EPSEs, drug interactions, Prescribing

Question 1

EPSEs causes? Mechanism?

Answer 1

Typical antipsychotics
 Rarely: metoclopramide, prochlorperazine - Esp. in young women

Dyskinesias and dystonias are common in antiparkinsonian
drugs.

D2 block in nigrostriatal pathway, excess AChM

Question 2

Tx of parkinsonian SEs? Time of onset of symtpoms?

Answer 2

procyclidine

w/i months

Question 3

Acute dystonia time of onset? Effectss who? Features? Tx?

Answer 3

Occurs w/i hrs-days of starting drugs
 Commoner in young males
 Involuntary sustained muscle spasm e.g. lock jaw, spasmodic torticollis, oculogyric crisis
 Rx: procyclidine

Question 4

Akathisa tiem of onset? define? Tx?

Answer 4

Occurs w/i days to months
Subjective feeling of inner restlessness
 Rx: propranolol (crosses BBB)

Question 5

Tardice dyskinesia features? Tx?

Answer 5

Rhythmic involuntary movements of head, limbs and
trunk.
Chewing, grimacing
Protruding, darting tongue

occurs after years of being on long-term neuroleptics

tx: Switch → atypical neuroleptic
 Clozapine may help
 (procyclidine worsens symptoms)

Question 6

Neuroleptic malignant syndrome time of onset? features? effects who? Tx?

Answer 6

4-10d after initiation or change of dose
Motor: severe muscular rigidity
Mental: fluctuating consciousness
Autonomic: hyperthermia, ↑HR, sweating, ↑/↓BP
Blood: ↑CK, leukocytosis

Tx: Dantrolene: inhibits muscle Ca release
Bromocriptine / apomorphine: reverse Da block
Cool pt.

Question 7

Drugs which alter absorptions which given together?

Answer 7

Tetracyclines and quinolones w/ Ca, Fe, Al

 Drugs chelate the metals and are not absorbed

Question 8

Drugs that cause displacement from plasma proteins?

Answer 8

Warfarin + some NSAIDs
 Often clinically insignificant as clearance ↑s
proportionally w/ displacement

Question 9

Drugs interactions with diuretics due to increased excretion?

Answer 9

Diuretics → ↓ Li clearance

Loop diuretics: ↑ aminoglycoside ototoxicity

Question 10

Indirect drug interactions?

Answer 10

Diuretics and steroids → ↑ risk of digoxin toxicity via ↓ K+
 NSAIDs + warfarin → ↑ risk of GI bleed
 Abx + warfarin → ↑ bleeding risk
 Abx kill GI microflora that make vit K

Question 11

P450 inducers? Inhibitors?

Answer 11

PC BRAGS - inducers

Phenytoin
 Carbamazepine
 Barbiturates
 Rifampicin
 Alcohol (chronic)
 Griseofulvin
 St. John’s Wart

VIP CEO GF
Valproate
Isoniazid 
Protease inhibitors
Cipro, cimetidine
Erythromycin + clarithromycin
 Omeprazole
 Grapefruit juice
 Fluconazole / Fluoxetine

Question 12

Importantt drugs metabolised by P450?

Answer 12

COWEST

Ciclosporin
 OCP
 Warfarin
 Epileptic drugs: phenytoin, CBZ
 Statins
 Theophylline

Question 13

Drug interactions with diuretics?

Answer 13

Potentiate: ACEi, Li, Digoxin
 Loop → ↑ risk of ototoxicity c¯ aminoglycosides
 K-sparing → ↑ risk of hyperkalaemia w/ ACEi

Question 14

Pharmakinetic considerations when prescribing for elderly patients?

Answer 14

Distribution: 
↓ body water → ↑ [water soluble drugs]
 ↑ body fat → ↓ [fat soluble drugs]
 ↓ albumin → ↑ [protein-bound drugs]
 ↓ wt.  standard dose → ↑ [drug]

Metabolism:
↓ oxidation
 ↓ first-pass metabolism (e.g. propranolol)
 ↓ induction of liver enzymes therefore ↑ age → ↑ t½ of hepatically metabolised drugs E.g. Warfarin

Question 15

Except for pharmacokinetic considerations, other cosniderations when prescribing for elderly patients?

Answer 15

Altered organ sensitivity:
ANS - Defective compensatory mechanisms. Also↓ β-receptor density therefore ↓ effectiveness of drugs targeting them

CNS: ↑ sensitivity to anxiolytics and hypnotics

Cardiac function reduced, therefore ↓ perfusion of liver and kidneys → ↓ function → ↓
metabolism or elimination of drug

Compliance issues: confusion, reduced vision, arthritic hands, living alone, polypharmacy

Question 16

Drugs causing major problems in elderly patients?

