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Path and therapeutics > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

drugs causing hepatitis/necrosis (increased ALT)

dose dependent

A

paracetamol OD

ADA

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2
Q

dose independent

drugs causing hepatitis/necrosis (increased ALT)

A
  • isoniazid, pyrazinamide
  • valproate
  • Methyldopa
  • NSAIDs
  • Phenytoin
  • statins
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3
Q

Drugs causing Cholestasis (ALP + Bi)

Dose dependent

A
  • Rifampicin

* Oestrogens + anabolic steroids (pure cholestasis)

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4
Q

Drugs causing Cholestasis (ALP + Bi)

Dose INdependent

A 
•chlorpromazine 
•clarythromycin 
•clavulanate-amox 
•cloxacillin flu- 
•chlorpropamide 
•carbimazole 
•cimetidine 
Often associated hepatitis
Impaired bile excretion from hepatocellular canaliculus (no obstruction in bile duct)
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5
Q

statosis (-hepatitis) = fatty liver

caused by

A 
Microvesicular fat: ‘VAT’  = Reye’s syndrome, Mitochondria, β-oxidation 
•Valproate 
•Aspirin 
•Tetracyclines 
 Macrovesicular fat  - and cirrhosis; Triglyceride accumulation 
•Alcoholic hepatitis 
•Amiodarone 
•Methotrexate
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6
Q

ADRs time dependent: RAPID

examples and implication

A

red man sydrome with iv vancomycin

|&raquo_space; administer slowly

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7
Q

ADR First dose example

A

hypotension with ACEi

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8
Q

type 1 hypersesnsitivity ADR example

A

penicilling

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9
Q

intermediate time (risk increases at first, then diminishes: examples

A

Agranulocytosis (carbimazole, 5-ASA’s) - first 3/12

|&raquo_space;> warn patient to report sore throat

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10
Q

late time ADR (risk increases with time

examples

A

osteoporosis with corticosteroids

tardive dyskinesia with dopamine

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11
Q

pharmacokinetics is

A

:“What the body does to drugs”

•Absorption •Distribution •Metabolism •Excretion

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12
Q

pharmacodynamics is

A

what the drug does to the body

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13
Q

interactions PK - absorbtion

A

•GI motility
–opioids/antimuscarinic: TCA↓; metoclopromide↑
•Absorption: –cholestyramine – ↓ digoxin, warfarin
•Chelation
–by antacids (Al, Mg, Ca) + milk of tetracyclines, iron + prednisolone
•Gut flora –
–antibiotics ↓ vit. K synthesis – potentiate warfarin

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14
Q

Interactions: PK - Metabolic Liver enzyme inducers:

A 
• Phenytoin 
PC BRAS`
• Carbamazepine 
• Barbiturates & BBQ’d foods 
• Rifampicin 
• Alcohol - chronic 
• Smoking, St. Johns Wort, Sulphinpyrazone (→theophylline)
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15
Q

PK interactions: Displacement

A

• Displaced drug metabolized & excreted
– usually need 2nd mechanism to be clinically significant, e.g.:
• Displacement from plasma proteins
– Valproate displaces phenytoin & inhibit metab.
– ASA + NSAIDs displace methotrexate & ↓ secretion → serious MTX toxicity
– Sulponamides, vit. K + indometacin displace bilirubin & immature metabolism in neonate →kernicterus
• Displacement from tissue binding
– Amiodarone displaces digoxin & impairs its excretion

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16
Q

Interactions: PK - Metabolic Liver enzyme inhibitors

A

GO DEVICES

  • Grapefruit juice
  • Omeprazole
  • Disulfiram
  • Erythromycin
  • Valproate
  • Isoniazid
  • Cimetidine
  • Ethanol (acute)
  • Sulphonamides
Allopurinol 
Metronidazole, ketoconazole 
Ciprofloxacin 
Verapamil + diltiazem 
Amiodarone 
Chloramphenicol 
SSRIs 
Sulphinpyrazone (→warfarin,phenytoin)
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17
Q

Interactions: PK – Metabolic; Clinically significant if narrow therapeutic range:

A 
WAC STOPS 
•Warfarin 
•Anti arrhythmics 
•Ciclosporin 
•Sulphonylureas 
•Theophyllines 
•Oral Contraceptive Pill 
•Phenytoin 
•Steroids, statins
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18
Q

Statins & CYP3A4 inhibitors

A
  • Risk of rhabdomyolysis, myositis, myopathy
  • Especially simvastatin
  • Caution atorvastatin
  • Fluvastatin CYP2C9
  • Pravastatin & rosuvastatin minimal CYP metab
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19
Q

