Clinical pharmacology Flashcards
1
Q
What is the mechanism of action of Quinolones?
A
Quinolones (e.g. ciprofloxacin) - inhibits DNA synthesis
Inhibit bacterial DNA duplication through inhibition of topoisomerase
2
Q
What class of antiarrhtymic is disopramide?
A
Class Ia agent
3
Q
What are examples of class 1a antiarrthmics?
A
Quinidine
Procainamide
Disopyramide
4
Q
Mechanism of action of class Ia antiarrhythmics?
A
Block sodium channels
Increases AP duration
5
Q
What are examples of class Ib antiarrhythmics?
A
Lidocaine
Mexiletine
Tocainide
6
Q
Mechanism of action of Ib antiarryhtmics?
A
Block sodium channels
Decreases AP duration
7
Q
Examples of calss Ic antiarrhythmics?
And mechanism of action
A
Flecainide
Encainide
Propafenone
Block sodium channels
No effect on AP duration
8
Q
Mechanism of action of class II antiarrhythmics and mechanism of action?
A
Propranolol
Atenolol
Bisoprolol
Metoprolol
Beta-adrenoceptor antagonists
9
Q
Examples of class III antiarrhtymics and mechanism of action ?
A
Amiodarone
Sotalol
Ibutilide
Bretylium
Block potassium channels
10
Q
A
11
Q
Mechanism of action of class IV antiarrhythmics? and examples?
A
Verapamil
Diltiazem
Calcium channel blcockers
12
Q
Mechanism of action of digoxin?
A
decreases conduction through the atrioventricular node which slows the ventricular rate in atrial fibrillation and flutter
increases the force of cardiac muscle contraction due to inhibition of the Na+/K+ ATPase pump. Also stimulates vagus nerve
digoxin has a narrow therapeutic index
13
Q
How should digoxin be monitored?
A
digoxin level is not monitored routinely, except in suspected toxicity
if toxicity is suspected, digoxin concentrations should be measured within 8 to 12 hours of the last dose
14
Q
Features of digoxin toxicity?
A
generally unwell, lethargy, nausea & vomiting, anorexia, confusion, yellow-green vision
arrhythmias (e.g. AV block, bradycardia)
gynaecomastia
15
Q
precipitating factors for digoxin toxicity?
A
classically: hypokalaemia
digoxin normally binds to the ATPase pump on the same site as potassium. Hypokalaemia → digoxin more easily bind to the ATPase pump → increased inhibitory effects
increasing age
renal failure
myocardial ischaemia
hypomagnesaemia, hypercalcaemia, hypernatraemia, acidosis
hypoalbuminaemia
hypothermia
hypothyroidism
drugs: amiodarone, quinidine, verapamil, diltiazem, spironolactone (competes for secretion in distal convoluted tubule therefore reduce excretion), ciclosporin. Also drugs which cause hypokalaemia e.g. thiazides and loop diuretics
16
Q
management of digoxin toxicity?
A
Digibind
correct arrhythmias
monitor potassium
17
Q
what types of caustic substance may be ingested?
A
Oxidising agents, e.g. hydrogen peroxide, sodium hypochlorite (found in household bleach)
Strong alkali, e.g. sodium hydroxide, potassium hydroxide (found in dishwasher cleaner, industrial cleaners) -> liquefactive necrosis, more commonly resulting in oesophageal injury
Strong acid, e.g. hydrochloric, nitric acid (found in car batteries, WC cleaner) -> coagulative necrosis, more commonly resulting in gastric injury
18
Q
How is Caustic substance ingestion managed?
A
Acute management
A-E assessment
Urgent uppeer GI surgical referral if signs of perforation present (surgical emphysema, medistinal widening on CXR)
Neutralisation of ingested substance (e.g. with milk) should be avoided as the resulting exothermic reaction will release heat and may cause further injury
High dose IV PPI
Symptomatic ingestion (drooling, vomiting, dysphagia, odynophagia, chest pain) requires urgent assessment with upper GI endoscopy to assess the degree of ulceration (Zargar classification). Extensive injury on endoscopy should prompt consideration of urgent surgical exploration
Asymptomatic ingestion can usually be discharged after a trial of oral fluid and a period of observation
19
Q
Acute complications after caustic substance ingestion?
