Pharmacology Flashcards
Atracurium
Nondepolarising muscular blocker. 20 minute half life, metabolised by plasma esterases so the drug of choice in hepatic and renal failure
Atropine
Inhibits muscarinic action of Acetylcholine on post ganglionic parasympathetic vagus nerve therefore reducing vagal tone. Side effects of anticholinergic or dry secretions, blurred vision and drowsiness.
Dantrolene
Treatment of malignant hyperthermia, neuroleptic malignant syndrome and may have a role in serotonin syndrome. Thought to interfere with calcium release from the sarcoplasmic reticulum. Difficult to mix and may need multiple repeat doses
Digoxin
2 main modes of action
- AV blockade via stimulation of the vagus nerve to slow conduction and increase the refractory period
- Positive ionotrope via inhibiting Na/K/ATPase pump. This increases intracellular sodium and therefore increases calcium which increases contractility.
Dobutamine
Predominantly a Beta1 angonist causing increased contractility and heart rate. Mild Beta2 and Alpha1 receptor effect causing decreased peripheral and pulmonary vascular resistance.
Esmolol
Cardio selective beta blocker with half life of 9 minutes due to metabolism by plasma esterases
Fentanyl
Synthetic Opioid 100x more potent than morphine. Onset within 1-2 minutes and peak effect 5 minutes, duration 20 minutes
Heparin
Activates antithrombin III to inactivate thrombin and factor Xa.
This prevents fibrin formation, platelet aggregation and inhibits factors 5+8
Hydralazine
Causes direct relaxation of arteriole smooth muscle lasting up to 12 hours. Reflex tachycardia can limit effect so works well in combination with beta blocker
Ipratropium
Antimuscarinic bronchodilator used in asthma and COPD
Isoprenaline
A strong beta 1 and beta 2 agonist causing
- increased heart rate
- increased automaticity
- increased contractility
- reduced diastolic pressure
- increased systolic pressure
-increased myocardial oxygen demand
- bronchodilation
Isoprenaline
A strong beta 1 and beta 2 agonist causing
- increased heart rate
- increased automaticity
- increased contractility
- reduced diastolic pressure
- increased systolic pressure
-increased myocardial oxygen demand
- bronchodilation
Ketamine
Non-comparative antagonist at NMDA receptors and also acts on the mu and kappa opioid receptors. This causes analgesia at low doses 0.25-0.5mg/kg and sedation at higher doses 1mg/kg.
bronchodilating properties probably deriving from two different mechanisms:
- central effect inducing catecholamine release, thereby stimulating B2 adrenergic receptors
- by inhibition of vagal pathways to produce an anticholinergic effect acting directly on bronchial smooth muscle.
Ketamine is metabolised in the liver to an active metabolite - norketamine. This has a potency of around one-third that of ketamine. The metabolites are then excreted renally with an elimination half-life of 2-3 hours in adults.
Cortisol
Endogenous steroid produced from adrenal cortex in response to ACTH from HPA axis.
5% free (active) cortisol the rest bound to albumin and cortisol binding globulin
Actions are complex and multi system
- vascular tone
- anti-inflammatory
- immunomodulating
- stress response (increasing blood glucose etc)
Heparin mode of action
Potentiates the action of antithrombin 3
Measured by APTT or ACT
Reversed by protamine (1mg reverses 100 units) . Give slowly to avoid pulmonary vasoconstriction.
Lactulose
Produces osmotic diarrhoea and discourages proliferation of ammonia-producing organisms
Levosimendan
Sensitises myocardium to calcium via the ATP sensitive sarcolemmal K-channels.
Increases contractility without increasing oxygen demand.
Causes coronary and systemic vasodilation so may need vasopressor (NA +/- vasopressin)
Haemodynamic effects of 24hr infusion persist for 7 days due to active metabolite.
Lidocaine
Anti-arrhythmic suppressing conduction and spontaneous depolarisation of ventricles during diastole.
