Pharmacology & Toxicology Flashcards
Causes of Hyperpyrexia (7)
- Salicylates *
- Ecstasy *
- Cocaine *
- Neuroleptic malignant syndrome
- Serotonin syndrome
- Thyroid storm
- Co poisoning *
3 Drugs casuse sensorineural deafness
- Lasix iv ( oral unlikely)
- Vancomycin iv
- Erythromycin iv
6 Drug induced impaired glucose tolerance
- Nicotinic acid ( Vit B3)
- Atypical antipsychotics ( olanzapine )
- Tacrolimus & cyclosporine
- Steroids
- Interferon alpha
- Thiazides & lasix
*NAT SIT
4 Drug causes of urticaria
- NSAIDS
- Opiates
- Penicillins
- ASA
- NOPA
7 Drugs causing photosensitivity
- NSAIDS
- ACEi/ ARBs
- Sulfphonylureas
- Thiazides
- Amiodarone
- Psoralens
- Tetracycline, sulphonamide, cipro
- NAS TAPT
3 Drug causes of gingival hyperplasia
- Cyclosporine
- Phenytoin
- CCB ( especially Nifedipine)
*CPC
5 Drug causing lung fibrosis
- Amiodarone
- Methotrexate & sulfasalazine
- Bleomycin & busulphan
- Nitrofurantoin
- Bromocriptine , cabergoline, pergolide
5 Drug induced urinary retention
- Disopyramide
- Opioids
- Tricyclic antidepressants
- Anticholinergics ( antipsychotics & antihistamine)
- NSAIDS
- DO TAN
Drug induced pancytopenia
- Cytotoxics
- Antibiotics: trimethoprim, chloramphenicol
- Anti-rheumatic: Gold , penicillamine
- Carbimazole
- Phenytoin, carbamazepine
- Sulphonylureas
Drug causes of agranulocytosis
- Antithyroid drugs - carbimazole, propylthiouracil
2.Antipsychotics - atypical antipsychotics (CLOZAPINE)
3.Antiepileptics - carbamazepine
4.Antibiotics - penicillin, chloramphenicol, co-trimoxazole
5.Antidepressant - mirtazapine
6.Cytotoxic drugs - methotrexat
1 Drugs causing Cataracts
steroids
2 Drugs causing Corneal opacities
amiodarone
indomethacin
3 Drugs causing Optic neuritis
amiodarone
ethambutol
metronidazole
Drugs causing Retinopathy
chloroquine, quinine
Drugs causing blue discolouration and non-arteritic anterior ischaemic neuropathy
Sildenafil
Alcohol drinking management
Ora thiamine
Benzodiazepines for acute withdrawal
Disulfram
Acamprosate
Stages of Ethylene toxicity
Stage 1: symptoms similar to alcohol intoxication: confusion, dizziness, dysarthria
Stage 2: metabolic acidosis, high Anion Gap & high osmolar gap, tachycardia, HTN
Stage 3: AKI
Treatment of ethylene toxicity
- fomepizole is preferred to ethanol
- hemodialysis
Treatment of Methanol poisoning
- fomepizole
- hemodialysis
- cofactor therapy with folinic acid to reduce ophthalmological complications
Ecstasy poisoning features
CNS: agitation, confusion , ataxia
CVS: tachycardia and HTN
Fever
Hypo Na
Rhabdomyolsis
Ecstasy poisoning management
- supportive
- dantrolene maybe used for fever if other simple measures fail
Carboxyhemoglobin level in non smoker
< 3 %
Carboxyhemoglobin level in smoker
< 10 %
Carboxyhemoglobin level in symptomatic
10-30 %
Carboxyhemoglobin level in severe toxicity
> 30 %
in Carbon monoxide poisoning , ECG is useful to look for …..
Cardiac ischemia
Treatment of CO poisoning
- 100 % high flow O2 via Non rebreather mask
- Minimum 6 hrs
- Target SPo2 100 %
5 Indication of hyperbaric oxygen in CO poisoning
- Level > 25 %
- Pregnancy
- Neurological signs
- Myocardial ischemia
- Arrhythmia
5 Features of Mercury poisoning
- Visual field defects
- Hearing loss
- Irritability
- Paraesthesia
- RTA
2 Risk factors of Paracetamol overdose
- Malnourished patients ( e.g anorexia nervosa) or patients who have not eaten for a few days
- Hepatotoxic Drugs ( rifampicin, phenytoin, carbamazepine, chronic alcohol excess
** acute alcohol intake is not risk factor
** maybe protective
Acetyl cysteine is used in ttt of paracetamol overdose as it’s …….
