Pharmacology Flashcards
How do you calculate maintenance dose?
Maintenance dose = Cp(ss) x CL / Bioavailability
Where Cp(ss) is plasma conc at steady state and CL is clearance. Bioavailability is 1.0 for IV drugs. Note that the units are in mg/min
How do you calculate half life?
Vd x 0.7 / CL
Where Vd is volume of distribution and CL is clearance.
How do you calculate loading dose?
Loading dose = Vd x Cp(ss) / Bioavailability
Where Vd is volume of distribution and Cp(ss) is plasma conc at steady state.
Describe the site of action for the following diuretics:
Acetazolamide
Mannitol
Frusemide
Thiazides
Amiloride
Spironolactone
Carbonic anhydrase works at proximal tubule (HC03-)
Mannitol is an osmotic diuretic and works at the PT and dLH
Loop D’s work at the aLH (NaK2CL-)
Thiazides work at the DCT (NaCl sym)
Pot sparing D’s work at CD
Describe the site of action for the following diuretics:
Acetazolamide
Mannitol
Frusemide
Thiazides
Amiloride
Spironolactone
Define Clearance:
How do you calculate Clearance?
“The volume of plasma CLEARED of drug per unit time”
CL = rate of elimination of drug / plasma drug concentration
CL = Vd x Ke
What is zero-order elimination?
What are some classic examples?
The rate of elimination is constatn regardless of plasma concentration.
Examples include Phenytoin, Ethanol, and Aspirin.
What is first-order elimination?
The rate of elimination is proportional to the drug concentration, i.e. a constant fraction is being eliminated per unit time.
Applies to most drugs.
How does urine pH affect drug elimination?
How do we take advantage of that?
Ionized species are trapped in urine and cleared quickly.
Weak acids such as Aspirin, Phenobarbital, and Methotrexate are trapped in basic urine (Rx - Bicarbonate)
Weak bases such as Amphetamines and TCAs are trapped in acidic urine (Rx - Ammonium chloride)
What are the two phases of Drug Metabolism?
Which phase is affected in older age?
Phase 1 - Reduction, Oxidation, Hydrolysis with Cytochrome P450.
Phase II - Conjugation; Methylation, Glucoronidation, Acetylation, Sulfation.
Geriatric patient have More GAS (phase II > I)
Drug efficacy versus drug potency?
Describe the changes seen with Vmax and EC50 when competitive and non-competitive antagonists are introduced (with examples):
Describe the divisions of the autonomic nervous system in terms of:
Preganglionic NT and length
Postganglionic NTs and effector groups
Describe the general schematic of the secondary messenger system:
List 5 examples of secondary messenger systems:
cAMP system
Phosphoinisitol system
Tyrosine Kinase system
Arachidonic acid system
cGMP system
What are the G-protein-coupled receptors?
(Alpha and Beta Males Don’t Hate Vegans)
Alpha 1 and Alpha 2
Beta 1, 2, 3
Muscarinic 1, 2, 3
Dopamine 1 and Dopamine 2
Histamine 1 and 2
Vasopressin 1 and 2
Match the G-protein coupled receptor to their G-protein class:
(after QISSeS, you get a QIQ out of SIQ, Super Qinky Sex)
(A1=Q) (A2=I) (B1=S) (B2=S) (B3=S)
(M1=Q) (M2=I) (M3=Q)
(D1=S) (D2=I)
(H1=Q) (H2=S)
(V1=Q) (V2=S)
What are the roles, effector molecules, and secondary molecules of Gs, Gi, and Gq?
Gs = Stimulatory Gi = inhibitory
Gq = both
Gs and Gi use Adenyl cyclase and Protein Kinase A
Gq uses Phospholipase C and Protein Kinase C
What are the two broad classes of cholinomimetic agents?
Direct agonists of the ACh receptor
and
Anticholinesterases
List the direct choline agonists:
Bethanechol
Carbachol
Methacholine
Pilocarpine
What is the action and application of:
Bethanechol?
Carbachol?
Bethanechol activates bladder and bowel smooth muscle (ileus, urinary retention)
Carbachol is a carbon copy of ACh (constricts pupil and relieves pressure in OAG)
Both are resistant to AChE
What is the action and application of:
Methacholine?
Pilocarpine?
Methacholine stimulates M receptors in airways for asthma testing.
Pilocarpine is a potent stimulator of sweat, tears, and saliva (OAG, CAG, Xerostomia)
List the commonly used anticholinesterases:
What are their uses?
Galantine, Donepezil, and Rivastigmine (Alzheimer’s)
Edrophonium (Dx MG)
Neostigmine (Reversal NM blockade)
Physostigmine (Antidote for Ach toxicity)
Pyridostigmine (Long acting Rx for MG)
What is the pathophysiology of Organophosphate poisoning?
