sertraline is not recommended in renal impairment
138
Pharmacokinetic changes in renal impairment (antipsychotics)
- Haloperidol does not require a dose reduction in renal impairment unless excessive sedation or hypotension occurs -Amisulpride is renally excreted almost exclusively so relatively contraindicated in renal failure
- Risperidone and its active metabolite 9-hydroxy-risperidone are substantially excreted in the urine so in renal impairment the elimination half-life is prolonged
139
Active metabolite of Imipramine
desipramine
140
Active metabolite of Amitriptyline
nortriptyline
141
Active metabolite of Trazodone, nefazodone
mCPP
142
Active metabolite of Fluoxetine
norfluoxetine
143
Active metabolite of Sertraline
desmethylsertraline
144
Which drugs inhibit TCA metabolism and therefore increase TCA plasma concentrations?
Quinidine, cimetidine, fluoxetine, paroxetine, phenothiazines, disulfiram, methylphenidate
145
Which drugs induce TCA metabolism and therefore decrease TCA plasma concentrations?
Smoking, phenytoin, carbamazepine, OC pills and barbiturates
146
What are the effects of TCAs on warfarin?
TCAs increase warfarin levels so there is a high risk of bleeding
147
What are the effects of TCAS on clonidine?
TCAs reduce clonidine levels and can cause Hypertensive crisis
148
What are the effects of TCAs on MOAIs?
- Synergistic serotonergic enhancement esp. with clomipramine
- TCAs reduce tyramine entry via monoamine reuptake channels
- There is a higher risk of serotonin syndrome but lower risk of cheese reaction
149
What are the effects of TCAS on ldopa?
TCAs reduce absorption of l-dopa and so lower l-dopa efficacy in Parkinsonism
150
What are the effects of TCAS on morphine?
Amitriptyline and clomipramine decrease the metabolism through UDP glucuronyl transferase interaction leading to increased opioid toxicity
151
What are the effects of TCAS on Phenothiazines?
Mutual inhibition of metabolism -> both antipsychotic and TCA levels increase
152
Which SSRI is the least protien bound?
Escitalopram (56%)
153
What's the half-life of norfluoxetine?
4–16 days
154
What's the half-life of fluoxetine?
4-6 days
155
Which SSRIs do not have active metabolites?
Fluvoxamine and paroxetine
156
Which is the most selective SSRI?
Citalopram
157
Which is the most potent SSRI?
Paroxetine
158
What's the relationship between fluvoxamine and diazepam?
Fluvoxamine reduces the clearance of both diazepam and its active metabolite
159
CYP450 profile of fluoxetine
metabolised by 2D6
| Inhibits 2C19, 2D6.
160
Which drugs does fluoxetine interact with?
All TCAs especially Clomipramine and Imipramine (both 2C19 & 2D6),
Citalopram, Sertraline, Moclobemide, Duloxetine, Mirtazapine Venlafaxine
*levels of these drugs are increased
161
CYP450 profile of paroxetine
Metabolised by 2D6
| Inhibits 2D6
162
Which drugs does paroxetine interact with?
All TCAs
Citalopram, Fluoxetine, Fluvoxamine, Duloxetine, Mirtazapine, Venlafaxine
*levels of these drugs are increased
163
CYP450 profile of fluvoxamine
Inhibits 1A2, 2C19, 3A4
164
Which drugs does fluvoxamine interact with?
Clomipramine, Doxepine, Trimipramine, Duloxetine, Mirtazapine, Citalopram, Escitalopram, Sertraline, Trazodone
theophylline (via CYP1A2 inhibition)
*levels of these drugs are increased
165
CYP450 profile of duloxetine
Inhibits 2D6
166
Which drugs does duloxetine interact with?
All TCAs
Citalopram, Fluoxetine, Paroxetine, Fluvoxamine, Mirtazapine, Venlafaxine.
*levels of these drugs are increased
167
CYP450 profile of Desipramine and Clomipramine
Inhibits 2D6
168
Which drugs do Desipramine and Clomipramine interact with?
All TCAs
Citalopram, Fluoxetine, Fluvoxamine, Duloxetine, Mirtazapine, Venlafaxine
*levels of these drugs are increased
169
What's the half life of:
1. paroxetine?
2. fluvoxamine?
3. sertraline?
4. citalopram?
5. fluoxetine?
6. Venlafaxine?
7. Duloxetine?
8. Buspirone?
1. 10 hours
2. 11 hours
3. 26 hours
4. 33 hours
5. 1.9 days
6. 3.5 hours
7. 8 hours
8. 2-11 hours (given TDS)
170
Which drug when used with MAOIs may cause a fatal excitatory reaction?
