Pharmacology Flashcards
(97 cards)
1
Q
What are examples of adrenoceptor agonists?
A
alpha 1 = phenylephrine
alpha 2= clonidine
beta 1= dobutamine
beta 2= salbutamol
2
Q
What are examples of adrenoceptor antagonists?
A
Alpha 1 = doxazosin
alpha 1a = tamsulosin
alpha 2 = yohimbine
non selective = phenoxybenzamine
beta 1 = atenolol
non selective = propranolol
3
Q
What do alpha 1 receptors do?
A
- vasoconstriction
- relaxation of GI smooth muscle
- salivary secretion
- hepatic glycogenolysis
4
Q
What do alpha 2 receptors do?
A
- mainly presynaptic: inhibition of transmitter release (inc NA, Ach from autonomic nerves)
- inhibits insulin
- platelet aggregation
5
Q
What do beta 1 receptors do?
A
- mainly located in the heart
- increase heart rate + force
6
Q
What do beta 2 receptors do?
A
- vasodilation
- bronchodilation
- relaxation of GI smooth muscle
7
Q
What do beta 3 receptors do?
A
lipolysis
8
Q
What are the specific features of propofol?
A
- GABA receptor agonist
- Rapid onset of anaesthesia
- Pain on IV injection
- Rapidly metabolised with little accumulation of metabolites
- Proven anti emetic properties
- Moderate myocardial depression
- Widely used especially for maintaining sedation on ITU, total IV anaesthesia and for daycase surgery
9
Q
What are the specific features of Sodium Thiopentone?
A
- Extremely rapid onset of action making it the agent of choice for rapid sequence of induction
- Marked myocardial depression may occur
- Metabolites build up quickly
- Unsuitable for maintenance infusion
- Little analgesic effects
10
Q
What are the specific features of ketamine?
A
- NMDA receptor antagonist
- May be used for induction of anaesthesia
- Has moderate to strong analgesic properties
- Produces little myocardial depression making it a suitable agent for anaesthesia in those who are haemodynamically unstable
- May induce state of dissociative anaesthesia resulting in nightmares
11
Q
What is the mechanism of action of Aspirin?
A
- blocking the action of both cyclooxygenase-1 and 2
- Cyclooxygenase is responsible for prostaglandin, prostacyclin and thromboxane synthesis. The blocking of thromboxane A2 formation in platelets reduces the ability of platelets to aggregate
12
Q
What is there a risk of when aspirin is used in under 16yrs?
A
Reye’s syndrome
Kawasaki disease is an exception to this.
13
Q
What are the features of beta blocker overdose?
A
- bradycardia
- hypotension
- heart failure
- syncope
14
Q
What is the management of beta blocker overdose?
A
Atropine if bradycardia
Glucagon in resistant cases
15
Q
What are some licensed indications for botulinum toxin?
A
- blepharospasm
- hemifacial spasm
- focal spasticity including cerebral palsy patients, hand and wrist disability associated with stroke
- spasmodic torticollis
- severe hyperhidrosis of the axillae
- achalasia
16
Q
What is the pathophysiology of carbon monoxide poisoning?
A
in carbon monoxide poisoning the oxygen saturation of haemoglobin decreases leading to an early plateau in the oxygen dissociation curve
17
Q
What are the features of carbon monoxide poisoning?
A
- headache: 90% of cases
- nausea and vomiting: 50%
- vertigo: 50%
- confusion: 30%
- subjective weakness: 20%
- severe toxicity: ‘pink’ skin and mucosae, hyperpyrexia, arrhythmias, extrapyramidal features, coma, death
18
Q
What is the management of carbon monoxide poisoning?
A
100% high-flow oxygen via a non-rebreather mask (decreases half life of CO and should be administered for at least 6 hrs)
hyperbaric oxygen
19
Q
What is the mechanism of action of ciclosporin?
A
immunosuppressant which decreases clonal proliferation of T cells by reducing IL-2 release. It acts by binding to cyclophilin forming a complex which inhibits calcineurin, a phosphatase that activates various transcription factors in T cells
20
Q
What are the adverse effects of ciclosporin?
A
- nephrotoxicity
- hepatotoxicity
- fluid retention
- hypertension
- hyperkalaemia
- hypertrichosis
- gingival hyperplasia
- tremor
- impaired glucose tolerance
- hyperlipidaemia
- increased susceptibility to severe infection
21
Q
What is the mechanism of action of cocaine?
