Week 1 Flashcards
1
Q
What is pharmacokinetics?
A
What your body does to a drug
Absorption, distribution, metabolism, elimination
2
Q
What is pharmacodynamics?
A
What a drug does to your body
Biochemistry and physiology
3
Q
What is bioavailability?
A
Fraction of the administered dose of drug that reaches the systemic circulation
4
Q
What letter represents bioavailability?
A
F
5
Q
How is volume of distribution calculated?
A
Volume of distribution = total drug in body/blood plasma concentration
6
Q
What is the volume of distribution if the total drug in body is 100mg and the plasma concentration is 1 mg/L?
A
100L
7
Q
What is clearance?
A
Volume of plasma/blood cleared of drug per unit time
8
Q
What is half-life?
A
Time required for plasma concentration of a drug to decrease by half
9
Q
What is half-life determined by?
A
Clearance and volume of distribution
10
Q
How many half lives does it take for a drug to reach steady state?
A
4-5
11
Q
What are loading doses used for?
A
When the drug being administered has a long-half life but its effects are required quickly
12
Q
What medications require loading doses?
A
Antibiotics (e.g. gentamicin)
Digoxin
13
Q
What is elimination half-life?
A
Time taken for the concentration to fall to half
14
Q
What is linear pharmacokinetics?
A
Concentration that results from a dose is proportional to the dose - double the dose, double the concentration
Rate of elimination is proportional to the concentration - 50% of drug will be eliminated in a given time frame
15
Q
What is non-linear pharmacokinetics?
A
Concentration that results is not proportional to dose; small increase in dose = large increase in concentration
Rate of elimination is constant regardless of amount of drug present
Dosage increases can saturate binding sites and result in non- proportional increase in drug levels; or opposite in dose decrease
16
Q
Why might changing administration of morphine from oral to subcutaneous cause opioid toxicity?
A
Morphine oral bioavailability is lower than subcutaneous - dose needs to be 1/3 of original
17
Q
Will the loading dose be the same in a large man and a frail woman? Why?
A
No
Depends on volume of distribution
18
Q
Will the loading dose be the same in a man with kidney failure and a woman with normal kidney funtion of comparable weights? Why?
A
Yes
Volume of distribution unaffected by kidney function
19
Q
How is a loading dose calculated?
A
Loading dose (mg) = target concentration (mg/L) x volume (L/kg)
20
Q
What are the 4 main receptor classes?
A
Enzyme-linked
Ion channel linked
G-protein linked
Nuclear/gene linked
21
Q
What is affinity?
A
Measure of propensity of a drug to bind receptor; the attractiveness of drug and receptor
22
Q
What is efficacy?
A
Ability of a bound drug to change the receptor in a way that produces an effect
23
Q
What is potency?
A
Relative position of the dose-effect curve along the dose axis
24
Q
Is a low potency drug considered disadvantageous?
A
Only if the dose is so large that it is awkward to administer
25
Do agonists have affinity and efficacy?
Yes
| Yes
26
Do antagonists have affinity and efficacy?
Yes
| No
27
Do partial agonists have affinity and efficacy?
Yes
| Yes, but less than full
28
What are agonists?
Drugs that interact with and activate
29
What is a full agonist?
An agonist with maximal efficacy
30
What is a partial agonist?
An agonist with less than maximal efficacy
31
What are the 2 types of agonist?
Full
| Partial
32
What are the 2 types of antagonist?
Competitive
| Non-competitive
33
What is an antagonist?
Interacts with the receptor but does not change the receptor
34
What is a competitive antagonist?
Competes with agonist for receptor
Surmountable with increasing agonist concentrations
Shifts dose response curve to the right
Reduces the apparent affinity of the agonist
35
Is a higher or lower therapeutic index more advantageous?
Higher
36
How is the therapeutic index calculated?
Therapeutic index = toxic/lethal dose 50/effective dose 50
37
How does renal disease affect pharmacology and what changes need to be made?
