People and Illness Week 1 Flashcards
(139 cards)
1
Q
Describe the mechanism of action of psychostimulant drugs
A
Act on D1 receptors in the prefrontal cortex and D2 in the striatum - boost noradrenaline/dopamine signalling
2
Q
How effective are psychostimulants in the treatment of ADHD?
A
Efficacy = 75%
3
Q
Describe the bonds which form between a drug and its receptor
A
Covalent bonds are stable and essentially irreversible Electrostatic bonds may be strong or weak, but are usually reversible
4
Q
Give examples of drug-disease interactions
A
- Patients with Parkinson’s disease have increased risk of drug induced confusion
- NSAID (COX-2) can exacerbate heart failure
- Urinary retention in BPH patients on decongestants or anticholinergics
- Constipation worsened by calcium, anticholinergics, calcium channel blockers
- Neuroleptics and quiolones lower seizure thresholds
5
Q
List the areas of questioning when taking a history for ADHD
A
- Parental/patient reports of symptoms
- Systemic enquiry
- Past history - pregnancy/delivery, past behaviour and development
- Developmental history
- Medical history - past/current illness, past operations, head injury, tics/funny turns/faints/seizures, current medication, allergies
- Family history - medical and social
6
Q
Which additional ADHD drugs are not used in children?
A
- Anti-depressants (enhance amount of monoamines at the synapse) e.g. nortriptyline, imipraine
- Modafinil - weak psychostimulant, weak affinity for dopamine uptake carrier sites, decrease GABA and increase glutamine and control degree of hypothalamic arousal
7
Q
Describe the dosage schedule of atomoxitine
A
Once daily or bi-daily dosing
8
Q
Compare the function of agonists, antagonists and partial agonists
A
Agonist has affinity and intrinsic activity Antagonist has affinity but no intrinsic activity, competitive and non-competitive Partial agonist has affinity but less intrinsic activity
9
Q
When are symptoms of ADHD often more pronounced?
A
In the afternoon
10
Q
What specialists are part of the CAMHS multi-disciplinary team?
A
- Psychiatrists
- Psychologists
- Social worker
- Nurses
- Support workers
- Occupational therapists
- Psychological therapists - child, family, play therapists and creative art therapists
- Primary mental health link workers
- Specialist substance misuse workers
11
Q
How long does it take for atomoxitine to provide a therapeutic effect?
A
Within 6 weeks
12
Q
Describe the mechanism of action of adrenergic drugs
A
Alpha 2 A adrenergic receptor agonist
13
Q
What requirements do drugs have to meet to bind to a specific receptor?
A
Size, shape, stereospecificity
14
Q
When is atomoxetine used in the treatment of ADHD?
A
When stimulants ineffective/not tolerated/co-morbidity
15
Q
Define pharmacodynamics
A
Study of the biochemical and physiological processes underlying drug action (mechanism of drug action, drug-receptor interaction, efficacy and safety profile) - ‘what the drug does to your body’
16
Q
How does renal disease affect drug metabolism and prescription?
A
Same hepatic metabolism Same/increased volume of distribution and prolonged elimination (half-life increased) Increase dosing interval
17
Q
List the side effects of guanfacine
A
Sedation, headache, fatigue, bradycardia, agitation, sinus arrhythmia
18
Q
Define elimination half-life
A
Time for concentration to fall to half
19
Q
What type of attention normally develops at age 5+ years?
A
Integrated - mature attention control
20
Q
Are nutritional supplements helpful in managing ADHD?
A
Omega 3/6 fish oils, iron, zinc, vitamin B - inconclusive evidence but may be beneficial
21
Q
How is phenytoin dosage calculated?
A
15mg/kg
22
Q
Why are enzymes often the therapeutic target of drugs?
A
Enzymes control metabolic processes - in patient (e.g. ACE inhibitors) or in microbes/tumours (e.g. penicillin)
23
Q
Describe the preparations of atomoxitine
A
Tablet, long-acting
24
Q
What is the difference between linear and non-linear pharmacokinetics?
