Tufts Pharmacology NBDE Part II

HTN, alpha1 blocker, inhibits release of norepinephrine

HTN, acts centrally to stimulate alpha receptors

HTN, stimulates alpha2 receptors in CNS

HTN, nonselective beta blocker

HTN, selective beta1 blocker

HTN, directly acts to vasodilate vascular smooth muscle

HTN, diuretic, thiazide, when administered with digitalis, will increase penetration of digitalis into myocardium

HTN, diuretic, high-ceiling or loop acting

Ethyacrinic acid
HTN, loop or high ceiling diuretic, is associated with deafness

HTN, diuretic, potassium sparing

HTN, neuronal blockers, only for severe hypertension, prevents release and causes depletion of catecholamines taken up into storage vesicles and is released like false transmitter, does not cross blood-brain barrier

Captopril, lisinopril
HTN, ACE inhibitors

angina, increases oxygen supply to heart by direct vasodilatory action on smooth muscle in coronary arteries

angina, reduces oxygen demand by preventing chronotropic responses to endogenous epinephrine

angina, Ca2+ channel blocker, decrease oxygen demand by reducing afterload by reducing peripheral resistance via vasodilation

Lidocaine (Type 1B drugs)
arrhythmia, decrease cardiac excitability, for ventricular arrhythmias

arrhythmia, to reverse digitalis induced arrhythmias

Quinidine (Type 1A drugs)
arrhythmia, increases refractory period of cardiac muscle, for supraventricular tachyarrhythmias and atrial fibrillation

arrhythmia, for supraventricular tachyarrhythmias and paroxysmal tachycardia and atrial fibrillation

arrhythmia, decreases rate of AV conduction, for atrial fibrillation and paroxysmal tachycardia

arrhythmia, for paroxysmal tachycardia

CHF, ex: digitalis and digoxin, have positive inotropic effect, increasing force of contraction of myocardium by inhibiting Na+/K+ ATPase and thus increasing Ca2+ influx, reduces compensatory changes associated with CHF like heart size, rate, edema

CHF, ACE inhibitor

Digitalis toxicity
nausea and vomiting, yellow-green vision, extrasystole, AV conduction block
related to coadministration with chlorothiazide

Aspirin mechanisms of action
analgesic effects: inhibits synthesis of prostaglandins
antipyretic effects: inhibits synthesis of prostaglandins in hypothalamus, cutaneous vasodilation
bleeding time: inhibits thromboxane A2 synthesis and thus platelet aggregation slows

Aspirin therapeutic effects
pain relief, antipyretic effects, antirheumatic, anti-inflammatory effects

Aspirin adverse/toxic effects
occult bleeding from GI tract, tinnitus, nausea and vomiting, acid-base disturbance, metabolic acidosis, decreased tubular resorption of uric acid, salicylism, delirium, hyperventilation

no anti-inflammatory activity, is hepatotoxic, does not cause GI upset, liver toxicity esp when combined with alcohol or taking 4g/day, is choice for feverish kid, may induce methemoglobinemia at high doses

Corticosteroids (like Prednisone, Hydrocortisone, Triamcinolone)
inhibit phospholipase A2, enzymatic step that precedes prostaglandin synthetase

much less GI irritation, is anti-inflammatory, will have gastric irritation and bleeding after prolonged use

Diflunisal (Dolobid)
salicylate analgesic, longer half-life than acetaminophen and ibuprofen

mixed agonist-antagonists, has both agonistic and antagonistic activities

mixed agonist-antagonists, has both agonistic and antagonistic activites

antagonist to treat overdose of morphine

used in detox of morphine addicts, is full agonist with analgesic properties, when taken orally is not euphoric in addicts, just acts to produce tolerance and physical dependence, withdrawal is less severe because of long half-life

Morphine effects
respiratory depression, euphoria, sedation, dysphoria, analgesia, constipation, urinary retention

Morphine overdose
coma, respiratory depression, miosis

Morphine mechanism of action
binds mu receptors in CNS
causes vomiting by stimulating medullary chemoreceptor trigger zone
decrease in ventilation due to loss of sensitivity of medullary resp center to CO2

