Antidepressants, Anxiolytics, Hypnotics, neuroleptics

Question 1

What is lithium used for?

Answer 1

Manic depression,

Reduces levels of cAMP and IP3 inside cells

Narrow therapeutic window

Question 2

Types of antidepressants

Answer 2

• TCAs
• MAOIs
• SSRIs
• SNRI

Question 3

How do TCAs work?

Answer 3

-Equally inhibits 5HT and NA reuptake by neurones

Other actions;

• inhibits a2, therefore more monoamines releases
• 5HT agonism
• H1, mAchR antagonism

Question 4

Pharmacokinetics of TCAs

Answer 4

• oral absorption
• highly plasma protein bound
• active metabolites
• renal Glucuronide excretion

Question 5

Half life of TCAs

Answer 5

10-20 hours

Question 6

What is Amitriptyline

Answer 6

a TCA

Question 7

Side effects of therapeutic dosage of TCAs

Answer 7

• atropine like effects (mAchR antagonism)
• sedation (H1 antagonism)
• postural hypotension (vasomotor centre effects)

Question 8

Over dose of TCAs

Answer 8

CNS: excitement, delirium, seizures, coma respiratory arrest

CVS: ventricular fibrillation, sudden death

Hence people may try and commit suicide

Question 9

What drugs increase the levels of free TCA in the blood?

Answer 9

Aspirin heparin and Phenytoin are heavily PPB hence displace TCAs

Question 10

Why must you take care with neuroleptic and OCPs when taken in conjunction with TCAs?

Answer 10

They use the same liver microsomal enzymes hence compete in metabolism. This leads to increased TCA effects

Note alcohol potentiates the effects of TCAs too

Question 11

How do MAOIs work?

Answer 11

Irreversible non selective inhibition of MAO enzymes

Increased leakage and release of NA and 5HT

LONG DURATION OF ACTION

Question 12

Clinical response to MAOIs

Answer 12

Rapid Oral absorption

Delayed effects, there is downregulation of Beta adrenoceptors and 5HT2 receptors

Question 13

Side effects of MAOIs

Answer 13

• atropine like effects
• postural hypotension
• sedation
• hepatotoxicity (hydrazines)
• weight gain

Question 14

Advantages of Mecloemide

Answer 14

Reversible MAO inhibitor with reduced side effects

Question 15

What happens if you take pethidine (opioid analgesic) and MAOIs?

Answer 15

• hyperpyrexia
• coma
• restlessness
• hypotension

Pethidine interacts with MAOIs toxic metabolites

Question 16

What is phenelzine?

Answer 16

A MAOi

Question 17

What is Venlafaxine?

Answer 17

An SNRI

2nd line treatment for depression

Question 18

What is fluoxetine?

Answer 18

An SSRI

Question 19

Why would you use SSRIs?

Answer 19

Less troublesome side effects and safer in over dose

But less effective for sever depression

Question 20

Pharmacokinetics of SSRIs

Answer 20

• oral administration
• plasma half life 18-24 hours
• delayed onset of action (2-4 weeks)

Question 21

Side effects of SSRIs

Answer 21

Nausea
Diarrhoea
Insomnia
Loss of libido

Question 22

What is Bicuculline?

Answer 22

Competitive GABA antagonist

Question 23

What is Flumazenil?

Answer 23

Benzodiazepine receptor antagonist

Question 24

How do Benzodiazepines work?

Answer 24

PAM

Increase the frequency of the GABAa opening hence enhance chloride influx

Question 25

How do Barbiturates work?

Answer 25

PAM | Increase the duration of GABAa opening hence enhanced chloride influx

Question 26

Why may BARBs induce surgical anaesthesia and have a lower margin of safety

Answer 26

Other effects of barbiturates may be: - decreased glutamate transmission - direct chloride ion channel opening

Question 27

What is aminobarbital used for.

Answer 27

As a sedative or hypnotic Used for severe intractable insomnia Half life: 20-25h

Question 28

Barbiturates are not first line treatment for anxiety or insomnia as they have many unwanted effects, what are they?

Answer 28

Low safety margins: - depresses respiration - overdosing easy and lethal

Question 29

How can BZs be administered

Answer 29

- IV for status epilepticus | - orally

Question 30

What are long acting benzodiazepines used for?

Answer 30

Anxiolytics

Question 31

What is diazepam used for?

Answer 31

Long acting BZ (32h) used for anxiety

Question 32

What is Oxazepam used for?

Answer 32

As an anxiolytic in Hepatically impaired people hence action is longer acting USUALLY used as a short acting (8h) BZ hence used as a sedative or hypnotic

Question 33

What is Tamazepam used for?

Answer 33

Short acting (8h) BZ used as a sedative or hypnotic

Question 34

What is Nitrazepam used for?

Answer 34

Long acting BZ but used as a daytime anxiolytic and for treating INSOMNIA

Question 35

Advantages of BZs over BARBs

Answer 35

- wide margin of safety - overdose leads to Rousable sleep - mild effect on REM sleep (less hangover) - do not induce liver enzymes

Question 36

Unwanted effects of BZs

Answer 36

- sedation in anxiolytics (confusion, amnesia, ataxia) - potentiate other CNS depressants - tolerance - withdrawal - heparin and aspirin increase plasma levels

Question 37

What is Zopiclone?

Answer 37

Short acting (5h) BZ receptor agonist with minimal hangover and dependancy Alternative Sedative or Hypnotic

Question 38

Other Anxiolytics

Answer 38

- SSRIs - Anti-epileptics - antipsychotics - propranolol - buspirone (5HT agonist)

Question 39

Types of first generation antipsychotics

Answer 39

Chlorpromazine | Haloperidol

Question 40

How does Chlorpromazine work?

Answer 40

D2 antagonist

Question 41

Side effects of Chlorpromazine

Answer 41

- sedation in anticholinergic effect | - low incidence of extrapyramidal side effects

Question 42

How does Haloperidol work?

Answer 42

Potent D2 antagonist decreases dopamine in the mesolimbic pathway Therapeutic effect takes 6 to 8 weeks

Question 43

Side effects of Haloperidol

Answer 43

High incidence of extrapyramidal side effects

Question 44

Types of second generation antipsychotics

Answer 44

- Clozapine - Risperidone - Quetiapine - Aripirazole

Question 45

What is the most effective antipsychotic and how does it work?

Answer 45

Clozapine 5HT2a receptor antagonist, can also tackle negative symptoms to certain extent

Question 46

Side effects of Clozapine

Answer 46

- agranulocytosis - neutropenia - myocarditis - weight gain Can be fatal

Question 47

How does risperidone work as an antipsychotic

Answer 47

potent 5HT2a and D2 antagonist Hence gives rise to side effects of: - EPS - hyperprolactinaemia

Question 48

How does Quetiapine work as a second gen antipsychotic?

Answer 48

Potent antagonist of a1 and H1 receptors Has lowest rate of EPS

Question 49

How does aripiprazole work as an antipsychotic

Answer 49

Partial agonist of D2 and 5HT2a (hence weak antagonist)

Question 50

Advantages of aripiprazole

Answer 50

Less: - weight gain - hyperprolactinaemia