Interactions: PK - Warfarin

A
  • protein binding displacement (99%)
  • salicylates/ NSAIDs, sulphonamides
  • inhibit metabolism
  • amiodarone, metronidazole, sulhinpyrazone, acute alcohol, cimetidine
  • induction of metabolism: ‘PC BRAS’’
  • Cranberry juice:↑INR/bleeding
  • Care with statins
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20
Q

Extramicrosomal inhibitor interactions

A

Precipitant Enzyme Object
allopurinol xanthine oxidase azathioprine
carbidopa dopa decarboxylase L-dopa
metronidazole aldehyde dehydrogenase alcohol
MAOIs MAO tyramine, amphetamine

21
Q

Interactions: PK - Excretion

A

Glomerular filtration (unbound drug only)
•Active tubular secretion
–also ↓ in renal failure
–penicillin inhibited by probenicid
–digoxin inhibited by amiodarone (MDR1) + CCBs
–MTX inhibited by salicylates – serious toxicity
–Uricosuric/uricostatic agents
•Passive tubular reabsorption
–weak acids (aspirin) inhibited in alkaline urine (more ionized )
–lithium ↑with Na depletion due to diuretics

Penicillin: probenicid
Nifedipine: digoxin
Digoxin: verapamil
Aspirin: methotrexate
Sodium bicarb: aspirin
Denrofluazide: lithium
22
Q

Interactions: PD

A

•Actions on receptors
•Antagonistic: naloxone for morphine OD, B blockers and salbutamol
•Actions on body systems
•Antagonistic: NSAIDs and diuretics/ BB’s
•Synergistic: iv verapamil & BB – asystole
–theophylline & B agonists – arrhythmias
–loop diuretic & aminoglycoside – both ototoxic
–Sedation with amitrityline + diazepam
–Aspirin & streptokinase

23
Q

Interactions: Adenosine

A
  • Dipyridamole – potentiates effect of adenosine +++
  • If essential to give adenosine, reduce initial dose to 0.5-1 mg.
  • Mechanism –Reversibly inhibits plt phosphodiesterase
  • ↑cAMP →↓plt thrombotic activity
  • Dipyridamole blocks adenosine uptake - increases adenosine levels
  • leading to inhibition of platelet aggregation and vasodilatation mainly in the coronary tree
  • Theophylline/caffeine – inhibit phosphodiesterase attenuate effects of adenosine
Naloxone:morphine
Atenolol: slabutamol
Ibuprofen: bedroflumathiazide
Atenolol: IV verapamil stat
Frusemide: digoxin (hypokalaemia)

Theophyline: salbutamol
Frusemide: gentamycin
Amitryptyline: diazepam
Aspirin: iboprufen

24
Q

Risks: Necessary prophylaxis exampels

A
  • ASA/NSAIDs: Hx bleeding, on anticoagulant, combination, Or 2 of: >60 y, corticosteroids, GORD; PPIs, e.g. lansoprazole
  • Opioids: Laxatives
  • corticosteroids: bone –if likely to take ≥7.5 mg pred - 3 months; eg. bisphosphonates – alendronate
25
Q

Allergies (immunological) & timing

Immediate

A

•Type I – Immediate Hypersensitivity

–Anaphylaxis and urticaria with penicillins

26
Q

Allergies (immunological) & timing

intermediate

A 
Type II – cytotoxic antibody 
–Haemolysis with methyldopa 
–Thrombocytopenia with quinine 
•Type III – immune complex 
–Interstitial nephritis with penicillins 
•Type IV – Delayed Hypersensitivity 
–Stevens-Johnson sy. with carbamazepine 
–Pseudoallergic rash with amoxycillin
27
Q

Disease susceptibility to allergy

A

Infectious Mononucleosis
•Increased likelihood of cutaneous reactions to penicillins and other antimicrobials
•? mechanism - virus alters the immune status of the host.
•drug can be readministered safely once the viral infection has resolved
Human Immunodeficiency Virus
•higher frequency of allergic reactions
•Hypersensitivity to trimethoprim–sulfamethoxazole in 20 to 80%, (cf. 1-3%)
•Mechanism -? altered drug metabolism or decreased glutathione levels

Cystic Fibrosis
•~ 30 % develop allergy to one or more antibiotics:
•Piperacillin, ceftazidime, and ticarcillin
•Mechanism: repeated exposure to antibiotics and immune hyper-responsiveness
•Use lower doses + monitor carefully, or avoid

28
Q

sex susceptability

A 
Women 
•Alcohol 
•Neuropsychiatric effects of mefloquine 
•ACE inhibitor cough 
•Drug-induced lupus 
•hepatitis: methyldopa, cholestasis: flucloxacillin 
Men 
•Cholestasis: co-amoxiclav 
•Use lower doses
29
Q

age susceptability

A 
•Elderly 
– diuretics, antihypertensives, beta-blockers 
–digoxin 
–NSAIDs 
–CNS-drugs – benzodiazepines 
–Tricyclic antidepressants 
–H1 antihistamines (chlorpheniramine) 
–H2-receptor antagonists (ranitidine) 
–Opiates
30
Q