Meperidine, morphine, codeine

is the best opioid for suppressing cough reflex

Competitive muscarinic receptor blockers
atropine, scopolamine, propantheline, are sometimes used to control salivary secretions

competitive muscarinic receptor blocker
blocks vagal reflexive control of heart rate => results in tachycardia

reversible anticholinesterase, acts both centrally and peripherally, sometimes for treating xerostomia

reversible anticholinesterase, acts peripherally only, has some direct ACh-like activity at NMJ => prolongs activity of endogenous ACh, sometimes for treating xerostomia

Direct acting cholinergic agonists
pilocarpine, methacholine, may be used for xerostomia

Irreversible inhibitors of cholinesterase
organophosphates and insecticides

enzyme regenerator used in organophosphate toxicity

agonist at nicotinic receptors, depolarizing NMJ blocker subject to rapid inactivation by plasma pseudocholinesterase, used to prevent laryngospasm
paralyzing dose causes muscle stimulation

non-depolarizing neuromuscular junction blocker

Ganglionic blockers
mecamylamine and hexamethonium, produce orthostatic hypotension

alpha blocker, competitive inhibitor of postjunctional adrenergic receptors, associated with epinephrine reversal

beta blocker, competitive inhibitor of postjunctional adrenergic receptors

depletes norepinephrine by inhibiting reuptake, causes depletiong from storage sites

inhibits release of catecholamines (like norepinephrine)

Alpha methyldopa
acts centrally as false neurotransmitter which gets taken up into storage vesicles and is released with norepinephrine, decreases sympathetic activity, reduces sympathetic outflow via alpha agonist action

stimulates alpha2 receptors in CNS with resulting decrease in sympathetic outflow

causes release of stored norepinephrine and acts at receptor itself

stimulates release of stored norepinephrine and stimulates alpha receptors in CNS

norepinephrine reuptake inhibition and release

TCA antidepressant
norepinephrine reuptake inhibition

MAO inhibitors
blocks enzymatic destruction of norepinephrine

Epinephrine reversal
when epinephrine is administered in the presence of an alpha blocker (Prazosin or Chlorpromaxine), will cause decrease in BP rather than increase because beta-mediated vasodilation predominates

Vagal reflex
injection of pressor dose of norepinephrine may result in decreased heart rate due to activation of baroreceptors that stimulate vagal reflex to reduce heart rate

Alpha1 receptor stimulation
vasoconstriction, urinary retention, mydriasis

Alpha2 receptor stimulation
hypotention, reduces sympathetic outflow from CNS

Beta1 receptor stimulation
increased heart rate, increased force of contraction, positive inotropic and chronotropic actions

Beta2 receptor stimulation
bronchodilation, vasodilation, dilation of skeletal muscle

Levodopa with Carbidopa
levodopa: is a dopamine precursor that can cross the blood brain barrier
carbidopa: is a dopa decarboxylase converter blocker
used to treat Parkinson’s

nonselective alpha blocker, will cause vasodilation

rise in BP due to myocardial stimulation that increases ventricular contraction, increase in heart rate, vasoconstriction because of alpha receptor stimulation

leads to decreased heart rate because of baroreceptor reflexes, stimulates alpha and beta1 receptors

beta2 receptor stimulator

alpha1 receptor agonist

vasoconstrictor that stimulates alpha receptors

beta2 agonist for bronchodilatory effects

Physiological antagonism
two drugs produce opposite effects but don’t act on the same receptor
ex: epinephrine and histamine, epinephrine and nitroglycerin

Idiosyncratic reactions
genetically determined abnormal responses to a drug, are most unpredictable because may not be shown until drug is taken for the first time by a pt
ex: succinylcholine and atypical plasma cholinesterase

modulates the action of inhibitory neurotransmitter GABA, many form active metabolites, is most common drug group given for oral sedation
ex: diazepam, chlordiazepoxide

Benzodiazepines > barbiturates
less addiction potential, less profound CNS depression, larger therapeutic index, less resp depression

