Medication Flashcards
1
Q
What is the mechanism of action of Agomelatin?
A
Agomelatine is an antidepressant that acts as a melatonin receptor agonist (MT1 and MT2) and a selective serotonin antagonist (5-HT2C).
2
Q
What are the symptoms of SSRI discontinuation syndrome?
A
- Flu-like symptoms
- Anxiety and suicidality
- Mood and concentration changes
- Stomach upset (nausea, diarrhoea)
- Dizziness and imbalance
- Insomnia
- Vivid dreams
- Irritability
- Crying spells
- Sensory symptoms (e.g. paraesthesia’s or brain zaps, sensations resembling electric shocks)
3
Q
What factors increase the risk of discontinuation syndrome?
A
- Taking antidepressants with shorter half lives
- Taking antidepressants for 8 weeks or longer
- Taking higher doses
- Patients who developed anxiety symptoms at the start of antidepressant therapy
- Taking other centrally active medications (e.g. antihypertensives, antihistamines, antipsychotics)
- Younger people
- Prior experiences of discontinuation symptoms
- Taking antipsychotics
4
Q
Which Antidepressants are associated with the highest potential risk for discontinuation syndrome?
A
Paroxetine
Duloxetine
Venlafaxine
Desvenlafaxine
Mirtazapine
MAOIs
5
Q
Which SSRI is least associated with discontinuation syndrome?
A
Fluoxetine
6
Q
What is the mechanism of action of mirtazapine?
A
Noradrenaline and serotonin specific antidepressant (NaSSa)
7
Q
What is the mechanism of action of venlafaxine?
A
Serotonin and noradrenaline reuptake inhibitor (SNRI).
8
Q
What is the mechanism of action of duloxetine?
A
Serotonin and noradrenaline reuptake inhibitor (SNRI), also weak inhibitor of dopamine reuptake.
9
Q
What is the mechanism of action of St John’s Wort?
A
Weak MAOI and weak SNRI (also considered by some to be a weak SSRI)
10
Q
What is the mechanism of action of reboxetine?
A
Noradrenaline reuptake inhibitor (NaRI)
11
Q
What is the mechanism of action of trazodone?
A
SARI (Serotonin antagonist and reuptake inhibitor)
12
Q
What is the mechanism of action of bupropion?
A
Norepinephrine-dopamine reuptake inhibitor (NDRI), and nicotinic acetylcholine receptor antagonist
13
Q
What is the mechanism of action of moclobemide?
A
Reversible inhibitor of monoamine oxidase type A
14
Q
What is the mechanism of action of donepezil and tacrine?
A
Reversible acetylcholinesterase inhibitor
15
Q
What is the mechanism of action of rivastigmine?
A
Reversible acetylcholinesterase inhibitor and butyrylcholinesterase inhibitor
16
Q
What is the mechanism of action of memantine?
A
Non-competitive NMDA antagonist
17
Q
What is the mechanism of action of valproate?
A
GABA modulation (increases GABA in the brain), sodium channel inhibition and NMDA antagonist
18
Q
What is the mechanism of action of carbamazepine and phenytoin?
A
Stabilises Na channels
19
Q
What is the mechanism of action of lamotrigine?
A
NMDA receptor modulation, stabilises Na channels and blocks calcium channels, some GABA modulation
20
Q
What is the mechanism of action of benzodiazepines?
A
Enhance action of GABA by action of non-specific positive allosteric modulation of GABA-A, in the absence of GABA they have no effect on GABA functioning
21
Q
What is the mechanism of action of Z drugs?
A
Enhance action of GABA by action of specific positive allosteric modulation of GABA-A (high affinity for α1-containing GABA-A receptors)
22
Q
What is the mechanism of action of amisulpride?
A
D2/D3 selective antagonist (low affinity selective antagonist of ‘D2 like’ receptors (D2=D3>D4) it has little affinity for D1 like’ receptors (D1 and D5) or non dopaminergic receptors (serotonin, histamine, adrenergic, and cholinergic)
23
Q
What is the mechanism of action of olanzapine?
A
Dopamine and 5HT2 antagonism
24
Q
What is the mechanism of action of aripiprazole?
A
Partial agonist at 5HT1A and D2, and 5HT2A antagonist
25
What is the mechanism of action of clozapine?
Dopamine and serotonin antagonist (5HT2A)
High affinity for D4, (to a lesser extent D1, D2, D3, D5) which may explain less EPSEs
5-HT 1A partial agonist which may explain reduction of negative symptoms
Muscarinic M1, M2, M3, M5, histamine, and alpha-1 adrenergic-receptor antagonist
Norclozapine, the metabolite of clozapine, actively works on the M1 and M4 receptors.
