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Flashcards in Week 1 Deck (45):
1

What should you know about common drugs?

MoA, indications, side effects, important pharmacokinetics/dynamics and what you would tell patient

2

What factors affect bioavailability of drugs?

Molecular weight/ ionisation, absorption (gastric pH/health of GI tract), first pass metabolism

3

What is the apparent volume of distribution?

Volume in which the amount of drug would need to be uniformly distributed to produce observed blood concentration

4

What is the half life of a drug?

Time required for serum plasma concentration to decrease by half, determined by clearance and volume of distribution

5

What are linear pharmacokinetics?

- 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)

6

What are 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
- Due to saturation of enzymes that metabolise drugs

7

Does phenytoin have linear or non-linear pharmacokinetics?

Non-linear

8

What are drug receptors?

Macromolecular component of a cell with which a drug interacts to produce a response (usually proteins- regulatory, enzymes, transport or structural)

9

What are 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)

10

What is affinity?

Measure of propensity of a drug to bind receptor, the attractiveness of drug and receptor

11

What is the efficacy of a drug?

Ability of a bound drug to change the receptor in a way that produces an effect; some drugs possess affinity but not efficacy

12

What is potency of a drug?

- Relative position of the dose-effect curve along the dose axis
- Low potency is a disadvantage only if the dose is so large that it is awkward to administer

13

How is therapeutic index calculated?

Therapeutic dose or lethal dose for 50% of population (TD50 or LD50) divided by efficacious dose for 50% of the population (ED50)

14

What special patient populations should be considered when prescribing drugs?

Renal disease, hepatic disease and cystic fibrosis

15

What drugs should be prescribed differently in renal disease?

- Antibiotics: reduce dose
- Low molecular weight heparins: reduce dose
- Metformin: avoid
- NSAIDs: avoid
- Digoxin: reduce loading dose
- Phenytoin: reduce dose
- ACE Inhibitors: caution

16

How does hepatic impairment affect pharmacokinetics?

- First pass metabolism
- Activation of prodrugs
- Decreased protein binding
- Decreased elimination

17

How does hepatic impairment affect pharmacodynamics?

Altered drug effect

18

What are the clinical features of ADHD?

Clinical features must be apparent before the child is age 7 years, excessive for the child's age and dev, pervasive (evident across more than 1 environments, normally 3), symptoms may worsen in the afternoon

19

What % is the brain of a child with ADHD smaller than their peers?

3%

20

What neurological factors affect/cause ADHD?

- Smaller brain volume
- Smaller basal ganglia
- Right dorso-lateral prefrontal lobe reduced
- Smaller cerebellar vermis
- Attentional systems involve anterior fronto-striatal network
- Posterior parieto-cerebellar circuits

21

What co-morbidities are associated with ADHD?

- sleep disorders
- behavioural difficulties
- specific learning disabilities
- development co-ordination disorders
- social communication difficulties
- anxiety symptoms
- tic disorders e.g tourette syndrome
- mood difficulties

22

How is ADHD assessed?

No specific diagnostic test, instead assessment includes:
- direct observations in more than 1 setting
- psychoeducational assessment
- structured questionnaires
- identifying co-morbid (mental) health problem
- developmental history
- develop a formulation

23

What is important to look for in a parental report?

- current behaviours, activity levels, impulsivity, emotional reactivity
- ability to sustain interest/attention (with/without adult involvement)
- eating and sleeping habits
- responses to and interactions with others
- parental management strategies
- structures questionnaires

24

What other features of a history are important to look at when diagnosing ADHD?

- pregnancy/delivery
- patterns of feeding, sleeping and play
- activity levels, impulsivity, emotional reactivity
- ability to sustain interest/attention
- is the developmental stage appropriate for the chronological age

25

How can the environment of a patient with ADHD be managed?

- provide calming environment
- avoid too many distracting stimuli when you want the child to concentrate
- initially, avoid situations that require quiet, still behaviour for long periods
- maintain structure and supervision longer than you think should be necessary

26

What are the medication options for ADHD?

1st Line: psychostimulants
1st/2nd Line: atomoxetine (acts on NA transporter in prefrontal cortex)
1st/3rd Line: clonidine (alpha-2 adrenergic receptor agonist)
2nd Line: guanfacine (alpha-2A receptor adrenergic receptor agonist)

27

What are the common psychostimulants used to manage ADHD and how do they work?

Methylphenidate (blocks DA and NA re-uptake via transporter) and Dexamphetamine (releases DA stored in presynaptic vacuoles)

Act on D1 receptors in the prefrontal cortex and D2 in the striatum

28

What is elvanse?

A pro-drug metabolised to dexamphetamine by red blood cells at set rate, with a rapid onset of action lasting 13 hours, though it may cause dizziness or drowsiness

29

What are the side effects of psychostimulants?

- Anorexia, weight loss, nausea, growth concerns
- Sleep difficulties
- Dizziness, headache
- Involuntary movements or tics
- Dysphoria, agitation
- Tachycardia, hypertension
- Syncope suspected to have cardiac origin

30

What is the prognosis for patients with ADHD?

Depends on co-morbidity. Factors associated with persistence into adulthood are progressive reduction in cerebellar and hippocampi volumes, maternal depression, martial discord, negative parent-child interaction, family socio-economic disadvantage and familial ADHD

31

What does dexamphetamine do?

Faciliates release of dopamine from presynaptic cytoplasmic storage vesicles in synapse and blocks dopamine transporter protein

32

What does methylphenidate do?

Primarily inhibits the dopamine transporter to increase dopamine

33

What effects do stimulants usually have

Improve attention span, hyperactivity and impulsivity decrease, and decreased aggression with rapid onset

34

What are the side effects of psychostimulants?

Growth retardation, anorexia, BP and HR irregularities, insomnia/sleep difficulties and others (sadness, irritability, abdominal pain and headaches)

35

What is the proposed mechanism of action of atomoxetine?

Noradrenaline re-uptake inhibitor, enhanced NA transmission in the prefrontal cortex area

1. NA is released into the synapse
2. NA reversibly attaches to receptors
3. Atomoxetine blocks reabsorption of NA from the synapse

(effective for co-morbidities, anxiety and depression)

36

What are the side effects of atomoxetine?

- nausea/vomiting
- excessive tiredness
- insomnia
- abdominal pain, appetite suppression, weight loss
- constipation
- headaches
- mood swings/rage
- hepatic impairment (monitor LFTs, recognise symptoms)
- increased HR/BP
- suicidal ideation (raised awareness amongst parents/carers)

37

How often is atomoxetine given?

Once daily or BD dosing (no need to administer during school)
6 weeks for onset, long delay before it works

38

What is the MoA of clonidine and guanfacine?

Central and peripheral adrenergic agonists- inhibit NA re-uptake at the synapse

Clinical effect takes time (4-6 weeks)

39

What are the side effects of clonidine and guanfacine?

Sedation, dizziness, hypotension (monitor BP and HR)

40

With which group patients are antidepressants used?

Adults, rarely used in children

41

How do antidepressants work?

Enhance the amount of monoamines at the synapse

42

What are the most common antidepressants?

Nortiptyline and Imipramine most common

43

What are the side effects of antidepressants?

Anticholinergic, cardiac SEs and seizures

44

What is modafinil?

Weak psychostimulant, weak affinity for dopamine uptake carrier sites: may work by decreased GABA and increasing release of glutamate, also by controlling degree of hypothalamic arousal

(not used in CAMHS)

45

What are the SEs of modafinil?

GI SEs, appetite, abdominal pain, dry mouth, tachycardia