Pharm Topics But /3 In 1 Big Topic Flashcards

1
Q

Pharmacodynamic principles. Receptors and subtypes

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2
Q

General description of parasympathetic nervous system from pharmacological point of view (neurotransmitters and receptors

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3
Q

Antihypertensive mode of action of thiazide diuretics and the side effects, osmotic diuretics

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Osmotic diuretics:

Mannitol – the prototypical osmotic diuretic – given intravenously:

10–20% solution

Freely filtered in the glomerulus, poorly reabsorbed in tubules. This results in it remaining in the lumen and “holding” water there by osmotic effects.

Mainly in proximal convoluted tubule (PCT)

Also in descending loop of Henle and collecting tubule.

These are all locations where the nephron is penetrable for water.

Minor Na+ excretion.

Used mainly in situations where it’s important to lose water volume without losing Na+:

Prevention of anuria in ARF due to load of pigments (e.g., hemolysis or rhabdomyolysis).

Infections and hemorrhage.

Used to decrease pathologically elevated intracranial or intraocular pressures (since they increase plasma osmolarity, leading to extraction of water from these compartments and an increase in urine output).

Adverse effects:

Pronounced water extraction from IC compartments and expansion of intravascular and interstitial fluid volume. This can result in:

Acute pulmonary edema.

Heart failure.

Common side effects: headaches, nausea, and vomiting.

Dehydration and hypernatremia in cases of overdose.

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4
Q

Dose-response relationships. Efficacy and potency

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5
Q

Directly acting parasympathomimetics

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Toxicity:
• Especially organophosphates that are used as pesticides have toxic behavior. Most toxic is parathion that can be rapidly lethal if antidote is not administered rapidly upon exposure (muscarinic antidote is atropine!– no effects on N receptor toxicity). Nicotinic toxicity is treated with regenerating active ChE (pralidoxime)
• DUMBBLESS symptoms (diarrhea, urination, miosis, broncoconstriction, bradicardia, excitation of sk.muscles and CNS, lacrimation, salivation and sweating)

Effects of direct and indirect cholinomimetics on major organ systems:
• CNS o o o Complex stimulatory effects Nicotine: elevates mood, alerts and is addictive Phyostigmine: convulsions and in excessive CC causes coma
• Eye o o
• Heart o o o o Contraction (miosis) of the sphincter muscle of the iris Contraction/cyclospasms of the ciliary muscle to accommodate near vision and facilitate outflow of aqueous humor into the canal of Schlemm SA node – negative chronotropic effects (decreased firing rate) Note: Baroreceptor reflexes are activated due to the lower ! blood pressure; this causes a compensatory sympathetic discharge to the heart that can cause tachycardia Atria – negative ionotropic effects (decrease in contractile force) This causes a decrease in the refractory period! AV node – negative dromotropic effects Decreased conduction velocity which causes an increase in ! the refractory period Ventricles – small negative ionotropic effects
• Blood vessels Dilation via the release of EDRF (endothel.derived relaxing factor) o ! NO and possibly other relaxing substances o Not a direct action of cholinomimetics on the blood vessels
• Bronchio Bronchoconstriction
• GI tract Increase in SM contraction, peristalsis – increased motility o o Decreased in tone, relaxation of sphincter muscles ! Except the gastroesophageal sphincters that contracts
• Urinary bladder o Increased contraction of the detrusor muscle o Relaxation of the bladder trigone and sphincters that causes voiding
• Skeletal muscles o Activation of NM end plates that results in contraction
• Exocrine glands o Increased secretion Thermoregulatory sweating, lacrimation, salivation, ! bronchial secretion and GI gland secretion

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6
Q

Calcium channel blockers

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7
Q

Graded and quantal dose-response relationships. Therapeutic index, therapeutic window

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8
Q

Parasympatholytics

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9
Q

Centrally acting sympathoplegic drugs

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10
Q

Agonists and antagonists. Antagonism on the receptor level

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11
Q

Sympathomimetics

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12
Q

Pharmacology of renin/angiotensin system

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o E.g. when ACE inhibitors cannot be tolerated

Used in treatment of hypertension and HF when ACE inhibitors cant be used (e.g. patients that get severe cough or angioedema)

Require once a day dosing

o Losartan differs from the others by undergoing first-pass hepatic metabolism to be converted into an active metabolite •

o Elimination of the drugs is via kidneys and feces Adverse effects are similar to those of ACE inhibitors

No dry cough
o Not used in pregnancy

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13
Q

Antagonism. Non-receptorial antagonism

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14
Q

Non-selective α-adrenoceptor blockers

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15
Q

General description of antiarrhythmic drugs. Vaughan Williams classification

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There are more graphs in the note, check!