A
- Linear - 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% o drug will be eliminated in a given time frame)
- Non-linear pharmacokinetics - Concentration that results is not proportional to dose 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)
25
Define ED50 and LD50
ED50 - dose for efficacy in 50% of the population LD50 - dose which causes death in 50% of the population
26
What structured questionnaire is used to diagnose ADHD?
SNAP-IV - teacher and parent rating scale
27
List the executive difficulties resulting from ADHD
- Organisation - Planning - Working memory - Attention - Response inhibition - Impulse control
28
How is a history from the patient/parent taken in diagnosis of ADHD?
- Current behaviours, activity levels, impulsivity, emotional reactivity - Ability to sustain interest/attention (with/without adult involvement) - Eating habits - Sleeping patterns - What is the impact on functioning? - Responses to and interactions with others - Parental management strategies - Structured questionnaires (parent and self-report)
29
To what extent do genetic factors cause ADHD?
Genetic-environment interactions - genes can either increase or reduce the impact of an environment or an environment can activate a genetic effect Twin adoption studies show that mean heritability of ADHD is 75% in children and adolescents
30
Describe the pathological changes which can be seen in a brain with ADHD
- Smaller brain volume - frontal and parietal cortex - Smaller basal ganglia - Right dorsolateral prefrontal lobe reduced - Smaller cerebellar vermis - Attentional systems involve anterior fronto-striatal networks - Posterior parieto-cerebellar circuits
31
In which co-morbidity is dexamphetamine more useful?
ADHD and foetal alcohol syndrome
32
Where are drug receptors found?
Extracellular or intracellular
33
Describe the changes which contribute to the development of an adult brain during adolescence
Morphological and functional changes in the brain, with increasing hormone levels and other biological changes, interact with cultural, economic and psychosocial factors to shape how adolescents think, feel and behave
34
How does hepatic impairment affect the pharmacokinetics of drugs?
First pass metabolism Activation of prodrugs Decreased protein binding Decreased elimination
35
Describe the preparations of dexamphetamine
5mg (three times daily) immediate release Elvanse (lisdexamphetamine dimesylate) - Prodrug (inactive) - less susceptible to abuse - Metabolised to dexamphetamine by RBC at set rate - Rapid onset of action, lasts 13 hours - Can be dissolved in water (ease of administration) Tablet, short and long-acting
36
How do drugs work?
Can stimulate (agonist) or inhibit (antagonist) the receptor action, this usually involves an effect on signal transduction pathway
37
Describe the neurobiology of arousal systems in ADHD
ADHD = deficiency in arousal systems
* Defective inhibitory response from prefrontal cortex - insufficient information processing
* Neurons in PFC are unable to distinguish between important signals and 'background noise'
* Hypo-arousal - low firing of dopamine/noradrenaline neurones, decreased efficiency of information processing
* Hyper-arousal - increased phasic firing of dopamine/noradrenaline neurons, stimulates additional receptors, signal-to-noise detection deteriorates causing poor attention and impulsivity
38
What type of attention normally develops at age 4-5 years?
Dual channelled - can do a task and listen to someone at the same time
39
What are the symptoms of opioid toxicity?
Drowsiness, pin-point pupils, decreased respiratory rate, altered blood gases (type II respiratory failure)
40
Describe management of a child's environment in the management of ADHD
- Provide a calm environment - reduce background noise e.g. TVs - Avoid too many distracting stimuli when you want the child to concentrate - Initially avoid situations that require quiet, still behaviours for long periods - Maintain structure and supervision longer than you think should be necessary
41
Describe the SIGN guidelines for diagnosis of ADHD
- Core symptoms have significant impact on child's development - They impair social, emotional and cognitive function - The symptoms are responsible for considerable morbidity and dysfunction for the child/young person and their family
42
How long does it take for the therapeutic effect of psychostimulants to become apparent?
Within days
43
Define antagonists
Interact with the receptor but do not change the receptor, have affinity but no efficacy, two types - competitive and non competitive
44
List the factors which affect bioavailability
Drug factors - molecular weight/ionisation Absorption - gastric pH/health of GI tract First pass metabolism (hepatic) - phenytoin may reduce F, grapefruit juice may increase
45
What could change volume of distribution between patients?