Pethidine/meperidine
171
What's the effect of st john's wort on CYP?
inducer
172
which enzymes mediate Mirtazapine metabolism?
CYP2D6 and CYP3A4
173
which enzymes mediate Agomelatine metabolism?
CYP1A2 (90%) and CYP2C9 (10%)
174
What is the effect of loss of sodium on lithium levels?
loss of body sodium can increase lithium reabsorption as compensation in error leading to toxicity.
175
Which agents increase lithium levels?
ACE inhibitors
Fluoxetine
NSAIDs
Thiazide diuretics
176
Which agents decrease lithium levels?
```
Osmotic diuretics
Caffeine
Aminophylline
Theobromine, Theophylline
Carbonic anhydrase inhibitors
```
177
Which agents can cause toxicity of lithium at normal levels?
```
Carbamazepine
Atracurium
Haloperidol, clozapine
Calcium channel blockers
metronidazole
```
178
What happens to the bioavailability of gabapentin as the dose increases?
It decreases
179
Kinetics of Flupenthixol decanoate
Peak levels 3–7 days post IM.
| Apparent half-life of 17 days
180
Kinetics of Fluphenazine decanoate
Peak levels are 24h post-IM.
| The apparent half-life of 7-14 days. Smoking reduces levels
181
Kinetics of Haloperidol decanoate
Peak levels 7 days post IM.
| The apparent half-life of 3 weeks. Smoking reduces levels
182
Kinetics of Perphenazine decanoate
Peak levels 1-7 days post IM.
| Apparent half-life of 2 weeks
183
Kinetics of Pipotiazine palmitate
Peak levels 1-2 weeks post IM.
| Apparent half-life of 2 weeks
184
Kinetics of Zuclopenthixol decanoate
Peak levels 1 week post IM.
| The apparent half-life of 7-20 days.
185
What's the half life of:
1. Risperidone?
2. Quetiapine?
3. Aripiprazole?
1. 15 hours
2. 6 hours
3. 75 hours - 96 hours (~3 days) --> active metabolite dihydroaripiprazole - 94 hours
186
What's the major active metabolite of risperidone?
Paliperidone
187
What's the active metabolite formed when risperidone undergoes first-pass hepatic metabolism?
9-hydroxyrisperidone (by CYP2D6)
188
Aripiprazole is metabolised by which enzymes?
CYP 3A4 and CYP2D6
189
What % of Aripiprazole is protein bound?
99%
190
What % of Risperidone is protein bound?
90%
191
How long should deport risperidone be supplemented with oral risperidone?
3 weeks
192
What is the oral bioavailability of Donepezil?
100%
193
Is donepezil protein bound?
Yes
194
What's the half life of donepezil?
70 hours
195
What's the half life of methypenidate?
2-3 hours
196
What are the long acting benzos?
Diazepam,
chlordiazepoxide,
clonazepam,
flurazepam
197
What are the short acting benzos?
Lorazepam, oxazepam,
temazepam,
Alprazolam
198
What is a Very short acting benzo?
Triazolam
199
Onset and half life of:
1. Zopiclone
2. Zaleplon
3. Zolpidem
1. Onset within 45 mins; half-life 3 to 6 hours (acts
up to 8 hours)
2. Onset within 30 mins; half-life 1 hour (acts
up to 4 hours).
3. Onset within 30 mins; half-life 1 to 3 hours (acts up to 6 hours).
200
What are pharmacodynamics?
What the drug does to the body
201
What are Ionotropic receptors?
ligand-gated ionic channels
*Their activation leads to a rapid
transient increase in membrane permeability to ions
e.g. nicotinic acetylcholine receptors, GABA-A
receptors, glutamate receptors and serotonin 5HT 3
202
What are Metabotropic receptors?
G-proteins bind to the intracellular portion of the receptor and activate a second messenger
*slow response
e.g. Dopamine (D1-5), Noradrenaline, and
Serotonin 5HT1-7 except 5-HT 3, muscarinic acetylcholine receptors and opioid receptors
203
What is a full agonist?
produces a maximal response
204
What is a partial agonist?
cannot elicit a maximal response and are less effective than full agonists -> have a ceiling effect
205
What is an inverse agonist?
binds to the same receptor but produces the opposite
| pharmacological effect
206
What is an antagonist?
drugs that interact with receptors to interfere with their activation by neurotransmitter or other agonistic molecules
- competitive (can be reversed)
- non competitive (change the receptor site)
- ->the effects can be reversed only partially by increasing the dose of the agonist drug (reduces both the potency and the efficacy of agonists)
- irreversible
207
What is Pharmacological antagonism?
opposing action of two molecules by acting via
| same receptors
208
What is physiological antagonism?
opposing action of two molecules by acting via
| same receptors
209
What is chemical antagonism?
opposing action of two molecules by acting via
| chemical reactions
210
What's the law of mass action?
drug response is proportional to the fraction of
| receptors occupied - as the concentration of drug increases, the responses increases until all receptors are occupied
211
How may receptor be up-regulated or down-regulated by drugs?
agonists may cause down-regulation (desensitivity) or reduction in receptor numbers
antagonists may cause upregulation (hypersensitivity) or increase in receptor numbers.