Class II (Beta-adrenoceptor blockers):
• ↓ SA and AV nodal activity (by blocking the pacemaker current)
• ↓ slope of phase 4
• Act by blocking the effects of catecholamines at the β1-receptors

Decreasing sympathetic activity on the heart

Making the parasympathetic system the predominant system
• Used in:

Prophylaxis post-MI

The negative inotropic effect decreases the O2 demand

Supraventricular tachyarrhythmias

Decrease conduction through the AV node
• Selective:

Acebutolol, esmolol, metaprolol, nebivolol
• Non-selective:

Propanolol, carvedilol, sotalol

Class III (K+-channel blockers):
• ↓ IK by slowing phase 3
• ↑ APD and ERP
• ↑ QT interval
• Prolongs repolarization markedly
• Used when other anti-arrhythmic fail
• Used in:

A-fib, atrial flutter

Ventricular tachycardias

Sotalol, amiodarone
• Toxicity:

Sotalol – torsades de pointes, excessive β-blockade

Ibutilide – torsades de pointes

Amiodarone – pulmonary fibrosis, hepatotoxicity, hypo/hyperthyroidism, corneal deposits, skin deposits (blue/gray) resulting in photodermatitis, neurologic effects, constipation, CV effects such as bradycardia, AV block and CHF

Class I, II, III, IV drugs

Class IV (Ca2+-channel blockers):
• ↓ conduction velocity, ↑ ERP, ↑ PR interval
• ↓ phase 0 and 4
• ↓ SA and AV nodal activity
• Used in: prevention of nodal arrhythmia, rate control in A-fib
• Toxicity: Constipation, flushing, edema, CV effects (CHF, AV block, sinus node depression)
• Verapamil, diltiazem

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16
Q

Control of receptor expression. Receptor diseases and receptors and disease

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17
Q

β-adrenoceptor blockers

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18
Q

Treatment of myocardial ischemia especially the treatment of angina pectoris

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Calcium channel blockers:
Several types are used in angina:
• Nifedipine, dihydropyridine, diltiazem, verapamil

Mechanism:
• Blockage of the voltage-gated L-type calcium channels
• Most important channels in cardiac and smooth muscle
• Reduce intracellular calcium concentration and m. contractility

Actions:
• Relax blood vessels (lesser extent – uterus, bronchi and gut)
• Rate and contractility of the heart reduced by diltiazem and verapamil
• Also used to treat AV-nodal arrhythmias
• Nifedipine and dihydropyridines evoke greater vasodilation
• Possible resulting in reflex tachycardia
• All reduce blood pressure and the double products in angina
• Effective prophylactic agents in effort and vasospastic angina
• Very important agents in combo with nitrates when treating severe/unstable angina

Other uses:
• Hypertension, supraventricular tachycardia, migraine, preterm labor, stroke and Reynaud’s phenomenon

Toxicity:
• Constipation, pretibial edema, nausea, flushing, dizziness
• Heart failure, AV blockade, sinus node depression
• Mainly in verapamil

Beta-blockers in angina:
• Beneficial antiangial effects
• Decreased heart rate, cardiac force, blood pressure
• Beneficial and detrimental effects
• Increased heart size, longer ejection period
• Reduce – cardiac work, double product and oxygen demand
• Only used prophylactically for angina
• No value in acute attacks
• Effective in preventing exercise-induced angina
• Ineffective against vasospastic form
• Useful in preventing the compensatory effects of the nitrates (tachycardia and increased cardiac force)