Increased half-life/prolonged elimination
| Dosing interval needs to be increased
38
What is VD?
Volume in which the amount of drug would need to be uniformly distributed to produce observed blood concentration
39
How does hepatic disease affect pharmacology and what changes need to be made?
Increased half-life/slower rate of enzyme metabolism
| Decrease dosage and increase dosing interval
40
How does cystic fibrosis affect pharmacology and what changes need to be made?
Increased metabolism and elimination
| Increase dosage and decrease dosing interval
41
How does ageing affect elimination of drugs?
Variable decrease in GFR
42
How are pharmacodynamic effects increased and decreased in the elderly?
Increased - alcohol, opiates
| Decreased - isoproterenol and β-blockers
43
Why are the elderly at high risk of adverse drug reactions?
The more medications a person is on, the higher the risk of drug-drug interactions/adverse drug reactions and non-adherence
44
Give some examples of drug-drug interactions
Statins and erythromycin/other antibiotics
Verapamil and β-blockers
Warfarin and aspirin/multiple drugs
ACE inhibitors and sulfonylureas
45
What conditions can be worsened by NSAIDs, decongestants and calcium channel blockers?
NSAIDs - chronic HF
Decongestants - BPH urinary retention
Calcium - constipation
46
What drugs should be avoided in renal disease?
Metformin
| NSAIDs
47
What drugs should be used with caution in renal disease?
ACE inhibitors
48
What drugs should be given in a reduced dose in renal disease
Antibiotics
Heparin
Digoxin
Phenytoin
49
What is TD50?
Dose at which there is a toxic effect in 50% of cases
50
What is LD50?
Dose at which there is death in 50% of cases
51
What is ED50?
Dose at which a drug is effective in 50% of cases
52
What is the ratio of males:females affected by hyperkinetic disorders?
3-4:1
53
What could be the reason for differences in prevalence reporting rates of hyperkinetic disorders?
Under-reporting
Lack of recognition in females
Differences in diagnostic practice
Differences in cultural expectations of behaviour
54
What are the 3 core features of ADHD?
Inattentiveness
Hyperactivity
Impulsiveness
55
What does ADHD stand for?
Attention deficit hyperactivity disorder
56
What are some common signs/symptoms of ADHD?
Tendency to move from one task to another without completion
Disorganisation
Fidgeting
Accident prone
Social disinhibition
Poor maintenance of personal relationships
57
What are the specifications for symptoms to fall under in order to diagnose ADHD?
Symptoms apparent before age 7/12
Symptoms excessive for child's age
Pervasive (symptoms occur in more than 1 environment)
58
Give some examples of genes which are thought to contribute to susceptibility to ADHD
DRD4 receptor 7-repeat alleles
Dopamine - SLC6A3/DAT1 and DRD5
Serotonin - SLC6A4/5HTT and HTR1B
59
What is the mean heritability of ADHD in children and adults?
Children - 75%
| Adults - 30%
60
What networks/circuits are involved in inattention?
Anterior fronto-striatal networks
| Posterior parieto-cerebellar circuits
61
What parts of the brain are smaller in adolescents?
Frontal and parietal cortex
Basal ganglia
Right dorso-lateral prefrontal lobe
Cerebellar vermis
62
What executive functions are controlled by the prefrontal cortex?
Regulation of attention
Planning
Impulse control
Processing
63
Where do projections from the prefrontal cortex go?
Cerebellum and striatum
64
What is the result of dysfunction of the prefrontal cortex?
```
Forgetfulness
Distractibility
Impulsivity
Impairment in working memory
Impairment of mental flexibility
```
65
What is the limbic system responsible for?
Regulation of emotion and memory
| Connects higher and lower brain functions
66
What is response inhibition?
Suppression of no-longer required or inappropriate actions, which supports flexible and goal-directed behaviour in ever-changing environments
67
What is working memory?