A
Upper GI ulceration, perforation
Upper airway injury and compromise
Aspiration pneumonitis
Infection
Electrolyte disturbance (e.g. hypocalcaemia in hydrofluoric acid ingestion)
20
Q
Acute complications after caustic substance ingestion?Chronic
A
Strictures, fistulae, gastric outlet obstruction
Upper GI carcinoma (estimated 1000-3000 fold increased risk)
21
Q
Features of Mercury Poisoning?
A
paraesthesia
visual field defects
hearing loss
irritability
22
Q
What is an oculogyric crisis?
A
A dystonic reaction to certain drugs or medical conditions
Characterized by involuntary upward eye movement
23
Q
What are the features of an oculogyric crisis?
A
- Restlessness
- Agitation
- Involuntary upward deviation of the eyes
24
Q
What are some causes of an oculogyric crisis?
A
- Antipsychotics
- Metoclopramide
- Postencephalitic Parkinson’s disease
25
What is the first step in managing an oculogyric crisis?
Cessation of causative medication if possible
26
Which intravenous antimuscarinic agents can be used in the management of an oculogyric crisis?
* Benztropine
* Procyclidine
27
What are common symptoms of mercury poisoning?
Visual field defects, hearing loss, paraesthesia
## Footnote
Mercury poisoning often results from ingestion via contaminated food, especially fish and whale.
28
What is the most common cause of mercury poisoning?
Ingestion via foodstuffs, particularly fish and whale
## Footnote
Fish and whale are known to accumulate mercury in their tissues.
29
Lead poisoning typically presents with which symptoms?
Abdominal pain, constipation, headaches
## Footnote
These symptoms are indicative of lead exposure and toxicity.
30
What are the typical symptoms of ethylene glycol poisoning?
Nausea, vomiting, headaches, intoxication, seizures
## Footnote
Ethylene glycol is commonly found in antifreeze and can be highly toxic.
31
Carbon monoxide poisoning typically presents with which symptoms?
Headache, dizziness, weakness, vomiting, chest pain, confusion
## Footnote
Carbon monoxide is a colorless, odorless gas that can be lethal.
32
What might an ibuprofen overdose present with?
Abdominal pain, nausea, vomiting, drowsiness, dizziness, headache, ear ringing, nystagmus
## Footnote
Ibuprofen is a common over-the-counter pain reliever.
33
What are the symptoms associated with lead poisoning?
Abdominal pain, constipation, headaches
## Footnote
These symptoms can vary in severity based on the level of exposure.
34
Features of Tricyclic overdose?
Early features relate to anticholinergic properties: dry mouth, dilated pupils, agitation, sinus tachycardia, blurred vision.
Features of severe poisoning include:
arrhythmias
seizures
metabolic acidosis
coma
35
ECG changes in Tricyclic overdose?
ECG changes include:
sinus tachycardia
widening of QRS
prolongation of QT interval
Widening of QRS > 100ms is associated with an increased risk of seizures whilst QRS > 160ms is associated with ventricular arrhythmias
36
Management of Tricyclic overdose?
IV bicarbonate (first line for hypotension or arrhythmias, indications include widening of the QRS interval >100 msec or a ventricular arrhythmia)
intravenous lipid emulsion is increasingly used to bind free drug and reduce toxicity
dialysis is ineffective in removing tricyclics
37
Methanol poisoning features?
Methanol poisoning causes both the effects associated with alcohol (intoxication, nausea etc) and also specific visual problems, including blindness.
These effects are thought to be secondary to the accumulation of formic acid. The actual pathophysiology of methanol-associated visual loss is not fully understood but it is thought to be caused by a form of optic neuropathy
38
Management of methanol poisoning?
fomepizole (competitive inhibitor of alcohol dehydrogenase) or ethanol
haemodialysis
cofactor therapy with folinic acid to reduce ophthalmological complications
39
What drugs may cause cataracts?
steroids
40
what drugs mau cause corneal opacities?
amiodarone
indomethacin
41
What drugs may cause optic neuritis?
ethambutol
amiodarone
metronidazole
42
what drugs may cause retinopathy?
chloroquine, quinine
43
what ocular problems may sildenafil cause?