212
What's the potency of a drug?
the amount of the drug needed to
| produce a particular effect compared to another standard drug with similar receptor profile
213
Which factors affect the potency of a drug?
a. The proportion of the drug reaching the receptor
b. The affinity for the receptor
c. Efficacy
214
What's the affinity of a drug?
ability of the drug to bind to its appropriate receptor (‘affection’)
215
What's the efficacy of a drug?
| What else might it be referred to as?
refers to how well the drug produces the expected response i.e. the maximum clinical response produced by a drug
The intrinsic activity
216
Which receptors do atypical antipsychotics work on?
.Atypical drugs show selectivity for D2
| receptors and also show high 5HT2: D2 blocking ratio
217
Amisulpride mechanism of action
D2 and D3 antagonism
| Some 5HT7 activity
218
Aripiprazole mechanism of action
Partial dopamine agonist at D2
5HT2A antagonist
Exhibits a Goldilocks’ phenomenon - stabilising action wherein anatagonising DA at sites of excessive
dopamine such as mesolimbic zones while mimicking DA (agonism) at dopamine deficient zones such as mesocortical areas that are linked negative symptoms.
219
Asenapine mechanism of action
D2 antagonist and serotonin 5HT2A blocker
| alpha-2 blockade effect
220
Chlorpromazine and promazine mechanism of action
moderate antimuscarinic effect in addition to D2 blockade
221
Clozapine mechanism of action
```
Low D2/high 5HT2 ratio activity
blocks D4 and 5HT6 receptors
alpha 1 antagonism and anticholinergic and antihistaminic properties
Weak D1 and D2 affinity
binds 5HT3
```
222
Lurasidone mechanism of action
D2 antagonist and serotonin 5HT2A blocker
high affinity for serotonin 5HT7
partial agonist at 5HT1A receptor
223
Olanzapine mechanism of action
Has high 5HT2 / high D2 blockade ratio.
| Potent D4 blockade and 5HT6 blockade also noted.
224
Quetiapine mechanism of action
lowD2/low 5HT2 activity
225
Risperidone mechanism of action
Has high 5HT2A antagonistic property
| High D2/high 5HT2 activity
226
Sulpiride mechanism of action
Pure D2 antagonist.
227
Thioridazine, pericyazine and pipotiazine mechanism of action
D2 antagonists. Marked antimuscarinic effect. Less EPSEs than other typicals.
228
Thioxanthenes mechanism of action
D2 antagonists
229
Ziprasidone mechanism of action
5-HT2A and D2 blockade
| Antagonizes 5-HT1D, 5-HT2C, D3, D4 receptors.
230
Zotepine mechanism of action
5HT2A, 5HT2C, D1, D2, D3, D4 antagonism.
| Potent noradrenaline reuptake inhibitor. Potent antihistaminic activity and some NMDA antagonism
231
Buspirone belongs to the chemical class of
Azaspirones
232
Which class of antidepressants can increase seizure risk heavily?
Aminoketone (Bupropion) is contraindicated in seizure disorder
233
Which antidepressant is an enantiomer of another antidepressant drug?
enantiomer = mirror image
| Escitalopram
234
Zopiclone belongs to the chemical class of
Cyclopyrrolones
235
Buspirone mechanism of action
partial agonist at the 5-HT1A autoreceptor
236
Why may escitalopram be more effective than citalopram?
Escitalopram binds to both the re-uptake site and an allosteric site causing conformational changes in the 5-HT Transporter and enhancing re-uptake blockade
*May also have earlier onset of action
237
Acamprosate is a
synthetic taurine analogue, which appears to act centrally on glutamate and GABA neurotransmitter systems
238
Triazolopyridine is the chemical class of which drugs?
Trazodone, Nefazodone
239
Imidazopyridine is the chemical class of which drug?
Zolpidem
240
Pyrazolopyrimidine is the chemical class of which drug?
Zaleplon
241
Benzothiazolyl piperazine is the chemical class of which drug?