It’s a precursor of glutathione and hence can increase hepatic glutathione production
Side effect of acetylcysteine ?
And how to treat?
Anaphylactoid reaction
- stop iv acetyl cysteine then restarting at slower rate
Criteria for liver transplant in paracetamol liver failure
- PH < 7.3 , 24 hrs after ingestion
Or
- PT > 100 sec & creat > 300 & encephalopathy grade III or IV
Paracetamol overdose occurs when glutathione stores run out leading to ….
Increase NAPQI ( N acetyl p benzoquinone imine)
Fomepizole is an inhibitor of ….
Alcohol dehydrogenase
Confusion and pink mucosae
CO poisoning
Features of organophosphate poisoning
Salivation
Lacrimation
Urination
Defecation
Hypotension
Bradycardia
Small pupils
Muscle fasciculation
Drugs that can be cleared with hemodialysis
BLAST
- Barbiturates
- Lithium
- Alcohol ( methanol & ethylene glycol)
- Salicylate
- Theophylline ( charcoal hemoperfusion is preferred)
Drugs that can ( not ) be cleared with hemodialysis
- Tricyclics & benzodiazepines
- BB & digoxin
- Dextropropoxyphene
BB overdose features & treatment
Hypotension
Bradycardia
HF
Syncope
Ttt:
If bradycardia»_space; >atropine
In resistant cases»_space;> glucagon
Treatment of organophosphate poisoning
- Atropine
- pralidoxime
Salicylate overdose features
- Mixed respiratory alkalosis and metabolic acidosis
- Hyperventilation
- Seizures and coma
- Sweating and fever
- Hyperglycemia and hypoglycemia
- Tinnitus and lethargy
Salicylate overdose treatment
- ABC
- Charcoal
- Urinary alkalinization with iv NaHco3
- Hemodialysis
6 Indications for hemodialysis in Salicylate overdose
- Serum concentration > 700 mg/l
- Persistent metabolic acidosis
- AKI
- Pulmonary edema
- Seizures
- Coma
Cyanide poisoning features
Classical features: Brick red skin & Smell of bitter almonds
Acute : hypoxia , hypotension, headache, confusion
Chronic: ataxia, peripheral neuropathy, dermatitis
Cyanide poisoning management
- 100 % O2
- Iv hydroxocobalamin
- combination of amyl nitrite , Na nitrite and Na thiosulfate
Botulinum toxin indications
- Achalasia
- Severe hyperhidrosis of the axillae
- Hemifacial spasm
- Blepharospasm
- Spasmodic torticollis
- Focal spasticity in cerebral palsy, hand& wrist disability associated with stroke
When should measure digoxin level If suspected digoxin toxicity
Within 8 -12 hrs of the last dose
Features of digoxin toxicity
Lethargy, confusion
Nausea and vomiting and anorexia
AV block , bradycardia
Gynecomastia
Precipitating factors for digoxin toxicity
- Hypo K , Hypo Mg , Hypoalbuminaemia
- hypothermia, hypothyroidism
- hyper Ca , Hyper Na
- renal failure, acidosis
- myocardial ischemia
- old age
- drugs
Precipitating factors for digoxin toxicity
( drugs )
- amiodarone, Verapamil, diltilazem
- quinidine
- ciclosporin , spironolactone
- drugs can cause Hypo K: thiazides, loop diuretics
Management of digoxin toxicity
- Digibind
- Correct arrhythmias
- Monitor potassium
Treatment of lead toxicity
Dimercaprol , Ca edetate
Treatment of benzodiazepines overdose
- Supportive care
- Flumazenil ( can cause seizure) only with severe or iatrogenic overdose
Lithium toxicity occurs when the concentration level
> 1.5 mmol/L
Lithium toxicity maybe precipitated by
Dehydration
Renal failure
Drugs: thiazides, ACEi/ARBs , NSAIDS, Flagyl
Features of lithium toxicity
- Coarse tremor ( fine tremor in therapeutic level )
- Hyperreflexia
- Confusion , seizure , coma
- Polyuria
Cocaine mechanism of action
Cocaine block the uptake of dopamine, noradrenaline and serotonin
Treatment of cocaine toxicity
- benzodiazepines first line
- chest pain: benzodiazepines + glyceryl trinitrate, if MI»_space; PCI
- HTN : benzodiazepines + Na nitroprusside
- BB in cocaine induced cardiovascular problems
Early features of tricyclic overdose
- Dry mouth
- dilated pupils , blurred vision
- agitation
- sinus tachycardia
4 features of severe poisoning in
tricyclic overdose
- seizures,
- coma
- metabolic acidosis
- arrhythmias
ECG changes in tricyclic overdose
- sinus tachycardia
- widening of QRS
- Prolongation of QT interval
In tricyclic overdose , Widening of QRS
- > 100 associated with …….