What are the characteristic signs/symptoms?
Organophosphates irreversibly bind AChE.
Diarrhoea, Urination, Meiosis, Bronchospasm, Bradycardia, Excitation of Skeletal muscle and CNS, Lacrimation, Sweating, Salivation.
Describe the type of drug, organ system, and application of:
Tropicamide
Benztropine
Glycopyrrolate
All are muscarinic antagonists:
Tropicamide - Eye - Mydriasis and Cycloplegia
Benztropine - CNS - Acute dystonia
Glycopyrrolate - GI - Reduce secretions
Describe the type of drug, organ system, and application of:
Hyoscyamine
Ipratropium
Oxybutynin
Scopolamine
All are muscarinic antagonists:
Hyoscyamine - GI - Antispasmodic
Ipratropium - Resp - COPD and Asthma
Oxybutynin - GU - Bladder spasm
Scopolamine - CNS - Nausea
What is the role of Atropine in Organophosphate poisoning?
Blocks DUMBBeLSS
Cannot block Excitation of CNS and Skeletal Muscle as these are mediated by nicotinic receptors.
What is the action and application of the following sympathomimetic/s?
Albuterol / Salmeterol
ß2 > ß1
Albuterol for acute asthma/COPD
Salmeterol is a LABA
What is the action and application of the following sympathomimetic/s?
Dobutamine
ß1 > ß2, a1
Used in heart failure (ino>chrono)
Cardiac stress testing.
What is the action and application of the following sympathomimetic/s?
Dopamine
D1 = D2 > ß > a
Can be used in unstable bradycardia, HF, shock
Inotropic and chronotropic effects at lower doses (ß)
Vasoconstriction at higher doses (a)
What is the action and application of the following sympathomimetic/s?
Epinephrine
ß > a
Used for anaphylaxis, asthma, OAG
Alpha effects predominate at higher doses
Significantly stronger ß2 than NE
What is the action and application of the following sympathomimetic/s?
Fenoldopam
D1
Postoperative hypotension, hypertensive crisis
Vasodilator and promotes natriuresis
What is the action and application of the following sympathomimetic/s?
Isoproterenol
ß1 > ß2
Bradycardia or heart block. By activating ß1 adrenergic receptor in the heart, it induces positive chronotropic and inotropic effects.
Can WORSEN ISCHAEMIA
What is the action and application of the following sympathomimetic/s?
Midodrine
a1
Autonomic insufficiency and postural hypotension.
What is the action and application of the following sympathomimetic/s?
Mirabegron
ß3
Urinary urge incontinence or overactice bladder.
What is the action and application of the following sympathomimetic/s?
Norepinephrine
a1 > a2 > ß1
Hypotension, shock.
What is the action and application of the following sympathomimetic/s?
Phenylephrine
a1 > a2
Hypotension, occular procedures, rhinitis.
What is the action of Amphetamine?
What are its applications?
Indirect general sympathetic agonist and reuptake inhibitor, also releases stored catecholamines.
Narcolepsy, obesity, ADHD.
What is the action of Cocaine?
What are its applications?
Indirect general sympathomimetic agnoist and reuptake inhibitor.
Causes vasoconstriction and LA.
What is the risk of using ß-blockers in the setting of cocaine intoxication?
Unopposed a1 activity and extreme hypertension.
What is the action of Ephedrine?
What are its applications?
Indirect general sympathetic agonist, releases stored catecholamines.
Nasal decongestion, urinary incontinence, hypotension.
What are the effects of NE, Epinephrine, Isoproterenol, and Dopamine on HR, BP, and PVR?
Name two sympatholytics:
What are their clinical roles?
(Both are alpha-2 agonists)
Clonidine - Hypertensive urgency
a-methyldopa - Hypertension in pregnancy
What are the actions and applications of:
Phenoxybenzamine
Phentolamine
Both are non-selective alpha blockers.
Phenoxybenzamine is irreversible (phaeo)
Phentolamine is reversible (MAOIs on tyramine)
What are the actions and applications of:
Prazocin
Terazocin
Doxazosin
Tamsulosin
Selective alpha-1 blockers.
BPH
Hypertension (not Tamsulosin)
Prazocin for PTSD
What is the action and application of:
Mirtazipine?
Selective alpha-2 blocker.
Depression.
Increased apettite.
What is the influence of phentolamine on the effects of:
Epinephrine?
Phenylephrine?
Phentolamine is a reversible non-selective alpha blocker.
It blunts the alpha agonism of Epinephrine and, because Epinephrine is both an alpha and beta agonist, the beta response (hypotension and reflex tachycardia) prevail.