Benzodiazepine adverse effects
IV injection of diazepam can cause irritation like thrombophletbitis due to solvent (propylene glycol)

benzodiazepine, Valium, is given most commonly for oral sedation

benzodiazepine, Halcion, is ultrashort acting version

benzodiazepine, water soluble (doesn’t cause thrombophlebitis), shorter acting than valium because it doesn’t have active metabolites, has more rapid and predictable onset of action when given IM than valium

reverses effect of benzodiazepines

CNS depressants, will depress all levels of CNS, are not analgesic, will often induce excessive salivation and bronchial secretion and require use of anticholinergic drug to reduce these, are metabolized by the liver, are classified according to duration of action

action is terminated by redistribution of drug out of the chain, will enter and exit the brain rapidly, thus quick onset and short duration of action

long acting barbiturate

Barbiturate toxicity
overdose kills you because of respiratory depression

Barbiturate contraindications
intermittent porphyria: will enhance porphyrin synthesis and will aggravate the disease
undiagnosed severe pain: may make the pain worse and result in arousal, rage, delirium

Barbiturate toxicity treatment
need to maintain open airway, increase input of afferent stimuli, maintain respiration, administer CNS stimulant

1st generation antipsychotic drugs
Phenothiazine or Haloperidol, specific D2 (dopamine) receptor blocker

Side effects of 1st generation antipsychotic drugs
anticholinergic effects and anti-alpha adrenergic side effects, extrapyramidal stimulation resulting in tardive dyskinesia, may have jaundice due to allergic reaction

2nd generation antipsychotic drugs
Clozapine, block dopamine receptors and serotonin 5HT receptors, treat negative and positive symptoms, have fewer extrapyramidal side effects

mostly dopaminergic receptor blockers, are often used as antiemetic drugs

prototypic phenothiazine, used in treatment of schizophrenia

Tricycline antidepressants
Imipramine or Amitriptyline, are reuptake inhibitors for amine neurotransmitters, were most commonly used in the past, are strong anticholinergics

MAO inhibitors
Tranylcypromine or Phenylene

2nd generation antidepressant drugs
Fluoxetine or Trazadone, much more commonly used now, block amine reuptake or alterations of receptor number

Side effects of 2nd generation antidepressant drugs
anticholinergic side effects

drug of choice for manic phase of manic depression (bipolar disorder)

Corticosteroids or glucocorticoids
suppress immune system in addition to anti-inflammatory activity, so latent infection like TB may go systemic and opportunistic infections like Candidiasis may become more of a problem

Side effects of corticosteroids or glucocorticoids
gastric ulcers, immunosuppression, acute adrenal insufficiency, osteoporosis, hyperglycemia, redistribution of body fat

General anesthesia onset and rate of induction
inversely proportional to solubility of anesthetic in the blood, also influenced by pulmonary ventilation, blood supply to lungs, concentration of anesthetic in inspired mixture

associated with hepatotoxicity, may use atropine before to reduce salivation and bronchial secretions

Stages of anesthesia
I: analgesia
II: delirium
III: surgical anesthesia
IV: medullary paralysis (once you start depressing medullary centers, pt will stop breathing and die)

Ester anesthetics
procaine, tetracaine, cocaine, metabolized by esterases in the plasma and some in the liver

Amide anesthetics
lidocaine, mepivacaine, bupivacaine, prilocaine, dibucaine, metabolized in the liver

Anesthetics mechanism of action
prevent generation of nerve impulses by interfering with sodium transport into neuron, only non-ionized form can penetrate tissue membranes
because inflamed tissue has a lower than normal pH, the amount of non-ionized form available to penetrate is decreased

Short acting anesthetics

Moderate acting anesthetics
prilocaine, mepivacaine, lidocaine

Long acting anesthetics
bupivacaine, tetracaine, etidocaine

interacts with propranolol by slowing down heart via beta receptor blockade and keeping lidocaine in the circulation longer and causing toxicity and by competing for the same enzyme in the liver

can cause methemoglobinemia because of toluidine metabolite called orthotoluidine

Toxic reactions to anesthetic
mostly related to excessive blood levels arising from inadvertent intravascular injection
CNS stimulation because of inhibition of central inhibitory neurons
at higher doses, will inhibit inhibitory and excitatory neurons => generalized state of CNS depression => respiratory depression and death

Epinephrine toxicity
elevated pulse rate
in pt’s with Grave’s disease, will have heightened sympathetic activity and could result in hypertensive crisis