- > 160 associated with ……
I. Seizures
- VT
Treatment of tricyclic overdose
- IV bicarbonate
- first-line therapy for hypotension or arrhythmias
- indications include widening of the QRS interval >100 msec or a ventricular arrhythmia
- other drugs for arrhythmias
CCB side effects
- Headache
- Flushing
- Ankle oedema - Verapamil also commonly causes constipation
BB side effects
- Bronchospasm (especially in asthmatics)
- Fatigue
- Cold peripheries
- Sleep disturbances
Nítrates side effects
- Headache
- Postural hypotension
- Tachycardia
Nicorandil side effects
- Headache
- Flushing
- Anal ulceration
Drug causing yellow green tinge in vision
Digoxin
Classical hallmark of Quinine toxicity
(cinchonism)
- Tinnitus, visual blurring
- dry skin
- arrhythmias
- pulmonary edema
- abdominal pain
- hypoglycemia
Arrhythmias in Quinine toxicity due to…
Blockade of Na & K channels prolonging QRS & QT interval and these generate into ventricular tachyarrythmias or fibrillation causing death.
Hypoglycemia in Quinine toxicity due to
Quinine stimulates pancreatic insulin secretion
Quinine toxicity vs Aspirin poisoning
Difficult to distinguish so measure salicylate levels is important
- tinnitus & deafness & visual defects are transient with Aspirin
But permanent with quinine
Management of Quinine toxicity
- supportive with fluids , Inotropes
- bicarbonate as needed
- positive pressure ventilation for pulmonary edema
Iron tables overdose features
- Hypotension
- Abdominal pain
- Coffee ground vomiting & black stool
- metabolic alkalosis 2ry to vomiting
- iron table radio-plaque in X-ray or CT
Treatment of Iron tables overdose
- Gastric lavage with desferrioxamine into stomach to reduce further iron absorption
- iv desferrioxamine at rate 15 mg/kg/hr is an initial ttt of choice and it’s important to start with it as soon as possible
- hemodialysis
- plasma exchange
Ethambutol inhibits
the enzyme arabinosyl transferase which polymerizes arabinose into arabinan
Pyrazinamide converted by pyrazinamidase into ….
converted by pyrazinamidase into pyrazinoic acid which in turn inhibits fatty acid synthase (FAS) I
Which anti TB can cause gout ?
Pyrazinamide
Isoniazid inhibits …….
inhibits mycolic acid synthesis
Rifampicin inhibits …….
inhibits bacterial DNA dependent RNA polymerase preventing transcription of DNA into mRNA
Phenytoin levels do not need to be monitored routinely but trough levels, immediately before dose should be checked if:
adjustment of phenytoin dose
suspected toxicity
detection of non-adherence to the prescribed medication
Tacrolimus is acalcineurin inhibitor
decreases clonal proliferation of T cells by …..
reducing IL-2 release
Which one of diabetes drugs can cause fluid retention
Glitazones
Which one of diabetes drugs can cause SIADH
Sulfonylureas
neuromuscular excitation
hyperreflexia
myoclonus
rigidity
autonomic nervous system excitation
hyperthermia
sweating
altered mental state
confusion
Features of……..?
