Pharmacology

Question 1

Catecholamines

Answer 1

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

Question 2

Addressing hypotension

Answer 2

1. Anticholinergic or reversal is a2
2. Fluid bolus if Hypovolaemia
3. Start dopamine CRI at pressor rates (lower rates will vasodilate)
4. Give antiarrhthmics
5. If no response to dopamine consider norepinephrine
6. No response to catecholamines consider vasopressin and/or hydrocortisone

Question 3

Dopamine

Answer 3

Precursor to epinephrine
B and A properties depending on dose (b at lower and a at higher)

Modest vasoconstriction and increase in BP

Question 4

Dobutmaine

Answer 4

Synthetic analog to dopamine with primary b1 agonism
Moderately vasodilate and increases forward blood flow in the face of normal BP (increasing CO)

Question 5

Ephedrine

Answer 5

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

Question 6

Norepinephrine

Answer 6

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

Question 7

Phenylephrine

Answer 7

A agonism only
Raises the BP after dopamine ruled ineffective

Question 8

Vasopressin

Answer 8

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

Question 9

Epinephrine

Answer 9

Works on all receptors
Not usually a first choice unless CPR
Increases HR, SVR and CO
Increases arterial BP and pacemaker activity

Question 10

Cardiovascular support drug choice

Answer 10

1. Dopamine and/or dobutamine as increases heart rate and contractility and potentially CO. Modestly increases vasomotor tone; dopamine “pressure” and dobutamine “output”.
2. Norepinephrine

Question 11

Combining catecholamines does what?

Answer 11

Midway effects of both drugs I.e. increases in heart rate and BP without arrhythmia (norepinephrine and dopamine)

Question 12

Which of vascular resistance and cardiac output is more powerful in determining arterial BP

Answer 12

Vascular resistance

Question 13

Arterial vasomotor tone

Answer 13

Primary determinant of visceral and tissue perfusion

Question 14

Vasoconstriction

Answer 14

Good thing unless affecting perfusion in which case dobutamine may be used to modestly vasodilate without affecting BP but improving the forward flow

Question 15

Cortisol and catecholamines

Answer 15

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

Question 16

What are some affects other than cardiovascular catecholamines can have

Answer 16

Increased glucose and lactate
Increased K uptake so Hypokalaemia
Increasing metabolic O2 demand
Impaired PLT

Question 17

Vasopressin

Answer 17

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

Question 18

V1 receptors

Answer 18

Smooth muscles
Vasoconstriction (vasodilation at cerebral, renal, pulmonary and mesenteric vessels)

Question 19

V2 receptors

Answer 19

Renal collecting ducts, endothelial cells, platelets and vascular endothelium
Increased water permeability
Increased vWF release
Stimulation of aggregation
Vasodilation

Question 20

V3 receptors

Answer 20

Posterior pituitary
ACTH release

Question 21

Oxytocin (vasopressin receptor)

Answer 21

Mammary gland, uterus, GIT and endothelium
Contraction
Vasodilation

Question 22

In vitro vasopressin

Answer 22

More potent vasoconstrictor compared to norepinephrine, angiotensin II, phenylephrine

Question 23

Apart from vaso effects what is AVP involved in

Answer 23

Sleep
Memory
Temperature regulation
ACTH release

Question 24

Uses of vasopressin

Answer 24

CPR
Vasodilatory shock
Central diabetes insipidus (desmopressin) - increased ADH action
vWD (desmopressin)
GI disease
Haemorrhagic shock

Question 25

Side effects of vasopressin

Answer 25

Local irritation Tissue necrosis Increased liver and TBil enzymes Reduced platelets Low sodium Anaphylaxis Bronchospasm Water intoxication

Question 26

What BP would warrant immediate therapy with anithypertensives

Answer 26

180/120(>140)

Question 27

Diseases that cause hypertension that warrant therapy

Answer 27

Cushings Hepatic diseases DM Chromocytomas EPO Anaemia

Question 28

ACE Inhibitors

Answer 28

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

Question 29

ATII receptor blockers

Answer 29

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

Question 30

Adrenergic receptor antagonists

Answer 30

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

Question 31

Aldosterone blockers

Answer 31

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

Question 32

Ca blockers

Answer 32

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

Question 33

Arteriolar vasodilators

Answer 33

Usually used in hypertensive crisis because they are very fast acting Dilate arteries and relax resistance I.e. hydralazine, sodium nitroprusside and fenoldopam

Question 34

Hypertensive emergency treatment

Answer 34

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

Question 35

Diuretics

Answer 35

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

Question 36

ADH requires

Answer 36

A functional tubular system otherwise there is inappropriate increase in ADH that requires therapeutic diuretics for water and solute excretion

Question 37

Na and water in the nephron and how this dictates diuretic therapy

Answer 37

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

Question 38

Mannitol (diuretic)