Answer 16

Affecting the Cardiovascular System
 Anti-hypertensives
 Digoxin
 Diuretics
Affecting the CNS
 Anti-depressants
 Ant-parkinsonian
 Hypnotics

Question 17

Pharmokinetic considerations in neonates?

Answer 17

Absorption: ↓ gastric motility
 Distribution: Immature BBB
↑ body water → ↓ [water soluble drugs]
↓ body fat → ↑ [fat soluble drugs]
↓ albumin → ↑ [protein-bound drugs]
 Metabolism
↓ P450 activity
↓ conjugation

Excretion
 ↓ GFR and ↓ tubular secretion

Question 18

Common teratogenic drugs?

Answer 18

ACEi: affect kidney growth
 AEDs: NTDs
 Li: Ebstein’s anomaly
 Anti-folate: e.g. trimethoprim → NTDs
 Tetracyclines: stain teeth
 Warfarin: cardiac defects, ↓IQ, saddle nose, blindness
 Statins

Question 19

Drugs to avoid in late pregnancy?

Answer 19

Aspirin: haemorrhage, kernicterus
 Aminoglycosides: CN8 damage
 Anti-thyroid: goitre, hypothyroidism
 Benzos: floppy baby syndrome
 Chloramphenicol: grey baby syndrome
 Warfarin: haemorrhage
 Sulphonylureas: kernicterus

Question 20

Drugs for HTN during pregnancy?

Answer 20

NB. Don’t prescribe ACEi to fertile young women.
 Labetalol
 Methyldopa
 Nifedipine
 Hydralazine

Question 21

Drugs for epilepsy during pregnancy?

Answer 21

Folic acid pre-conception
 Drug levels tend to fall in pregnancy
 Avoid valproate
 Use lamotrigine (or CBZ)

Question 22

Anticoagulation during pregnancy?

Answer 22

1st trimester: LMWH
 2nd trimester – 36wks: LMWH or warfarin
 36wks – term: LMWH
 Term onwards: warfarin

Question 23

Drugs to be wary of during breast-feeding?

Answer 23

Sedatives (benzos, alcohol - drowsiness
Anti-thyroid - goitre
Tolbutamide - hypoglycaemia in infant

Question 24

Drugs affected by renal impairment? Toxicity symptoms?

Answer 24

Digoxin - Nausea, xanthopsia, gynaecomastia, A / V tachyarrhythmias, heart block

gentamycin - Ototoxic: hearing + vestibular, Nephrotoxic tubules - ↑ risk of toxicity if ↓ Na (e.g. diuretics) or dehydration

atenolol - Bradycardia, hypotension, Worsening of PVD and heart failure, Confusion
amoxicillin - Seizures (in meningitis: impaired BBB), Rashes

captopril - Hypotension, Taste disturbance, Cough, ↓ GFR, Angioedema

Question 25

CI of atenolol?

Answer 25

Asthma / bronchospasm
 Severe heart failure
 PVD

Question 26

Types of vitamin D in human body? mechanism of production?

Answer 26

Colecalciferol / D3: formed in skin and found in food
 Calcifediol: 25 OH-Vit D3 produced by the liver
 Calcitriol: 1, 25, (OH)2 Vit D3, produced by the kidney

Question 27

Why you get vit D deficiency in renal disease? Tx?

Answer 27

25 OH-Vit D3 (calcifediol) undergoes renal 1α-hydroxylation to the active form: 1, 25, (OH)2 Vit D3 (calcitriol)
 Impaired 1α-hydroxylase function in renal disease

alfacalcidol

Question 28

Drugs causing nephrotoxicity? effect? Monitoring?

Answer 28

Gentamycin: renal tubular damage - accumulation - increased nephro/ototoxicity
must monitor drug levels

Li: Inhibits Mg-dependant enzymes e.g. adenylate cyclase - ADH requires adenylate cyclase therefore Li → nephrogenic DI
 Also causes direct tubular damage
 Must monitor drug levels

ciclosporin: reduces GFR (reversible), damages renal tubules (irreversible)

ACEi/ARBs: ↓GFR: inhibit efferent arteriorlar vasoconstriction

NSAIDs: ↓ GFR: prevent afferent arteriolar vasodilatation
 Papillary necrosis

Question 29

Cautions in hepatic impairment?

Answer 29

hypoalbuminaemia: ↑ proportion of free drug - Phenytoin, CBZ; Prednisolone; Diazepam; Tolbutamide

↓ Synthesis of Clotting Factors- Warfarin, Abx (kill GI microflora)

reduces First Pass Metabolism: Opiates, Phenothiazines, Imipramine

Encephalopathy
 Sedatives / Opiates: may → coma
 Caution with drugs that may → constipation
 Anxiolytics: temazepam safest (short t½) -Avoid chlormethiazole
Anti-depressants: TCAs safest (but ↓ dose) - Avoid MOAIs