Serotonin syndrome
Side effects of Quinolones
- lengthens QT interval
- tendon damage
- Cartilage damage
- lower seizure threshold
Contraindications of Quinolones
avoid inG6PD
Pregnancy
Breastfeeding
Amiloride blocks …..
the epithelial sodium channel in the distal convoluted tubule
Side-effects of PDE5 inhibitors
visual disturbances
blue discolouration
non-arteritic anterior ischaemic neuropathy
nasal congestion
flushing
gastrointestinal side-effects
headache
priapism
Features of oculogyric crisis
restlessness, agitation
involuntary upward deviation of the eyes
Causes of oculogyric crisis
antipsychotics
metoclopramide
postencephalitic Parkinson’s disease
Management of oculogyric crisis
cessation of causative medication if possible
Iv antimuscarinic:benztropine or procyclidine
somatostatin is released from …..1….
and inhibits …..2…….
- D cells of pancreas
- the release of growth hormone, glucagon and insulin
Side effects of Octreotide
gallstones (secondary to biliary stasis)
Management of Motion sickness
- transdermal patch hyoscine
- non-sedating antihistamines such as cyclizine or cinnarizine are recommended in preference to sedating preparation such as promethazine
Mechanism of action of Metformin
acts byactivation of the AMP-activated protein kinase (AMPK)
increases insulin sensitivity
decreases hepatic gluconeogenesis
may also reduce gastrointestinal absorption of carbohydrates
Metformin should be stopped if
1. creatinine
Or
2. eGFR
- > 150
- GFR < 30
Half life of iv Ig
3 weeks
Gentamicin can cause nephrotoxicity secondary to……
secondary to acute tubular necrosis
HMG CoA reductase inhibitors ?
Statins
Decreases cholesterol absorption in the small intestine?
Ezetimibe
Decreases hepatic VLDL secretion?
Nicotinic acid
Agonist of PPAR-alpha therefore increases lipoprotein lipase expressionMyositis, pruritus ?
Fibrates
Decreases bile acid reabsorption in the small intestine, upregulating the amount of cholesterol that is converted to bile acid ?
Cholestyramine
Activates antithrombin III. Forms a complex that inhibits thrombin, factors Xa, IXa, Xia and XIIa
Which drug ?
Heparin
Activates antithrombin III. Forms a complex that inhibits factor Xa
Which drug ?
LMWH
Heparin-induced thrombocytopaenia (HIT) is immune mediated -antibodies form against ……
complexes of platelet factor 4 (PF4) and heparin
Finasteride is an inhibitor of……
5 alpha-reductase, an enzyme which metabolises testosterone into dihydrotestosterone.
Indications for Finasteride
benign prostatic hyperplasia
male-pattern baldness
Finasteride & serum prostate-specific antigen
Finasteride causes decreased levels of serum prostate-specific antigen
sumatriptan is ….
a 5-HT1D receptor agonist
pizotifen & Methysergide & cyproheptadine are
a 5-HT2 receptor antagonist
extensive skin rash, high fever, and organ involvement,
Eosinophilia a and abnormal liver function tests.
Features of….?
DRESS
the diagnosis of DRESS syndrome conformed by …
Skin biopsy
DRESS syndrome treatment
all medications that are a possible culprits to be stopped and supportive care started.
Antihistamines, topical steroids
Systemic steroids may be started in severe cases where exfoliative dermatitis / pneumonitis / hepatitis is present.
Occasionally immunosuppressants, intravenous immunoglobulin and plasmapheresis may be started
ergot-derived dopamine receptor agonists (bromocriptine, cabergoline, pergolide*) have been associated with
pulmonary, retroperitoneal and cardiac fibrosis.