Sildenafil can cause both blue discolouration and non-arteritic anterior ischaemic neuropathy
44
Adrenoceptor antagonists?
Alpha antagonists
alpha-1: doxazosin
alpha-1a: tamsulosin - acts mainly on urogenital tract
alpha-2: yohimbine
non-selective: phenoxybenzamine (previously used in peripheral arterial disease)
Beta antagonists
beta-1: atenolol
non-selective: propranolol
Carvedilol and labetalol are mixed alpha and beta antagonists
45
Examples of alpha antagonists?
alpha-1: doxazosin
alpha-1a: tamsulosin - acts mainly on urogenital tract
alpha-2: yohimbine
non-selective: phenoxybenzamine (previously used in peripheral arterial disease)
46
Examples of beta antagnoists?
beta-1: atenolol
non-selective: propranolol
47
examples of mixed alpha and beta antagonists?
Carvedilol and labetalol are mixed alpha and beta antagonists
48
Paracetamol overdose metabolic pathway?
The liver normally conjugates paracetamol with glucuronic acid/sulphate. During an overdose the conjugation system becomes saturated leading to oxidation by P450 mixed function oxidases*. This produces a toxic metabolite (N-acetyl-B-benzoquinone imine)
Normally glutathione acts as a defence mechanism by conjugating with the toxin forming the non-toxic mercapturic acid. If glutathione stores run-out, the toxin forms covalent bonds with cell proteins, denaturing them and leading to cell death. This occurs not only in hepatocytes but also in the renal tubules
49
How doe NAC work in paracetamol overdose?
N-acetyl cysteine is used in the management of paracetamol overdose as it is a precursor of glutathione and hence can increase hepatic glutathione production
50
What are the two types of biochemical reactions involved in drug metabolism?
Phase I and Phase II reactions
## Footnote
Phase I reactions include oxidation, reduction, and hydrolysis, while Phase II involves conjugation.
51
What are the main processes involved in phase I reactions?
Oxidation, reduction, hydrolysis
## Footnote
Mainly performed by P450 enzymes, but some drugs are metabolized by specific enzymes.
52
What types of products do phase I reactions typically produce?
More active and potentially toxic products
## Footnote
These products can contribute to drug effects and side effects.
53
What is the main process in phase II reactions?
Conjugation
## Footnote
Products of phase II reactions are typically inactive and excreted.
54
Where do the majority of phase I and phase II reactions take place?
In the liver
## Footnote
The liver is the primary site for drug metabolism.
55
What is first-pass metabolism?
A phenomenon where drug concentration is reduced before reaching systemic circulation
## Footnote
This occurs due to hepatic metabolism.
56
Why do larger oral doses of some drugs need to be administered compared to other routes?
Due to first-pass metabolism
## Footnote
Many drugs undergo significant metabolism before entering systemic circulation.
57
Name drugs affected by first-pass metabolism.
* Aspirin
* Isosorbide dinitrate
* Glyceryl trinitrate
* lignocaine
* propranolol
* verapamil
* isoprenaline
* testosterone
* hydrocortisone
## Footnote
Many other drugs are also affected.
58
What is zero-order kinetics?
Metabolism independent of reactant concentration
## Footnote
It occurs when metabolic pathways become saturated.
59
What is a consequence of zero-order kinetics?
A constant amount of drug is eliminated per unit time
## Footnote
This can affect drug testing results.
60
Name a drug that exhibits zero-order kinetics.
* Phenytoin
* Salicylates (e.g., high-dose aspirin)
* Heparin
* Ethanol
## Footnote
These drugs show unique elimination patterns.
61
What percentage of the UK population is deficient in hepatic N-acetyltransferase?
50%
## Footnote
This status affects drug metabolism in certain individuals.
62
Name a drug affected by acetylator status.
* Isoniazid
* Procainamide
* Hydralazine
* Dapsone
* Sulfasalazine
## Footnote
These drugs can have altered effects based on acetylator status.