Anesthetics that are vasodilators
procaine, lidocaine, tetracaine, mepivacaine

AHA limit of epinephrine that pt with CV disease can have
normal pt is 0.2mg

Penicillin G
more sensitive to acid degradation, so is usually injected rather than taken orally, not really used that much anymore

best gram negative spectrum

Cross-allergenic with penicillin
cephalosporins and ampicillins are
erythromycin is not

penicillin useful against penicillinase-producing bugs (like staphylococcus)

extended spectrum, specific for Pseudomonas infections and indole-positive Proteus species

higher concentration in bone than in serum, mostly affects gram positive organisms

higher concentration in gingival fluid than in serum, pretty broad spectrum against gram positive and negative cocci and bacilli

Cephalosporins 1st gen
effective against both gram negative and gram positive organisms

Cephalosporins 3rd gen
increased activity against gram negative, greatly decreased activity against gram positive

Prophylaxis no-no’s
don’t use tetracycline because endocarditis is streptococcal infection and some are resistant to tetracyclines

Prophylaxis for prosthetic joint
Keflex 2g, take 1hr before tx

compete with PABA in folic acid synthesis so there is folic acid deficiency

Allergic reactions to penicillins
dermatitis, stomatitis, bronchoconstriction, cardiovascular collapse

Clindamycin side effects
GI upset and pseudomonas colitis

antbiotic, associated with aplastic anemia

Tetracycline adverse effects
liver damage or hepatotoxicity, esp in pregnant pts with history of renal disease, superinfection, photosensitivity, discoloration of newly forming teeth, GI symptoms, diarrhea

Erythromycin estolate
associated with allergic cholestatic hepatitis

Streptomycin adverse effects
8th nerve damage, will affect balance and healing

Amphotericin B adverse effects
nephrotoxicity and hypokalemia

Tetracycline and penicillin
cancel each other out because they ahve opposing mechanisms of action

Tetracycline interactions
will chelate with calcium, reduced by concurrent ingestion of antacids or dairy products

alters rate of renal clearance of penicillin, is a uricosuric agent that tends to enhance excretion of uric acid by reducing renal tubular transport mechanisms

Antibiotics interaction with coumarin
deplete vitK sources so will enhance coumarin anticoagulants

Antibiotics interaction with oral conctraceptives
suppress normal flora involved in active steroids from bile conjugates => more rapid excretion of steroid from body

Macrolide interactions
inhibit metabolism of drugs like seldane, digoxin
erythromycin blocks the metabolism of seldane to antihistamine metabolity => will stay unmetabolized and cause cardiac arrhythmias

What local anesthetics are Amides? All the rest Where are Esters metabolized? Plasma WE WILL WRITE A CUSTOM ESSAY SAMPLE ON ANY TOPIC SPECIFICALLY FOR YOU FOR ONLY $13.90/PAGE Write my sample Where are Amides metabolized? Liver Short acting LAs …

Drugs that effect the sympathetic nervous system are termed adrenergic agonists and adrenergic blockers Adrenergic agonists are also called sympathomimetics or adrenomimetics WE WILL WRITE A CUSTOM ESSAY SAMPLE ON ANY TOPIC SPECIFICALLY FOR YOU FOR ONLY $13.90/PAGE Write my …

Two groups of drugs that affect the sympathetic nervous system: The adrenergic agonists (sympathomimetics or adrenomimetics) and the adrenergic blockers (sympatholytics or adrenolytics) The alpha adrenergic receptors are located in the: vasculature tissues (vessels) of muscle WE WILL WRITE A …

First-Pass Effect Drug absorbed from GI tract and carried to the liver through portal circulation. Some drugs extensively metablized by liver. Only part of drug reaches systemic circulation for distribution theses types of drugs should not be administered PO (lidocaine/some …

alpha 1- found where? – vascular smooth muscle in skin and gut alpha 1- effect? – activates vasoconstriction – during flight or fight want reduced blood flow to skin and gut – End result: VASOCONSTRICTION at skin and gut WE …

parasympathethic nervous system decrease heart rate, nonvascular smooth muscle contracts (increase mobility of digestive muscles, increased bladder motility) sphincters relax eye ciliary muscles contract increase in exocrine gland secretion Sympathetic nervous system Fight or flight increase in HR increase in …

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