Hepatic cirrhosis effects on drugs

A 
•CAFÉ: 
Clotting↓   
Albumin↓    
Fluid↑  
Électrolytes 
•METRO: 
Metabolism↓   
Encephalopathy  
Toxic (hepato-) drugs  
Renal

–toxicity: hepatocellular necrosis, cholestasis, steatosis
–recovery affected > likelihood of developing

  • Screen for abnormalities (U+Es, INR, LFTs)
  • avoid/ reduce doses of specific drugs
31
Q

Acetylator status & lupus

A 
These drugs are acetylated ‘HIPS’: 
•Hydralazine     
•Isoniazid    
•Procainamide    
•Sulphonamides

Slow acetylators (low N-acetyl transferase) ↑ incidence of drug-induced lupus

32
Q

P450 Polymorphisms

A 
CYP2D6: 8% of UK lack this enzyme (AR) 
•metoprolol - bradycardia 
•flecainide - arrhythmias 
•amitriptyline - confusion 
•codeine - lack of effect (morphine) 
CYP2C9 
•Warfarin – haemorrhage – as mean dose required is only 1.6 mg, not 5.5 mg 
•Tolbutamide - hypoglycaemia
33
Q

G6PD deficiency & Haemolysis

A

‘favism’ (children who eat Broad bean Vicia Faba)
•100 M people:
•Africa, Med, Mid East, SE Asians

  • Acute haemolysis 2-3 d after oxidant substance
  • Self-limiting: only older cells (least enzyme) affected
Drugs causing haemolysis (oxidizing agents) 
•dapsone 
•methylene blue 
•nitrofurantoin 
•primaquine 
•quinolones 
•sulphonamides
34
Q

drugs conttraindicated with simvastatin

A
  • Itraconazole
  • Ketoconazole
  • Posaconazole (New)
  • Erythromycin
  • Clarithromycin
  • Telithromycin
  • HIV protease inhibitors
  • Nefazodone
  • Gemfibrozil
  • Cyclosporine
  • Danazol
35
Q

does glomerulus filtrate bound or unbound drug?

A

unbound only

36
Q

what inhibits active excretion of penicillin?

A

probenicid

37
Q

what inhibits active excretion of digoxin?

A

amiodarone and CCBs (verapamil)

38
Q

what inhibits active excretion of methotrexate?

A

salycilates

39
Q

what affects passive tubular reabsorption of drugs?

A 
weak acids (aspirin) are inhibited in alkaline urine (more ionized)
ie sodium bicarb affects aspirin
40
Q

what affects the reabsorption of lithium?

A

diuretics, due to Na depeletion

41
Q

Pseudocholinesterase deficiency

prevalence and effects

A

•Pseudocholinesterase deficiency

1/2500

–↓↓metabolism of suxamethonium; rolonged paralysis ;

screen relatives

42
Q

malignant hyperthermia prevalence and effects

A

1/20,000 GA (AD)

–esp. gaseous halogenated agents,
–release sarcoplasmic Ca – contraction, hypermetabolic

–Dantrolene, cooling, O2, fluids,

–Neuroleptic malignant sy. - clinically similar – haloperidol

•Rx: dantrolene, dopamine agonists

43
Q

cautions with azathioprine?

A

Thiopurine Methyl Transferase (TPMT) defy

(AR: 1 in 300)

–azathioprine – severe toxicity ; screen to avoid

44
Q

Thiopurine Methyl Transferase (TPMT) deficiency

A

(AR: 1 in 300)

–azathioprine – severe toxicity ; screen to avoid

45
Q

drugs unsafe in porphyria

A

alcohol
amphetamines
antidepressants
antihistamines

barbs + benzos (**diazepam is safe)

cephalosporins
diuretics

Ergot
Gold
sex steroids (OCP)

sulphonylamides
sulphonylureas

46
Q

things to check before administering drugs

A 
I DRAFFT 
•ID of patient & drug   
•Dose 
•Route 
•Allergy-check 
•Formulation 
•Frequency 
•Timing
47
Q

drugs that are renally excreted + have narrow therapeutic window

A

digoxin
gentamycin
cancomycin
lithium

also metformin

48
Q

drugs that require loading dose

A

digoxin - high tissue binding
lidocaine - lipid soluble
heparin warfarin phenytoin - high plasma protein binding

49
Q

photosensitivity occurs with these drugs@

A

amiodarone

chlorpromazine

Path and therapeutics (14 decks)

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