26
What is the mechanism of action of lurasidone?
Dopamine D2, 5-HT2A, 5-HT7, alpha2A- and alpha2C- adrenoceptor antagonist, and is a partial agonist at 5-HT1a receptors. Lurasidone does not bind to histaminergic or muscarinic receptors.
27
What is the mechanism of action of cariprazine?
D3/D2 partial agonist, 5-HT1A partial agonism, 5-HT2B and 5-HT2A antagonism.
28
What is the mechanism of action of dexamphetamine and methylphenidate?
Inhibiting DA (dopamine) and NA (noradrenaline) reuptake
29
What is the mechanism of action of lisdexamphetamine?
Prodrug, absorbed by GI tract, converted to dexamfetamine which inhibits the reuptake of NA and DA. Converted by enzymes in red blood cells into dexamfetamine and L-lysine (amino acid). The activation of the prodrug results in longer action and a reduced abuse potential
30
What is the mechanism of action of atomoxetine?
Targets the NET (noradrenaline transporter), inhibiting the reuptake of NA, therefore increasing NA levels in the synaptic cleft. Selective NA reuptake inhibitor
31
What is the mechanism of action of guanfacine?
Selective agonist of α2A-adrenergic receptors. Binds to postsynaptic α2A-adrenergic receptors, mimicking NA
32
What is the mechanism of action of clonidine?
Agonist of α2-adrenergic receptors, mimic NA
33
What is the mechanism of action of methadone?
Mu-opioid receptor agonist, NMDA receptor antagonist, Inhibition of serotonin and norepinephrine reuptake
34
What is the mechanism of action of acamprosate?
NMDA glutamate receptor antagonist and positive allosteric modulator of GABAA receptors (effect on both receptors is indirect)
35
What is the mechanism of action of naloxone?
Pure opioid antagonist (will reverse mu, delta, and kappa)
36
What is the mechanism of action of naltrexone?
Long acting (compared to naloxone) opioid antagonist, targeting endogenous opioid receptors
(mu, delta, and kappa receptors), but particularly the mu-opioid receptor
37
What is the mechanism of action of varenicline?
Nicotinic receptor partial agonist
38
What is the mechanism of action of disulfiram?
Binds irreversibly to enzyme aldehyde dehydrogenase (ALDH) and causes acetaldehyde to accumulate following ingestion of alcohol. Elevated blood acetaldehyde causes facial flushing, severe headache, palpitations, tachycardia, hypertension, respiratory distress, nausea and vomiting. These symptoms commence within 15-30 min of ingesting alcohol and persist for several hours
39
What is the mechanism of action of sildenafil?
Inhibits cGMP-specific phosphodiesterase type 5 (PDE5)
40
What is the mechanism of action of prazosin?
Alpha-1 adrenergic receptor antagonist
41
What are common early side effects of MAOIs?
Orthostatic hypotension, daytime drowsiness, insomnia and nausea
42
What are common late side effects of MAOIs?
Weight gain, muscle pain, myoclonus, paraesthesia and sexual dysfunction
43
Which drugs should be avoided with MAOIs?
SSRIs
SNRIs
TCAs (clomipramine and imipramine)
Opioids
St John's Wort
Cold remedies (dextromethorphan and chlorpheniramine)
Triptans
44
What foods should be avoided with MAOIs?
Foods containing Tyramine as they can cause a hypertensive crisis. E.g. hard cheeses, wine, fermented meats, draught beers, vegemite, soy sauce
45
What type of diuretics are most likely to increase lithium levels?
Thiazide diuretics due to sodium depletion.
When sodium levels drop, the kidneys reabsorb more lithium, which leads to elevated serum lithium levels and a high risk of lithium toxicity
46
What are the pharmacokinetics of lithium?
Lithium salts are rapidly absorbed following oral administration. It does not bind to plasma proteins. It is not metabolised so does not have an active metabolite. It is almost exclusively excreted by the kidneys unchanged.
47
What are contraindications to lithium therapy?