Newer drugs for angina:
• Ranolazine – reduces the late prolonged sodium current in the myocardial cells
• Reduction in cardiac force
• Might alter cardiac metabolism and switch the preference for FA out for glucose
• Moderately effective in prophylaxis of angina
• Ivabradine – experimental drug that inhibits funny current in SA node
• Decreased HR and cardiac work

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19
Q

Desensitization, tachyphylaxys and tolerance

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20
Q

Indirectly acting parasympathomimetics

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21
Q

Drugs used in the treatment of hyperlipidemias

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Niacin (nicotinic acid):
• Reduces LDL, cholesterol, triglycerides, and VLDL in addition to often increasing HDL
• In the liver – reduces VLDL synthesis that reduces LDL levels
• In adipose – activates a signaling pathway that reduces hormone-sensitive lipase (HSL) activity and thus decreases plasma FA and TAG
o Consequently reduces LDL formation
• Increased clearance of VLDL by lipoprotein lipase
• Reduces catabolic rate for HDL
• Decreases circulating fibrinogen and increases tissue-plasminogen activator
• Widely used in treatment of hypercholesterolemia, hypertriglyceridemia, and in low levels of HDL

Adverse effects:
• Cutaneous flushing (prevented with aspirin or NSAIDs)
o Probably due to prostaglandins
o Tolerance develops in few days
• Dose-dependent nausea and abdominal problems
• Pruritus and other skin causes
• Moderate increase in liver enzymes
• Severe hepatotoxicity
• Hyperuricemia – 20%
• Impaired carbohydrate tolerance

Fibric acid derivatives (gemfibrozil, fenofibrate):
• Ligands for peroxisome proliferator-activated receptor-alpha (PPAR-α)
o Receptor that regulates transcription of genes involved in lipid metabolism
• Interaction with PPAR-α results in increased synthesis by adipose tissue of lipoprotein lipase
o Enhanced clearance of TAG-rich lipoproteins – endothelial cells
o Stimulation of fatty acid oxidation in liver
• Limits supply of TAG and decreases VLDL synthesis
• Can increase LDL in patients with familial combined hyperlipoproteinemias (increase in VLDL and LDL)
• Used to treat hypertriglyceridemia and are often combined with other cholesterol-lowering drugs for better results on LDL and VLDL

Adverse effects:
• Nausea – very common
• Skin rashes – gemfibrozil
• Decrease in white blood count and hematocrit
• Increased risk of cholesterol gallstones
• In combo with reductase inhibitors, the fibrate increases risk of myopathy

Combination therapy:
• All patients are treated first and foremost with modification of their diet
• Combinations of drugs are often needed to achieve optimal effects

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22
Q

The movement of drugs through biological membranes

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23
Q

Structure-activity relationships demonstrated among sympathomimetics

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24
Q

Drugs used for the treatment of congestive heart failure

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Cardiac glycosides – Digoxin:
• No longer considered first-line drugs in heart failure
• Digoxin inhibits Na+/K+ ATPase of the cell membrane
o Results in small increase in IC Na+
o This changes the transport of Ca2+ out of the cell via Na+/Ca2+
o Increased IC Ca2+ increases the contractile force

• Modifies autonomic outflow – influences electrical properties of the heart

• Effects:
o Increased contractility results in increased ejection
o Decreased end-systolic and end-diastolic size
o Increased cardiac output
o Decrease in the compensatory sympathetic and renal responses
o Decreased sympathetic tone – decreased HR, preload, afterload – this permits the heart to function better
o Early cardiac parasympathomimetic responses
o Increased PR interval and flattening of T waves
o Parasympathetic effects on AV and atria can be blocked with atropine – so we don’t slow the firing rate of AV too much (slow ventricular rate compared to atria)
o Shorter QT, inversion of T and ST depression
o Later arrhythmogenic actions

• Toxic responses:
o Increased automaticity (due to increased IC Ca2+)
o Delayed afterdepolarizations
o Extrasystoles, tachycardia, fibrillation in any parts of the heart
o Premature ventricular beats and bigeminy
o Amplified toxicity occurs in hypokalemia, hypomagnesemia and hypercalcemia
o Interactions with other drugs such as quinidine may increase the serum levels of digoxin even more and cause more toxicity and problems
o Also with amiodarone, verapamil, etc.