Difference in weight
46
With which co-morbidities is atomoxitine more helpful?
Tics Anxiety Autism spectrum
47
Define half-life
Time required for serum plasma concentration to decrease by half
48
How is apparent volume of distribution calculated?
Total amount of drug in the body/drug blood plasma concentration
49
List the side effects of clonidine
Sedation, constipation, headaches, hypotension, depression, bradycardia
50
How does cystic fibrosis affect drug metabolism and prescription?
Increased metabolism/elimination Larger volume of distribution Increase dose, decrease dosage interval
51
Describe the main symptoms associated with ADHD
Inattention and lack of persistence in activities requiring attention - e.g. a tendency to move from 1 task to another without completion, defective filtering of information Excessive activity - disorganised/ill-regulated, restless/fidgety, motor hyperactivity/psychomotor agitation Impulsivity - poor awareness of danger/accident prone, social inhibition/excessively talkative, poor peer relationships, emotional dysregulation
52
How is therapeutic index calculated?
TD50 or LD50/ED50
53
What determines half-life?
Clearance and volume of distribution
54
Describe the mechanism of action of dexamphetamine
Facilitates release of dopamine from presynaptic cytoplasmic storage vesicles in synapse and blocks dopamine transporter protein (inhibits re-uptake) - increase in dopamine
55
Give examples of drugs with non-linear pharmacokinetics
Phenytoin, digoxin
56
What type of attention normally develops at age 3-4 years?
Focus - attention is single-channelled, but the child can control this themselves
57
Describe the prevalence of ADHD
Male:female - 3-4:1 Females often go undiagnosed 1-5% of child-adolescent population
58
What is the effect of renal disease on the pharmacodynamics of drugs?
Altered sensitivity to drug effect Adverse effects
59
List the functional types of drug receptors
Regulatory - change the activity of cellular enzymes Enzymes - may be inhibited or activated Transport - e.g. Na/K ATPase Structural - form cell parts
60
What is adolescence?
The period following puberty during which a young person develops from a child to an adult
61
How is a treatment plan for ADHD determined?
Preschool children - behavioural parent training by trained facilitators School aged children - - Mild ADHD - consider behavioural approaches in the first instance - Moderate/severe: 1. No comorbidity - medication recommended 2. ODD/aggressive behaviour - combination of medication and behavioural treatment 3. Generalised anxiety disorders - combination of medication and behavioural treatments
62
Define bioavailability
Fraction of the administered dose of drug that reaches the systemic circulation, expressed as letter F
63
How can morphine dosage be converted from oral to parenteral?
Parenteral dose is 1/3 of oral dose
64
What determines loading dose?
Desired concentration and volume of distribution
65
How long does it take for drugs to reach a steady state?
4-5 half lives
66
How is renal function determined?
Serum creatinine is unreliable marker, if accuracy is needed creatinine clearance is used
67
How long does the therapeutic effect of guanfacine take?
Within 3 weeks
68
What criteria must clinical features fit in order to diagnose ADHD?
Must be - - Apparent before child is age 7 (12 in adults) - Excessive for the child's age and development - Pervasive i.e. evident in more than 1 environment
69
What behavioural changes occur during adolescence due to changes in brain structure/function?
Increased risk taking, sensation seeking and alcohol/drug use due to development of the reward pathway Enhanced reactivity but reduced responsiveness to aversive stimuli/consequences, heightened arousal and emotions (amygdala development) Development of inhibitory self-control
70
Define hyperkinetic disorders and list the types of hyperkinetic disorders
Disturbance of activity and attention - hyperkinetic conduct disorder, other hyperkinetic disorder, hyperkinetic disorder unspecified
71
What type of attention normally develops at age 2-3 years?
Single-channelled - can only focus on one thing at a time
72
When should a cardiologist assess a patient on psychostimulants?
