Pharmacology Flashcards
Catecholamines
Augment arterial BP, contractility and cardiac output
They will not work without cortisol so may require glucocorticoid given simultaneously in the critically ill
Increase the metabolic O2 demand
Addressing hypotension
- Anticholinergic or reversal is a2
- Fluid bolus if Hypovolaemia
- Start dopamine CRI at pressor rates (lower rates will vasodilate)
- Give antiarrhthmics
- If no response to dopamine consider norepinephrine
- No response to catecholamines consider vasopressin and/or hydrocortisone
Dopamine
Precursor to epinephrine
B and A properties depending on dose (b at lower and a at higher)
Modest vasoconstriction and increase in BP
Dobutmaine
Synthetic analog to dopamine with primary b1 agonism
Moderately vasodilate and increases forward blood flow in the face of normal BP (increasing CO)
Ephedrine
Increases norepinephrine release from the SNS and is a bronchodilator
Modest decrease in HR whilst increasing CO, SVR and arterial BP
Can deplete norepinephrine stores
Norepinephrine
Primarily a agonism
Potent vasoconstriction to increase arterial BP
Will have varying affect on HR and CO depending on volume status
Used when ineffective to dopamine
Phenylephrine
A agonism only
Raises the BP after dopamine ruled ineffective
Vasopressin
Not technically a catecholamine but is a pure vasoconstrictor that may be useful if no response to catecholamines
Will increase SVR due to baroreceptor reflex in response to a decrease in HR/Vol
Epinephrine
Works on all receptors
Not usually a first choice unless CPR
Increases HR, SVR and CO
Increases arterial BP and pacemaker activity
Cardiovascular support drug choice
- Dopamine and/or dobutamine as increases heart rate and contractility and potentially CO. Modestly increases vasomotor tone; dopamine “pressure” and dobutamine “output”.
- Norepinephrine
Combining catecholamines does what?
Midway effects of both drugs I.e. increases in heart rate and BP without arrhythmia (norepinephrine and dopamine)
Which of vascular resistance and cardiac output is more powerful in determining arterial BP
Vascular resistance
Arterial vasomotor tone
Primary determinant of visceral and tissue perfusion
Vasoconstriction
Good thing unless affecting perfusion in which case dobutamine may be used to modestly vasodilate without affecting BP but improving the forward flow
Cortisol and catecholamines
The cardiovascular system doesn’t operate well without cortisol; low cortisol causes vasoparesis and impaired response to catecholamines (CIRCI/RAI) and so low dose hydrocortisone in the critically ill that aren’t responding to catecholamines will likely help improve catecholamine activity
What are some affects other than cardiovascular catecholamines can have
Increased glucose and lactate
Increased K uptake so Hypokalaemia
Increasing metabolic O2 demand
Impaired PLT
Vasopressin
Or known as ADH or AVP
Normally released in response to an increase in osmolality, decreased blood volume or decreased BP
G-coupled receptors that primarily induce vasoconstriction
Inhibited by glucocorticoids, opiates, natriuretic factors and GABA
V1 receptors
Smooth muscles
Vasoconstriction (vasodilation at cerebral, renal, pulmonary and mesenteric vessels)
V2 receptors
Renal collecting ducts, endothelial cells, platelets and vascular endothelium
Increased water permeability
Increased vWF release
Stimulation of aggregation
Vasodilation
V3 receptors
Posterior pituitary
ACTH release
Oxytocin (vasopressin receptor)
Mammary gland, uterus, GIT and endothelium
Contraction
Vasodilation
In vitro vasopressin
More potent vasoconstrictor compared to norepinephrine, angiotensin II, phenylephrine
Apart from vaso effects what is AVP involved in
Sleep
Memory
Temperature regulation
ACTH release
Uses of vasopressin
CPR
Vasodilatory shock
Central diabetes insipidus (desmopressin) - increased ADH action
vWD (desmopressin)
GI disease
Haemorrhagic shock
Side effects of vasopressin
Local irritation
Tissue necrosis
Increased liver and TBil enzymes
Reduced platelets
Low sodium
Anaphylaxis
Bronchospasm
Water intoxication
What BP would warrant immediate therapy with anithypertensives
180/120(>140)
Diseases that cause hypertension that warrant therapy
Cushings
Hepatic diseases
DM
Chromocytomas
EPO
Anaemia
ACE Inhibitors
Inhibit the conversion of ATI > ATII increasing bradykinin and reducing plasma volume
They induce arterial and veno dilation
Reduce aldosterone release so sodium and water excretion increased
Used for all forms of hypertension but can reduce it too much
I.e. enalipril, benazipril, ramipril and lisonopril
ATII receptor blockers
May be a safer antihyprtensive for those experiencing renal insufficiency
Dose-dependant fall in BP with minimal effects on HR and CO
I.e. Losartan, irbesartan, telmisartan
Adrenergic receptor antagonists
Block A and/or B
I.e. propranolol, atenolol, prazosin
B blockade = decreased renin, decreased HR, decreased adrenergy and decreased contractility
A blockade = antagonise contriction
Used when other anti hypertensives fail or in tachydysrhythmias, may also decrease bladder sphincter tone
Aldosterone blockers
I.e spironalactone
DCT and collecting ducts and decrease sodium reabsorption and decrease K excretion
Weak diuretic effect
If used with other hypertensives may induce renal insufficiency
Ca blockers
I.e. amlodipine, diltiazem
Reduce the Ca influx into smooth muscle cells reduces peripheral VR