4 Indications of dopamine receptor agonists
Parkinson’s disease
prolactinoma/galactorrhoea
cyclical breast disease
acromegaly
4 Side effects of dopamine receptor agonists
nausea/vomiting
postural hypotension
hallucinations
daytime somnolence
Ciclosporin is an immunosuppressant which decreases clonal proliferation of T cells by…….
reducing IL-2 release
Ciclosporin acts by binding to cyclophilin forming a complex whichinhibits …….
calcineurin
11 Adverse effects of ciclosporin
- Nephrotoxicity
- Hepatotoxicity
- HTN
- Fluid retention
- impaired glucose tolerance
- hyperlipidaemia
- Hyperkalaemia
- Tremor
- gingival hyperplasia
- increased susceptibility to severe infection
- hypertrichosis ( excessive hair growth)
ciclosporin & cannabidiol
cannabidiol: may increase the concentration of ciclosporin
Allopurinol is
xanthine oxidase inhibitor
Patients at a high risk of severe cutaneous adverse reaction of allopurinol should be screened for
HLA-B *5801 allele
Allopurinol & Azathioprine
allopurinol can therefore lead to high levels of 6-mercaptopurine
a much reduced dose (e.g. 25%) must therefore be used if the combination cannot be avoided
Allopurinol & Cyclophosphamide
allopurinol reduces renal clearance, therefore may cause marrow toxicity
Allopurinol & Theophylline
allopurinol causes an increase in plasma concentration of theophylline by inhibiting its breakdown
What is the Wolff-Chaikoff effect?
autoregulatory phenomenon where thyroxine formation is inhibited due to high levels of circulating iodide
Amiodarone-induced thyrotoxicosis
Type 1 vs type 2
- Goiter ?
MANAGEMENT?
- Goiter
Type 1 present
Type 2 absent - Management
Type 1: Carbimazole or potassium perchlorate
Type 2: Corticosteroids
Pathophysiology of Amiodarone-induced thyrotoxicosis Type 1
Excess iodine-induced thyroid hormone synthesis
Pathophysiology of Amiodarone-induced thyrotoxicosis Type 2
Amiodarone-related destructive thyroiditis
Cyclooxygenase is responsible for …………… synthesis.
prostaglandin, prostacyclin and thromboxane synthesis.
The blocking ofthromboxane A2formation in platelets reduces ………….
the ability of platelets to aggregate
Mechanism of action of Aspirin
Non reversible COX 1 and COX 2 inhibitor
6 Drugs which may precipitate attack of Acute intermittent porphyria
barbiturates
halothane
benzodiazepines
alcohol
oral contraceptive pill
sulphonamides
Tamoxifen is a…….
Selective oEstrogen Receptor Modulator (SERM)which acts as an oestrogen receptor antagonist and partial agonist.
Tamoxifen is used for
management of oestrogen receptor positive breast cancer
4 Side effects of Tamoxifen
- menstrual disturbance:
- Hot flushes
- VTE
- endometrial cancer
Trastuzumab (Herceptin) is amonoclonal antibody directed against the ………
HER2/neu receptor
Trastuzumab is used for…
It is used mainly in metastatic breast cancer although some patients with early disease are now also given trastuzumab.
Side effects of Trastuzumab
flu-like symptoms and diarrhoea are common
cardiotoxicity
* more common when anthracyclines have also been used
an echo is usually performed before starting treatment
Alpha-1
- salivary secretion
- hepatic glycogenolysis
- relaxation of GI smooth muscle
- vasoconstriction
- SHRV
Alpha-2 adrenoceptors
mainly presynaptic: inhibition of transmitter release (inc NA, Ach from autonomic nerves)
inhibits insulin
platelet aggregation
Beta-1 adrenoceptors
mainly located in the heart
increase heart rate + force
Beta-2
vasodilation
bronchodilation
relaxation of GI smooth muscle
Beta-3 adrenoceptors
lipolysis
phenylephrine is …
Alpha-1 agonists
clonidine is
Alpha-2 agonists
dobutamine is
Beta-1 agonists
doxazosin is
alpha-1 blocker
tamsulosin is
alpha-2 blocker
phenoxybenzamine is
non-selective Alpha blocker
Management of accidental injection e.g. resulting in digital ischaemia
local infiltration of phentolamine
Types ( phases ) of Drug metabolism
phase I reactions: oxidation, reduction, hydrolysis
phase II reactions: conjugation.