If: - History of congenital heart disease or previous cardiac surgery - History of sudden death in first degree relative under 40 - Shortness of breath on exertion compared with peers - Fainting on exertion or in response to fright/noise - Palpitations that are rapid, regular and start/stop suddenly - Chest pain suggesting cardiac origin - Signs of heart failure - Murmur heard on cardiac examination
73
Describe the mechanism of action of atomoxitine
Enhances noradrenaline transmission in the prefrontal cortex
74
How should ACE inhibitors prescription be altered in renal disease?
With caution
75
Define clearance
Volume of plasma (blood etc) cleared of drug per unit time (e.g. ml/min or L/hour)
76
How does age generally influence pharmacodynamics of drugs?
Some effects increased - alcohol (increased drowsiness and lateral sway), fentanyl, diazepam, morphine, theophylline Some effects decreased - diminished HR response to isoproterenol and beta-blockers
77
How does oral morphine administration differ from subcutaneous/intravenous administration?
Morphine has low bioavailability when given orally (25-30%), much higher when given IV/subcutaneously (approx 1)
78
Which processes contribute to the changes which occur in the adolescent brain?
- Synaptic pruning - loss of approximately 50% of synaptic connections in some areas - Myelination - less grey matter, more white matter - Development of areas modulating social, aversive and emotional stimuli e.g. amygdala and ventral striatum
79
List the side effects of psychostimulants
Common: Reduce sleep and appetite (anorexia) Abdominal discomfort Headaches Potential for growth retardation Less common: Hypertension Tachycardia
80
What determines the prognosis in ADHD?
Co-morbidities - organic disorders, psychiatric disorders, learning difficulties Socio-economic disadvantage, negative parent-child interaction, familial ADHD
81
How long does the therapeutic take in alpha adrenergic drugs?
4-6 weeks
82
Define a drug receptor
A macromolecular component of a cell with which a drug interacts to produce a response, usually a protein
83
Give examples of drugs which are affected by reduced first pass metabolism
Profound changes in bioavailability - chlormethiazole, verapamil, paracetamol First pass activation reduced - enalapril, perindopril
84
How does therapeutic index impact the choice of drug?
The higher the TI the better the drug, drugs acting on the same receptor or enzyme system often have the same TI
85
How should assessment for ADHD be carried out in a school setting?
- Speak with education staff - behaviours during structured/less structured activities, inattentive/'daydream' behaviours, concentration and speed of work, impulsivity, quality of relationships with peers/adults, levels of attainment e.g. reading, spelling and numbers - Observation in school setting - Standardised questionnaires for education staff
86
List the subtypes of ADHD
Predominantly inattentive, predominantly hyperactive-impulsive and combined type
87
How is IV loading dose calculated?
Target concentration (mg/L) x V (L/kg)
88
Define affinity
Measure of a propensity of a drug to bind to a receptor, the attractiveness of drug and receptor
89
How is ADHD diagnosed?
- Direct observations in \>1 setting - home, school etc. - Psychoeducational assessment - Structured questionnaires - Identifying co-morbid health problems - Developmental history
90
Describe behavioural management of ADHD
- Encourage consistency in managing less desirable behaviour - Do not personalise the behaviour problems - Positively reinforce appropriate and acceptable behaviour - Assist parents to be firm and in control without being coercive - set clear rules with consequences, use routine, countdowns and reminders, use quiet time, planned ignoring and timeout (age appropriate) - Provide feedback using direct observation of interactions between child and parents
91
Compare guanfacine and clonidine use
Guanfacine is licensed for ADHD treatment of 6-17 year olds so is being increasingly used as 2nd line treatment, clonidine is not
92
How is education used in the management of ADHD?
- Parents/carers/teaching staff and older patients should be given psychoeducation on ADHD, potential co-morbidities, possible management options - Regular communication between health/education/social work etc.
93
What are the risks associated with methylphenidate?
Abuse Tics Epilepsy Increased BP Hyperthyroid
94
What should be considered in patients with decreased elimination?
Determination of renal function Alteration of dosing schedule Monitoring drug concentrations
95
Which genes contribute to increased risk of ADHD?