Phenylephrine, which only stimulates alpha receptors, merely has a suppression of its usual pressor effect.
How can you recall the selectivity of Beta-blockers?
Selective beta antagonists (ß1 > ß2) start with letters from the first half of the alphabet (A-M), non-selective antagonists mostly start wtih letters from N-Z.
What is the role of non-selective alpha + beta antagonists?
What additional property do they have?
Beta blockade AND vasodilatory properties.
NB: odd suffixes (-alol, -ilol)
What are the sources and actions of:
Tetrodotoxin?
Ciguatoxin?
Tetrodotoxin comes from pufferfish.
Ciguatoxin comes from reef fish (moray, barracuda, snapper).
Both affect (bind to, and open respectively) Na+ channels.
What is Scombroid poisoning?
Histamine poisoning by spoiled dark-meat fish species.
Bacterial histadine decarboxylase converts histidine to histamine. Mimics anaphylaxis. Similar treatment.
List 8 common medication classes that are included in the Beers criteria:
Anticholinergics, antihistamines, antidepressants, benzodiazepines, opioids
Alpha-blockers
PPIs
NSAIDS
What is the toxicity treatment for:
Antimuscarinic OD
Arsenic
Copper
Cyanide
Physostigmine
Dimercaprol
Penicillamine
Nitrite + thiosulphate, hydroxycobalamin
What is the toxicity treatment for:
Digitalis
Mercury
Lead
Methemoglobin
Anti-dig Fab fragments
Dimercaprol, succimer
Dimercaprol, succimer, EDTA
Methylene blue, vitamin C.
What drug can be used to treat pulmonary hypertension?
How does it work?
Bosentan.
An endothelial-receptor antagonist that blocks the effects of endothelin (a potent vasocontrictor and promoter of endothelial proliferation).
How does Timolol treat glaucoma?
How do cholinergic agonists treat glaucoma?
Timolol and other non-selective beta-blockers work by diminishing the secretion of aqueous humour by the ciliary epithelium.
Pilocarpine causes miosis, opening up the angle and access to the meshwork. Cholinergic agonists also promote a more spherical lens, which helps relieve the angle.
Compare the action of Propranolol in thyrotoxicosis to the action of PTU and Methimazole:
Propranolol reduces the sympathetic outflow characteristic of a thyroid storm, and also reduces the peripheral conversion of T4 to T3 by inhibiting iodothyronine deiodinase.
PTU and Methimazole decrease thyroid hormone synthesis by inhibiting thyroid peroxidase.
Describe which part of the cardiac action potential curve the various classes of anti-arrhythmic agents work:
List the Class 1A antiarrhythmic agents:
What channel do the Class 1 antiarrhythmic agents block?
(the Queen Proclaims Diso’s Pyramid)
Quinidine, Procainamide, Disopyramid
Sodium channels.
List the Class 1B antiarrhythmic agents:
(I’d Buy Liddy’s Mexican Taco’s)
Lidocaine, Mexiletine
List the Class 1C antiarrhythmic agents:
(Can I have Fries, Please)
Flecainide, Propafenone
List the Class II antiarrhythmic agents:
What receptors do they block?
Metoprolol, Propanolol, Esmolol, Atenolol, Timolol, Carvedilol.
Beta receptor blockers.
List the Class III antiarrhythmic agents:
What channel do they block?
(AIDS)
Amiodarone
Ibultilide, Dofetilide
Sotalol
Potassium channels.
List the Class IV antiarrhythmic agents:
What channel do they block?
Verapimil, Diltiazem.
Calcium channels.
Lispro, Aspart, and Glulisine are what type of Insulin preparations?
Rapid acting.
Detemir and Glargine are what type of Insulin preparations?
Long acting.
How do Lumacaftor and Ivacaftor work?
Lumacaftor and Ivacaftor are drugs used to treat CF.
They demonstrate the pathophysiology of CF nicely; Lumacaftor is a chaperone protein and Ivacaftor is a potentiator of CFTR.
In conjunction they can be used to treat the deltaF508 mutation, (67% of CF). Ivacaftor alone can be used to treat the G551 mutation (4-5% of CF).
What class of lipid-lowering agent are:
Cholestyramine
Colestipol
Colesecelam
How do they work?
What are the side effects?
Bile acid resins work by oreventing intestinal reabsorption of bile acids. The liver must utilise cholesterol to make more.
Side effects include GI upset and reduced absorption of drugs and vitamins.
What class of lipid-lowering therapy are the statins?
How do they work?
What are the side effects?
Statins inhibit the conversion of HMG-CoA to mevalonate, a cholesterol precursor.
Side effects include hepatotoxicity and myopathy.