Ziprasidone
242
Lofexidine mechanism of action
Alpha-2 agonist
(In opioid detoxification, if short duration of treatment is desirable, a2 adrenergic agonists such as lofexidine and clonidine are preferred to methadone)
243
What's the 'standardised difference in effectiveness'?
The difference in the effect of treatment in the active treatment group compared to the placebo group after taking into account the variation in the treatment effect
244
Which drugs were nown as major tranquilisers?
Antipsychotics came to be known as major tranquilizers while barbiturates and benzodiazepines were called minor tranquilizers
245
Which psychotropic is well known to cause sudden death?
thioridazine, droperidol - via cardiac arryythmias
246
Ethnic differences in psychiatric drug effects are noted in which pharmacological actions?
1. Blood levels of haloperidol - Maximal haloperidol concentration in plasma after rapid tranquillisation is significantly high for Asians than Caucasians.
2. Hydroxylation of tricyclics - Caucasians appear to have lower plasma levels of tricyclic antidepressants and attain plasma peaks later when compared with Asians. These differences have been attributed to a greater incidence of slow hydroxylation among Asians when compared with Caucasians
3. Prolactin response to antipsychotics - Asian subjects were reported to produce greater serum prolactin levels than Caucasian subjects.
4. Alcohol metabolism - Nearly 40% Asians and around 60% South American Native Indians lack Aldehyde dehydrogenase enzyme in sufficient amounts to metabolise alcohol.
247
Who is associated with the use of valproate in mania?
Bowden in 1994
248
Placebo response is likely if patient is of lower social class T/F?
T
249
Which drug could be used for the treatment of mixed affective episodes of bipolar disorder?
Valproate
250
What is cyproterone acetate?
Testosterone antagonist
251
What is linked with intentional nonadherence?
A desire for self-efficacy
252
Reserpine is extracted from which plant?
Rauwolfia serpentina
253
Which hormone is most commonly used in the treatment of depression?
Thyroid
254
A potential advancement in the treatment of dementia is
Drugs acting on intracellular mechanisms - Drugs acting on ß-secretase are promising candidates to enter clinical trial for Alzheimer's disease as of now
255
Advantages of buspirone over benzodiazepines when used for anxiety
Buspirone cause no dependence
Buspirone can be withdrawn more easily
Buspirone has no street value
Buspirone causes no tolerance usually
256
Which drug undergo direct phase 2 metabolism reactions?
lorazepam, temazepam and oxazepam
257
Which drug is excreted unchanged in urine?
Gabapentin
258
Is lithium protein bound?
no
259
What happens to lithium clearance when sodium is depleted?
It's reduced
260
Which drugs act on presynaptic receptors as the main mechanism of action?
Clonidine, lofexidine act at alpha2 presynaptic receptor.
261
Urinary acidification can help eliminate which medications on overdose?
amphetamines and phencyclidine
262
Volume of distribution
- Drugs with high affinity for tissues such as fat have high volume of distribution
- The drug distribution in plasma to various tissues depends on plasma protein binding
- The drug distribution in plasma to various tissues depends on tissue permeability
- Tissue distribution leads to a fall in plasma concentration
263
How many minimum weeks of interval should be given between fluoxetine and phenelzine when switching from the SSRI to the MAOI?
5 weeks
264
Drugs eliminated by zero order kinetics
Ethanol, Phenytoin, high dose Salicylates, high dose Fluoxetine, high dose Omeprazole.
Venlafaxine XL
Depot antipsychotics
265
The enhancement of drug effects following the repeated administration of the same dose of a drug is called
sensitisation
266
Valproate levels are decreased by
Carbamazepine
267
Which drugs are enzyme inducers?
Smoking
268
Which drugs are enzyme inhibitors?
Caffeine is an inhibitor. Paroxetine, to some extent fluoxetine, neuroleptics, amitriptyline and clomipramine inhibit
269
What is true about the use of TCAs in children compared to adults?
Due to more extensive metabolism, young people require higher mg/kg doses than adults.
270
Which drug has its plasma levels reduced even after regular administration of the same dose for a month?
Carbamezapine - due to autoinduction
271
The area under the curve after a single dose allows determination of the
Bioavailability of the drug
272
What is clearance?
Clearance is defined as the volume of blood cleared of a particular drug in unit time - It helps calculating half life of a drug in the body
273
Enzyme autoinhibition is most likely to be seen with which antidepressants?
fluoxetine, paroxetine and sertraline show autoinhibition of CYP2D6 though paroxetine is the one that is most affected.
274
Formula for volume of distribution
(Volume of distribution) Vd =Q/Cp, where Vd-volume of distribution, Q-quantity of drug and Cp-plasma
275
There is poor oral absorption of most psychotropics in which part of the gastrointestinal system?