Addison's disease
Brugada syndrome
Cardiac disease associated with rhythm disorders
Clinically significant renal impairment
Untreated or untreatable hypothyroidism
Low sodium levels, including people that are dehydrated and those on low-sodium diets
48
Common side effects of lithium
Nausea / diarrhoea
Fine tremor
Polyuria, polydipsia
Rash/dermatitis
Blurred vision
Dizziness
Decreased appetite (however weight gain is more common than weight loss)
Drowsiness
Metallic taste
49
Long term effects of lithium therapy
- Hypothyroidism and hyperthyroidism
- Hypercalcemia / hyperparathyroidism (lithium increases renal calcium reabsorption and independently stimulates parathyroid hormone release)
- Irreversible nephrogenic diabetes insipidus
- Reduced GFR (chronic kidney disease)
50
How does lithium cause nephrogenic diabetes insipidus?
Characterized by the inability of the kidney to concentrate urine.
Urine concentration is mediated by the principal cells of the collecting duct. Lithium can cause dysregulation of the principal cells in the short-term and cell loss in the long-term.
This dysfunction of principal cells renders them unresponsive to ADH (vasopressin) which induces expression of water transport proteins in the late distal tubule and collecting duct to increase water reabsorption.
51
Treatment options for lithium induced diabetes insipidus
- stop lithium (if feasible)
- keep levels within 0.4-0.8 mmol/L (although DI can still occur within these levels)
- once-daily dose of the drug taken at bedtime (results in lower trough levels which enables renal repair)
- amiloride (k sparing diuretic) - generally considered first-line as less likely to increase serum-lithium concentrations to toxic levels and will not contribute to the development of hypokalemia. Lithium uses Na channels to gain access into principal cells where it exerts a toxic effect. Amiloride blocks these Na channels therefore prevents access of Lithium.
- thiazide diuretics
- indomethacin (blocks prostaglandin activity which augments the action of AHD on the principal cells)
- desmopressin (synthetic vasopressin)
52
What are the risk factors for lithium toxicity?
- Drugs altering renal function
- Decreased circulating volume
- Infections (viral infections, gastroenteritis with diarrhoea and vomiting)
- Fever
- Decreased oral intake of water
- Renal insufficiency
- Nephrogenic diabetes insipidus
53
What are the features of lithium toxicity?
- GI symptoms
(nausea, vomiting, diarrhoea, and cramping abdominal pains)
- Neuro symptoms
(coarse tremor, confusion, seizures, dystonia, hyperreflexia, nystagmus and ataxia)
54
What four drug classes are likely to increase lithium levels?
1. NDAIDs
2. Thiazides
3. Loop diuretics (unlikely to esult in toxicity)
4. ACE inhibitors
55
In lithium toxicity what are the ratings of the AMDISEN scale?
0 No clinical signs or symptoms
1 Mild (nausea, vomiting, tremor, hyperreflexia, agitation, weakness, and ataxia)
2 Moderate (stupor, rigidity, hypertonia and hypotension)
3 Severe (myoclonus, cardiovascular collapse, seizure and coma)
56
What is required before prescribing lithium?
Maudsley Guidelines advise that the following must be checked:-
- Renal function (U&E and eGFR)
- Cardiac function (ECG)
- Thyroid function (TFTs)
The BNF states that FBC and a BMI should also be done.
In addition, women of childbearing age should be advised regarding contraception, and information about toxicity should be provided.
57
What is zero order kinetics?
Zero order kinetics is where the plasma concentration of a drug decreases at a constant rate, despite the concentration of the drug.
There is no fixed half life.
This typically occurs when the drug-metabolising enzymes are saturated, meaning that the body's capacity to eliminate the drug is maximised and remains unchanged irrespective of increases or decreases in the drug's concentration
58
When is the steady state achieved?
The the amount of drug being eliminated from the body is the same as the amount of drug being administered
59
How long does it take for clozapine to reach steady state?
2-3 days
60
How long does it take for lithium to reach steady state?
4-5 days
61
How long does it take for aripiprazole to reach steady state?
14-16 days
62
How long does it take for paliperidone depot to reach steady state?
2 months
63
How long does it take for olanzapine to reach steady state?
7 days
64
How many half lives does it take for a drug to be ~97% eliminated
5 half lives
65
What is first order kinetics?
Elimination at a proportional rate.
The majority of drugs are eliminated in this way.
Drugs that follow first order kinetics have a fixed half-life.
66
How long would it take a drug with a long half-life to reach a steady state if no loading dose is given?
5 half-lives
67
Which anti-convulsant medication can cause emotional dysregulation (inc. irritability, anger, aggression, depression)
Keppra (levetiracetam)
68
Which antipsychotics are most likely to cause postural hypotension?