A
cocaine blocks the uptake of dopamine, noradrenaline and serotonin
22
Q
What are the adverse effects of cocaine?
A
Cardiac:
- coronary artery spasm → myocardial ischaemia/infarction
- both tachycardia and bradycardia
- hypertension
- QRS widening and QT prolongation
- aortic dissection
Neurology:
- seizures
- mydriasis
- hypertonia
- hyperreflexia
Psychiatric:
- agitation
- hallucinations
- psychosis
Ischaemic colitis
Hyperthermia
Rhabdomyolitis
Metabolic acidosis
23
Q
What is the management for cocaine toxicity?
A
Chest pain : benzodiazepines + GTN
HTN: benzodiazepines + sodium nitroprusside
24
Q
What conditions are UKMEC3 level for contraindications to COCP?
A
- more than 35 years old and smoking less than 15 cigarettes/day
- BMI > 35 kg/m^2*
- family history of thromboembolic disease in first degree relatives < 45 years
- controlled hypertension
- immobility e.g. wheel chair use
- carrier of known gene mutations associated with breast cancer (e.g. BRCA1/BRCA2)
- current gallbladder disease
25
What are complete contraindications to COCP?
- more than 35 years old and smoking more than 15 cigarettes/day
- migraine with aura
- history of thromboembolic disease or thrombogenic mutation
- history of stroke or ischaemic heart disease
- breast feeding < 6 weeks post-partum
- uncontrolled hypertension
- current breast cancer
- major surgery with prolonged immobilisation
- positive antiphospholipid antibodies (e.g. in SLE)
26
What are the features of cyanide poisoning?
- 'classical' features: brick-red skin, smell of bitter almonds
- acute: hypoxia, hypotension, headache, confusion
- chronic: ataxia, peripheral neuropathy, dermatitis
27
What is the mechanism of action of cyanide?
Inhibits the enzyme cytochrome c oxidase, resulting in cessation of the mitochondrial electron transfer chain.
28
What is the management for cyanide poisoning?
- supportive measures: 100% oxygen
- definitive: hydroxocobalamin (intravenously), also combination of amyl nitrite (inhaled), sodium nitrite (intravenously), and sodium thiosulfate (intravenously)
29
What is the mechanism of action of digoxin?
- 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
30
What are the features of digoxin toxicity?
- generally unwell, lethargy, nausea & vomiting, anorexia, confusion, yellow-green vision
- arrhythmias (e.g. AV block, bradycardia)
- gynaecomastia
31
Which drugs may precipitate digoxin toxicity?
- amiodarone, quinidine, verapamil, diltiazem, spironolactone (competes for secretion in distal convoluted tubule therefore reduce excretion)
- ciclosporin
- thiazides/loop diuretics
32
What are common drugs that cause DRESS syndrome?
allopurinol
anti-epileptics
antibiotics
immunosuppresants
HIV treatment
NSAIDS
33
What are the features of DRESS syndrome?
extensive skin rash + high fever + organ involvement, supported by a finding of eosinophilia and abnormal liver function tests.
34
Which drugs cause agranulocytosis?
* Antithyroid drugs - carbimazole, propylthiouracil
* Antipsychotics - atypical
* antipsychotics (CLOZAPINE)
* Antiepileptics - carbamazepine
* Antibiotics - penicillin, chloramphenicol, co-trimoxazole
* Antidepressant - mirtazapine
* Cytotoxic drugs - methotrexate
35
Which drugs may cause impaired glucose tolerance?
- thiazides, furosemide (less common)
- steroids
- tacrolimus, ciclosporin
- interferon-alpha
- nicotinic acid
- antipsychotics
36
Which drugs may cause thrombocytopenia?
- quinine
- abciximab
- NSAIDs
- diuretics: furosemide
- antibiotics: penicillins, sulphonamides, rifampicin
- anticonvulsants: carbamazepine, valproate
- heparin
37
Which drugs may cause urinary retention?
- tricyclic antidepressants e.g. amitriptyline
- anticholinergics e.g. antipsychotics, antihistamines
- opioids
- NSAIDs
- disopyramide
38
Which drugs may cause lung fibrosis?
- amiodarone
- cytotoxic agents: busulphan, bleomycin
- anti-rheumatoid drugs: methotrexate, sulfasalazine
- nitrofurantoin
- ergot-derived dopamine receptor agonists (bromocriptine, cabergoline, pergolide)
39
Which drugs may cause optic neuritis?
ethambutol
amiodarone
metronidazole
40
Which drugs may cause photosensitivity?