Used in prevention of ventricular ectopics, VT and VF.
Infusion plus loading dose of 1.5mg/kg
Lidocaine side effects
- Paraesthesia, Muscle twitching, Tinnitus
- Anxiety, Drowsiness, confusion and Convulsions
- Hypotension, bradycardia and asystole
Lorazepam
First line antiepileptic treatment
Slower onset but lower risk of resp depression
6-12 hours duration of action
Metaraminol
Peripheral vasopressor
Sympathomimetic
- alpha 1 adrenergic receptor agonist
- increases NA release to stimulate further alpha 1 and mild Beta 1 adrenergic action
- minimal beta adrenergic effects
Metoclopramide
5-HT3 antagonist working at chemoreceptor trigger zone
Anti emetic which promotes gastric emptying and increases lower oesophageal sphincter tone
Risk of
- neuroleptic malignant syndrome
- extrapyramidal movements
Metformin
• Mechanism of Action:
• Metformin reduces hepatic glucose production (gluconeogenesis) and increases insulin sensitivity in peripheral tissues, particularly muscles.
• It also delays intestinal absorption of glucose, contributing to lower postprandial blood glucose levels.
• Pharmacology:
• Metformin is generally well tolerated, but common side effects include gastrointestinal disturbances (e.g., diarrhea, nausea).
• Rarely, it can cause lactic acidosis, particularly in those with kidney impairment or heart failure.
• Weight-neutral and doesn’t cause hypoglycemia when used alone.
Sulphonylureas
Mechanism of Action:
• Sulfonylureas bind to sulfonylurea receptors (SUR1) on pancreatic beta cells, stimulating insulin release by depolarizing the cells and promoting calcium influx.
• This insulin secretion is independent of blood glucose levels, which can sometimes lead to hypoglycemia.
Pharmacology:
• Taken orally, typically once or twice a day before meals.
• Can cause weight gain and has a higher risk of hypoglycemia, particularly in the elderly or those with kidney impairment.
• Less commonly used as first-line therapy due to the side effect profile but often combined with metformin.
DPP-4 inhibitors e.g. sitagliptin
DPP-4 inhibitors block the enzyme dipeptidyl peptidase-4 (DPP-4), which degrades incretins like GLP-1 (glucagon-like peptide-1).
• Incretins increase insulin secretion and inhibit glucagon release in a glucose-dependent manner (i.e., only when blood glucose is high), thus reducing the risk of hypoglycemia.
Pharmacology:
• Taken orally, generally well-tolerated, and doesn’t cause weight gain or hypoglycemia.
• Common side effects are mild and include upper respiratory tract infections, headaches, or gastrointestinal disturbances.
GLP-1 receptor antagonists e.g Liraglutide
GLP-1 receptor agonists mimic the effects of endogenous GLP-1, stimulating insulin secretion and inhibiting glucagon release in response to meals.
• They also slow gastric emptying and increase satiety, leading to weight loss.
Pharmacology:
• Administered via subcutaneous injections, usually once daily or once weekly.
• Common side effects include nausea, vomiting, diarrhea, and potential risk of pancreatitis.
• They are associated with weight loss and have a low risk of hypoglycemia when used alone.
SGLT2 inhibitors e.g. Dapagliflozin
SGLT2 inhibitors block the sodium-glucose co-transporter 2 in the kidneys, preventing the reabsorption of glucose in the proximal tubule and leading to the excretion of glucose through urine (glycosuria).
• This mechanism lowers blood glucose levels and also has a mild diuretic effect, which may reduce blood pressure.
Pharmacology:
• Taken orally, once daily.
• Side effects include an increased risk of genital and urinary tract infections, dehydration, and ketoacidosis (though rare).
• Associated with modest weight loss and blood pressure reduction.