Cognitive short-term memory buffer with a limited capacity that is responsible for the transient holding, processing, and manipulation of stored information
Important process for reasoning and the guidance of decision making and behaviour
68
What co-morbidities are associated with ADHD?
```
Sleep disorders
Behavioural difficulties
Learning disabilities
Social communication problems
Anxiety and mood
Tic disorders
```
69
Prenatal exposure to what substances has been linked with development of ADHD?
```
Lead
Alcohol
Sodium valproate
Cocaine
Opiates
```
70
How is ADHD assessed?
```
Direct observations in >1 setting
Psychoeducational assessment
Questionnaires/interviews
Identification of co-morbidities
Developmental history
```
71
What information should be obtained from an ADHD history?
```
Current behaviours
Activity levels
Impulsivity
Emotional reactivity
Ability to sustain interest/attention (with/without adult involvement)
Eating and sleep habits; impact
Responses to and interactions with others
Parental management strategies
Developmental and prenatal/perinatal
```
72
What are the early signs of ADHD?
```
Increased foetal movements in pregnancy
Difficult feeder
Irregular sleeper
Unusually active/distractible toddler
Language delay
Increasingly challenging behaviour
Socially disinhibited with adults
Learning difficulties
```
73
What aspects of family history are important in ADHD?
Medical/social history
Learning difficulties in the family (specific and global)
Current parental use of alcohol and/or illicit drug use
Current stressors on the family
Structure of extended family
Child’s care history
74
What aspects of the child's school life are important to explore in ADHD?
Kind of school
Presentation during structured/less structured activities Inattentive/‘daydream’ behaviours in class
Concentration and speed of work
Impulsivity
Quality of relationships with peers/adults
Levels of attainment
75
What additional assessments can be done for a child with suspected ADHD?
Hearing and vision screening checks
Previous health problem investigation
Screening for neurological signs and physical anomalies
Baseline height and weight (record on growth chart)
Baseline blood pressure and heart sounds
76
Why must there be regular communication between health and education staff when a child has ADHD?
Promotes understanding of the difficulties of ADHD
Ensures a consistent approach to patient across settings
Monitors effectiveness of interventions
77
How would ADHD in pre-school children be managed?
Behavioural
78
How would mild ADHD in a school aged child be treated?
Behavioural
79
How would moderate/severe ADHD in a school age child be treated if there are no co-morbidities?
Medication
80
How would moderate/severe ADHD in a school age child be treated if there is aggressive behaviour/ODD?
Behavioural and medication
81
How would moderate/severe ADHD in a school age child be treated if there is GAD?
Behavioural and medication
82
What behaviour training strategies can be used for children with ADHD?
Encourage consistency
Positively reinforce appropriate behaviour
Be firm and in control without being coercive
Set clear rules with consequences
Use routine, count-downs and reminders
Use quiet time, planned ignoring and timeout (age appropriate)
Do not give instructions without first gaining the child’s attention
Ask the child to repeat the instructions back to ensure they have heard and understood them
83
What type of drug is given as a 1st line treatment for ADHD? Give 2 examples
Psychostimulants
| Methylphenidate (MPH) and dexamphetamine (DEX)
84
How does the psychostimulant methylphenidate work?
Blocks dopamine and noradrenaline re-uptake via their transporters
85
How does the psychostimulant dexamphetamine work?
Released dopamine stored in pre-synaptic vesicles
86
What 2nd line drug is used to treat ADHD? How does it work?
Atomoxetine
Inhibits re-uptake of noradrenaline, blocks noradrenaline transporter and increases noradrenaline and dopamine in prefrontal cortex
87
What 3rd line drugs are used to treat ADHD? How do they work?
Clonidine and guanfacine
| α2-receptor agonists
88
What is the difference between clonidine and guanfacine?