Antiarrhythmics: Vaughan Williams classification
Class 4
CCB
- Verapamil
- diltiazem
Antiarrhythmics: Vaughan Williams classification
Class 3
Potassium Chanel blockers
- amiodarone
- Sotalol
- Ibutilide
- Bretylium
Antiarrhythmics: Vaughan Williams classification
Class 2
BB
- Propranolol
- Atenolol
- Bisoprolol
- Metoprolol
Antiarrhythmics: Vaughan Williams classification
Class 1a
Block sodium channels
Increases AP duration
- Procainamide
- Disopyramide
- Quinidine
*PDQ
Antiarrhythmics: Vaughan Williams classification
Class 1b
Block sodium channels
Decreases AP duration
- Lidocaine
- Mexiletine
- Tocainide
Antiarrhythmics: Vaughan Williams classification
Class 1c
Block sodium channels
No effect on AP duration
- Propafenone
- Encainide
- Flecainide
*PEF
Contraindications of Flecainide
- post MI
- structural heart disease: e.g. heart failure
- sinus node dysfunction; second-degree or greater AV block
- atrial flutter
Adverse effects of Flecainide
- negatively inotropic
- bradycardia
- proarrhythmic
- oral paraesthesia
- visual disturbances
Indications of Flecainide
- AFib
- SVT associated with WPW
Actions of adrenaline on α adrenergic receptors:
inhibits insulin secretion by the pancreas
stimulates glycogenolysis in the liver and muscle
stimulates glycolysis in muscle
Actions of adrenaline onβ adrenergic receptors:
stimulates glucagon secretion in the pancreas
stimulates ACTH
stimulates lipolysis by adipose tissue
adrenaline doses
- anaphylaxis
- cardiac arrest
anaphylaxis: 0.5ml 1:1,000 IM
cardiac arrest: 10ml 1:10,000 IV or 1ml of 1:1000 IV
increased risk of……..with combined oral contraceptive pill
breast cancer
cervical cancer
very small risk of heart attacks and strokes
Metformin should be titrated slowly, leave at …….. before increasing dose
least 1 week
Avoidance of using hypotonic (0.45%) in paediatric patients - risk of ……
hyponatraemic encephalopathy
Drugs affected by acetylator status
Hydralazine
Isoniazid
Sulfasalazine
Procainamide
Dapsone
*HI SPeeD
Drugs exhibiting zero order kinetics
Heparin
Ethanol
Phenytoin
ASA
P450 enzymes inductors (7)
Smoking
St John’s wort
Chronic alcohol intake
Carbamazepine
Phenytoin
Phenobarbitone
Rifampicin
GRiseofulvin
Lithium toxicity maybe precipitated by
Dehydration
Renal failure
Drugs
- ACEi/ARBs
- thiazides
- NSAIDs
- metronidazole
Levothyroxine acts via
Nuclear receptors
To give NaHCO3 in TCA overdose if (4)
PH < 7.1
QRS > 160 ms
Arrhythmias
Hypotension
Abciximab is
Glycoprotein IIb / IIIa receptor blocker
Cocaine can cause abdominal pain due to …..
Ischemic colitis
Pilocarpine is …….. agonist
muscarinic
P450 enzyme inductors …1…. Warfarin
P450 enzyme inhibitors…2…. Warfarin
- Reduce the effect of warfarin
- Increase the effect of warfarin
Heparin activates …1?…. Which inhibits……2?.
- Antithrombin III
- Thrombin III & IX, X, XI, XII
MI 2ry to cocaine treated by
Iv benzodiazepines
Which One of Anti TB medications need adjustment In renal impairment?
Ethambutol
Cocaine in pregnancy can cause
Induce preterm labour
Local anesthetic toxicity can be treated with
Iv 20 % lipid emulsion
Ketamine is ……… receptor blocker
NMDA
What is the most common feature of CO poisoning?
Headache
What is The most common side effects of progesterone pills ?
Irregular vaginal bleeding
Sidenafil is contraindicated by nitrates and …..
Nicordanil
Enzymes are involved in phase I drug metabolism?
- Alcohol dehydrogenase
- Xanthine oxidase
Drug monitoring
1. Ciclosporin
- Phenytoin
- Digoxin
- Lithium
1&2 immediately before the dose
- 6 hours post dose
- 12 hours post dose
Cyanide …… the enzyme cytochrome C oxidase
Inhibits
Which drug selectively blocks the epithelial Na transport channels ?
Amiloride
Adrenaline vs Glucose, lactate, K
Adrenaline induced
hyperglycemia
Hyperlactatemia
Hypokalemia