Metoprolol
Selective B1 antagonist (B2 at higher levels)
Short acting with plasma half time 3-7 hours
Bolus up to 5 mg at 1-2mg per minute
Echinocandin
Caspofungin and micafungin
Covers wide range of Candida
Midazolam
Half life 1-4 hours
Infusion of 0.5-6mg/hr…
CYP450 metabolised so effected by those considerations
Milrinone
Selective phosphodiesterase 3 inhibitor
Causes
- increased cardiac output
- reduced PCWP and SVR
- no significant change in HR or myocardial oxygen consumption
Infusion and loading dose
0.375-0.75 mcg/kg/min
Long half life so hard to titrate
Neostigmine
Cholinesterase inhibitor prolonging ACh action
- enhances parasympathetic activity and motility of the gut
- can be used in NMB reversal
May need atropine / glycopyrolate to counteract associated bradycardia due to increased vagal tone
Nimodipine
Calcium channel blocker with preferential smooth muscle relaxation in the cerebral arteries.
Used to prevent vasospasm in SAH
Nystatin
Antifungal that is not absorbed orally and too toxic for IV use
Used topically for Candida
Octreotide
Somatostatin analogue used to treat carcinoid tumours and acromegaly
Can be used post pancreatic surgery to reduce complications
Second line to terlipressin in variceal haemorrhage
Lidocaine
Class: Amide-type local anesthetic
• Onset: Fast (2-5 minutes)
• Duration: Moderate (1-2 hours for infiltration)
• Metabolism: Hepatic (CYP450 enzymes)
• Mechanism of Action: Blocks voltage-gated sodium channels, stabilizing the neuronal membrane and preventing initiation and propagation of action potentials.
Uses in ICU:
• Local infiltration for minor procedures (e.g., central line placement).
• Antiarrhythmic use (Class IB agent) for ventricular arrhythmias.
• Topical anesthesia for intubation (e.g., nebulized lidocaine).
Adverse Effects:
• Systemic toxicity: CNS effects like dizziness, tinnitus, seizures; cardiovascular effects such as hypotension, bradycardia, and, in high doses, cardiac arrest.
• Allergy: Rare, more common with ester-type LAs.
Bupivicaine
Class: Amide-type local anesthetic
• Onset: Slower than lidocaine (5-10 minutes)
• Duration: Long (4-8 hours depending on dose and administration route)
• Metabolism: Hepatic (CYP450)
• Mechanism of Action: Blocks sodium channels, like lidocaine, but has more potent and longer-lasting effects.
Uses in ICU:
• Epidural or nerve blocks for postoperative or trauma-related pain.
• Peripheral nerve blocks for longer-duration pain relief.
Adverse Effects:
• Cardiotoxicity: Bupivacaine is more cardiotoxic than lidocaine. It can cause severe arrhythmias, bradycardia, hypotension, and cardiac arrest.
• CNS toxicity: Similar to lidocaine, with potential for seizures and coma.
• Lipid Rescue: In case of systemic toxicity, intravenous lipid emulsion can be used to treat bupivacaine-induced cardiotoxicity.
Local anaesthetic toxicity
This is a rare but life-threatening condition that can occur when local anesthetics are accidentally injected into the bloodstream or are administered in high doses.
Symptoms include:
• CNS toxicity: Dizziness, tinnitus, metallic taste, seizures, and coma.
• Cardiovascular toxicity: Hypotension, arrhythmias, bradycardia, and cardiac arrest.
• Management: Involves airway management, cardiovascular support, and administration of intravenous lipid emulsion therapy (lipid sink).
Vasopressin
= antidiuretic hormone
Acts via V1 receptors (G protein coupled) to cause vasoconstriction, more widely distributed receptors than alpha 1 adrenergic receptors
NB preserved vaopressor activity even when acidotic, unlike adrenoceptors which
reduce vasopressor effect when acidotic
V2 receptors on kidney manage antidiuresis and optimise volume status with improved renal perfusion
Phentolamine
- Short acting alpha blocker (alpha-1 + alpha-2)
- typically for patients with phaeochromocytoma
Reduces pulmonary vascular resistance and pulmonary artery pressure