• Used in chronic heart failure (positive ionotropic agent)
o Reduces symptoms and improves functional status
o Does not prolong life
o More toxic than the previously discussed drugs
o Long half-life that makes them accumulate in the body
o Dosing is very important and proper monitoring!!!!!
• Used in atrial fibrillation but needs to be monitored closely

Symptoms of toxicity:
• Arrhythmias, nausea, vomiting and diarrhea, confusion and hallucinations (rare) and visual or endocrine abnormalities may occur
• Severe/acute intoxication (suicide/accidental) can result in cardiac arrest
• Detoxification is done with:
o Correcting potassium or magnesium problems
o Antiarrhythmic drugs in not so severe cases
o Digoxin antibodies (digibind) are extremely effective and should always be used if other therapies seem to be failing

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25
Q

Distribution of drugs in the body: the apparent volume of distribution (Vd)

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26
Q

General description of sympathetic nervous system from pharmacological point of view (neurotransmitters and receptors)

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27
Q

Characterization of quinidine, lidocaine, and amiodarone

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o o o Most serious is interstitial lung disease (pulmonary fibrosis)
Risk factors: high dose for prolonged time, patients with decreased lung functions, increased age and preexisting pulmonary disease

Thyroid abnormalities are common since amiodarone is structurally similar to thyroxine (T4)
• Under and overactivity may occur:
o Hypothyroidism and hyperthyroidism

Eye problems:
• Corneal microdeposits (cornea verticillata (vortex)) – 90% when patients take the drug for more than 6 months in high doses (>400mg/day) – not causes any symptoms
• Bluish halo (1/10)
• Optic neuropathy (1–2%)
• Bilateral optic disc swelling and mild/reversible visual field defects can also occur

o o o o GI tract and liver problems:
• Abnormal liver enzymes are common
• Jaundice, hepatitis and hepatomegaly are less common
• Pseudoalcoholic cirrhosis

Skin problems:
• Occurs after long-term treatment (>18 months)
• Light-sensitive blue-gray discoloration of the skin
o Patients should avoid the sun and UV light

Peripheral neuropathy with long-term use
Epididymitis – as the drug accumulates in the head and can cause uni- or bilateral inflammation – resolves with cessation of drug

o o Gynecomastia
Cancer – increased risk in males (dose-dependent)

28
Q

Elimination of drugs: the half-life (T1/2)

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29
Q

Pharmacological tools to influence the sympathetic neurotransmission

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30
Q

Expectorants and antitussives

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31
Q

The clearance

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32
Q

Selective α-adrenoceptor blockers

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33
Q

Pharmacology of the liver and the gall bladder

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There is a graph in tnote, check!

Patterns of injury:
• Biochemical markers (e.g. alanine transferase (ALT), alkaline phosphatase (ALP) and bilirubin) are often used to indicate liver damage
• Hepatocellular (predom. ALT elevation) or cholestatic (predom. ALP increase)
o Mixed injury is very common

Examples:

Hepatocellular: Acetaminophen, Allopurinol, Amiodarone, HAART, NSAIDs

Cholestatic: Anabolic steroid, Chlorpromazine, Clopidogrel, Erythromycin, Hormonal contraception

Mixed: Amitriptyline, Enalapril, Carbamazepine, Sulfonamide, Phenytoin

Zonal necrosis:
• Most common type of drug-induced liver cell necrosis
o Very high levels of ALP leading to acute liver failure
o Caused by:
- Paracetamol (acetaminophen)
- Carbon tetrachloride

Hepatitis:
• Hepatocellular necrosis is associated with infiltration of inflammatory cells
o Three types of hepatitis:
- Viral form: Most common – similar to viral hepatitis
o Phenytoin, isoniazide, halothane
- Focal form: Scattered foci of necrosis with lymphocytes
o Aspirin
- Chronic form: Similar to autoimmune hepatitis
o Methyldopa, diclofenac

Cholestasis:
• Leads to itching and jaundice, biliary cirrhosis
o Three forms:
- Bland: Oral contraceptives, anabolic steroids, androgens
- Inflammatory: Allopurinol, co-amoxiclav, carbamazepine
- Ductal: Chlorpromazine, flucloxacillin