Stomach
276
Which medications have low protein-binding?
Venlafaxine (25%-30%)
277
TCAs may reduce their own absorption T/F?
T
| Due to anticholinergic effects, they may reduce their own absorption (delayed gastric emptying esp. amitryptiline)
278
Some drugs such as fluoxetine move from first order to zero order kinetics in supratherapeutic doses. What happens to their t1/2 in such cases?
t1/2 becomes dependent on doset1/2 becomes dependent on dose
279
interaction of fluoxetine with other drugs
Fluoxetine increases concentration of haloperidol, carbamazepine and phenytoin. Fluoxetine enhances the effects of oral anticoagulants and propranolol.
280
Which of the following can be given as a loading dose in acute mania?
Valproate
281
Tyramine gains neuronal access and releases stored catecholamines via which route?
Catecholamines reuptake channels
282
The pharmacological activity of benzodiazepines depends on its action on which of the following receptors?
GABA-a receptor complex
283
Which drug is not suitable for treating acute mania?
Topiramate
284
Gabapentin has antiepileptic properties T/F?
T
285
Receptor blockade in which dopaminergic pathway results in increased prolactin levels in the body?
Tuburoinfundibular pathway
286
Receptor blockade in which dopaminergic pathway results in the therapeutic effects of antipsychotics?
Blockade of dopamine-2 receptors in the mesolimbic pathway leads to the therapeutic effects
287
The mechanism of action of varenicline tartrate is
Partial nicotinic agonism - relieves symptoms of nicotine withdrawal and cigarette craving through its agonist actions while blocking the reinforcing effects of continued nicotine use through an antagonist action.
288
Which SSRIs are potent enzyme inhibitors?
Fluoxetine, Fluvoxamine and Paroxetine are potent inhibitors of several hepatic cytochrome enzyme
289
Which SSRI is a weak enzyme inhibitors?
Citalopram
290
The enzyme/s that metabolise/s most of the body dopamine:
MAO-B and COMT
291
Which actions can cause anorgasmia?
Alpha 1 antagonism
| 5HT2A/2C stimulation (delayed ejaculation in SSRIs)
292
Which neurotransmitter receptor explains Mirtazapine's sedative effects?
5HT Type 2 receptors
293
Mechanism of action of buprenorphine is via partial agonism at
µ-opioid receptors
294
What increases the risk of withdrawal reactions to therapeutic drugs?
The drug having anticholinergic properties
295
The mechanism of action for Sodium valproate
GABA potentiation
296
Which antidementia drug acts directly on nicotine receptors?
Galantamine
It is a reversible, competitive inhibitor of acetylcholinesterase with some inhibitory action on butyrylcholinesterase. It is also an agonist at nicotinic receptor sites.
297
The mechanism of action of cyproheptadine is
Histamine H1 receptor blockade
298
Which drug acts as a full agonist at Mu receptor and has a long half-life?
Methadone
299
Least sedative of tricyclic antidepressants?
Nortriptyline
300
Most sedative of tricyclic antidepressants?
trimipramine
301
Which of the following groups of medications are associated with bruxism?
Stimulants
302
What is a potentially life-threatening side effect of mirtazapine, occurring with a risk of up to 1 in 1,000 instances?
Severe neutropenia,
303
trazodone mechanism of action
It is a mixed serotonin antagonist/agonist.
304
Endogenous substrates for monoamine oxidase (MAO) isoenzymes include
Epinephrine, dopamine, and serotonin
| MAO-A is more selective for serotonin while MAO-B is more so for dopamine.
305
Haloperidol acts on which receptors?
Haloperidol has a High D2/low 5HT2 activity
306
Evidence-based support when prescribing antidementia drug donepezil
Reduces caregiver burden
Improves the amount of daily activities in some patients
Improves neuropsychiatric symptoms
Reduces the progression of cognitive decline
307
Which medication has been found to be effective in patients with premature ejaculation?
Due to the inhibitory effects of serotonin on the central ejaculatory reflex, selective serotonin reuptake inhibitors (SSRIs) are useful in the treatment of Premature Ejaculation.
308
The mechanism of action of barbiturates is by
Barbiturates act on GABA receptors and serve to increase the duration of chloride channel opening.
309
How much Zuclopenthixol depot is equivalent to 50mg of haloperidol given every four weeks?
200mg / 2 weeks or 400mg/4 weeks of zuclopentixol depot
310
What leads to worsening of negative symptoms in schizophrenia?
Blockade of dopamine-2 receptors in the mesocortical pathway leads to production or worsening of negative symptoms.
311
What leads to EPSEs in schizophrenia?