Answer 38

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

Question 39

Acetazolamide/CA inhibitor

Answer 39

Decreases proximal reabsorption resulting in a self-limiting metabolic acidosis Increases distal Na reabsorption Used in glaucoma

Question 40

Furosemide/loop diuretic

Answer 40

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

Question 41

Aquaretics

Answer 41

Act in V2 receptors to promote solute free water clearance Treat FW retention in hypervolaemic and hyponateaemic patients (HF, liver failure, SIADH)

Question 42

Diuretic therapy in renal disease

Answer 42

I.e. mannitol or furosemide Converts Oliguria Will increase dieresis but not improve renal function

Question 43

Diuretic therapy in heart failure

Answer 43

Combination of LOH and DCT diuretics particularly if not fully responsive to furosemide alone

Question 44

Diuretic use in liver failure

Answer 44

Try to reduce portal hypertension and oedema

Question 45

Common causes of GUE and treatment options

Answer 45

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

Question 46

H2RA

Answer 46

Cimeditine, ranitidine Work at gastric parietal cells and compete for gastric acid secretion > reduce gastric acid secretion P450 metabolism Work rapidly

Question 47

PPI

Answer 47

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

Question 48

Sucralfate

Answer 48

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

Question 49

Misoprostal

Answer 49

PG analog that has mucosal protective and antacid properties Acts on parietal cells to reduce gastric acid Helpful in NSAID toxicity

Question 50

Effects of increasing gut pH

Answer 50

More susceptible to bacterial infections

Question 51

Neurokinin-1 antagonist

Answer 51

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

Question 52

5HT3 antagonists

Answer 52

Ondanserron, granisetron, dolasteron Block serotonin receptors (5HT3) both peripherally and centrally to reduce vomiting Liver metabolism Eliminated in urine and bile

Question 53

Metoclopramide

Answer 53

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

Question 54

Promazine derivatives in vomiting patients

Answer 54

Centrally act I.e. chlorpromazine and acepromazine Travel sickness Cardiovascular changes so caution to be used Avoid if substantial liver disease

Question 55

Best prokinetic

Answer 55

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

Question 56

Cholinomimetics as prokinetics

Answer 56

Bethanechol/ranitidine Inhibit ACh Increase colonic motility and gastric emptying

Question 57

Erythromycin

Answer 57

Powerful prokinetic working on motilin receptors Increases lower oesophageal sphincter tone to reduce reflux Increases lower bowel peristalsis ‘Gastric hunger’

Question 58

Opioids

Answer 58

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

Question 59

Morphine, meripidine and methadone can..

Answer 59

Release histamine inducing vasodilation and bronchoconstriction

Question 60

Strongest and weakest analgesic opioids

Answer 60

Fentanyl/remifentanil = strongest Butorphanol = weakest

Question 61

Morphine

Answer 61

Mu opioid agonist Sedation and analgesia May cause histamine release, vomiting, diarrhoea, bradycardia Lasts 4-6h

Question 62

Methadone

Answer 62

Similar to morphine Some NMDA activity Sedation & analgesia Lasts 4-6h

Question 63

Fentanyl/remifentanil

Answer 63

Use to treat severe pain Rapid onset and short duration May induce dysphoria Available in transdermal patches

Question 64

Butorphanol

Answer 64

Kappa agonist Mild pain relief but good sedation Lasts 1-2h Partial mu reversal Ceiling effect

Question 65

Buprenorphine

Answer 65

Partial agonist Mild to moderate pain Longer DOA 8-12h

Question 66

Benzodiazepines

Answer 66

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

Question 67

A2 agonists

Answer 67

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

Question 68

A2 agonist biphasic response

Answer 68

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

Question 69

Drugs eliminated via what body system are subject to enterohepatic recycling? a. Renal b. Hepatic c. Urinary d. Biliary

Answer 69

D

Question 70

Which of the following drugs is an example of an osmotic diuretic? a. Furosemide b. Mannitol c. Atropine d. Vasopressin

Answer 70

B

Question 71

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

Answer 71

C

Question 72

Mycophenolate, ciclosporin, leflunomide, and azothiaprine are examples of what type of drug? a. Immunosuppressive agents b. Antifungals c. Macrolides d. Calcium channel blockers

Answer 72

A

Question 73

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

Answer 73

A

Question 74

Which process is inefficient in the feline, which leads to their reduced ability to metabolize NSAIDs? a. P450 b. Glucuronidation c. Sulfonation d. Reduction

Answer 74

B

Question 75

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

Answer 75

D

Question 76

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

Answer 76

B

Question 77

Which antiemetic is known to inhibit substance P in the vomiting center in the brain? a. Metoclopramide b. Ondansetron c. Chlorpromazine d. Maropitant

Answer 77

D

Question 78

Which of the following would be considered a potassium-sparing diuretic? a. Spironolactone b. Furosemide c. Mannitol d. Torsemide

Answer 78

A