63
Mechanism of action and side effects of Rifampicin?
mechanism of action: inhibits bacterial DNA dependent RNA polymerase preventing transcription of DNA into mRNA
potent liver enzyme inducer
hepatitis, orange secretions
flu-like symptoms
64
Mechanism of action and sife effects of Isoniazid?
mechanism of action: inhibits mycolic acid synthesis
peripheral neuropathy: prevent with pyridoxine (Vitamin B6)
hepatitis, agranulocytosis
liver enzyme inhibitor
65
Mechanism of action and side effects of pyrazinamide?
mechanism of action: converted by pyrazinamidase into pyrazinoic acid which in turn inhibits fatty acid synthase (FAS) I
hyperuricaemia causing gout
arthralgia, myalgia
hepatitis
66
Mechanism of action and side effects of ethambutol ?
mechanism of action: inhibits the enzyme arabinosyl transferase which polymerizes arabinose into arabinan
optic neuritis: check visual acuity before and during treatment
dose needs adjusting in patients with renal impairment
67
TB management side effects?
68
What is the mechanism of action of ocreatide?
long-acting analogue of somatostatin
somatostatin is released from D cells of pancreas and inhibits the release of growth hormone, glucagon and insulin
69
What is ocreotide used for?
acute treatment of variceal haemorrhage
acromegaly
carcinoid syndrome
prevent complications following pancreatic surgery
VIPomas
refractory diarrhoea
70
Adverse effects of ocreotide?
gallstones (secondary to biliary stasis)
71
Heprin vs LMWH
Administration
duration of action
mechanism of action
Side effects
monitoring
72
What is Trastuzumab ?
Trastuzumab (Herceptin) is a monoclonal antibody directed against the HER2/neu receptor. It is used mainly in metastatic breast cancer although some patients with early disease are now also given trastuzumab.
73
What are the adverse effects of Trastuzumab?
Adverse effects
flu-like symptoms and diarrhoea are common
cardiotoxicity
more common when anthracyclines have also been used
an echo is usually performed before starting treatment
74
What is Acute intermittent porphyria?
Acute intermittent porphyria (AIP) is an autosomal dominant condition caused by a defect in porphobilinogen deaminase, an enzyme involved in the biosynthesis of haem. It characteristically presents with abdominal and neuropsychiatric symptoms in 20-40 year olds. AIP is more common in females (5:1)
75
What drugs may precipitate and attack of acute intermittent porphyria?
barbiturates
halothane
benzodiazepines
alcohol
oral contraceptive pill
sulphonamides
76
when should quinolones be avoided?
Quinolones should generally be avoided in women who are pregnant or breastfeeding
avoid in G6PD
77
what may be protective for heapatoxicity in paracetamol?
Interestingly, acute alcohol intake, as opposed to chronic alcohol excess, is not associated with an increased risk of developing hepatotoxicity and may actually be protective.
78
who may be more at rism of hepatoxicity if the patient takes a paracetamol overdose?
patients taking liver enzyme-inducing drugs (rifampicin, phenytoin, carbamazepine, chronic alcohol excess, St John's Wort)
malnourished patients (e.g. anorexia nervosa) or patients who have not eaten for a few days
79
Mechanism of action of tetracyclines?
Mechanism of action
protein synthesis inhibitors
binds to 30S subunit blocking binding of aminoacyl-tRNA
80
Mechanism of resistance for tetracyclines?
increased efflux of the bacteria by plasmid-encoded transport pumps, ribosomal protection
81
Inidcation for tetracylines?
acne vulgaris
Lyme disease
Chlamydia
Mycoplasma pneumoniae
82
Notable adverse effects of tetracyclines?
Notable adverse effects
discolouration of teeth: therefore should not be used in children < 12 years of age
photosensitivity
angioedema
black hairy tongue
Tetracyclines should not be given to women who are pregnant or breastfeeding due to the risk of discolouration of the infant's teeth.
83
what drugs may causes cataracts?
steroids
84
What drugs may cause corneal opacities?
amiodarone
indomethacin
85
What drugs may cause optic neuritis?
ethambutol
amiodarone
metronidazole
86
What drugs may cause retinopathy?
chloroquine, quinine
87
What is the most important prognostic indicator in paracetamol overdose?
Acidosis
88
King's college Hospital criteria for liver transplantation?
Arterial pH < 7.3, 24 hours after ingestion
or all of the following:
prothrombin time > 100 seconds
creatinine > 300 µmol/l
grade III or IV encephalopathy
88
when shoud acetylcysteine be given in paracetamol OD?