Used in hypertensive crisis (arterial vasodilators may also be preferable)
#1 choice in CKD
Tachycardia, constipation, vomiting and weakness not uncommon
Arteriolar vasodilators
Usually used in hypertensive crisis because they are very fast acting
Dilate arteries and relax resistance
I.e. hydralazine, sodium nitroprusside and fenoldopam
Hypertensive emergency treatment
Aim to reduce BP 25% in first hour
Aim to reduce BP to 160/110-100 in the next 2-6h
I.e. sodium nitroprusside, hydralazine (may elect amlopidine)
* ischaemia will occur if done too rapidly
Diuretics
Correct water and electrolyte excess
Act on the nephron to block the reabsorption of water and solute I.e. Na increasing there urinary excretion
Kidneys: regulate the absorption and excretion of water and solutes and rely on ADH to do so
ADH requires
A functional tubular system otherwise there is inappropriate increase in ADH that requires therapeutic diuretics for water and solute excretion
Na and water in the nephron and how this dictates diuretic therapy
Na highest in the PCT and LOH therefore diuretics such as mannitol, acetazolamide and furosemide better for dieresis and spironalactone and thiazides weaker as act on the more distal convoluted tubule area
Mannitol (diuretic)
Osmotic diuretic that increases the osmolality of the ECF so fluid moves into this compartment and into IVS
Freely filtered by the glomerulus
No tubular reabsorption
Increasing fluid dieresis
Decrease renal vascular resistance
Decreases cerebral oedema
0.25-1g/kg
Acetazolamide/CA inhibitor
Decreases proximal reabsorption resulting in a self-limiting metabolic acidosis
Increases distal Na reabsorption
Used in glaucoma
Furosemide/loop diuretic
Inhibits Na-K-Cl at the loop of Henle
Marked natriuesis and dieresis and causes an osmotic gradient shift
Increases renal O2 parenchymal supply and decreases renal resistance
Increases ECF fluid removal
Used in CHF and fluid overload as well as Oliguria
Aquaretics
Act in V2 receptors to promote solute free water clearance
Treat FW retention in hypervolaemic and hyponateaemic patients (HF, liver failure, SIADH)
Diuretic therapy in renal disease
I.e. mannitol or furosemide
Converts Oliguria
Will increase dieresis but not improve renal function
Diuretic therapy in heart failure
Combination of LOH and DCT diuretics particularly if not fully responsive to furosemide alone
Diuretic use in liver failure
Try to reduce portal hypertension and oedema
Common causes of GUE and treatment options
Anoxia to the gastrointestinal mucosa such as in hypovolaemic shock and drugs such as NSAIDS. Stress also (SIRS, masses etc)
H2RA, PPI, prostaglandin analogs are some options for treatment
H2RA
Cimeditine, ranitidine
Work at gastric parietal cells and compete for gastric acid secretion > reduce gastric acid secretion
P450 metabolism
Work rapidly
PPI
Irreversible inhibit H-K ATP in luminal parietal cells > stopping gastric secretion and reducing gastric reflux and duodenal ulcers
I.e. omeprazole, pantoprazole, esomeprazole
First pass metabolism
Peak effect after 2-5 days
More effective than H2RA
Sucralfate
Viscous and binds tightly to epithelial cells creating a physical barrier whilst adhered to gastric ulcer or erosion
Signals PG to promote mucosal repair
Can absorb some drugs I.e. enro
Misoprostal
PG analog that has mucosal protective and antacid properties
Acts on parietal cells to reduce gastric acid
Helpful in NSAID toxicity
Effects of increasing gut pH
More susceptible to bacterial infections
Neurokinin-1 antagonist
Maropitant
Reduces substance P in CNS and NK-1 in the gut
Must be over 11 weeks to avoid bone marrow suppression
Good for visceral pain
First-pass metabolism in the liver
5HT3 antagonists
Ondanserron, granisetron, dolasteron
Block serotonin receptors (5HT3) both peripherally and centrally to reduce vomiting
Liver metabolism
Eliminated in urine and bile
Metoclopramide
Both antidopaminergic and 5HT3 blocker reducing nausea and vomiting (block CRTZ)
Less effective in cats as lower dopaminergic receptors
Gastric prokinetic when given as CRI (increases transit time and reduces reflux)
- don’t give if GI obstruction
Promazine derivatives in vomiting patients
Centrally act
I.e. chlorpromazine and acepromazine
Travel sickness
Cardiovascular changes so caution to be used
Avoid if substantial liver disease
Best prokinetic
Cisapride as stronger effects than most other prokinetics I.e. metoclopramide and erythromycin
Increases gastric emptying
Increases lower oesophageal sphincter tone
Not helpful in megaoesophagus as this is striated muscle
Good for idiopathic constipation
Cholinomimetics as prokinetics
Bethanechol/ranitidine
Inhibit ACh
Increase colonic motility and gastric emptying
Erythromycin
Powerful prokinetic working on motilin receptors
Increases lower oesophageal sphincter tone to reduce reflux
Increases lower bowel peristalsis
‘Gastric hunger’
Opioids
Have little cardiovascular effects when given within therapeutic range
Have substantial effects on the respiratory system so care to be taken (pontine and medullary centres)
Stereospecific receptor binding throughout CNS and the peripheral system
Metabolised by the liver and excreted by the kidneys
Some can induce an excitatory response particularly if given with MAOIS and other antidepressants
Most increase ADH so cause urine retention
Decrease GI motility
Morphine, meripidine and methadone can..