* Candidate susceptibility ADHD genes
* Associated LD disorders e.g. fragile X syndrome, Klinefelter syndrome, William's syndrome
96
How is loading dose affected by renal function?
It isn't - loading dose only depends on desired concentration and volume of distribution
97
In which co-morbidities is clonidine helpful?
Tics, aggression, sleep disorder
98
What type of attention normally develops at age 1-2 years?
Rigid - can attend to a task of their choosing
99
Describe the preparations of guanfacine
Oral prolonged release tablet formulation, available as 1mg, 2mg, 3mg and 4mg Tablets should not be crushed, chewed or broken before swallowing
100
What are the risks associated with dexamphetamine?
Abuse Tics Epilepsy Increased BP
101
What is elimination half-life used to determine?
Time to eliminate drug, time to reach steady state and dosage interval
102
Describe the mechanism of action of methylphenidate
Blocks dopamine and noradrenaline re-uptake via transporter
103
What additional physiological assessments should be carried out in diagnosis of ADHD?
- Hearing screening checks - Vision screening checks - As appropriate to previous/current health problems e.g. cardiac, epilepsy - Examination for neurological signs and physical anomalies - Baseline height and weight (record on centile growth chart) - Baseline blood pressure/pulse/heart sounds
104
Define agonists
Drugs that interact with and activate receptors, they possess both affinity and efficacy Two types - full and partial
105
How should a patient on ADHD medication be monitored?
Regular review (\<6 monthly) but more frequent when titrating medicines Monitor response to medication Monitor side effects Monitor height, weight, pulse and BP
106
What effect does hepatic impairment have on pharmacodynamics?
* Sensitivity to sedatives
* Sensitivity to oral anticoagulants
* Precipitation of encephalopathy
* Fluid retention
* Hepatorenal syndrome
107
Must drug holidays be taken on psychostimulants?
Yes
108
Define volume of distribution
The volume in which the amount of drug would need to be uniformly distributed to produce observed blood concentration
109
What co-morbidities are often seen alongside ADHD?
- Sleep disorders (up to 50%) - Behavioural difficulties - oppositional defiant disorder or conduct disorder (25-50%) - Specific learning disabilities e.g. dyslexia (30%) - Developmental coordination disorders (30%) - Social communication difficulties (25%) - Anxiety symptoms (25%) - Tic disorders e.g. Tourette syndrome (20%) - Mood difficulties (20%)
110
Which drugs should have a lower dose prescribed in renal disease?
Antibiotics, LMWH, digoxin, phenytoin
111
How does myelination occur during adolescence?
- Myelination increases speed of transmission while reducing energy needed - thinning of grey matter but increase in white matter - Occurs back to front - sensory/motor function areas first, prefrontal cortex and other areas involved in advanced cognitive function last
112
Define potency and explain its significance
Relative position of the dose-effect curve along the dose axis Has little clinical significance for a given therapeutic effect (a more potent drug is not clinically superior) Low potency is a disadvantage only if the dose is so large that it is awkward to administer
113
How does hepatic disease affect drug metabolism and prescription?
Same renal elimination Same/increased volume of distribution and slower rate of enzyme metabolism (half life and bioavailability increased) Decrease dose, increase dosing interval
114
Which drugs should be avoided in renal disease?
Metformin, NSAIDs
115
List the risk factors for ADHD
- Premature birth - Low birth weight - Prenatal tobacco exposure - Non-intact family/single parent household - Paternal history of anti-social behaviour - Maternal depression - Lower maternal education - Lower social class - Young maternal age at birth of affected child - Inconsistent parenting - Adverse childhood environment/psychosocial distress
116
What should be monitored in patients on psychostimulants?
Height/weight BP, pulse Efficacy Side-effects
117
How is arousal normally mediated?