Abive the treatment line at 4 hours
If there has been a staggered OD or there is doubt about the time of ingestions - give it regardless
if patients present 8-24 hrs after ingestions and took more than 150mg/kg even if concentration not yet available
if it is > 24 hours and they are clearly jaundices or have hepatic tenderness
acetylcysteine should be continued if the paracetamol concentration or ALT remains elevated whilst seeking specialist advice
89
What kind of reaction is commonly seen in acetylcystine?
Acetylcysteine commonly causes an anaphylactoid reaction (non-IgE mediated mast cell release). Anaphylactoid reactions to IV acetylcysteine are generally treated by stopping the infusion, then restarting at a slower rate.
90
mechanism of action of buprenorphine?
buprenorphine is a partial agonist of the mu-opioid receptor and an antagonist of the kappa-opioid
91
What is the mechanism of action of cyanide poisoning?
Cyanide may be used in insecticides, photograph development and the production of certain metals. Cyanide inhibits the enzyme cytochrome c oxidase, resulting in cessation of the mitochondrial electron transfer chain.
92
How dies Cyanide poisoning present?
Presentation
'classical' features: brick-red skin, smell of bitter almonds
acute: hypoxia, hypotension, headache, confusion
chronic: ataxia, peripheral neuropathy, dermatitis
93
What is the menagament of cyanide poisoning?
Management
supportive measures: 100% oxygen
definitive: hydroxocobalamin (intravenously), also combination of amyl nitrite (inhaled), sodium nitrite (intravenously), and sodium thiosulfate (intravenously)
94
Indications for dopamine receptor agnoists?
Parkinson's disease
prolactinoma/galactorrhoea
cyclical breast disease
acromegaly
95
examples of dopamine receptor agnoists?
e.g. bromocriptine, ropinirole, cabergoline, apomorphine
ergot-derived dopamine receptor agonists (bromocriptine, cabergoline, pergolide*) have been associated with pulmonary, retroperitoneal and cardiac fibrosis. The Committee on Safety of Medicines advice that an ESR, creatinine and chest x-ray should be obtained prior to treatment and patients should be closely monitored
96
Adverse effects of dopamine receptor agonists?
nausea/vomiting
postural hypotension
hallucinations
daytime somnolence
97
Who is more at risk of adverse effects to allopurinol and how should they be screened?
Certain ethnic groups such as the Chinese, Korean and Thai people seem to be at an increased risk of these dermatological reactions.
Patients at a high risk of severe cutaneous adverse reaction should be screened for the HLA-B *5801 allele.
98
What antibodies are seen in heparin induced thrombocytopenia?
antibodies form against complexes of platelet factor 4 (PF4) and heparin
99
Indications for Botox?
blepharospasm
hemifacial spasm
focal spasticity including cerebral palsy patients, hand and wrist disability associated with stroke
spasmodic torticollis
severe hyperhidrosis of the axillae
achalasia
100
How does Quinine toxicity present?
Quinine toxicity (cinchonism) presents with myriad ECG changes, hypotension, metabolic acidosis, hypoglycaemia and classically tinnitus, flushing and visual disturbances. Flash pulmonary oedema may occur
## Footnote
***Clinically, quinine toxicity is difficult to distinguish from aspirin poisoning and so measurement of serum salicylate levels is important when this clinical picture is seen.
101
Why due to you get cardiac arrhythmias in quinine toxicity?
Cardiac arrhythmia is a common finding in cinchonism due to blockade of sodium and potassium channels prolonging QRS and QT intervals respectively and these rhythms may degenerate into ventricular tachyarrhythmias or fibrillation causing death
102
Why do you get hypoglycaemia in quinine toxicity?
Hypoglycaemia is also a common finding in cinchonism since quinine stimulates pancreatic insulin secretion and this should be corrected rapidly if presen
103
Management of quinine toxicity?
Management of quinine poisoning is largely supportive with fluids, inotropes and bicarbonate as needed as well as positive pressure ventilation for pulmonary oedema
104
what are first order kinetics and zero order kinetics?