- thiazides
- tetracyclines, sulphonamides, ciprofloxacin
- amiodarone
- NSAIDs e.g. piroxicam
- psoralens
- sulphonylureas
41
What are the features of ecstasy poisoning ?
- neurological: agitation, anxiety, confusion, ataxia
- cardiovascular: tachycardia, hypertension
- hyponatraemia
this may result from either syndrome of inappropriate ADH secretion or excessive water consumption whilst taking MDMA
- hyperthermia
- rhabdomyolysis
42
What are the stages of ethylene glycol toxicity (anti-freeze)?
- Stage 1: symptoms similar to alcohol intoxication: confusion, slurred speech, dizziness
- Stage 2: metabolic acidosis with high anion gap and high osmolar gap. Also tachycardia, hypertension
- Stage 3: acute kidney injury
43
What is the management of ethylene glycol toxicity?
- ethanol has been used for many years (works by competing with ethylene glycol for the enzyme alcohol dehydrogenase
this limits the formation of toxic metabolites (e.g. glycoaldehyde and glycolic acid) which are responsible for the haemodynamic/metabolic features of poisoning)
- fomepizole, an inhibitor of alcohol dehydrogenase, is now used first-line in preference to ethanol
- haemodialysis also has a role in refractory cases
44
What is the mechanism of action of finasteride?
5 alpha-reductase, an enzyme which metabolises testosterone into dihydrotestosterone
45
What are the indications for commencing flecainide?
- atrial fibrillation
- SVT associated with accessory pathway e.g. Wolf-Parkinson-White syndrome
46
What is the mechanism of action of Flecainide?
Class 1c anti arrhythmic
slows conduction of the action potential by acting as a potent sodium channel blocker (specifically the Nav1.5 sodium channels)
47
What are the contraindications to flecainide?
- post myocardial infarction
- structural heart disease: e.g. heart failure
- sinus node dysfunction; second-degree or greater AV block
- atrial flutter
48
What are the adverse effects of flecainide?
- negatively inotropic
- bradycardia
- proarrhythmic
- oral paraesthesia
- visual disturbances
49
Which drugs can be cleared by haemodialysis in overdose?
- Barbiturate
- Lithium
- Alcohol (inc methanol, ethylene glycol)
- Salicylates
- Theophyllines (charcoal haemoperfusion is preferable)
50
What is the mechanism of action of standard 'unfractionated' heparin?
Activates antithrombin III. Forms a complex that inhibits thrombin, factors Xa, IXa, Xia and XIIa
51
What is the mechanism of action of low molecular weight heparin?
Activates antithrombin III. Forms a complex that inhibits factor Xa
52
What test is used to monitor infraction rated heparin?
APTT
53
What test is used to monitor LMWH?
No routine monitoring
Anti-factor Xa
54
What are the features of heparin induced thrombocytopenia (HIT)?
- immune mediated - antibodies form against complexes of platelet factor 4 (PF4) and heparin
- antibodies bind to the PF4-heparin complexes on the platelet surface and induce platelet activation by cross-linking FcγIIA receptors
- usually does not develop until after 5-10 days of treatment
- despite being associated with low platelets HIT is actually a prothrombotic condition
- features include a greater than 50% reduction in platelets, thrombosis and skin allergy
- address need for ongoing anticoagulation: direct thrombin inhibitor e.g. argatroban
danaparoid
55
What are the causes of hypomagnesaemia?
- drugs: diuretics, PPIs
- total parenteral nutrition
- diarrhoea
- alcohol
- hypokalaemia
- hypercalcaemia e.g. secondary to hyperparathyroidism
calcium and magnesium functionally compete for transport in the thick ascending limb of the loop of Henle
- metabolic disorders: Gitleman's and Bartter's
56
What are the features of hypomagnesaemia?
- paraesthesia
- tetany
- seizures
- arrhythmias
- decreased PTH secretion → hypocalcaemia
- ECG features similar to those of hypokalaemia
- exacerbates digoxin toxicity
57
What may precipitate lithium toxicity?
- dehydration
- renal failure
- drugs: diuretics (especially thiazides), ACE inhibitors/angiotensin II receptor blockers, NSAIDs and metronidazole.
58
What are the features of lithium toxicity?
- coarse tremor (a fine tremor is seen in therapeutic levels)
- hyperreflexia
- acute confusion
- polyuria
- seizure
- coma
59
What is the management of lithium toxicity?