Steatosis:
• TAG accumulation that leads to accumulation of fatty droplets within the hepatocytes
• Accumulation of phospholipids (similar to Tay-Sachs)
• Types:

Granuloma:
• Microvesicular: Aspirin (Reye’s syndrome in children), ketoprofen, tetracycline
• Macrovesicular: Acetaminophen, methotrexate
• Phospholipidosis: Amiodarone, total parenteral nutrition
• Drug-induced hepatic granulomas are usually associated with granulomas in other tissues, and patients tend to have systemic vasculitis and hypersensitivity
o Cause:
- Allopurinol, phenytoin, isoniazid, penicillin

Vascular lesions:
• Due to injury to the vascular endothelium
o Venoocclusive: Chemodrugs and bush tea
o Peliosis hepatitis: Anabolic steroids
o Hepatic vein thrombosis: Oral contraceptives

Neoplasms:
• Described with prolonged exposure to some medications or toxins
o Hepatocellular carcinoma, angiosarcoma, and liver adenomas
o Causes:
- Vinyl chloride, combined oral contraceptive pill, anabolic steroid, arsenic, aflatoxin

Enterohepatic system for drugs:
• If the drug gets stuck in the enterohepatic circulation for a longer time, it might start accumulating in the liver
• Over time, this could result in a normally “harmless” drug accumulating to dangerously high levels in this system, turning into a hepatotoxin

Additional topics to review:
• Drug excretion process in topic 18.1
• Alcoholic hepatitis causing encephalitis

34
Q

Plasma concentrations after repeated administration: loading dose and maintenance dose

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35
Q

Metabolism of chatecholamines and pharmacological modulation

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COMT inhibitors:
• Used in the treatment of Parkinson’s
• COMT usually methylates L-Dopa and dopamine – hence turning them inactive
o Inhibiting this process results in increased concentrations of dopamine and L-Dopa from the corpus striatum
o Decrease fluctuations, improves response, and prolongs “on-time”

• Entacapone (peripheral activity) – non-hepatotoxic
• Tolcapone & Nitecapone (CNS + peripheral) – hepatotoxic

36
Q

Pharmacological treatment of bronchial asthma

A

There is a pic in the note!

• Was commonly used in children

Corticosteroids:
• Beneficial anti-inflammatory agents used for severe asthma
• Systemic (oral) corticosteroids – prednisone
o Toxic and are only used as prolonged treatment when all other drugs have failed to manage asthma
• Local (aerosols) corticosteroids – beclomethasone, budesonide, dexamethasone, flunicolide, fluticasone, and mometasone
o Surface-active and relatively safe
o 1st-line treatment for moderate to severe asthma
• IV corticosteroids are used in acute severe asthma (status asthmaticus) – prednisolone, hydrocortisone
• Corticosteroids reduce synthesis of arachidonic acid by PLA2 and inhibit expression of COX-2
o Bind to intracellular receptors and activate glucose response element
o Results in prevention of inflammation and allergic responses mediated by various cytokines and leukotrienes
• Child treatment with aerosol corticosteroids is thought to prevent the severe, progressive inflammatory changes characteristic of long-standing asthma

Adverse effects of aerosols:
• Oral candidiasis, small degree of adrenal suppression
• Mild growth retardation in children, usually reversible as they grow into adults

Leukotriene antagonists:
• Drugs that interfere with synthesis or action of leukotrienes
• Not as effective as corticosteroids in severe asthma
• Zafirlukast & Montelukast
o Antagonists of LTD4
o Orally active and effective in prevention of exercise-, antigen-, and aspirin-induced bronchospasms
o Not recommended for acute episodes of asthma

Adverse effects:
• Very rarely, Churg-Strauss syndrome and allergic granulomatous angiitis occur – no established connection yet
• Toxicity is generally very low

37
Q

Absorption of drugs and ion trap

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38
Q

Comparison of elimination of acetylcholine (Ach) and norepinephrine/noradrenaline from the synaptic cleft and the possibilities of pharmacological modulation