Release histamine inducing vasodilation and bronchoconstriction
Strongest and weakest analgesic opioids
Fentanyl/remifentanil = strongest
Butorphanol = weakest
Morphine
Mu opioid agonist
Sedation and analgesia
May cause histamine release, vomiting, diarrhoea, bradycardia
Lasts 4-6h
Methadone
Similar to morphine
Some NMDA activity
Sedation & analgesia
Lasts 4-6h
Fentanyl/remifentanil
Use to treat severe pain
Rapid onset and short duration
May induce dysphoria
Available in transdermal patches
Butorphanol
Kappa agonist
Mild pain relief but good sedation
Lasts 1-2h
Partial mu reversal
Ceiling effect
Buprenorphine
Partial agonist
Mild to moderate pain
Longer DOA 8-12h
Benzodiazepines
Used as first line anticonvulsants in most patients unless HE/PSS
Works on inhibitory GABA receptors to potentialities GABA and may antagonise serotonin
Sedation, hypnosis, amnesia, anticonvulsant, skeletal muscle relaxation
Diazepam highly protein bound whilst midazolam is water soluble
Effects from sedative to excitatory and best given with an opioid to combat this
Midazolam at 0.005-0.4mg/kg may stimulate the appetite
A2 agonists
Used for sedation and analgesia
Decrease autonomic responses by reducing norepinephrine release
Inhibit ADH/insulin (Diuresis and increased glucose)
Potentiate opioid analgesia even at low doses
Can decrease anaesthetic drug requirements <80%
Cardiovascular response is biphasic
Arrhythmia associate with bradycardia and reduced CO warrants reversal and +- anticholinergic
A2 agonist biphasic response
Initially increased BP and SVR, decrease HR and CO
Then… decreased BP, HR and CO may remain reduced, variable SVR.
- watch whole body perfusion, core organs usually remain perfused but other tissues may not
Drugs eliminated via what body system are subject to enterohepatic recycling?
a. Renal
b. Hepatic
c. Urinary
d. Biliary
D
Which of the following drugs is an example of an osmotic diuretic?
a. Furosemide
b. Mannitol
c. Atropine
d. Vasopressin
B
Which of the following drugs is the best choice for a patient in congestive heart failure with hypotension?
a. Dopamine
b. Epinephrine
c. Dobutamine
d. Norepinephrine
C
Mycophenolate, ciclosporin, leflunomide, and azothiaprine are examples of what type of drug?
a. Immunosuppressive agents
b. Antifungals
c. Macrolides
d. Calcium channel blockers
A
What is the movement of a drug from the site of administration to the circulatory system called?
a. Absorption
b. Distribution
c. Metabolism
d. Elimination
A
Which process is inefficient in the feline, which leads to their reduced ability to metabolize NSAIDs?
a. P450
b. Glucuronidation
c. Sulfonation
d. Reduction
B
In the absence of an initial loading dose, a CRI will not reach steady-state plasma concentrations for how long?
a. One hour
b. One half-life
c. 3–5 hours
d. 3–5 half-lives
D
A drug that binds to a receptor and blocks its response is known as what?
a. Agonist
b. Antagonist
c. Partial agonist
d. Mixed agonist/antagonist
B
Which antiemetic is known to inhibit substance P in the vomiting center in the brain?
a. Metoclopramide
b. Ondansetron
c. Chlorpromazine
d. Maropitant
D
Which of the following would be considered a potassium-sparing diuretic?
a. Spironolactone
b. Furosemide
c. Mannitol
d. Torsemide
A