- mild-moderate toxicity may respond to volume resuscitation with normal saline
* IV fluids with isotonic saline, until euvolemic, then typically twice maintenance rate
* monitor serum sodium closely (every 4 hours with serial lithium concentrations) if there is a concern about lithium-induced nephrogenic diabetes insipidus
- haemodialysis may be needed in severe toxicity
- sodium bicarbonate is sometimes used but there is limited evidence to support this, by increasing the alkalinity of the urine it promotes lithium excretion
60
What are some key features of lidocaine?
- An amide
- Local anaesthetic and a less commonly used antiarrhythmic (affects Na channels in the axon)
- Hepatic metabolism, protein bound, renally excreted
- Toxicity: due to IV or excess administration. Increased risk if liver dysfunction or low protein states. Note acidosis causes lidocaine to detach from protein binding. Local anesthetic toxicity can be treated with IV 20% lipid emulsion
- Drug interactions: Beta blockers, ciprofloxacin, phenytoin
- Features of toxicity: Initial CNS over activity then depression as lidocaine initially blocks inhibitory pathways then blocks both inhibitory and activating pathways. Cardiac arrhythmias.
- Increased doses may be used when combined with adrenaline to limit systemic absorption.
61
What are the key features of bupivacaine?
- Binds to the intracellular portion of sodium channels and blocks sodium influx into nerve cells, which prevents depolarization.
- much longer duration of action than lignocaine and this is of use in that it may be used for topical wound infiltration at the conclusion of surgical procedures with long duration analgesic effect.
- It is cardiotoxic and is therefore contra indicated in regional blockage in case the tourniquet fails.
- Levobupivicaine (Chirocaine) is less cardiotoxic and causes less vasodilation.
62
What is the mechanism of action of macrolides?
inhibiting bacterial protein synthesis by blocking translocation
63
What are the adverse effects of macrolides?
- prolongation of the QT interval
- GI side-effects are common. Nausea is less common with clarithromycin than erythromycin
- cholestatic jaundice: risk may be reduced if erythromycin stearate is used
- P450 inhibitor (see below)
- azithromycin is associated with hearing loss and tinnitus
64
What are the features of Mercury poisoning?
- paraesthesia
- visual field defects
- hearing loss
- irritability
- renal tubular acidosis
65
What is the mechanism of action of metformin?
- acts by activation of the AMP-activated protein kinase (AMPK)
- increases insulin sensitivity
- decreases hepatic gluconeogenesis
- may also reduce gastrointestinal absorption of carbohydrates
66
What are the adverse effects of metformin?
GI upset common
reduced vitamin B12 absorption
lactic acidosis
67
How are monoclonal antibodies manufactured?
somatic cell hybridization:
fusion of myeloma cells with spleen cells from a mouse that has been immunized with the desired antigen. The resulting fused cells are termed a hybridoma and act as a 'factory' for producing monoclonal antibodies
68
What is oculogyric crisis?
- dystonic reaction to certain drugs or medical conditions
- restlessness, agitation
- involuntary upward deviation of the eyes
69
What is the management of oculogyric crisis?
- cessation of causative medication if possible
- intravenous antimuscarinic: benztropine or procyclidine
70
Which drugs may cause an oculogyric crisis?
- antipsychotics
- metoclopramide
- postencephalitic Parkinson's disease
71
What may induce the P450 enzyme system?
- antiepileptics: phenytoin, carbamazepine
- barbiturates: phenobarbitone
- rifampicin
- St John's Wort
- chronic alcohol intake
- griseofulvin
- smoking (affects CYP1A2, reason why smokers require more aminophylline)
72
What may inhibit the P450 enzyme system?
- antibiotics: ciprofloxacin, erythromycin
- isoniazid
- cimetidine,omeprazole
- amiodarone
- allopurinol
- imidazoles: ketoconazole, fluconazole
- SSRIs: fluoxetine, sertraline
- ritonavir
- sodium valproate
- acute alcohol intake
- quinupristin
73
What is the criteria for liver transplantation secondary to paracetamol overdose?
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
74
What is zero order kinetics?
- metabolism which is independent of the concentration of the reactant
- metabolic pathways becoming saturated resulting in a constant amount of drug being eliminated per unit time
75
Which drugs exhibit zero order kinetics?
- phenytoin
- salicylates (e.g. high-dose aspirin)
- heparin
- ethanol
76
What are some examples of phosphodiesterase type V (PDE5) inhibitors?