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39
Q

Therapeutic importance of diuretics, mode of action and classification. Antialdosterone compounds and other potassium-sparing diuretics

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40
Q

Bioavailability. AUC

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41
Q

Compare the effects of norepinephrine/noradrenaline, epinephrine/adrenaline and isoprenaline

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42
Q

Inhibitors of carboanhydrase enzyme, thiazides and other sulfonamide type diuretics, high-ceiling diuretics (loop diuretics) and antidiuretics

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Desmopressin:

Ineffective in nephrogenic diabetes insipidus (DI) and is treated by reversing the underlying cause (if possible) and replacing the free water deficit.

Treatment options for nephrogenic DI:

The diuretic hydrochlorothiazide (a thiazide diuretic) or indomethacin can be used to create mild hypovolemia, encouraging salt and water uptake in the proximal tubule and improving nephrogenic DI.

Amiloride: Blocks lithium uptake and has additional benefits.

Thiazide diuretics are sometimes combined with amiloride to prevent hypokalemia.

Mechanism:

It may seem paradoxical to treat extreme diuresis with a diuretic, but the exact mechanism is not entirely understood.

Thiazide diuretics decrease distal convoluted tubule reabsorption of sodium and water, causing diuresis.

This decreases plasma volume, lowering GFR and enhancing sodium and water absorption in the proximal nephron.

Less fluid reaches the distal nephron, leading to overall fluid conservation.

Antagonists (Conivaptan & Tolvaptan):

Oppose actions of ADH and other naturally occurring peptides acting on the V2 receptor.

These peptides can be overly produced in certain types of tumors (e.g., small cell carcinoma of the lung), causing significant water retention and dangerous hyponatremia.

Condition called syndrome of inappropriate ADH secretion (SIADH).

Treatment of SIADH:

Antidiuretic antagonists (e.g., conivaptan, tolvaptan).

Lithium is also used but has greater toxicity.

43
Q

First pass effect

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44
Q

Synthesis, storage, release and elimination of acetylcholine (Ach). Demonstration of Dale’s experiment

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45
Q

Agents used in anemias

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46
Q

Drug elimination: I. Biotransformation

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• Different types of cytochromes:
o 1A2
o 2C9
o 2C19
o 2E1
o 3A4 and 2D6 – approx. 75% of the active cytochromes

47
Q

Non-adrenergic, non-cholinergic (NANC) transmission

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48
Q

Drugs used in coagulation disorders

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Graph in note.

Direct thrombin inhibitors:
• Based on proteins made by Hirudo medicinalis (medicinal leech):
o Lepirudin, desirudin, bivalirudin, argatroban
- All these are given parenterally
o Dabigatran – orally active
• Used as alternatives in HIT
• Bivalirudin is used in combo with aspirin during percutaneous coronary angioplasty

Direct oral factor Xa inhibitors:
• Rivaroxaban & apixaban
• Rapid onset of action and shorter half-lives than warfarin

Warfarin and other coumarin anticoagulants:
• Small, lipid-soluble molecules that are readily absorbed after oral administration
• Warfarin is highly bound to plasma proteins (>99%)
• Elimination depends on metabolism by cytochrome P450
• Warfarin interferes with the normal post-translational modification of clotting factors in the liver (a process that depends on an adequate supply of reduced vitamin K)
o Inhibits vitamin K epoxide reductase (VKOR) that normally converts vitamin K epoxide to reduced vitamin K
o Actions can be reversed with vitamin K, but recovery requires synthesis of new clotting factors and hence the process is slow
o Rapid reversal can be done by injecting fresh or frozen plasma that contains normal clotting factors

• Warfarin is monitored by prothrombin test (PT) and INR values

• Uses:
o Chronic anticoagulation in all of the clinical situations described before for heparin
o However, warfarin is NEVER used during pregnancy

• Narrow therapeutic window – needs to be monitored tightly since bleeding tendencies are very common

Thrombolytic agents:
• Endogenous tissue plasminogen activator (alteplase, tenecteplase) or protein synthesized by streptococci (streptokinase)
• All are given intravenously and turn plasminogen into plasmin, degrading clots

Uses:
• Alternative drug for percutaneous coronary angioplasty
• Emergency treatment of coronary artery thrombosis
• Contraindicated in patients with cerebral hemorrhage
• Used in acute pulmonary embolism treatment

• Streptokinase:
o Can evoke the production of antibodies that cause it to lose its effectiveness or induce severe allergic reactions.
o Streptokinase can only be used once during a whole lifetime.