Clearance
majority of drugs exhibit 'first-order' elimination kinetics i.e. the rate of drug elimination is proportional to drug concentration
certain drugs exhibit zero-order kinetics where the rate of excretion is constant despite changes in plasma concentration, this is due to saturation of the metabolic process
examples of drugs exhibiting zero-order kinetics include phenytoin and salicylates
105
what drugs can be used in alochol addiction?
benzodiazepines for acute withdrawal
disulfram: promotes abstinence - alcohol intake causes severe reaction due to inhibition of acetaldehyde dehydrogenase. Patients should be aware that even small amounts of alcohol (e.g. In perfumes, foods, mouthwashes) can produce severe symptoms. Contraindications include ischaemic heart disease and psychosis
acamprosate: reduces craving, known to be a weak antagonist of NMDA receptors, improves abstinence in placebo controlled trials
106
If a patient gets myalgia with statin what other drug should be avoided?
the Committee on Safety of Medicines has produced guidance which specifically warns about the concomitant prescription of fibrates with statins in relation to muscle toxicity
107
Examples of drugs used in hyperlipidaemia?
108
What is Nivolumab?
Nivolumab is a PD-1 (programmed cell death) inhibitor. PD-1 receptors are found on the surface of T cells. When a T cell is alerted to a cancer cell the cancer cell can express the PD-L1 protein. This is a ligand which binds to the T cell receptor and deactivates it. It is therefore a mechanism cancer cells use to evade the immune system and disable T cells. The PD-1 inhibitors are antibodies which block this receptor, leaving the T cells to remain active and alert other immune cells for example macrophages to the cancer cells.
109
what is the mechanism of action of pilocarpine?
Pilocarpine is a muscarinic agonist
## Footnote
Pilocarpine is a muscarinic agonist that causes pupillary constriction and contraction of the ciliary muscles, which opens up the trabecular meshwork allowing greater drainage of aqueous humour and reduces intraocular pressure.
110
what drugs are linked to gingival hyperplasia?
Classically, phenytoin, cyclosporin and calcium-channel blockers are linked to this side effect
111
Indications for Verapamil?
Angina, hypertension, arrhythmias
Highly negatively inotropic
Should not be given with beta-blockers as may cause heart block
112
Adverse side effects of verapamil?
Heart failure, constipation, hypotension, bradycardia, flushing
113
Indications for Diltiazem?
Angina, hypertension
Less negatively inotropic than verapamil but caution should still be exercised when patients have heart failure or are taking beta-blockers
114
Adverse effects of Diltiazem?
Hypotension, bradycardia, heart failure, ankle swelling
115
Inidcations for Nifedipine, amlodipine, felodipine
(dihydropyridines)?
Hypertension, angina, Raynaud's
Affects the peripheral vascular smooth muscle more than the myocardium and therefore do not result in worsening of heart failure but may therefore cause ankle swelling
Shorter acting dihydropyridines (e.g. nifedipine) cause peripheral vasodilation which may result in reflex tachycardia
## Footnote
Side effects: Flushing, headache, ankle swelling
116
Features of hypomagnesaemia?
paraesthesia
tetany
seizures
arrhythmias
decreased PTH secretion → hypocalcaemia
ECG features similar to those of hypokalaemia
exacerbates digoxin toxicity
117
Which drugs can be cleared with haemodialysis?
Drugs that can be cleared with haemodialysis - mnemonic: BLAST
Barbiturate
Lithium
Alcohol (inc methanol, ethylene glycol)
Salicylates
Theophyllines (charcoal haemoperfusion is preferable)
118
What drugs can not be cleared with haemodialysis?
Drugs which cannot be cleared with haemodialysis include
tricyclics
benzodiazepines
dextropropoxyphene (Co-proxamol)
digoxin
beta-blockers
119
What do alpha-1 adrenoceptors cause?
vasoconstriction
relaxation of GI smooth muscle
salivary secretion
hepatic glycogenolysis
120
What do alpha-2 adreoceptora cause?
mainly presynaptic: inhibition of transmitter release (inc NA, Ach from autonomic nerves)
inhibits insulin
platelet aggregation
121
What do beta-1 adrenoceptors cause?
mainly located in the heart
increase heart rate + force
122
What do beta-1 adrenoceptors cause?
vasodilation
bronchodilation
relaxation of GI smooth muscle
123
What do beta-3 adrenoceptors cause?
Lipolysis
124
what kind of drug is infliximab?
Infliximab is an anti-TNF monoclonal antibody