- sildenafil (Viagra)
* this was the first phosphodiesterase type V inhibitor
* short-acting - usually taken 1 hour before sexual activity
- tadalafil (Cialis)
* longer acting than sildenafil, may be taken on a regular basis (e.g. once daily)
- vardenafil (Levitra)
77
What are some contraindications to phosphodiesterase type V (PDE5) inhibitors?
- patients taking nitrates and related drugs such as nicorandil
- hypotension
- recent stroke or myocardial infarction
78
What are the side effects of phosphodiesterase type V (PDE5) inhibitors?
- visual disturbances
- blue discolouration
- non-arteritic anterior ischaemic neuropathy
- nasal congestion
- flushing
- gastrointestinal side-effects
- headache
- priapism
79
What is the mechanism of action of amiloride?
- blocks the epithelial sodium channel in the distal convoluted tubule
- weak diuretic, usually given with thiazides or loop diuretics as an alternative to potassium supplementation (remember that thiazides and loop diuretics often cause hypokalaemia)
80
What is the mechanism of action of quinolones?
inhibit topoisomerase II (DNA gyrase) and topoisomerase IV
81
What are the adverse effects of quinolones?
- lower seizure threshold in patients with epilepsy
- tendon damage (including rupture) - the risk is increased in patients also taking steroids
- cartilage damage has been demonstrated in animal models and for this reason quinolones are generally avoided (but not necessarily contraindicated) in children
- lengthens QT interval
82
What are then features of salicylate overdose?
- hyperventilation (centrally stimulates respiration)
- tinnitus
- lethargy
- sweating, pyrexia*
- nausea/vomiting
- hyperglycaemia and hypoglycaemia
- seizures
- coma
- mixed respiratory alkalosis and metabolic acidosis.
83
What is the management of salicylate overdose?
- general (ABC, charcoal)
- urinary alkalinization with intravenous sodium bicarbonate - enhances elimination of aspirin in the urine
- haemodialysis
84
What are the indications for haemodialysis in salicylate overdose?
- serum concentration > 700mg/L
- metabolic acidosis resistant to treatment
- acute renal failure
- pulmonary oedema
- seizures
- coma
85
What are some causes of serotonin syndrome?
- monoamine oxidase inhibitors
- SSRIs
- St John's Wort, often taken over the counter for depression, can interact with SSRIs to cause serotonin syndrome
- tramadol may also interact with SSRIs
- ecstasy
- amphetamines
86
What are the features of serotonin syndrome?
- neuromuscular excitation:
* hyperreflexia
* myoclonus
* rigidity
- autonomic nervous system
* excitation
* hyperthermia
* sweating
- altered mental state
* confusion
87
What is the management for serotonin syndrome?
- supportive including IV fluids
- benzodiazepines
- more severe cases are managed using serotonin antagonists such as cyproheptadine and chlorpromazine
88
What are the features of tricyclic overdose?
- Anticholinergic: dry mouth, dilated pupils, agitation, sinus tachycardia, blurred vision.
- arrhythmias
- seizures
- metabolic acidosis
- coma
89
What are the ECG changes in tricyclic overdose?
sinus tachycardia
widening of QRS
prolongation of QT interval
90
What is the management 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
- IV lipid emulsion is increasingly used to bind free drug and reduce toxicity
- dialysis is ineffective in removing tricyclics
91
What are the features of Rifampicin?
- mechanism of action: inhibits bacterial DNA dependent RNA polymerase preventing transcription of DNA into mRNA
Side effects:
- potent liver enzyme inducer
- hepatitis, orange secretions
- flu-like symptoms
92
What are the features of Isoniazid?
- mechanism of action: inhibits mycolic acid synthesis
Side effects:
- peripheral neuropathy: prevent with pyridoxine (Vitamin B6)
- hepatitis, agranulocytosis
- liver enzyme inhibitor
93
What are the features of ethambutol?
- mechanism of action: inhibits the enzyme arabinosyl transferase which polymerizes arabinose into arabinan
Side effects:
- optic neuritis: check visual acuity before and during treatment
- dose needs adjusting in patients with renal impairment
94
What are the features of pyrazinamide?
- mechanism of action: converted by pyrazinamidase into pyrazinoic acid which in turn inhibits fatty acid synthase (FAS) I
Side effects:
- hyperuricaemia causing gout
arthralgia, myalgia
- hepatitis
95
What is used to treat adrenaline induced ischaemia?
Phentolamine (competitive α-adrenoreceptor antagonist)
96
How does erythromycin help in gastroparesis?
Promotes gastric emptying
97