Antiplatelet drugs:
• Aspirin, NSAIDs, GP IIb/IIIa receptor inhibitors (abciximab, tirofiban, eptifibatide), antagonists of ADP receptors (clopidogrel, ticlopidine), inhibitors of phosphodiesterase 3 (dipyridamole, cilostazol).

49
Q

Factors influencing the drug elimination

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50
Q

Uptake mechanisms, substrates and inhibitors

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51
Q

Drugs used in acid-peptic disease

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52
Q

Drug elimination: II. Excretion

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53
Q

α2 sympathomimetics and the concept of “false transmitter”

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54
Q

Laxatives, antidiarrheal drugs. Drugs in the treatment of chronic inflammatory bowel disease, antiobesity drugs

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55
Q

Factors influencing the drug effect. Preclinical phase of drug development

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56
Q

Pharmacology of cardiac glycosides

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57
Q

Drugs promoting gastrointestinal motility. Emetics and antiemetic drugs

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58
Q

Drug interactions. Biologicals (biological therapy), special considerations with respect to their development.

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Alterations in pharmacodynamic properties of drugs:
• Co-administration of a receptor antagonist and an agonist for the same receptor.
• Additive interactions: Summing of the effects of two drugs.
o Examples: Combining alcohol with sedatives or combining antihypertensive drugs.
• Potentiation and supra-additive (synergistic) interactions are more rare:
o Synergism: Occurs when two drugs together have a greater combined effect than the sum of their individual effects (e.g., sulfonamide antibiotics and trimethoprim).
o Potentiation: When a drug’s effect is increased by another drug that doesn’t have any related effect (e.g., beta-lactamase inhibitors and clavulanic acid).

Interactions of herbal medications with other drugs:
• Several herbal products are suspected to enhance the activity of:
o Anticoagulants (e.g., garlic, gingko).
o Antidepressants (e.g., ginseng).

Biological therapy (immunotherapy):
• Defined as treatment to stimulate or restore the ability of the immune system.
• Biological therapy is any form of treatment that uses the body’s natural immune system to fight infection or disease, or to protect the body from the immune system (immunosuppressants).
• Forms of biological therapy include:

Monoclonal antibodies (e.g., rituximab for non-Hodgkin’s lymphoma).

Interferons.

Interleukins.

Colony-stimulating factors (CSFs).

59
Q

Positive inotropic substances except cardiac glycosides

A
60
Q

Pharmacotherapeutic approach to exocrine pancreatic diseases

A
61
Q

Clinical phase of drug development.

A
62
Q

Adrenergic neuron blockers and reserpine. Antihypertensive mode of action of β-blockers

A

Tyramine: Cheese effect!!!
• Not a clinically useful drug, but important because it is found in fermented foods such as ripe cheese and Chianti wine.
• A normal byproduct of tyrosine metabolism.
• Normally oxidized by MAO in the GIT, but if the patient is taking MAO inhibitors, it can precipitate serious vasopressor episodes.
• It can enter the nerve terminal and displace stored NE, with released catecholamines acting on adrenoreceptors.

Antihypertensive mode of β-blockers:
• Effective in hypertension because they:
o Decrease heart rate and cardiac output.
o Decrease renin release.
o Neutralize reflex tachycardia caused by vasodilators.
• Especially useful in patients with associated conditions benefiting from the cardioprotective effects of these agents.

Side effects:
• Inducing or exacerbating bronchospasm in predisposed patients.
• Sinus node dysfunction and AV conduction depression.
• Nasal congestion.
• Reynaud phenomenon.
• CNS symptoms such as nightmares, excitement, depression, confusion.

• β-blockers have traditionally been considered contraindicated in patients with congestive heart failure.

63
Q

Botanical/herbal remedies

A