Olanzapine
Risperidone
Clozapine
Paliperidone
Queitapine
Ziprasidone
69
Which antipsychotics are recommended when postural hypotension is a problem?
Amisulride
Aripiprazole
Haloperidol
Sulpiride
Trifluoperaznie
70
What are the two types of adverse drug reactions?
Type A (Pharmacological reactions) account for up to 80% of ADRs. Include common side effects.
Type B (Idiosyncratic reactions) unpredictable reactions not accounted by the drugs pharmacology e.g. agranulocytosis on clozapine of SJteven-Johnson Syndrome on lamotrigine
71
Describe type 1 allergic reactions
IgE mediated
Immediate hypersensitivity reaction
Symptoms include urticaria, pruritis, angioedema and anaphylaxis
72
Describe type 2 allergic reactions
Cytotoxic reactions
Activation of complement proteins and destruction of cells by antibodies
e.g. drug-induced haemolytic anaemia or thrombocytopenia
e.g. carbamazepine in rare idiosyncratic blood dyscrasias
73
Describe type 3 allergic reactions
Immune complex reactions
Antigen-antibody aggregates form and deposit in tissues causing inflammation
e.g. drug-induced lupus with chlorpromazine
74
Describe type 4 allergic reactions
Cell mediated reactions
Delayed hypersensitivity reaction
mediated by T-cells e.g. Stevens-Johnson syndrome
75
What is the mechanism of action. of aripiprazole?
Atypical antipsychotic, has a unique mechanism of action as a dopamine D2 receptor partial agonist. This means it can act as both an antagonist and agonist depending on the local concentration of dopamine.
76
What is a useful scale to assess sexual function / dysfunction prior to commencing psychotropic medication.
Arizona Sexual Experiences Scale (ASEX)
77
Which anti-psychotic carries the highest risk of sudden death?
Thioridazine
due to its high propensity for causing QT prolongation and Torsades de Pointes
78
Which psychotropic medication can aggravate psoriasis?
Lithium
79
What are the three GABA receptors and what are they responsible for?
BZ1: sedative effects
BZ2: myorelaxant and anticonvulsant effects
BZ3: anxiolytic effects
80
What is the mechanism of action of benzodiazepines?
Positive allosteric modulators of the GABA-A receptor
Benzodiazepines increase the frequency of the GABA-A receptor Cl– channel opening in the presence of GABA.
81
According to the NICE guidelines how gradually do you taper benzodiazepines?
Reduction of 5-10% every 1-2 weeks OR and eighth of the daily dose every two weeks
82
Which class of psychotropic medication can cause heart block?
TCAs
83
Which medications act on sodium channel stabilisation?
Phenytoin, carbamazepine and lamotrigine
84
Which medications act on GABA receptors?
Valproate, benzodiazepines and z-drugs
85
Which medication has a dual action on sodium channel stabilisation and GABA receptors?
Topiramate
86
Regarding depot medication, what is post-injection syndrome?
Thought to happen from accidental entry into a blood vessel on administration.
Resultant significant plasma level increase - delirium and somnolence.
Incidence is < 0.1%
Almost all reactions occur within 1 hour of injection
Associated with olanzapine depot
87
What is the mechanism of action of buprenorphine?
Partial agonist of the mu-opioid receptor with a high affinity.
88
What are the effects of the mu opioid receptor?
Analgesia
Euphoria
Constipation
Respiratory depression
Dependence
89
What are the effects of the kappa opioid receptor?
Analgesia
Diuresis
Dysphria
90
What are the effects of the delta opioid receptor?
Analgesia
Axiolysis
91
Regarding drugs with the potential for abuse, which classes interfere with ionotropic receptors or ion channels?
Alcohol
Benzodiazepines
Ketamine
Nicotine
92
Which drugs with the potential for abuse interfere with G coupled receptors?
Opioids
Cannabinoids
GHB (y-hydroxybutyrate)
93
Which drugs with the potential for abuse target monoamine transporters?
Amphetamine
Ecstacy
Cocaine
94
Which drugs with the potential for abuse target 5HT receptors?
Hallucinogens - LSD, psilocybin, DMT and mesculin (peyote)
95
Which drugs with the potential for abuse target the glutamate system (NMDA antagonists)?
Dissociatives - Katamine, PCP, dextromorphan, nitrous oxide
96
Which drugs with the potential for abuse target cannabinoid receptors?
THC
97
Which drugs with the potential for abuse target GABA?
Benzodiazepines, GHB
98
What is the mechanism of action of Acetylcholinesterase (AChE) inhibitors?