Blockade of dopamine-2 receptors in the nigrostriatal pathway leads to EPSEs
312
Excitotoxicity that is secondary to glutamatergic overstimulation results in neuronal damage. This is the basis of treating patients with neurodegenerative disorders with which medication?
Memantine
313
Which TCA has a stimulant effect?
Desipramine
314
What has been postulated as the pharmacological basis of clozapine related hypersalivation?
Muscarinic M-4 agonism
315
The chronic administration of tricyclics results in
Downregulation of beta-adrenergic receptors
316
Which class of antidepressant drugs must be avoided while treating depression in a patient who does not want to gain weight?
TCAs
317
Which drug is associated with nephrolithiasis?
Topiramate
318
Antibiotic that can cause serotonin syndrome if combined with MAOIs:
Linezolid
319
common side effect of MAOIs
Postural hypotension
320
Which AED may cause appetite suppression and weight loss?
Topiramate
321
What is an important difference between NMS and serotonin syndrome clinically?
Symptoms such as hyperreflexia and myoclonus are attributed to the enhanced release of serotonin in serotonin syndrome and are not seen in NMS.
322
Which mood stabiliser can cause SJS?
Lamotrigine (1% of the population with the risk being greatest in the first 8 weeks)
323
treatment of clozapine-induced hypersalivation
Pirenzepine is a selective M1, M4 antagonist. Other drugs of use include benzhexol (trihexyphenidyl), hyoscine, Amitriptyline, and combination of benztropine and terazosin.
324
Which of the following diuretics can be used to control lithium-induced polyuria without causing lithium toxicity?
Amiloriide
325
The most common side effects with methylphenidate
nervousness, agitation, anxiety, and insomnia.
326
common side effect of rivastigmine
nausea, vomiting, diarrhea, high blood pressure and hallucinations
327
Which antidepressant is contraindicated in closed-angle glaucoma?
Paroxetine
328
The mechanism by which weight gain occurs during treatment with psychotropics
5HT2-c antagonism
Hyperprolactinaemia
H-1 antagonism
Increased serum leptin leading to leptin desensitisation.
329
The tricyclic with highest antihistaminic activity is
Doxepine
330
A specific side effect of mianserin that requires regular monitoring is
A specific side effect of mianserin that requires regular monitoring is
331
In treating serotonin syndrome which receptor antagonism is useful for controlling neurological signs
5HT2A
332
Lithium induced hypothyroidism is much more common in
Young females
333
Postural hypotension as a side effect of tricyclic antidepressants are related to
Alpha-adrenergic blockade
334
Risk factors for TD
Older patients, females, patients with organic brain damage and patients with affective disorders, and those who have had acute EPSEs (Extra pyramidal side effects) early on treatment.
335
The CNS side effects like anxiety and agitation in the initial few weeks of treatment with SSRIs are proposed to be due to
Over stimulation of 5HT2 receptors in the limbic system
336
The sexual side effects caused by SSRI antidepressants are related to the consequence of stimulating which receptors?
5HT-2 receptors
337
Which benzodiazepine is more toxic than others in overdose?
Alprazolam
338
Symptoms of anticholinergic delirium
hot, dry skin; dry mucous membranes; dilated pupils; absent bowel sounds; and tachycardia.
339
Management of of anticholinergic delirium
Discontinue anticholinergic drugs
| Atropine can be used to treat anticholinergic delirium symptoms once the agent has been removed.
340
The toxic confusional state caused by antipsychotics is mainly due to which mechanism?
Muscarinic receptor blockade
341
Which SSRI is relatively unsafe for post-MI patients?
Citalopram
342
Most common adverse effect of valproate?
Diarrhoea
343
Which SSRI is present in high concentrations in breast milk?
Fluoxetine
344
In managing the hypertensive crisis associated with monoamine oxidase (MAO) inhibitors and the ingestion of food with tyramine, the agent of choice is:
phentolamine or phenoxybenzamine
345
Agranulocytosis as a side effect of Clozapine occurs most commonly during the
First 18 weeks of treatment
346
Drugs with a high effect on QTc include
sertindole, thioridazine, pimozide and droperidol (and haloperidol)
347
What is a prominent side effect of venlafaxine controlled by terazosin, alpha-adrenergic blocker?
Sweating
348
What percentage of patients with Tardive Dyskinesia may show recovery within a year with antipsychotic reduction?
Approximately 50-55%
349
The patients who are prescribed clozapine or olanzapine should have their serum lipids measured every
3 months for the first year of treatment
350
Sustained abnormal postures or positions called tardive dystonias are sometimes seen during neuroleptic treatment. Tardive dystonia occurs after
Months to years of antipsychotic treatment
351
Urinary hesitancy can be an uncomfortable side effect during treatment with antidepressants such as the selective noradrenaline reuptake inhibitor reboxetine.