Clonidine stimulates all subtypes of α-adrenoceptor; more potent at presynaptic
Guanfacine is more selective for α2-adrenoceptor; more potent at postsynaptic
89
What are the common side-effects of psychostimulants?
```
Insomnia
Decreased appetite
Abdominal discomfort
Headaches
Emotional lability
Depression and psychosis
Tolerance
```
90
What are the common side-effects of clonidine?
Sedation
Constipation
Headaches
Hypotension
91
What ADHD drugs can be taken in liquid and tablet form?
Methylphenidate
| Clonidine
92
What ADHD drugs are the quickest to act?
Psychostimulants
93
Which ADHD drugs take longer to act?
Guanfacine - 3 weeks
| Clonidine and atomoxetine - 6 weeks
94
What is lisdexamfetamine?
Elvanse
Pro-drug which is metabolised to dexampthetamine by RBCs
Increases dopamine and noradrenaline
Rapid onset, long (13 hours) duration
95
How can anorexia/weight loss/growth concerns while taking psychostimulants be addressed?
Administer with food
Reduce dose
Monitor height and weight
Provide dietary advice
96
How can sleep difficulties while taking psychostimulants be addressed?
Sleep hygiene advice
Reduce evening dose/administer earlier
Consider atomoxetine
97
How can dizzziness/headaches while taking psychostimulants be addressed?
Monitor, may be temporary
| Reduce or discontinue
98
How can involuntary movements/tics while taking psychostimulants be addressed?
Monitor, may be temporary
| Change to non-psychostimulant
99
How is medication monitored for ADHD?
Regular review (<6 monthly) but more frequent when titrating meds
Monitor response to medication
Monitor side-effects
Monitor height, weight, pulse and BP
Safe prescribing – compliance, misuse, medical history, access to regular monitoring
100
What factors are associated with persistence of ADHD into adulthood?
```
Progressive reduction in cerebellar and hippocampal volumes
Maternal depression
Marital discord
Negative parent-child interaction
Family socio-economic disadvantage
Familial ADHD
```
101
How can family circumstances influence ADHD prognosis?
Those living in adverse social-economic conditions have more impairment and increased co-morbid problems and poorer long-term outcomes
102
What is the prognosis for adults with ADHD?
~50% will improve with less hyperactivity but they may still have problems organising and planning, not attain academically as well as expected, find relationships and jobs harder to sustain
103
What co-morbidities are associated with ADHD in adulthood?
Mood disorders
Substance abuse
Antisocial/borderline personality disorders
104
What neurotransmitter is involved in alertness, concentration and energy?
Noradrenaline
105
What neurotransmitter is involved in pleasure, reward, motivation and drive?
Dopamine
106
What neurotransmitter is involved in obsession, compulsion and memory?
Serotonin
107
What neurotransmitters are involved in anxiety, impulse and irritability?
Noradrenaline and serotonin
108
What neurotransmitters are involved in attention and arousal?
Noradrenaline and dopamine
109
What neurotransmitters are involved in appetite, sex and aggression?
Serotonin and dopamine
110
What neurotransmitters are involved in mood and cognitive function?
Noradrenaline, serotonin and dopamine
111
What are the 3 components of ADHD?
Attention deficit
Motor hyperactivity
Impulsivity
112
How are the functions of dopamine related to ADHD?
Enhances signal
| Improves attention - behaviour and cognition
113
How are the functions of noradrenaline related to ADHD?
Dampens noise
Executive operations
Increases inhibition
114
How is the prefrontal cortex involved in ADHD/arousal systems?
Defective inhibitory response - insufficient information processing (inattention, hyperactivity, impulsivity)
Unable to distinguish between important signals and background noise - easily distracted/can't focus
115
What is hypo-arousal?
Low tonic firing of dopamine/noradrenaline neurons
116
How can improving the signal to noise ratio relieve ADHD symptoms and what is used to do this?