By dopamine and noradrenaline, mostly in prefrontal cortex Dopamine - mesocortical, nigrostriatal and mesolimbic pathways from substantia nigra/ventral tegmental area to pre-frontal cortex Noradrenaline - from locus ceruleus to frontal and limbic regions
118
List the side effects of atomoxitine
- Nause/vomiting - Excessive tiredness - Insomnia - Abdominal pain, appetite suppression, weight loss - Constipation - Headaches - Mood swings/rage - Hepatic impairment (monitor LFTs, parents should recognise symptoms) - Increased HR/BP - Suicidal ideation (raised awareness amongst parents/carers)
119
What is CAMHS?
Child and adolescent mental health services - Work with children or young people who have difficulties with their emotional/behavioural wellbeing - Multidisciplinary teams - Up to age 16/18 or later - Support in depression, problems with food, self-harm, abuse, violence or anger, bipolar, schizophrenia, anxiety etc. - Referred by parents, teacher, GP or self if old enough
120
In which co-morbidities is guanfacine helpful?
Tics, poor sleep
121
Describe the preparations of methylphenidate
Tablet and liquid, short and long-acting - Immediate release 5mg tablets (3-4x per day) - Various preparations - duration 8-12 hours - Rapid onset of action - Cannot be manipulated for ease of administration (can't break capsule) - Usually give long acting in morning with immediate release later afternoon/early evening - Brand names e.g. Ritalin, Medikinet
122
How does hepatic impairment affect the pharmacodynamics of drugs?
Altered drug effect
123
Compare the potency of common analgesic drugs
Hydromorphone \> morphine \> codeine \> aspirin
124
List the types of drug receptor
1. Enzyme linked (multiple actions) 2. Ion-channel linked (speedy) 3. G protein linked (amplifier) 4. Nuclear (gene) linked (long-lasting)
125
Define efficacy
Intrinsic activity - ability of a bound drug to change the receptor in a way that produces an effect (some drugs possess affinity but not efficacy)
126
What is the effect of renal disease on the pharmacokinetics of drugs?
Decreased elimination Decreased protein binding Decreased hepatic metabolism
127
What is the action of a competitive antagonist?
Competes with agonist for receptor Surmountable with increasing agonist concentration Displaces agonist dose response curve to the right (dextral shift) Reduces the apparent affinity of the agonist
128
What is the difference between a full and partial agonist?
Full - agonist with maximal efficacy Partial - an agonist with less than maximal efficacy
129
What is the legal status of pschyostimulants? How does this impact prescribing?
- Schedule 2 controlled drugs - prescription required - Rx has 28-day validity - Rx signed on collection (need proof of identity) - 30-day supply (may give more if requested but prescriber must state why) - Must state - form and strength of preparation, total quantity to be supplied in words and figures, dose to be administered, signed and dated by prescriber
130
How long does the therapeutic effect of clonidine take?
Within 6 weeks
131
Define pharmacokinetics
The science of the rate of movement of drugs within biological systems, as affected by the absorption, distribution, metabolism and elimination of medications - 'what your body does to the drug'
132
Define ADHD
Attention deficit hyperactivity disorder, hyperkinetic neurodevelopmental mental disorder
133
What type of attention normally develops at age 0-12 months?
Fleeting - focuses very briefly and very quickly distracted
134
What commonly occurs when prescribing for the elderly?
Under-treatment: Coronary artery disease - beta blockers/aspirin Anticoagulation in atrial fibrillation Hypertension Pain Particular fear of narcotics in the elderly
135
List the pharmacological treatment options for ADHD
1st line - psychostimulants (methylphenidate, dexamphetamine) 2nd line - atomoxetine 3rd line - adrenergic drugs (guanfacine or clonidine)
136
Give examples of drug-drug interactions
Statins and erythromycin and other antibiotics Verapamil (calcium channel blocker) and beta-blockers Warfarin and multiple drugs (including aspirin) ACE inhibitors increase hypoglycaemic effect of sulfonylureas
137
How does having a long half-life impact administration of a drug?
Need to use loading dose to quickly reach therapeutic index
138
How effective is atomoxitine in ADHD treatment?
Efficacy = ?75%
139
How does age influence GFR?
GFR generally declines with age, but is extremely variable - 30% have little change 30% have moderate decrease 30% have severe decrease