The use of selective a1A-adrenoceptor antagonists such as doxazosin or tamsulosin can treat the urinary hesitancy - especially in the elderly with associated prostate enlargement.
352
the receptors responsible for side effects by psychotropic medications?
1 . weight gain caused by antipsychotics
2. hyperprolactinemia induced by antipsychotics
3. EPSEs of antipsychotics
4. Gastrointestinal discomfort caused by SSRIs
5. Postural hypotension induced by antipsychotics
1. 5HT2C Antagonism
2. D2 blockade
3 D2 blockade
4. 5HT3 stimulation
5. Alpha-1 antagonism
353
Drugs most likely to cause the following adverse effects:
1. Seizures
2. Ovarian cysts
3. SJS
4. Prolonged qTC
1. Bupropion (doses >400mg/day)
2. valproate
3. lamotrigine, carbamazepine
4. Ziprasidone (more than other atypicals)
354
Psychiatric side effects of non-psychiatric medications
1. Treatment for resting tremors that results in acute confusional state with paranoia and visual hallucinations
2. Treatment for swollen legs that results in visual halos, which are green in colour and confusion
3. Treatment for polymyalgia rheumatica that results in hypomania and confusion
1. Levedopa
2. Digoxin
3. Prednisolone
355
Sexual side effects
1. Painfully prolonged erection caused by treatment for low mood and insomnia
2. Decreased sexual interest, abnormal ejaculation caused by treatment for chronic auditory hallucinations
3. New onset pain during intercourse caused treatment for depression.
1. Trazodone
2. Risperidone
3. Paroxetine
356
Teratogenicity of psychotropics
1. Newborn with anencephaly
2. Newborn with defect of the tricuspid valve
3. Newborn with spina bifida
1. Valproate
2. lithium
3. Valproate
357
antidepressant drug that is most likely to interact and should be avoided in the following situations
1. A 33-year-old woman treated for mixed anxiety & depressive disorder. She is on diazepam, started by her GP
2. A 21-year-old asthmatic on theophylline is suffering from depression
3. A 67-year-old gentleman with a previous history of stroke and is now depressed. He is on regular warfarin.
1. Fluvoxamine reduces the clearance of both diazepam and its active metabolite, N-desmethyldiazepam
2. Fluvoxamine reduces the clearance of theophylline approximately 3-fold via CYP1A2 inhibition
3. When fluvoxamine is administered with warfarin, warfarin plasma levels increases by 98% and prothrombin times are prolonged.
358
appropriate treatment option for the toxic symptoms produced by psychotropic drug
1. Aspirin overdose
2. Amphetamine overdose
3. Diazepam overdose
4. Amitryptyline overdose
5. lithium toxicity following diarrhoea and presents with tremors and ataxia
6. Methadone overdose
7. Phenelzine (MAOI) + cheese and wine - high BP
8. Barbiturate overdose
1. Alkalinisation of urine - for salicylate (aspirin) overdose, and barbiturate overdose
2. Acidification of urine - for amphetamines and phencyclidine
3. Flumazenil
4. Diazepam
5. Haemofyalisis
6. Naloxone
7. phentolamine
8. Alkalinisation of urine
359
target plasma levels.
1. sodium valproate
2. Clozapine
3. Lithium
4. Carbamazepine
5. Pehytoin
6. Amitriptyline
1. 50-100mg/L
2. 350-500 mcg/L
3. 0.6-1 mmol/L
4. >7 mg/L
5. 10-20mg/L
6. 100-200 mcg/L
360
primary mechanism of action for:
1. Ramelteon
2. Riluzole
3. Atomoxetine
4. Clonidine
5. Varenicicline
1. MT1/MT2 receptor agonist
2. NMDA glutamate receptor antagonist
3. Selective presynaptic norepinephrine reuptake inhibition
4. Presynaptic alpha-2 agonist
5. Partial agonist at the α4β2 unit of nicotinic acetylcholine receptor
361
In addition to a marked ST elevation in inferior leads, what other feature can be expected in case of acute myocardial infarction presenting with bradycardia?
RR interval is prolonged reflecting the bradycardia.