Preventing cholinesterase from breaking down acetylcholine.
Acetylcholine is thought to be deficient in Alzheimer's (due to loss of cholinergic neurons).
99
Name two common Acetylcholinesterase (AChE) inhibitors used in the treatment of Alzheimers
Donepezil
Rivastigmine
100
What is the mechanism of action of memantine?
NMDA receptor antagonist that blocks the effects of pathologically elevated levels of glutamate that may lead to neuronal dysfunction
101
What are some common side effects of Acetylcholinesterase (AChE) inhibitors?
Nausea
Diarrhoea
Headache
Agitation
Fatigue
102
What are some common side effects of memantine?
Somnolence
Dizziness
Hypertension
Dyspnoea
Constipation
Headache
Elevated liver function tests
103
How can first generation anti-histamines help EPSEs?
Unlike second generation antihistamines, first generation antihistamines cross the blood brain barrier and have anticholinergic effects.
104
Which receptors are affected by clozapine?
Dopaminergic
Histaminergic
Serotonergic
Adrenergic
Cholinergic
105
Which enzyme is responsible for the metabolism of clozapine?
Cytochrome P450 enzyme CYP1A4
106
In relation to clozapine, what are common (need to know) inducers and inhibitors of the CYP1A4 enzyme?
Inducers: Tobacco (hence lowering clozapine levels)
Inhibitors: Grapefruit and fluvoxamine (hence increasing clozapine levels)
107
What is the hypothesised mechanism of action of dexamphetamine and lisdexamphetamine (prodrug)?
Increases synaptic levels of dopamine and noradrenaline
108
What is the mechanism of action of methylphenidate?
Inhibits the dopamine transporter (DAT) and the norepinephrine transporter (NET), preventing the reuptake of dopamine and norepinephrine into the presynaptic neuron.
Also binds to α-adrenergic receptors linked to cognitive effects and increased peripheral resistance.
It also has agonist activity at the 5-HT1A receptor.
109
What is the mode of action of atomoxetine?
Selective norepinephrine reuptake inhibitor (SNRI)
Binds to the NE reuptake transporter on the presynaptic membrane of the nerve and inhibits NE reuptake.
This increases the NE concentration in the synaptic cleft.
110
5HT2 angonism can cause what side effect?
Anorgasmia (due to inhibition of dopamine and norepinephrine release)
111
What is special about 5HT3? And what common side effect does agonism at this receptor cause?
It is the only ligand-gated serotonin receptor.
Associated with nausea
112
Which two TCAs are the most dangerous in overdose?
Amitriptyline and dothiepin
113
What is the mechanism of action of secondary (second generation) TCAs?
Primarily inhibits reuptake of noradrenaline, which increases the levels of this neurotransmitter in the synaptic cleft and enhances noradrenergic neurotransmission. This mechanism is associated with improved mood and analgesic effects, particularly useful in treating neuropathic pain.
114
Which are said to have fewer side effects with regards to TCAs, secondary amines or tertiary amines?
Secondary amines e.g. nortriptyline
115
What is the mechanism of action of tertiary (first generation) TCAs?
Inhibit the reuptake of both serotonin and noradrenaline, which increases the levels of these neurotransmitters in the synaptic cleft and enhances serotonergic and noradrenergic neurotransmission.
This dual action makes them effective in treating depression but also contributes to a broader side effect profile.
116
Name some comon side effects of TCAs?
Dry mouth (xerostomia)
Sedation/drowsiness
Constipation
Blurred vision
Weight gain
Dizziness
Urinary retention
Postural hypotension
Tachycardia
Sweating (hyperhidrosis)
Cognitive impairment
Sexual dysfunction
Increased appetite
Headache
Tremor
Nausea
Palpitations
117
Which antidepressants are safe to use post myocardial infarction?
SSRIs
Mirtazapine
118
How is amisulpride metabolised?
Primarily through the kidneys with minimal liver metabolism
119
How do you calculate the volume of distribution?
Amount of drug in the body divided by plasma concentration
120
Which drugs are inducers of the Cytochrome P450 system?
Tobacco, alcohol, barbituates, carbamazepine, Phenytoin, St John's Wort
121
Which drugs are inhibitors of the Cytochrome P450 system?
Chlorpromazine, SSRIs, and grapefruit juice
122
What factors increase the risk of paradoxical reactions to benzos?
Learning disability
Young or old age
History of aggression or poor impulse control
Benzos with a short half life
High dose benzos
IV benzos