Increases the drive of the arousal network to improve efficiency of information processing
Stimulants - amplify tonic firing rates
117
What is hyper-arousal?
Excess stimulation of receptors by dopamine and noradrenaline which causes signal to noise detection to deteriorate (poor attention and impulsivity)
Increased phasic firing of dopamine and noradrenaline
118
What drugs are used to treat ADHD?
1st - psychostimulants (methylphenidate, dexamphetamine)
2nd - atomoxetine
3rd - adrenergic drugs (clonidine, guanfacine); antidepressants (venlafaxine, TCAs, MAOIs); dopaminergic drugs (modafinal); all used to augment therapy
119
How does dexamfetamine work?
Facilitates release of dopamine from presynaptic cytoplasmic storage vesicles and blocks dopamine transporter protein (inhibits reuptake) - net increase in dopamine
120
How does methylphenidate work?
Acts on dopamine transporter - increase in dopamine
121
How effective are psychostimulants?
75%
122
How is methylphenidate given?
5mg tablets 3-4 times a day
| Preparation cannot be manipulated for easier administration
123
What brand names of methylphenidate are available?
Ritalin
Equasym
Medikinet
Concerta
124
How is dexamfetamine given?
5mg tablets/trans-dermal patch
| Can be dissolved in water
125
What is the onset and duration of methylphenidate?
Rapid onset
| Duration 8-12 hours
126
What is the onset and duration of dexamfetamine?
Rapid onset
| Duration 13 hours
127
What brand names of dexamfetamine are available?
Elvanse (pro-drug)
| Daytrana (patch)
128
What are the side-effects of psychostimulants?
```
Growth retardation
Anorexia
BP/HR irregularities
Insomnia
Sadness, irritability, abdominal pain, headaches
```
129
What are the components of physical health monitoring for psychostimulants?
HR and BP
Height and weight
History of medicines, disorders, family sudden cardiac/unexplained death
130
What is the legal status of psychostimulants?
Schedule 2 controlled drugs - prescription required with a 28 day validity and signed on collection as proof of identity
Private prescription must have prescriber's ID number; standardised forms
30 days supply
131
What information is required for a controlled drugs prescription to be dispensed?
Form and strength of preparation
Total quantity to be supplied in words and figures
Dose to be administered
Signature and date from prescriber
132
How does atomoxetine work?
Enhances noradrenaline transmission in prefrontal cortex by inhibiting its reuptake from the synaptic cleft
133
Which ADHD drug is effective for co-morbid anxiety and depression?
Atomoxetine
134
What are the side effects of atomoxetine?
Nausea/vomiting, excessive tiredness, insomnia, abdominal pain, appetite suppression, weight loss, constipation, headaches, mood swings, hepatic impairment, increased HR/BP, suicidal ideation
135
What adrenergic drugs are used to treat ADHD?
Clonidine
| Guanfacine
136
How do adrenergic agonists act on the brain to treat ADHD?
Increased action of adrenoreceptors
137
What are the side effects of clonidine and guanfacine?
Sedation, dizziness, hypotension
138
What is the onset of adrenergic agonists used for ADHD?
4-6 weeks
139
Why are antidepressants used to treat ADHD?
Enhance the amount of monoamines at the synapse
140
What antidepressants are used to treat ADHD and what are their side-effects?
Nortriptyline and imipramine
| Anticholinergic effects, seizures, heart effects
141
What ADHD drugs are not used in CAMHS?
Antidepressants
| Modafinil
142
What is modafinil?
Weak psychostimulant
Decreases GABA and increases glutamate
Effects on hypothalamic arousal
143
How is modafinil taken and what are its side effects?
100-300mg in divided doses
| GI problems, appetite, abdominal pain, dry mouth, tachycardia
144
What is the role of vitamins/minerals/diet in ADHD?
Omega 3/6, Fe, B vitamins and zinc have all been linked or are marketed to improve concentration etc/ but evidence is lacking