362
most significant effect of these receptors
1. Blockade of postsynaptic alpha-1 adrenoreceptor
2. Blockade of M3 cholinergic receptors
3. Blockade of H1 histamine receptors
4. Downregulation of 5-HT2A receptors.
5. D-2 receptor blockade
6. SSRI-induced nausea
7. Lower incidence of EPSEs of newer atypical antipsychotics
1. Sedation and orthostatic hypotension,
2. Dry mouth, constipation
3. Sedation and weight gain
4. Tolerance to hallucinogenic drugs
5. Neuroleptic malignant syndrome
6 gastrointestinal side effects like nausea, vomiting, anorexia, and diarrhoea
7. Serotonin 5HT2 receptor blockade
363
1. Noncompetitive antagonist
2. Competitive antagonist
3. Partial agonist
1. Ketamine at NMDA receptors
2. Propranalol at beta adrenergic receptors
3. Buprenorphine
364
Active metabolite of:
1. Amitriptyline
2. Clomipramine
3. Dosulepin
4. Doxepin
5. Imipramine
6. Lofepramine
7. Fluoxetine
8. Trazodone
9. Mirtazapine
10. Venlafaxine
1. Nortriptyline
2. Desmethyl-clomipramine
3. Desmethyldosulepin
4. Desmethyldoxepin
5. Desipramine
6. Desipramine
7. Norfluoxetine
8. mCPP
9. Demethyl-mirtazapine
10. O-desmethyl-venlafaxine
365
Common side-effects of TCAs include:
```
drowsiness
dry mouth
blurred vision
constipation
urinary retention
```
366
Drugs with a low effect on QTc include
```
Amisulpride Low
Clozapine Low
Olanzapine Low
Risperidone Low
Aripiprazole None
Palperidone None
```
367
Anticholinergic (antimuscarinic) effects
Dry mouth, blurred vision, urinary retention, constipation
368
Antidopaminergic effects
Galactorrhoea, gynecomastia, menstrual disturbance, lowered sperm count, reduced libido, Parkinsonism, dystonia, akathisia, tardive dyskinesia
369
Antiadrenergic effects
Postural hypotension, ejaculatory failure
370
Histaminergic effects
Drowsiness
371
alternative routes of administration of:
1. fluoxetine
2. citalopram
3. Mirtazapine
4. Amitriptyline
5. clomipramine
6. Selegiline
1. Sublingual
2. IV
3. IV
4. IV/IM
5. IV
6. Transdermal
372
Drugs unsuitable for compliance aids include
```
Sodium valproate
Zopiclone
Venlafaxine
Topiramate
Methylphenidate
Mirtazapine
Olanzapine
Amisulpride
Aripiprazole
```
373
Which drug exerts its action through the action on the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system?
Pregabalin
374
What's the half life of:
1. Diazepam
2. Lorazepam
3. Chlordiazepoxide
4. Nitrazepam
5. emazepam
1. Diazepam 20-100 hrs (36-200 hrs for active metabolite)
2. Lorazepam 10-20hrs
3. Chlordiazepoxide 5-30 hrs (36-200 hrs for active metabolite)
4. Nitrazepam 15-38 hrs
5. Temazepam 8-22 hrs
375
Types of adverse reactions
```
Type I (IgE-mediated) reactions
Type II (cytotoxic) reactions
Type III (immune complex) reactions
Type IV (cell mediated) reactions
```
376
What's Memantine's MOA?
Non competitive NMDA receptor agonist
| 5HT2 receptor antagonist
377
What's Galantamine's MOA?
Nicotinic receptor modulator
| Selective and reversible AChe
378
What's Rivastigmine's MOA?
Pseudo irreversible AChe
| Butyrylcholinesterase inhibitor
379
The somatodendriric inhibition of 5HT is regulated by which receptors?
5HT1A
380
What increases the incidence of cleft palate in baby when used in pregnancy?
SSRIs
| Lamotrigine
381
Which side effect has not been reported in association with therapeutic doses of SSRIs?
Which have been?
Hypertension
Hallucinations, akathisia, galactorrhoea, photosensitivity
382
The risk of developing seizures with the use of clozapine is increased by?
0.1
383
Which AP is fastest to dissociate from D2 receptors?
Clozapine
384
What's the explanation for Chlorpromazine antiemetic property?
D2 blockade in the chemoreceptor trigger zone
385
Which drugs should be avoided with cyclosporine use?
Fluoxetine Fluvoxamine and Trazodone
| They are potent CYP34A inhibitors and can affect the levels
386
Which diuretics can be used with lithium?
Furosemide is safest
387
Which antidepresant's plasma levels correlate with therapeutic response?
Imipramine
388
Most important side effect associated with Galantamine?
Bradycardia
389
Most important side effect associated with Venlafaxine?
Diastolic hypertension
390
Most important side effect associated with Topiramate?
Weight loss
391
Which drugs can cause nocturnal myoclonus?
SSRIs
